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Sample records for carcinoma invasive progression

  1. Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma

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    Shin, Kunyoo; Lim, Agnes; Odegaard, Justin I.; Honeycutt, Jared D.; Kawano, Sally; Hsieh, Michael H.; Beachy, Philip A.

    2014-01-01

    Understanding how malignancies arise within normal tissues requires identification of the cancer cell of origin and knowledge of the cellular and tissue dynamics of tumor progression. Here we examine bladder cancer in a chemical carcinogenesis model that mimics muscle-invasive human bladder cancer. With no prior bias regarding genetic pathways or cell types, we prospectively mark or ablate cells to show that muscle-invasive bladder carcinomas arise exclusively from Sonic hedgehog ( Shh )-expr...

  2. Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness.

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    Xu, Y; Chen, Q; Li, W; Su, X; Chen, T; Liu, Y; Zhao, Y; Yu, C

    2010-06-10

    Amplified in breast cancer 1 (AIB1) is a transcriptional coactivator for nuclear receptors and other transcription factors. AIB1 has an important role in malignancy of several cancers such as breast and prostate cancers. However, its involvement in human hepatocellular carcinoma (HCC) progression remains unclear. Here, we found that AIB1 protein was overexpressed in 23 of 34 human HCC specimens (68%). Down-regulation of AIB1 reduced HCC cell proliferation, migration, invasion, colony formation ability and tumorigenic potential in nude mice. These phenotypic changes caused by AIB1 knockdown correlated with increased expression of the cell cycle inhibitor p21(Cip1/Waf1) and decreased Akt activation and the expression of proliferating cell nuclear antigen (PCNA) and matrix metallopeptidase MMP-9. In agreement with these findings, clinical AIB1-positive HCC expressed higher levels of PCNA than AIB1-negative HCC. A positive correlation was established between the levels of AIB1 protein and PCNA protein in HCC, suggesting that AIB1 may contribute to HCC cell proliferation. In addition, MMP-9 expression in AIB1-postive HCC was significantly higher than that in AIB1-negative HCC, suggesting that AIB1-postive HCC may be more invasive. Collectively, our results show that overexpression of AIB1 promotes human HCC progression by enhancing cell proliferation and invasiveness. Therefore, AIB1 is a master regulator of human HCC growth and might be a useful molecular target for HCC prognosis and treatment.

  3. Relationship between the Expression of CD44v6 and Development, Progress, Invasion and Metastasis of Laryngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    LIU Banghua; KONG Weijia; GONG Shusheng; YANG Chengzhang; WANG Guangping; ZHU Lixin

    2005-01-01

    Summary: The expression of CD44v6 and its relationship with the development, progress, invasion and metastasis of laryngeal carcinoma was investigated. The expression and content of CD44v6 mRNA in tissuess were detected by both RT-PCR and FCM which were respectively extracted from normal laryngeal mucosa, leukoplakia of larynx, laryngeal papilloma, polyp of vocal cord, tissues of laryngeal carcinoma, metastatic and nonmetastatic lymph nodes of neck, and tissues close to carcinoma. The outcome of RT-PCR indicated that the expression rate of CD44v6 mRNA involved in tissues of laryngeal carcinoma and metastatic lymph nodes of neck was the highest (90 %-100 %) compared with that of leukoplakia of larynx, laryngeal papilloma, tissues close to carcinoma by 0.5 cm (55.56 %-60.00 %) and that of normal laryngeal mucosa, polyp of vocal cord, nonmetastatic lymph nodes and tissues close to carcinoma by 1.0 cm was the lowest ( 13.33 %-20 %). The result from FCM was highly consistent with that from RT-PCR. It was suggested that CD44v6 was closely related with the development, progress, invasion and metastasis of laryngeal carcinoma. The outcome from the tissues close to carcinoma by different distance could do help to the determination of incisal edge in surgery abstractly.

  4. Elevated expression of LSD1 (Lysine-specific demethylase 1 during tumour progression from pre-invasive to invasive ductal carcinoma of the breast

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    Serce Nuran

    2012-08-01

    Full Text Available Abstract Background Lysine-specific demethylase1 (LSD1 is a nuclear protein which belongs to the aminooxidase-enzymes playing an important role in controlling gene expression. It has also been found highly expressed in several human malignancies including breast carcinoma. Our aim was to detect LSD1 expression also in pre-invasive neoplasias of the breast. In the current study we therefore analysed LSD1 protein expression in ductal carcinoma in situ (DCIS in comparison to invasive ductal breast cancer (IDC. Methods Using immunohistochemistry we systematically analysed LSD1 expression in low grade DCIS (n = 27, intermediate grade DCIS (n = 30, high grade DCIS (n = 31 and in invasive ductal breast cancer (n = 32. SPSS version 18.0 was used for statistical analysis. Results LSD1 was differentially expressed in DCIS and invasive ductal breast cancer. Interestingly, LSD1 was significantly overexpressed in high grade DCIS versus low grade DCIS. Differences in LSD1 expression levels were also statistically significant between low/intermediate DCIS and invasive ductal breast carcinoma. Conclusions LSD1 is also expressed in pre-invasive neoplasias of the breast. Additionally, there is a gradual increase of LSD1 expression within tumour progression from pre-invasive DCIS to invasive ductal breast carcinoma. Therefore upregulation of LSD1 may be an early tumour promoting event.

  5. Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing’s Disease to Pituitary Carcinoma

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    Clarissa Groberio Borba

    2015-01-01

    Full Text Available Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH. It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing’s disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15% and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.

  6. Reduced 5-Methylcytosine Level as a Potential Progression Predictor in Patients with T1 or Non-Invasive Urothelial Carcinoma

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    Chi-Jung Chung

    2014-12-01

    Full Text Available This study aims to elucidate the level of DNA methylation in urothelial carcinomas (UCs using 5-methylcytosine (5-MeC immunohistochemistry (IHC. We examined the relationship among 5-MeC levels, DNA (cytosine-5-methyltransferase 1 (DNMT1 immunostaining levels, and clinicopathologic features. Tissue samples included 23 normal urothelia and 150 urothelial neoplasia, which comprised 40 non-invasive and 110 invasive UCs. The levels of 5-MeC and DNMT1 were assessed based on their immunoreactivities and then divided into low and high levels. In addition, we collected information on clinical variables, pathologic features, and recurrent status from patient questionnaires and medical records. Chi-square test and multivariate logistic regression model were used for analyses. Results showed that 5-MeC levels were positively associated with DNMT1 levels in UC (p = 0.0288. Both 5-MeC and DNMT1 were low in approximately 50% (76/150 of UC. The percentage of low 5-MeC levels was higher in invasive UC (65/110; 59% than in normal urothelia (2/23; 13% and non-invasive UC (18/40; 45%. Clinical factors were independently associated with low 5-MeC levels after adjusting for age and sex, including cancer stages II–IV, presence of UC in situ, and marked inflammation. Low 5-MeC levels in stage I invasive UC were not significantly different from those of non-invasive tumors (p = 0.8478. Low DNMT1 levels were only associated with UC with squamous differentiation (p = 0.0365. Neither 5-MeC nor DNMT1 levels were associated with UC recurrence. In conclusion, a low 5-MeC level could predict the progression of UC invasion into muscle.

  7. Knockdown of Histone Methyltransferase hSETD1A Inhibits Progression, Migration, and Invasion in Human Hepatocellular Carcinoma.

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    Cheng, Xin-Sheng; Sun, Shi-Bo; Zhong, Feng; He, Kun; Zhou, Jie

    2016-01-01

    Our aim was to study the expression of human SET domain containing protein 1A (hSETD1A) in hepatocellular carcinoma patients and its relationship with human hepatocellular carcinoma cell function. A total of 30 patients with hepatocellular carcinoma were enrolled in this study. The expression of hSETD1A was detected by real-time polymerase chain reaction (PCR) and Western blotting. The immortalized normal human liver cell line including SMMC-7721 was subjected to real-time PCR for hSETD1A mRNA. Furthermore, hSETD1A-small hairpin RNA (shRNA) was used to knock down hSETD1A expression in SMMC-7721 cells. Cell proliferation, cell apoptosis, and cell migration were determined by CCK8, flow cytometry, and Transwell assays. The positive expression rate level of hSETD1A mRNA and protein in liver carcinoma tissues was 73.33%. hSETD1A knockdown using a specific hSETD1A-shRNA inhibited cell proliferation and promoted cell apoptosis in SMMC-7721 cells. It was also found that downregulation of hSETD1A inhibited cell migration ability but did not affect cell invasion. In conclusion, the expression of hSETD1A occurs at a high rate in hepatocellular carcinoma patients. The expression state of hSETD1A may be a prognostic factor in hepatocellular carcinoma. PMID:27656834

  8. Impact of lymphovascular invasion on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection

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    Sha N

    2015-11-01

    Full Text Available Nan Sha,* Linguo Xie,* Tao Chen,* Chen Xing, Xiaoteng Liu, Yu Zhang, Zhonghua Shen, Hao Xu, Zhouliang Wu, Hailong Hu, Changli Wu Department of Urology, Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China *These authors contributed equally to this work Objective: To evaluate the clinical significance of lymphovascular invasion (LVI on recurrence and progression rates in patients with pT1 urothelial carcinoma of bladder after transurethral resection.Methods: This retrospective study was performed with 155 patients with newly diagnosed pT1 urothelial carcinoma of bladder who were treated with transurethral resection of bladder tumor at our institution from January 2006 to January 2010. The presence or absence of LVI was examined by pathologists. Chi-square test was performed to identify the correlations between LVI and other clinical and pathological features. Kaplan–Meier method was used to estimate the recurrence-free survival (RFS and progression-free survival curves and difference was determined by the log-rank test. Univariate and multivariate analyses were performed to determine the predictive factors through a Cox proportional hazards analysis model.Results: LVI was detected in a total of 34 patients (21.9%. While LVI was associated with high-grade tumors (P<0.001 and intravesical therapy (P=0.009. Correlations with age (P=0.227, sex (P=0.376, tumor size (P=0.969, tumor multiplicity (P=0.196, carcinoma in situ (P=0.321, and smoking (P=0.438 were not statistically significant. There was a statistically significant tendency toward higher recurrence rate and shorter RFS time in LVI-positive patients. However, no statistically significant differences were observed in progression rate between the two groups. Moreover, multivariate Cox proportional hazards analysis revealed that LVI, tumor size, and smoking were independent prognostic predictors of

  9. Expression microarray meta-analysis identifies genes associated with Ras/MAPK and related pathways in progression of muscle-invasive bladder transition cell carcinoma.

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    Jonathan A Ewald

    Full Text Available The effective detection and management of muscle-invasive bladder Transition Cell Carcinoma (TCC continues to be an urgent clinical challenge. While some differences of gene expression and function in papillary (Ta, superficial (T1 and muscle-invasive (≥T2 bladder cancers have been investigated, the understanding of mechanisms involved in the progression of bladder tumors remains incomplete. Statistical methods of pathway-enrichment, cluster analysis and text-mining can extract and help interpret functional information about gene expression patterns in large sets of genomic data. The public availability of patient-derived expression microarray data allows open access and analysis of large amounts of clinical data. Using these resources, we investigated gene expression differences associated with tumor progression and muscle-invasive TCC. Gene expression was calculated relative to Ta tumors to assess progression-associated differences, revealing a network of genes related to Ras/MAPK and PI3K signaling pathways with increased expression. Further, we identified genes within this network that are similarly expressed in superficial Ta and T1 stages but altered in muscle-invasive T2 tumors, finding 7 genes (COL3A1, COL5A1, COL11A1, FN1, ErbB3, MAPK10 and CDC25C whose expression patterns in muscle-invasive tumors are consistent in 5 to 7 independent outside microarray studies. Further, we found increased expression of the fibrillar collagen proteins COL3A1 and COL5A1 in muscle-invasive tumor samples and metastatic T24 cells. Our results suggest that increased expression of genes involved in mitogenic signaling may support the progression of muscle-invasive bladder tumors that generally lack activating mutations in these pathways, while expression changes of fibrillar collagens, fibronectin and specific signaling proteins are associated with muscle-invasive disease. These results identify potential biomarkers and targets for TCC treatments, and

  10. Isolated Uterine Metastasis of Invasive Ductal Carcinoma

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    Deniz Arslan

    2013-01-01

    Full Text Available Introduction. Most common metastasis sites of breast cancer are the lungs, bones, liver, and brain, whereas uterine involvement by metastatic breast disease is rare. Metastatic carcinoma of the uterus usually originates from other genital sites, most commonly being from the ovaries. Invasive lobular carcinoma spreads to gynecologic organs more frequently than invasive ductal carcinoma. Case Report. A 57-year-old postmenopausal woman was diagnosed with breast carcinoma 2 years ago and modified radical mastectomy was performed. Pathological examination of tumor revealed invasive ductal carcinoma, stage IIIc. She presented with abdominal pain and distension. Diagnostic workup and gynecologic examination revealed lesions that caused diffuse thickening of the uterus wall. Endometrial sampling was performed for confirmation of the diagnosis. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Breast carcinoma metastases in endometrium and myometrium were confirmed histopathologically and immunohistochemically. Conclusion. We herein report the first case of isolated uterine patient who had invasive ductal carcinoma of breast.

  11. Invasive breast carcinoma arising in microglandular adenosis: two case reports.

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    Choi, Jung Eun; Bae, Young Kyung

    2013-12-01

    Microglandular adenosis (MGA) is a rare benign disease that shows an infiltrative growth pattern of small glands, and it may progress to include atypia and carcinoma. Here we report two cases of breast carcinoma arising in MGA. Case 1 was a 44-year-old woman with a previous history of ductal carcinoma in situ in her right breast. During a follow-up, a 1.8 cm mass-like lesion was found in her left breast. An excisional biopsy suggested that the lesion was breast carcinoma. Case 2 was a 57-year-old woman with a 2.9 cm mass in her right breast. A core needle biopsy of the lesion suggested invasive carcinoma. Both patients underwent modified radical mastectomy with sentinel lymph node biopsy. Both tumors lacked a myoepithelial cell layer and stained positively for S-100, lysozyme, and α1-antitrypsin, which is typical of MGA. Both cases showed invasive carcinoma arising in MGA. PMID:24454466

  12. Regulation of In Situ to Invasive Breast CarcinomaTransition

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    Hu, Min; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen,Haiyan; Carrasco, Daniel; Richardson, Andrea; Bissell, Mina; Violette,Shelia; Gelman, Rebecca S.; Schnitt, Stuart; Polyak, Kornelia

    2007-03-13

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  13. Regulation of in situ to invasive breast carcinoma transition

    Energy Technology Data Exchange (ETDEWEB)

    Polyak, Kornelia; Hu, Min; Yao, Jun; Carroll, Danielle K.; Weremowicz, Stanislawa; Chen, Haiyan; Carrasco, Daniel; Richardson, Andrea; Violette, Shelia; Gelman, Rebecca S.; Bissell, Mina J.; Schnitt, Stuart; Polyak, Kornelia

    2008-05-07

    The transition of ductal carcinoma in situ (DCIS) to invasive carcinoma is a key event in breast tumor progression that is poorly understood. Comparative molecular analysis of tumor epithelial cells from in situ and invasive tumors has failed to identify consistent tumor stage-specific differences. However, the myoepithelial cell layer, present only in DCIS, is a key distinguishing and diagnostic feature. To determine the contribution of non-epithelial cells to tumor progression, we analyzed the role of myoepithelial cells and fibroblasts in the progression of in situ carcinomas using a xenograft model of human DCIS. Progression to invasion was promoted by fibroblasts, but inhibited by normal myoepithelial cells. The invasive tumor cells from these progressed lesions formed DCIS rather than invasive cancers when re-injected into naive mice. Molecular profiles of myoepithelial and epithelial cells isolated from primary normal and cancerous human breast tissue samples corroborated findings obtained in the xenograft model. These results provide the proof of principle that breast tumor progression could occur in the absence of additional genetic alterations and that tumor growth and progression could be controlled by replacement of normal myoepithelial inhibitory signals.

  14. Progress in minimally invasive therapy for hepatoceilular carcinoma%微创技术治疗肝细胞癌的进展

    Institute of Scientific and Technical Information of China (English)

    刘允怡; 赖俊雄; 刘晓欣

    2009-01-01

    Minimally invasive therapy is gaining increasing attention as an important part of therapies in hepatocellular carcinoma (HCC). It includes laparoseopic liver resection, transarterial therapy, local ablative therapy and some new extraeorporeal energy therapies. The theoretical advantages of laparoscopic liver resection are those of minimally invasive surgery in general, such as early recovery, shorter hospital stay, and better cosmetic outcome. However, laparoseopie liver resection for HCC is still considered as controversial because of the uncertainty of the long-term results, and fear of compromising the principles of oncologic resection. Transarterial chemoembolization is the most promising palliative medality for uuresectable HCC, but other techniques, such as transarterial radioembolization and local ablative therapy, have also shown promising results. Recent evidence suggests that local ablative therapy may offer comparable survival outcomes in patients with small HCC and preserved liver function when compared with partial hepatectomy. This article focuses on the development in minimally invasire therapy of HCC.

  15. Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ

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    Fernando N. Aguiar

    2013-05-01

    Full Text Available OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1 and 146 samples associated with invasive carcinoma (group 2. Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER and progesterone receptor (PR status, human epidermal growth factor receptor 2 (HER2 expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2 and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease.

  16. A Catalogue of Altered Salivary Proteins Secondary to Invasive Ductal Carcinoma: A Novel In Vivo Paradigm to Assess Breast Cancer Progression.

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    Streckfus, Charles F; Bigler, Lenora

    2016-08-01

    The objective of this manuscript is to introduce a catalogue of salivary proteins that are altered secondary to carcinoma of the breast. The catalogue of salivary proteins is a compilation of twenty years of research by the authors and consists of 233 high and low abundant proteins which have been identified by LC-MS/MS mass spectrometry, 2D-gel analysis and by enzyme-linked immunosorbent assay. The body of research suggests that saliva is a fluid suffused with solubilized by-products of oncogenic expression and that these proteins may be useful in the study of breast cancer progress, treatment efficacy and the tailoring of individualized patient care.

  17. FGFR1 amplification and the progression of non-invasive to invasive breast cancer

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    Gru, Alejandro A.; Allred, D. Craig

    2012-01-01

    The incidence of invasive breast cancer (IBC) can be dramatically reduced by improving our abilities to detect and treat ductal carcinoma in situ (DCIS). Progress will be based on a detailed understanding of molecular mechanisms responsible for tumor progression. An interesting study by Jang and colleagues evaluated and compared the frequency of amplification of four oncogenes (HER2, c-MYC, CCND1 and FGFR1) in large cohorts of pure DCIS, in the DCIS component of IBC, and in corresponding IBC....

  18. Minimally invasive follicular thyroid carcinomas: prognostic factors.

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    Stenson, Gustav; Nilsson, Inga-Lena; Mu, Ninni; Larsson, Catharina; Lundgren, Catharina Ihre; Juhlin, C Christofer; Höög, Anders; Zedenius, Jan

    2016-08-01

    Although minimally invasive follicular thyroid carcinoma (MI-FTC) is regarded as an indolent tumour, treatment strategies remain controversial. Our aim was to investigate the outcome for patients with MI-FTC and to identify prognostic parameters to facilitate adequate treatment and follow-up. This retrospective follow-up study involved all cases of MI-FTC operated at the Karolinska University Hospital between 1986 and 2009. Outcome was analysed using death from MI-FTC as endpoint. Fifty-eight patients (41 women and 17 men) with MI-FTC were identified. The median follow-up time was 140 (range 21-308) months. Vascular invasion was observed in 36 cases and was associated with larger tumour size [median 40 (20-76) compared with 24 (10-80) mm for patients with capsular invasion only (P = 0.001)] and older patients [54 (20-92) vs. 44 (11-77) years; P = 0.019]. Patients with vascular invasion were more often treated with thyroidectomy (21/36 compared to 7/22 with capsular invasion only; P = 0.045). Five patients died from metastatic disease of FTC after a median follow-up of 114 (range 41-193) months; all were older than 50 years (51-72) at the time of the initial surgery; vascular invasion was present in all tumours and all but one were treated with thyroidectomy. Univariate analysis identified combined capsular and vascular invasion (P = 0.034), age at surgery ≥50 years (P = 0.023) and male gender (P = 0.005) as related to risk of death from MI-FTC. MI-FTC should not be considered a purely indolent disease. Age at diagnosis and the existence of combined capsular and vascular invasion were identified as important prognostic factors. PMID:26858184

  19. Synchronous unilateral triple breast cancers composed of invasive ductal carcinoma, invasive lobular carcinoma, and Paget's disease.

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    Onoe, Shunsuke; Tsuda, Hitoshi; Akashi-Tanaka, Sadako; Hasebe, Takahiro; Iwamoto, Eriko; Hojo, Takashi; Kinoshita, Takayuki

    2014-03-01

    We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed. PMID:21140247

  20. Molecular Insights on the Transition of Non-invasive DCIS to Invasive ductal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Dihua YU

    2009-01-01

    @@ More than 90% of breast cancer-related deaths are caused by metastasis not primary tumor. To effectively reduce cancer mortality, it is extremely im-portant to predict the risk of, and to intervene in, the critical transition from non-invasive ductal carcinoma in situ (DCIS) to life-threatening invasive ductal carcinoma (IDC).

  1. Development of poorly differentiated invasive squamous cell carcinoma in giant Bowen’s disease: a case report with dermatoscopy

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    Akay, Bengu Nisa; Maden, Aysenur; Kocak, Oguzhan; Bostanci, Seher; Boyvat, Ayşe; Kocyigit, Pelin; Heper, Aylin Okcu

    2016-01-01

    Bowen’s disease (BD) is an in situ form of squamous cell carcinoma (SCC), often occurring in the chronically UV-damaged skin of elderly people. The risk of progression of BD to invasive SCC varies between 3% and 5%, and one-third of invasive tumors may metastasize. Herein we discuss the dermatoscopic findings of a case of giant Bowen’s disease, which progressed to poorly differentiated invasive SCC.

  2. Soft tissue invasion of papillary thyroid carcinoma.

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    Lin, Jen-Der; Hsueh, Chuen; Chao, Tzu-Chieh

    2016-08-01

    Extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC) is common and clinical presentation can vary from minimal to extensive locoregional involvement. Although PTC is generally considered the most benign among all thyroid carcinomas, it may present with local invasion with poor prognosis. Our retrospective study involved 3267 PTC patients undergoing regular follow-up at Chang Gung Medical Center in Linkou, Taiwan. Among them, 269 were PTC cases with ETE, having tumors greater than 1 cm in size and treated with total or complete thyroidectomy with or without lymph node dissection for which the follow-up period was over 10 years. The mean age of 269 cases was 46.8 ± 15.1 (range 11-83 years) years. The number of females was 204 (75.8 %). Patients were categorized into minimal ETE (175 cases) and extensive ETE (94 cases) groups according to surgical findings and pathological reports. Mean follow-up period was 13.3 ± 5.5 (range 0.2-29.3) years, during which 28 (10.4 %) patients died of thyroid cancer; and 63 (23.4 %) of all-cause mortality. Multivariate analysis showed that age, gender, extensive ETE, and lymph node metastasis had a statistically significant effect on thyroid cancer mortality. Survival rates were significantly different between minimal ETE and extensive ETE groups (p < 0.0001). In conclusion, perithyroidal soft tissue involvement by PTC is an important factor that determines patient prognosis and a closer follow-up and more aggressive treatment is necessary for patients who are old, male, extensive ETE, and with lymph node involvement. PMID:27154220

  3. A Prognostic Dilemma of Basal Cell Carcinoma with Intravascular Invasion

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    Niumsawatt, Vachara; Castley, Andrew

    2016-01-01

    Summary: Basal cell carcinoma is the most common malignancy; however, it very rarely metastasizes. Despite the low mortality caused by this cancer, once it spreads, it has dim prognosis. We report a case of basal cell carcinoma with rare intravascular invasion and review the literature for risk factors and management of metastasis.

  4. Diagnosis and minimally invasive treatment of early stage breast carcinoma

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    van Esser, S.

    1979-01-01

    In this thesis the diagnostic work up and minimally invasive surgical treatment of early stage breast carcinoma is studied. Although the surgical treatment of breast carcinoma has improved significantly over the past decades, there is still room for improvement. On the one hand the focus is on early

  5. ILEOCYSTOPLASTY IN INVASIVE URINARY BLADDER CARCINOMA

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    V. N. Pavlov

    2009-01-01

    Full Text Available Objective: to assess the results of surgical treatment of patients with the intestinal urinary bladder, to characterize its early and late postoperative complications, and to develop their correction tactics.  Subjects and methods. The results of treatment in 198 patients who had undergone ileocystoplasty were analyzed.  Results. The developed diagnostic approach and the determined examination periods could reduce the number of late postoperative complications of ileocystoplasty: acute and chronic pyelonephritis from 19.4 to 7.6%, urolithiasis from 17.2 to 1.9%, bladder dysfunction from 25.8 to 7.6%, and metabolic acidosis from 4.3 to 1.9%, and prevent the development of ureterovesical anastomosis stricture.  Conclusion. Radical cystectomy with the ileoplasty using an isolated segment of the ileum in patients with invasive urinary bladder carcinoma has been the operation of choice no longer; it has become an essential surgical adjunct. This method permits overall 5-year survival to be achieved in 69.7% of patients.  

  6. Invasive follicular thyroid carcinoma infiltrating trachea

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    Filipović Aleksandar

    2011-01-01

    Full Text Available Introduction. Although follicular thyroid carcinoma is a rare malignant tumor, up to 20% of the patients are threatened by potential complications resulting from infiltrating tumor growth into surrounding tissues. Case report. A 66- year-old female came to hospital with the presence of a growing thyroid nodule of the left lobe. Ultrasonic examination showed a 8 cm hypoechoic nodule in the left lobe. Thyroid scintigraphy showed a cold nodule. CT scan and tracheoscopy showed tracheal infiltration without tracheal obstruction. An extended total thyroidectomy was done, with the left jugular vein, strap muscles and tracheal 2 cm long circular resection. The pathologist confirmed invasive follicular thyroid cancer. After the surgery the patient was treated with radioiodine therapy and permanent TSH suppressive therapy. The patient was followed with measurements of the thyroid hormone and serum thyroglobulin level every six months, as well as the further tests (chest xray, ultrasound of the neck and a whole body scintigraphy were done. After more than three years the patient had no evidence of the recurrent disease. Conclusion. Radical resection of the tracheal infiltrating thyroid cancer with circular tracheal resection and terminoterminal anastomosis followed by radioiodine therapy should be considered the treatment of choice.

  7. ASPN and GJB2 Are Implicated in the Mechanisms of Invasion of Ductal Breast Carcinomas

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    Bàrbara Castellana, Daniel Escuin, Gloria Peiró, Bárbara Garcia-Valdecasas, Tania Vázquez, Cristina Pons, Maitane Pérez-Olabarria, Agustí Barnadas, Enrique Lerma

    2012-01-01

    Full Text Available The mechanism of progression from ductal carcinoma in situ (DCIS to invasive ductal carcinoma (IDC remains largely unknown. We compared gene expression in tumors with simultaneous DCIS and IDC to decipher how diverse proteins participate in the local invasive process.Twenty frozen tumor specimens with concurrent, but separated, DCIS and IDC were microdissected and evaluated. Total RNA was extracted and microarray analysis was performed using Affymetrix GeneChip® Human Gene 1.0 ST Arrays. Microarray data were validated by quantitative real time reverse transcription-PCR (qRT-PCR and immunohistochemistry. Controls included seven pure in situ carcinomas, eight fragments from normal breast tissue, and a series of mouse breast carcinomas (MMTV-PyMT.Fifty-six genes were differentially expressed between DCIS and IDC samples. The genes upregulated in IDC samples, and probably associated with invasion, were related to the epithelial-mesenchymal transition (ASPN, THBS2, FN1, SPARC, and COL11A1, cellular adhesion (GJB2, cell motility and progression (PLAUR, PLAU, BGN, ADAMTS16, and ENPP2, extracellular matrix degradation (MMP11, MMP13, and MMP14, and growth/proliferation (ST6GAL2. qRT-PCR confirmed the expression patterns of ASPN, GJB2, ENPP2, ST6GAL2, and TMBS10. Expression of the ASPN and GJB2 gene products was detected by immunohistochemistry in invasive carcinoma foci. The association of GJB2 protein expression with invasion was confirmed by qRT-PCR in mouse tumors (P < 0.05.Conclusions: The upregulation of ASPN and GJB2 may play important roles in local invasion of breast ductal carcinomas.

  8. Cutaneous Squamous Cell Carcinoma with Invasion through Ear Cartilage

    Directory of Open Access Journals (Sweden)

    Julie Boisen

    2016-01-01

    Full Text Available Cutaneous squamous cell carcinoma of the ear represents a high-risk tumor location with an increased risk of metastasis and local tissue invasion. However, it is uncommon for these cancers to invade through nearby cartilage. Cartilage invasion is facilitated by matrix metalloproteases, specifically collagenase 3. We present the unusual case of a 76-year-old man with an auricular squamous cell carcinoma that exhibited full-thickness perforation of the scapha cartilage. Permanent sections through the eroded cartilage confirmed tumor invasion extending to the posterior ear skin.

  9. Positive association of long telomeres with the invasive capacity of hepatocellular carcinoma cells.

    Science.gov (United States)

    Ko, Eunkyong; Jung, Guhung

    2014-05-01

    Invasion, the representative feature of malignant tumors, leads to an increase in mortality. The malignant liver tumor - hepatocellular carcinoma (HCC) - has an enhanced invasive capacity that results in increased patient mortality. Moreover, this enhanced invasive capacity is due to the up-regulation of invasion promoters such as zinc finger protein SNAI1 (Snail) and matrix metalloproteinases (MMPs), and the down-regulation of invasion suppressor molecules such as E-cadherin. Telomerase reverse transcriptase (TERT), which encodes the catalytic subunit of telomerase, is highly expressed in a variety of invasive cancers, including HCC. Telomerase activation induces telomere elongation, thereby leading to cell immortalization during malignant tumor progression. However, the relationship between telomere length and invasion is yet to be experimentally corroborated. In this paper, we revealed that invasive HCC cells passing through the Matrigel display significantly longer telomeres than non-invasive HCC cells. Moreover, we established a method that can distinguish and sort cells containing long telomeres and short telomeres. Using this system, we observed that the HCC cells containing long telomeres had a high-level expression of invasion-promoting genes and a low-level expression of invasion-suppressing E-cadherin. Furthermore, HCC cells containing long telomeres exhibited a higher invasive capacity than HCC cells containing short telomeres. Taken together, our findings suggest that long telomeres are positively associated with the invasive capacity of HCC cells and may be a potent target for malignant liver cancer treatment. PMID:24732358

  10. Cortactin is associated with perineural invasion in the deep invasive front area of laryngeal carcinomas

    DEFF Research Database (Denmark)

    Ambrosio, Eliane Papa; Rosa, Fabíola Encinas; Domingues, Maria Aparecida Custódio;

    2011-01-01

    The cortactin gene, mapped at 11q13, has been associated with an aggressive clinical course in many cancers because of its function of invasiveness. This study evaluated CTTN protein and its prognostic value in the deep invasive front and superficial areas of laryngeal squamous cell carcinomas......, suggesting that this area should be considered a prognostic tool in laryngeal carcinomas. Although most cases had moderate to strong CTTN expression on the tumor surface, 2 sets of cases revealed a differential expression pattern in the deep invasive front. A group of cases with absent to weak expression...... be considered a grading system in laryngeal carcinomas and that cortactin is a putative marker of worse outcome in the deep invasive front of laryngeal carcinomas....

  11. Sinonasal verrucous carcinoma with oral invasion

    Directory of Open Access Journals (Sweden)

    Karthikeya P

    2006-01-01

    Full Text Available Verrucous carcinoma is a rare warty variant of squamous cell carcinoma, most often seen in the oral cavity and larynx. Its occurrence in the sinonasal tract is rare. This tumor constitutes approximately 1% of all sinonasal neoplasms. The clinical presentation and the histopathological features of verrucous carcinoma are a subject of continuous discussion amongst diagnosticians and pathologists. A case with oral and nasal presentation of this tumor is reported here.

  12. Mandibular Destruction Secondary to Invasion by Carcinoma Cuniculatum.

    Science.gov (United States)

    Shapiro, Michael C; Wong, Brian; O'Brien, Michael J; Salama, Andrew

    2015-12-01

    Carcinoma cuniculatum is a rare form of well-differentiated squamous cell carcinoma that is often misdiagnosed. It has a propensity for local invasion and rarely metastasizes. Oral carcinoma cuniculatum is exceedingly rare, with very few reported cases in the English-language literature. Classically, its presentation mimics osteomyelitis or a dental abscess, resulting in misdiagnosis, multiple biopsy examinations, and procedures before a final diagnosis of carcinoma cuniculatum. This case report describes the case of a 71-year-old woman who was referred to the authors' clinic for evaluation of persistent pain and swelling of the mandible. Multiple biopsy examinations were negative for malignancy, and the patient was misdiagnosed with osteomyelitis and dental abscess before obtaining an accurate diagnosis of carcinoma cuniculatum. The aim of this report is to provide a thorough clinical and histopathologic report of carcinoma cuniculatum of the mandible, provide a brief review of the literature, and highlight the difficulties in arriving at this uncommon diagnosis.

  13. A rare case of isolated adrenal metastasis of invasive ductal breast carcinoma

    Directory of Open Access Journals (Sweden)

    Anđelić-Dekić Nataša

    2014-01-01

    Full Text Available Introduction. Isolated adrenal metastases of invasive ductal breast carcinoma are extremely rare. We report a case with isolated left adrenal metastases, verified three years after diagnosed breast carcinoma. Case Outline. A 58-year-old female patient with a right breast tumor, clinically staged as IIIA (T2N2M0 started neoadjuvant anthracycline chemotherapy after biopsy which revealed invasive ductal breast carcinoma. Immunohistochemical findings of tumor biopsy showed hormonal steroid receptors for estrogen and progesterone negative, and human epidermal growth factor receptor 2 (HER2 positive. After 4 cycles of chemotherapy and partial tumor regression the patient underwent radical mastectomy. Definite histopathological analysis confirmed the diagnosis of invasive ductal carcinoma. The patient continued treatment with adjuvant chemotherapy to cumulative dose of anthracyclines, postoperative radiotherapy and adjuvant trastuzumab for one year. Three years later abdominal computerized tomography showed tumor in the left adrenal gland as the only metastatic site. Left adrenalectomy was performed and histopathological finding confirmed breast cancer metastases. Postoperatively, the patient received 6 cycles of docetaxel with trastuzumab and continued trastuzumab until disease progression. One year after left adrenalectomy control abdominal computerized tomography showed a right adrenal tumor with retroperitoneal lymphadenopathy. Treatment with capecitabine was continued for one year, but eventually she developed brain metastasis causing lethal outcome. Conclusion. In order to better understand metastatic pathways of invasive ductal breast carcinoma, publications of individual patient cases diagnosed with rare metastatic sites should be encouraged. This might improve our understanding of metastatic behavior of breast cancer and stimulate further clinical research.

  14. The role of MR imaging in invasive cervical carcinoma

    International Nuclear Information System (INIS)

    In this article the role of MR imaging in the management of cervical cancer is reviewed and illustrated. The appearance of the normal uterine cervix and of cervical carcinoma is shown. Important factors for optimal MR imaging of cervical carcinoma are reviewed. The value of MR imaging in the staging of cervical carcinoma is illustrated by showing parametrial invasion and lymph node involvement. Finally, the value of MR imaging staging is compared with clinical staging, CT staging, and surgical findings. The role of new imaging techniques, such as fast dynamic enhanced MR imaging, is described. (orig.)

  15. Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local Invasion and Distant Metastasis

    OpenAIRE

    Pàez-Ribes, Marta; Allen, Elizabeth; Hudock, James; Takeda, Takaaki; Okuyama, Hiroaki; Viñals, Francesc; Inoue, Masahiro; Bergers, Gabriele; Hanahan, Douglas; Casanovas, Oriol

    2009-01-01

    Multiple angiogenesis inhibitors have been therapeutically validated in preclinical cancer models, and several in clinical trials. Here we report that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and distant metastasis. Increased i...

  16. Ezrin Is Associated with Disease Progression in Ovarian Carcinoma

    Science.gov (United States)

    Horwitz, Vered; Davidson, Ben; Stern, Dganit; Tropé, Claes G.; Tavor Re’em, Tali; Reich, Reuven

    2016-01-01

    Objective Ezrin and p130Cas are structural proteins with an important role in signaling pathways and have been shown to promote cancer dissemination. We previously reported on overexpression of both ezrin and p130Cas in breast carcinoma effusions compared to primary carcinomas. Since ovarian and breast carcinomas share the ability to disseminate by forming malignant effusions, we sought to study the role of these molecules in ovarian carcinoma (OC). Methods OC cell lines were cultured in two different 3-dimensional conditions, on alginate scaffolds and as spheroids, which served as models for solid tumor and malignant effusions, respectively. shRNA was used to reduce protein expression in the cells. The malignant potential was evaluated by chemo-invasion assay, branching capacity on Matrigel and rate of proliferation. Subsequently, clinical specimens of high-grade serous carcinoma effusions, ovarian tumors and solid metastases were analyzed for ezrin and p130Cas expression. Results Higher ezrin expression was found in cells composing the spheroids compared to their counterparts cultured on alginate scaffold and in clinical samples of malignant effusions compared to solid tumors. In addition, reduced Ezrin expression impaired the invasion ability and the branching capacity of OC cells to a greater extent than reduced p130Cas expression. However, ezrin and p130Cas expression in effusions was unrelated to clinical outcome. Conclusions The 3-dimensional cell cultures were found to mimic the different tumor sites and be applicable as a model. The in vitro results concur with the clinical specimen analysis, suggesting that in OC, the role of ezrin in disease progression is more pronounced than that of p130Cas. PMID:27622508

  17. Cervical invasion of endometrial carcinoma - evaluation by parasagittal MR imaging

    International Nuclear Information System (INIS)

    Twenty-seven consecutive patients were examined by T2-(1800/70 ms) and postcontrast T1-weighted (600/15) spin echo (SE) or dynamic (200/15) SE MR imaging to determine the usefulness of parasagittal MR imaging in assessing cervical invasion of endometrial carcinoma. The images were obtained in a direction parallel to the longitudinal axis of the uterus (parasagittal). The cervical epithelium, being hyperintense on the late phase dynamic and postcontrast T1-weighted SE images, had disappeared partially or totally in all 4 patients with cervical invasion. The enhanced cervical epithelium was completely seen in one patient with the tumor protruding into the cervical canal in a polyp-like form without cervical epithelial invasion. The same was also seen in the 22 patients with the tumor remaining in the corpus cavity. The enhanced parasagittal MR images facilitated the evaluation of the extent of the endometrial carcinoma. (orig.)

  18. Matrix metalloproteinase 13 is induced in fibroblasts in polyomavirus middle T antigen-driven mammary carcinoma without influencing tumor progression

    DEFF Research Database (Denmark)

    Nielsen, Boye S; Egeblad, Mikala; Rank, Fritz;

    2008-01-01

    intraepithelial neoplasias. To determine if MMP13 plays a role in tumor progression, we crossed MMTV-PyMT mice with Mmp13 deficient mice. The absence of MMP13 did not influence tumor growth, vascularization, progression to more advanced tumor stages, or metastasis to the lungs, and the absence of MMP13 was not......Matrix metalloproteinase (MMP) 13 (collagenase 3) is an extracellular matrix remodeling enzyme that is induced in myofibroblasts during the earliest invasive stages of human breast carcinoma, suggesting that it is involved in tumor progression. During progression of mammary carcinomas in the...... polyoma virus middle T oncogene mouse model (MMTV-PyMT), Mmp13 mRNA was strongly upregulated concurrently with the transition to invasive and metastatic carcinomas. As in human tumors, Mmp13 mRNA was found in myofibroblasts of invasive grade II and III carcinomas, but not in benign grade I and II mammary...

  19. Aberrant E-cadherin staining patterns in invasive mammary carcinoma

    Directory of Open Access Journals (Sweden)

    Brogi Edi

    2005-11-01

    Full Text Available Abstract Background E-cadherin, a cell surface protein involved in cell adhesion, is present in normal breast epithelium, benign breast lesions, and in breast carcinoma. Alterations in the gene CDH1 on chromosome 16q22 are associated with changes in E-cadherin protein expression and function. Inactivation of E-cadherin in lobular carcinomas and certain diffuse gastric carcinomas may play a role in the dispersed, discohesive "single cell" growth patterns seen in these tumors. The molecular "signature" of mammary lobular carcinomas is the loss of E-cadherin protein expression as evidenced by immunohistochemistry, whereas ductal carcinomas are typically E-cadherin positive. Patients and methods We report on E-cadherin immunostaining patterns in five cases of invasive mammary carcinoma Results These were five exceptional instances in which the E-cadherin immunophenotype did not correspond to the apparent histologic classification of the lesion. These cases which are exceedingly rare in our experience are the subject of this report. Conclusion Findings such as those illustrated in this study occur in virtually all biologic phenomena and they do not invalidate the very high degree of correlation between the expression of E-cadherin and the classification of breast carcinomas as ductal or lobular type on the basis of conventional histologic criteria.

  20. Invasive ductal carcinoma of the pancreas showing exophytic growth

    Institute of Scientific and Technical Information of China (English)

    Yuichi Sanada; Kazuhiro Yoshida; Masaoki Itoh; Riki Okita; Morihito Okada

    2009-01-01

    BACKGROUND: Invasive pancreatic carcinoma generally appears as poorly deifned mass relfecting the inifltrative growth. We aimed to identify the histological and immunohistochemical features in a rare case of pancreatic carcinoma showing exophytic growth. METHODS: A 67-year-old woman presented with a mass of 5.0 cm in diameter in the pancreatic head. Preoperative computed tomography revealed a well-demarcated, primarily solid mass with a central low-density area. Magnetic resonance cholangiopancreatography revealed neither encasement nor dilation of the main pancreatic duct. An incorrect preoperative diagnosis was made of solid pseudopapillary tumor of the pancreas. Elevated serum carcinoembryonic antigen (CEA) levels and abnormal FDG positron emmission tomography accumulation suggested that the tumor had malignant potential requiring a pancreatoduodenectomy. RESULTS: The head of the pancreas contained a well-circumscribed encapsulated mass of 5.0 cm in diameter, comprising 50% adenocarcinoma, with mucinous carci-noma in the center and anaplastic carcinoma at the periphery. The anaplastic carcinoma comprised pleo-morphic cells (PCs) and pleomorphic giant cells (PGCs). The PGCs phagocytozed mononuclear PCs and lymphocytes adjacent to the capsule without inifltrating the capsule itself. Immunohistochemistry revealed that the anaplastic carcinoma cells including PGCs were positive for the tumor antigen Mucin 1 and CEA but negative for vimentin. CONCLUSION: Our observations suggest anaplastic carcinoma components in the present tumor have a ductal origin and that the exophytic tumor growth is associated with the phagocytotic activity of PGCs.

  1. Acantholytic Variant of Bowen's Disease with Micro-invasive Squamous Cell Carcinoma: A Case Report of a Unique Variant

    OpenAIRE

    Kanthilatha Pai; Shricharith Shetty; J Padmapriya; Sathish Pai; Lakshmi Rao

    2014-01-01

    Bowen′s disease is generally regarded as premalignant dermatoses. The disease affects both skin and the mucosa and has the potential to progress to invasive squamous cell carcinoma. There are descriptions of several histological variants of Bowen′s disease like psoriasiform, atrophic, pagetoid, etc. Acantholysis of anaplastic keratinocytes with bullae/cleft formation is described in premalignant condition like actinic keratosis and adenoid variant of squamous cell carcinoma, but there is lack...

  2. Invasive micropapillary carcinoma of the breast: MR imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyo Soon; Jeong, Seo In; Choi, You Ri; Kim, Jin Woong; Lee, Ji Shin; Park, Min Ho [Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Kuzmiak, Cherie M. [Department of Radiology, University of North Carolina, Chapel Hill (Korea, Republic of)

    2013-08-15

    To analyze the magnetic resonance (MR) imaging findings of invasive micropapillary carcinoma of the breast. MR images were retrospectively evaluated in 14 patients (age range: 37-67, mean age: 49 years) with pathologically confirmed invasive micropapillary carcinoma of the breast. The enhancement type (mass/non-mass), shape, margin, contrast enhancement, and time-intensity curve pattern on the dynamic study were correlated with the histopathologic features. Associated findings, such as edema, nipple change, skin change and enlarged axillary lymph nodes were also studied. The most common features of the masses were irregular shape (12 of 14 patients, 85.8%) and irregular or spiculated margin (11 of 14 patients, 78.7%). The contrast enhancement was heterogeneous in 11 patients (78.7%), rim enhancement in 2 cases (14.2%), and homogeneous in one patient (7.1%). The predominant kinetic pattern was rapid increase (14 of 14, 100%) in the initial phase and washout (11 of 14, 78.7%) in the delayed phase. Associated non-mass like enhancement was shown in 4 patients, representing ductal carcinoma in situ. MR imaging helped detect additional sites of cancer other than the index lesion in 3 patients (21.4%). Enlarged axillary lymphadenopathy was identified in 7 of the 14 patients (50%). Invasive micropapillary carcinoma appears as a mass with an irregular shape, irregular or spiculated margin and heterogeneous enhancement on MR imaging. Though these findings are not specific and are also observed with other breast malignancies, invasive micropapillary carcinoma frequently showed multiple lesions, accompanying non-mass enhancement and axillary lymph node enlargement.

  3. Histopathological Features of Invasion of Breast Invasive Ductal Carcinoma and Safety of Breast-conserving Surgery

    Institute of Scientific and Technical Information of China (English)

    Chunping LIU; Huaxiong PAN; Zhi LI; Lan SHI; Tao HUANG

    2009-01-01

    In order to investigate the relationship between the extent of tumor invasion and the tu-mor size,axillary lymph nodes metastasis,Her-2 gene overexpression,and histologic grading in breast invasive ductal carcinoma as well as the optimal extent of excision during the breast-serving surgery,the clinical data of 104 patients with breast invasive ductal carcinoma who had received modified radical mastectomy were analyzed.The correlation analysis on invasive extent,which was evaluated by serial sections at an interval of 0.5 cm from 4 different directions taking the focus as the centre,and the tumor size,axillary lymph nodes metastasis,Her-2 gene overexpression,and his-tologic grading was processed.There was a significant correlation between invasive extent and tumor size (r=0.766,P0.05),and histologic grading (r=0.228,P>0.05).The 100% negative rate of infiltration in patients without nipple discharge with tumor size 3 cm was obtained at 1.5,2.0 and 2.5 cm away from the tumor respectively.It is concluded that the performance of breast-serving surgery in patients with breast invasive ductal carcinoma should be evaluated by tumor size in combination with axillary lymph nodes involvement to decide the possibility of breast-serving and the secure excision extent.

  4. Management of periorbital basal cell carcinoma with orbital invasion.

    Science.gov (United States)

    Sun, Michelle T; Wu, Albert; Figueira, Edwin; Huilgol, Shyamala; Selva, Dinesh

    2015-11-01

    Basal cell carcinoma (BCC) is the most common eyelid malignancy; however, orbital invasion by periocular BCC is rare, and management remains challenging. Established risk factors for orbital invasion by BCC include male gender, advanced age, medial canthal location, previous recurrences, large tumor size, aggressive histologic subtype and perineural invasion. Management requires a multidisciplinary approach with orbital exenteration remaining the treatment of choice. Globe-sparing treatment may be appropriate in selected patients and radiotherapy and chemotherapy are often used as adjuvant therapies for advanced or inoperable cases, although the evidence remains limited. We aim to summarize the presentation and treatment of BCC with orbital invasion to better guide the management of this complex condition. PMID:26437207

  5. Hypofractionated radiation therapy for invasive thyroid carcinoma in dogs: a retrospective analysis of survival

    International Nuclear Information System (INIS)

    Thirteen dogs with invasive thyroid carcinoma (WHO classification T2b or T3b) seen between January 1991 and October 1997 were treated by external beam Irradiation. Four once-weekly fractions of 9 gray of 4 MeV X-rays were administered. Four of the dogs died of progression of the primary disease and four from metastatic spread. Of the remaining dogs, three died of unrelated problems, although two were still alive at the time of the censor. Kaplan-Meier analysis of the survival time from first dose to death from either primary or metastatic disease gave a median survival time of 96 weeks (mean 85 weeks, range six to 247 weeks). Radiographic evidence of pulmonary metastatic disease at presentation had no prognostic value whereas crude growth rate was a highly significant factor. The present series Indicates that radiation therapy should be considered an important modality for the control of invasive thyroid carcinoma in the dog

  6. Bronchogenic Carcinoma with Cardiac Invasion Simulating Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Anirban Das

    2016-01-01

    Full Text Available Cardiac metastases in bronchogenic carcinoma may occur due to retrograde lymphatic spread or by hematogenous dissemination of tumour cells, but direct invasion of heart by adjacent malignant lung mass is very uncommon. Pericardium is frequently involved in direct cardiac invasion by adjacent lung cancer. Pericardial effusion, pericarditis, and tamponade are common and life threatening presentation in such cases. But direct invasion of myocardium and endocardium is very uncommon. Left atrial endocardium is most commonly involved in such cases due to anatomical contiguity with pulmonary hilum through pulmonary veins, and in most cases left atrial involvement is asymptomatic. But myocardial compression and invasion by adjacent lung mass may result in myocardial ischemia and may present with retrosternal, oppressive chest pain which clinically may simulate with the acute myocardial infarction (AMI. As a result, it leads to misdiagnosis and delayed diagnosis of lung cancer. Here we report a case of non-small-cell carcinoma of right lung which was presented with asymptomatic invasion in left atrium and retrosternal chest pain simulating AMI due to myocardial compression by adjacent lung mass, in a seventy-four-year-old male smoker.

  7. Curcumin suppresses migration and invasion of human endometrial carcinoma cells

    OpenAIRE

    Chen, Qian; Gao, Qing; Chen, Kunlun; Wang, Yidong; Chen, Lijuan; Li, Xu

    2015-01-01

    Curcumin, a widely used Chinese herbal medicine, has historically been used in anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism of curcumin in endometrial carcinoma (EC) are still poorly understood. The purpose of this study was to detect the anti-metastatic effects of curcumin and the associated mechanism(s) in EC. Based on assays carried out in EC cell lines, it was observed that curcumin inhibited EC cell migration and invasion in vitro. Furthermore, follo...

  8. FBX8 Acts as an Invasion and Metastasis Suppressor and Correlates with Poor Survival in Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Feifei Wang

    Full Text Available F-box only protein 8 (FBX8, a novel component of F-box proteins, is lost in several cancers and has been associated with invasiveness of cancer cells. However, its expression pattern and role in the progression of hepatocellular carcinoma remain unclear. This study investigated the prognostic significance of FBX8 in hepatocellular carcinoma samples and analyzed FBX8 function in hepatocellular carcinoma cells by gene manipulation.The expression of FBX8 was detected in 120 cases of clinical paraffin-embedded hepatocellular carcinoma tissues, 20 matched pairs of fresh tissues and five hepatocellular carcinoma cell lines by immunohistochemistry with clinicopathological analyses, real-time RT-PCR or Western blot. The correlation of FBX8 expression with cell proliferation and invasion in five HCC cell lines was analyzed. Moreover, loss of function and gain of function assays were performed to evaluate the effect of FBX8 on cell proliferation, motility, invasion in vitro and metastasis in vivo.We found that FBX8 was obviously down-regulated in HCC tissues and cell lines (P<0.05. The FBX8 down-regulation correlated significantly with poor prognosis, and FBX8 status was identified as an independent significant prognostic factor. Over-expression of FBX8 decreased proliferation, migration and invasion in HepG2 and 97H cells, while knock-down of FBX8 in 7721 cells showed the opposite effect. FBX8 negatively correlated with cell proliferation and invasion in 7701, M3, HepG2 and 97H cell lines. In vivo functional assays showed FBX8 suppressed tumor growth and pulmonary metastatic potential in mice. Our results indicate that down-regulation of FBX8 significantly correlates with invasion, metastasis and poor survival in hepatocellular carcinoma patients. It may be a useful biomarker for therapeutic strategy and control in hepatocellular carcinoma treatment.

  9. Progression of oral squamous cell carcinoma accompanied with reduced E-cadherin expression but not cadherin switch.

    Directory of Open Access Journals (Sweden)

    Takashi Hashimoto

    Full Text Available The cadherin switch from E-cadherin to N-cadherin is considered as a hallmark of the epithelial-mesenchymal transition and progression of carcinomas. Although it enhances aggressive behaviors of adenocarcinoma cells, the significance and role of cadherin switch in squamous cell carcinomas (SCCs are largely controversial. In the present study, we immunohistochemically examined expression of E-cadherin and N-cadherin in oral SCCs (n = 63 and its implications for the disease progression. The E-cadherin-positive carcinoma cells were rapidly decreased at the invasive front. The percentage of carcinoma cells stained E-cadherin at the cell membrane was reduced in parallel with tumor dedifferentiation (P<0.01 and enhanced invasion (P<0.01. In contrast, N-cadherin-positive cells were very limited and did not correlate with the clinicopathological parameters. Mouse tongue tumors xenotransplantated oral SCC cell lines expressing both cadherins in vitro reproduced the reduction of E-cadherin-positive carcinoma cells at the invasive front and the negligible expression of N-cadherin. These results demonstrate that the reduction of E-cadherin-mediated carcinoma cell-cell adhesion at the invasive front, but not the cadherin switch, is an important determinant for oral SCC progression, and suggest that the environments surrounding carcinoma cells largely affect the cadherin expression.

  10. Invasive Micropapillary Carcinoma in Breast Presented as Hyperechoic Mass with Coarse Macrocalcifications: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Sun; Seo, Bo Kyung; Song, Sung Eun; Kim, Young Sik [Dept. of Radiology, Korea University Ansan Hospital, Ansan (Korea, Republic of); Cho, Kyu Ran [Dept. of Radiology, Korea University Anam Hospital, Seoul (Korea, Republic of); Woo, Ok Hee [Dept. of Radiology, Korea University Guro Hospital, Seoul (Korea, Republic of)

    2012-06-15

    Invasive micropapillary carcinoma is a rare, clinically aggressive variant of invasive ductal carcinoma. Imaging findings of invasive micropapillary carcinoma are not specific, and associated microcalcifications are frequent. Our case presented with unique radiological features: a mass with coarse macrocalcifications on mammography and breast computed tomography and a hyperechoic mass on breast ultrasound. Macrocalcifications and hyperechogenicity are not usual malignant characteristics. We report here on our experience with a 55-year-old woman who had invasive micropapillary carcinoma in the breast with unique radiological and pathological findings.

  11. Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type.

    Science.gov (United States)

    Lacroix-Triki, Magali; Suarez, Paula H; MacKay, Alan; Lambros, Maryou B; Natrajan, Rachael; Savage, Kay; Geyer, Felipe C; Weigelt, Britta; Ashworth, Alan; Reis-Filho, Jorge S

    2010-11-01

    Mucinous carcinomas are a rare entity accounting for up to 2% of all breast cancers, which have been shown to display a gene expression profile distinct from that of invasive ductal carcinomas of no special type (IDC-NSTs). Here, we have defined the genomic aberrations that are characteristic of this special type of breast cancer and have investigated whether mucinous carcinomas might constitute a genomic entity distinct from IDC-NSTs. Thirty-five pure and 11 mixed mucinous breast carcinomas were assessed by immunohistochemistry using antibodies against oestrogen receptor (ER), progesterone receptor, HER2, Ki67, cyclin D1, cortactin, Bcl-2, p53, E-cadherin, basal markers, neuroendocrine markers, and WT1. Fifteen pure mucinous carcinomas and 30 grade- and ER-matched IDC-NSTs were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). In addition, the distinct components of seven mixed mucinous carcinomas were microdissected separately and subjected to aCGH. Pure mucinous carcinomas consistently expressed ER (100%), lacked HER2 expression (97.1%), and showed a relatively low level of genetic instability. Unsupervised hierarchical cluster analysis revealed that pure mucinous carcinomas were homogeneous and preferentially clustered together, separately from IDC-NSTs. They less frequently harboured gains of 1q and 16p and losses of 16q and 22q than grade- and ER-matched IDC-NSTs, and no pure mucinous carcinoma displayed concurrent 1q gain and 16q loss, a hallmark genetic feature of low-grade IDC-NSTs. Finally, both components of all but one mixed mucinous carcinoma displayed similar patterns of genetic aberrations and preferentially clustered together with pure mucinous carcinomas on unsupervised clustering analysis. Our results demonstrate that mucinous carcinomas are more homogeneous between themselves at the genetic level than IDC-NSTs. Both components of mixed mucinous tumours are remarkably similar at the

  12. Telomere length alterations unique to invasive lobular carcinoma.

    Science.gov (United States)

    Heaphy, Christopher M; Asch-Kendrick, Rebecca; Argani, Pedram; Meeker, Alan K; Cimino-Mathews, Ashley

    2015-08-01

    Telomeres are nucleoprotein complexes located at the extreme ends of eukaryotic chromosomes and protect chromosomal ends from degradation and recombination. Dysfunctional telomeres contribute to genomic instability, promote tumorigenesis, and, in breast cancer, have been associated with increased cancer risk and poor prognosis. Short telomere lengths have been previously associated with triple-negative and human epidermal growth factor receptor (Her2)--positive ductal carcinomas. However, these investigations have not specifically assessed invasive lobular carcinomas (ILCs), which accounts for 5% to 15% of all invasive breast cancers. Here, we evaluate telomere lengths within 48 primary ILCs with complete characterization of estrogen receptor (ER), progesterone receptor (PR), and Her2 status, including 32 luminal/Her2- (ER+/PR+/Her2-), 8 luminal/Her2+ (ER+/PR+/Her2+), 3 Her2+ (ER-/PR-/Her2+), and 5 triple-negative (ER-/PR-/Her2-) carcinomas. A telomere-specific fluorescence in situ hybridization assay, which provides single-cell telomere length resolution, was used to evaluate telomere lengths and compare with standard clinicopathological markers. In contrast to breast ductal carcinoma, in which more than 85% of cases display abnormally short telomeres, approximately half (52%) of the ILCs displayed either normal or long telomeres. Short telomere length was associated with older patient age. Interestingly, 3 cases (6%) displayed a unique telomere pattern consisting of 1 or 2 bright telomere spots among the normal telomere signals within each individual cancer cell, a phenotype that has not been previously described. Additional studies are needed to further evaluate the significance of the unique bright telomere spot phenotype and the potential utility of telomere length as a prognostic marker in ILC.

  13. Invasive lobular carcinoma: a rare presentation in the male breast.

    Science.gov (United States)

    Melo Abreu, Elisa; Pereira, Pedro; Marques, José Carlos; Esteves, Gonçalo

    2016-01-01

    Breast cancer in men is uncommon, accounting for ratio and familial history (BRCA 2 and 1). The authors present a case of a 52-year-old man with no relevant predisposing factors to breast cancer, who presented with a painless, firm nodule, fixed to the nipple on the left breast, associated with nipple retraction and ulceration, and fully characterised by mammogram and ultrasound. Histopathological and immunohistochemical analysis revealed the diagnosis of invasive lobular breast carcinoma and the patient underwent left radical mastectomy, followed by adjuvant chemotherapy, radiotherapy and hormonotherapy. A brief review of the literature is presented. PMID:27151060

  14. Expression of e-cadherin, n-cadherin and snail and their correlation with clinicopathological variants: an immunohistochemical study of 132 invasive ductal breast carcinomas in Egypt

    Directory of Open Access Journals (Sweden)

    Hanan Mohamed Abd ElMoneim

    2011-01-01

    Full Text Available OBJECTIVE: To evaluate the expression of the cell adhesion molecules E-cadherin and N-cadherin and the transcription factor Snail in invasive ductal breast carcinomas and to determine their relationships with clinicopathological features. METHODS: Immunohistochemistry was used to examine E-cadherin, N-cadherin, and Snail protein expression in 132 invasive breast carcinomas. RESULTS: The expression of E-cadherin was decreased (negative or weak in 37.1% of invasive carcinomas, while N-cadherin and Snail overexpression were detected in 51.9% and 40.9% of carcinomas, respectively. Low E-cadherin expression was significantly correlated with poorly differentiated carcinoma (53.1%, positive node status (80.9%, poor Nottingham Prognostic Index (64.7%, and the presence of estrogen and progesterone receptors. Overexpression of N-cadherin and Snail were also significantly correlated with poorly differentiated carcinoma, positive node status, and poor Nottingham Prognostic Index but were correlated with the absence of hormone receptors. Loss of E-cadherin immunoexpression was strongly associated with the presence of membranous N-cadherin (87.8% and nuclear Snail (69.4%. CONCLUSION: Loss of E-cadherin and overexpression of N-cadherin and Snail in breast carcinomas may play a central role in the development of invasive ductal breast carcinoma. These biomarkers may provide a valuable reference for the study of invasive ductal carcinoma progression and to characterize the biological behavior of the tumor. In the future, increased N-cadherin and decreased E-cadherin expression may be used as indicators of the progression and prognosis of invasive ductal carcinoma.

  15. Tumor and Stromal-Based Contributions to Head and Neck Squamous Cell Carcinoma Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Markwell, Steven M.; Weed, Scott A., E-mail: scweed@hsc.wvu.edu [Department of Neurobiology and Anatomy, Program in Cancer Cell Biology, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506 (United States)

    2015-02-27

    Head and neck squamous cell carcinoma (HNSCC) is typically diagnosed at advanced stages with evident loco-regional and/or distal metastases. The prevalence of metastatic lesions directly correlates with poor patient outcome, resulting in high patient mortality rates following metastatic development. The progression to metastatic disease requires changes not only in the carcinoma cells, but also in the surrounding stromal cells and tumor microenvironment. Within the microenvironment, acellular contributions from the surrounding extracellular matrix, along with contributions from various infiltrating immune cells, tumor associated fibroblasts, and endothelial cells facilitate the spread of tumor cells from the primary site to the rest of the body. Thus far, most attempts to limit metastatic spread through therapeutic intervention have failed to show patient benefit in clinic trails. The goal of this review is highlight the complexity of invasion-promoting interactions in the HNSCC tumor microenvironment, focusing on contributions from tumor and stromal cells in order to assist future therapeutic development and patient treatment.

  16. Acantholytic variant of bowen′s disease with micro-invasive squamous cell carcinoma: A case report of a unique variant

    Directory of Open Access Journals (Sweden)

    Kanthilatha Pai

    2014-01-01

    Full Text Available Bowen′s disease is generally regarded as premalignant dermatoses. The disease affects both skin and the mucosa and has the potential to progress to invasive squamous cell carcinoma. There are descriptions of several histological variants of Bowen′s disease like psoriasiform, atrophic, pagetoid, etc. Acantholysis of anaplastic keratinocytes with bullae/cleft formation is described in premalignant condition like actinic keratosis and adenoid variant of squamous cell carcinoma, but there is lack of report describing this phenomena in Bowen′s disease. We present a case of unusual acantholytic variant of Bowen′s disease with focus of micro-invasive carcinoma.

  17. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    NARCIS (Netherlands)

    E.J. Sawyer (Elinor); R. Roylance (Rebecca); C. Petridis (Christos); R.H. Brook; S. Nowinski (Salpie); E. Papouli (Efterpi); O. Fletcher (Olivia); S. Pinder (Sarah); A. Hanby (Andrew); K. Kohut (Kelly); P. Gorman (Patricia); M. Caneppele (Michele); J. Peto (Julian); I. dos Santos Silva (Isabel); N. Johnson (Nichola); R. Swann (Ruth); M. Dwek (Miriam); K.-A. Perkins (Katherine-Anne); C. Gillett (Cheryl); R. Houlston (Richard); G. Ross (Gillian); P. de Ieso (Paolo); M.C. Southey (Melissa); J.L. Hopper (John); E. Provenzano (Elena); C. Apicella (Carmel); J. Wesseling (Jelle); S. Cornelissen (Sten); J.N. Keeman; P.A. Fasching (Peter); S.M. Jud (Sebastian); A.B. Ekici (Arif); M.W. Beckmann (Matthias); M. Kerin (Michael); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); B. Burwinkel (Barbara); P. Guénel (Pascal); T. Truong (Thérèse); P. Laurent-Puig (Pierre); P. Kerbrat (Pierre); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); R.L. Milne (Roger); J.I.A. Perez (Jose Ignacio Arias); P. Menéndez (Primitiva); J. Benítez (Javier); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); P. Lichtner (Peter); R.K. Schmutzler (Rita); M. Lochmann (Magdalena); H. Brauch (Hiltrud); H.-P. Fischer; Y-D. Ko (Yon-Dschun); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J. Hartikainen (Jaana); G. Chenevix-Trench (Georgia); D. Lambrechts (Diether); C. Weltens (Caroline); E. van Limbergen (Erik); S. Hatse (Sigrid); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P. Radice (Paolo); P. Peterlongo (Paolo); B. Bonnani (Bernardo); S. Volorio (Sara); G.G. Giles (Graham); G. Severi (Gianluca); L. Baglietto (Laura); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); V. Kristensen (Vessela); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.M. Mulligan (Anna Marie); P. Devillee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); M. Kriege (Mieke); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); M.E. Sherman (Mark); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); C.H.M. van Deurzen (Carolien); J. Li (Jingmei); K. Czene (Kamila); M.K. Humphreys (Manjeet); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); M. Shah (Mitul); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); F.J. Couch (Fergus); B. Hallberg (Boubou); A. González-Neira (Anna); G. Pita (G.); M.R. Alonso (M Rosario); Y. Tessier (Yann); D. Vincent (Daniel); F. Bacot (Francois); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); K. Michailidou (Kyriaki); A.M. Dunning (Alison); P. Hall (Per); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); M.K. Schmidt (Marjanka); I.P. Tomlinson (Ian); M. García-Closas (Montserrat)

    2014-01-01

    textabstractInvasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to b

  18. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    DEFF Research Database (Denmark)

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos;

    2014-01-01

    Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast can...

  19. Erythropoietin Signaling Promotes Invasiveness of Human Head and Neck Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmed Mohyeldin

    2005-05-01

    Full Text Available Erythropoietin (Epo is used for managing anemia in cancer patients. However, recent studies have raised concerns for this practice. We investigated the expression and function of Epo and the erythropoietin receptor (EpoR in tumor biopsies and cell lines from human head and neck cancer. Epo responsiveness of the cell lines was assessed by Epoetin-α-induced tyrosine phosphorylation of the Janus kinase 2 (JAK2 protein kinase. Transmigration assays across Matrigel-coated filters were used to examine the effects of Epoetin-A on cell invasiveness. In 32 biopsies, we observed a significant association between disease progression and expression of Epo and its receptor, EpoR. Expression was highest in malignant cells, particularly within hypoxic and infiltrating tumor regions. Although both Epo and EpoR were expressed in human head and neck carcinoma cell lines, only EpoR was upregulated by hypoxia. Epoetin-α treatment induced prominent JAK2 phosphorylation and enhanced cell invasion. Inhibition of JAK2 phosphorylation reduced both basal and Epo-induced invasiveness. Our findings support a role for autocrine or paracrine Epo signaling in the malignant progression and local invasiveness of head and neck cancer. This mechanism may also be activated by recombinant Epo therapy and could potentially produce detrimental effects in rhEpo-treated cancer patients.

  20. Quantitative histopathological variables in in situ and invasive ductal and lobular carcinomas of the breast

    DEFF Research Database (Denmark)

    Ladekarl, M; Sørensen, Flemming Brandt

    1993-01-01

    This study was carried out to compare quantitative histopathological estimates obtained in normal breast epithelium (N = 15), lobular carcinoma in situ (N = 29), ductal carcinoma in situ (N = 24), invasive lobular carcinoma (N = 39), and invasive ductal carcinoma (N = 71) of the female breast......) with those obtained in tumors of pure lobular carcinoma in situ (N = 7), only the difference in mean NI reached statistical significance (2p = 0.001). Several significant differences were found between means of quantitative histopathological estimates obtained in normal breast epithelium, pure in situ...... value of the investigated variables in the diagnostic separation of normal breast epithelium, in situ lesions, and invasive carcinomas. The quantitative variables obtained in the situ lesions did not indicate whether an accompanying invasive tumor was present or not....

  1. Reduced CTGF expression promotes cell growth, migration, and invasion in nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Yan Zhen

    Full Text Available BACKGROUND: The role of CTGF varies in different types of cancer. The purpose of this study is to investigate the involvement of CTGF in tumor progression and prognosis of human nasopharyngeal carcinoma (NPC. EXPERIMENTAL DESIGN: CTGF expression levels were examined in NPC tissues and cells, nasopharynx (NP tissues, and NP69 cells. The effects and molecular mechanisms of CTGF expression on cell proliferation, migration, invasion, and cell cycle were also explored. RESULTS: NPC cells exhibited decreased mRNA expression of CTGF compared to immortalized human nasopharyngeal epithelial cell line NP69. Similarly, CTGF was observed to be downregulated in NPC compared to normal tissues at mRNA and protein levels. Furthermore, reduced CTGF was negatively associated with the progression of NPC. Knocking down CTGF expression enhanced the colony formation, cell migration, invasion, and G1/S cell cycle transition. Mechanistic analysis revealed that CTGF suppression activated FAK/PI3K/AKT and its downstream signals regulating the cell cycle, epithelial-mesenchymal transition (EMT and MMPs. Finally, DNA methylation microarray revealed a lack of hypermethylation at the CTGF promoter, suggesting other mechanisms are associated with suppression of CTGF in NPC. CONCLUSION: Our study demonstrates that reduced expression of CTGF promoted cell proliferation, migration, invasion and cell cycle progression through FAK/PI3K/AKT, EMT and MMP pathways in NPC.

  2. Invasive thyroglossal duct cyst papillary carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Aghaghazvini Shirin

    2009-12-01

    Full Text Available Abstract Introduction A thyroglossal duct cyst is the most common congenital anomaly of the thyroid gland and midline masses in childhood (70% abnormality in childhood, 7% in adult. Carcinomas arising from a thyroglossal duct cyst are rare (only 1% of thyroglossal duct cyst cases and characterized by relatively non-aggressive behavior and rare lymphatic spread. They are also diagnosed mostly during the third and fourth decades of life. About 85% to 92% of all thyroglossal duct cyst carcinomas are papillary carcinomas. Case presentation We present the case of a 44-year-old Iranian woman with Cacausian ethnicity with a painless anterior neck mass that appeared gradually over three months. She had a history of frequent painful swelling of the anterior part of her neck, which subsided with antibiotic therapy. Thyroid functional tests were normal and a thyroid scinitigraphy showed a cold nodule in the left lobe of her thyroid. A computed tomography scan revealed a large, heterogeneous enhancing soft tissue mass with cystic components in the midline of the anterior neck space. This extended from the base of the tongue,(completely separated from its muscles, to the inferior aspect of the thyroid gland and showed the destruction of the hyoid bone and the thyroid cartilage. The diagnosis of a thyroglossal duct cyst with malignant transformation was maintained. A fine needle aspiration revealed papillary carcinoma. Conclusion This patient's case is presented because of its rare, aggressive, and invasive nature and rare and unusual manifestation, as well as its rapid increase in size, the destruction of the hyoid bone, chondrolysis of the thyroid cartilage, lymph adenopathy and the existence of a cold nodule in the thyroid gland.

  3. Bone Morphogenetic Proteins stimulate mammary fibroblasts to promote mammary carcinoma cell invasion.

    Directory of Open Access Journals (Sweden)

    Philip Owens

    Full Text Available Bone Morphogenetic Proteins (BMPs are secreted cytokines that are part of the Transforming Growth Factor β (TGFβ superfamily. BMPs have been shown to be highly expressed in human breast cancers, and loss of BMP signaling in mammary carcinomas has been shown to accelerate metastases. Interestingly, other work has indicated that stimulation of dermal fibroblasts with BMP can enhance secretion of pro-tumorigenic factors. Furthermore, treatment of carcinoma-associated fibroblasts (CAFs derived from a mouse prostate carcinoma with BMP4 was shown to stimulate angiogenesis. We sought to determine the effect of BMP treatment on mammary fibroblasts. A large number of secreted pro-inflammatory cytokines and matrix-metallo proteases (MMPs were found to be upregulated in response to BMP4 treatment. Fibroblasts that were stimulated with BMP4 were found to enhance mammary carcinoma cell invasion, and these effects were inhibited by a BMP receptor kinase antagonist. Treatment with BMP in turn elevated pro-tumorigenic secreted factors such as IL-6 and MMP-3. These experiments demonstrate that BMP may stimulate tumor progression within the tumor microenvironment.

  4. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment

  5. Expression of the stromelysin-3 gene in fibroblastic cells of invasive carcinomas of the breast and other human tissues: a review.

    Science.gov (United States)

    Basset, P; Wolf, C; Chambon, P

    1993-01-01

    Stromelysin-3 (ST3) is a putative new matrix metalloproteinase (MMP) which may play a role in the progression of human carcinomas, and exhibits unique structural and functional characteristics among the MMP family. The ST3 gene, which is generally not expressed at significant levels in benign breast tumors, has been found to be expressed in all invasive breast carcinomas tested so far. The gene is also expressed in some in situ breast carcinomas, which have a higher probability to become invasive. ST3 RNA and protein are specifically found in fibroblastic cells immediately surrounding the neoplastic cells, both in invasive and in situ breast carcinomas. The same expression pattern is observed in other types of human carcinomas, and the highest ST3 RNA levels are observed in tumors that exhibit high local invasiveness. The ST3 gene is also expressed in fibroblastic cells during the inflammatory phase of wound healing, which suggests that ST3 gene expression in stromal fibroblasts may be under the control of factors produced by inflammatory cells during wound healing, and by cancer cells during carcinoma progression. ST3 may thus represent a stroma-derived factor necessary for the progression of epithelial malignancies, and its manipulation may possibly be used to develop new anti-cancer agents. PMID:8435474

  6. Significance of color doppler ultrasonography in the assessment of pancreatic carcinoma vascular invasion

    Directory of Open Access Journals (Sweden)

    Alempijević Tamara

    2006-01-01

    Full Text Available Background/Aim. It is highly appreciated to provide exact data on vascular invasion of pancreatic carcinoma relying as much as possible on non-invasive diagnostic procedures. Color Doppler ultrasonography has been proven as an efficient method for clinical staging of pancreatic carcinoma essential for therapeutic decisions. The aim of this study was to provide an analysis of the sensitivity and specificity for color Doppler ultrasonography in patients suffering from pancreatic carcinoma. Methods. We performed color Doppler ultrasonography examination in 43 patients with pancreatic carcinoma prior to the surgery. The findings of ultrasonography on neoplasm vascular invasion were correlated to the findings obtained during the subsequent surgical procedures. An estimation of neoplastic invasion of certain blood vessels including portal vein, celiac trunk, and superior mesenteric artery and vein is critical for decision making regarding surgical treatment. The patients with metastases of pancreatic carcinoma were excluded from the study. Results. Comparing color Doppler and the surgical findings we estimated the sensitivity for detection of neoplastic vascular invasion ranging from 79−93%, whereas the specificity range was from 83−93%. Conclusion. Color Doppler ultrasonography is a sufficiently sensitive and specific method for evaluation of vascular invasion in pancreatic carcinoma patients. Since color Doppler ultrasonography is a non-invasive, radiation free, and inexpensive diagnostic tool, considering also the results of this and similar studies we could strongly recommend its use for an initial presurgical evaluation of vascular invasion in pancreatic carcinoma patients.

  7. Hypoxia-induced enhancement of cell invasiveness in SMMC7721 hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To explore the effects of hypoxia(1% O2)on the ability of cell invasiveness and expression of KAI1/CD82 in SMMC7721 hepatocellular carcinoma cells.Methods SMMC7721 hepatocellular carcinoma cells were cultured by hypoxia(1% O2)in vitro,and the ability of cell invasiveness was analyzed by cell invasion assay.Immunohistochemistry staining technique was used to evaluate the protein expression of KAI1/CD82.Results Cell invasion assay revealed that hypoxia enhanced the ability of invasiveness of hepatoc...

  8. International collaborative validation of intraneural invasion as a prognostic marker in adenoid cystic carcinoma of the head and neck

    DEFF Research Database (Denmark)

    Amit, Moran; Binenbaum, Yoav; Trejo-Leider, Leonor;

    2015-01-01

    BACKGROUND: The purpose of this study was to characterize the incidence, pattern of spread, and prognostic correlation of nerve invasion in patients with adenoid cystic carcinoma (ACC). METHODS: Using 3 different pathological categories of perineural invasion, intraneural invasion, and perineural...

  9. Complexity in regulation of microRNA machinery components in invasive breast carcinoma.

    Science.gov (United States)

    Kwon, Sun Young; Lee, Jae-ho; Kim, Bora; Park, Jong-Wook; Kwon, Taeg Kyu; Kang, Sun Hee; Kim, Shin

    2014-07-01

    Altered expression of microRNA (miRNA) machinery components may play an important role in breast cancer progression. The objective of the current study was to evaluate Drosha, the DiGeorge syndrome critical region gene 8 (DGCR8), Dicer, and Argonaute 2 (AGO2) mRNA expression in invasive breast carcinoma (IBC) and to assess the value of clinical parameters on their expression. By using quantitative real-time PCR, we examined the expression of the four miRNA machinery components in 52 breast tumor tissues which are diagnosed as invasive ductal carcinoma and adjacent non-neoplastic tissues. In the present study, decreased mRNA expression levels of major miRNA machinery components were observed in IBC. The altered mRNA expression levels of DGCR8 and AGO2 are positively correlated with to each other. This study revealed for the first time that expression alterations of DGCR8 are significantly associated with estrogen receptor and Ki-67 status in IBC. Moreover, AGO2 mRNA expression level was significantly correlated with N stage. These results provided evidences that down-regulated the four miRNA machinery components may play an important role in breast pathobiology and that DGCR8 and AGO2 might be associated with important clinical factors.

  10. DNAJC6 promotes hepatocellular carcinoma progression through induction of epithelial–mesenchymal transition

    International Nuclear Information System (INIS)

    Highlights: • DNAJC6 is up-regulated in hepatocellular carcinoma tissues. • DNAJC6 promotes hepatocellular carcinoma cell proliferation and invasion. • DNAJC6 induces epithelial–mesenchymal transition by activating transforming growth factor β signaling. - Abstract: Epithelial–mesenchymal transition (EMT) is a developmental program, which is associated with hepatocellular carcinoma (HCC) development and progression. DNAJC6 (DNA/HSP40 homolog subfamily C member 6) encodes auxilin, which is responsible for juvenile Parkinsonism with phenotypic variability. However, the role of DNAJC6 in HCC development and progression is limited. Here, we report that DNAJC6 is up-regulated in HCC tissues and up-regulation of DNAJC6 expression predicts poor outcome in patients with HCC. Furthermore, overexpression of DNAJC6 enhances the ability for acquisition of mesenchymal traits, enhanced cell proliferation and invasion. DNAJC6 positively regulated expression of EMT-related transcription factor, also activating transforming growth factor β (TGF-β) pathway to contribute to EMT. Our findings demonstrated an important function of DNAJC6 in the progression of HCC by induction of EMT, and they implicate DNAJC6 as a marker of poor outcome in HCC

  11. DNAJC6 promotes hepatocellular carcinoma progression through induction of epithelial–mesenchymal transition

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Tao [Hepatobiliary Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China); Li, Xiao-Na [General Surgery, Sports Science Institute of Hebei Province, Shijiazhuang 050011 (China); Li, Xing-Guang; Li, Ming [General Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China); Gao, Peng-Zhi, E-mail: pengzhigaovip@163.com [Hepatobiliary Surgery, The First Hospital of Shijiazhuang City, Shijiazhuang 050011 (China)

    2014-12-12

    Highlights: • DNAJC6 is up-regulated in hepatocellular carcinoma tissues. • DNAJC6 promotes hepatocellular carcinoma cell proliferation and invasion. • DNAJC6 induces epithelial–mesenchymal transition by activating transforming growth factor β signaling. - Abstract: Epithelial–mesenchymal transition (EMT) is a developmental program, which is associated with hepatocellular carcinoma (HCC) development and progression. DNAJC6 (DNA/HSP40 homolog subfamily C member 6) encodes auxilin, which is responsible for juvenile Parkinsonism with phenotypic variability. However, the role of DNAJC6 in HCC development and progression is limited. Here, we report that DNAJC6 is up-regulated in HCC tissues and up-regulation of DNAJC6 expression predicts poor outcome in patients with HCC. Furthermore, overexpression of DNAJC6 enhances the ability for acquisition of mesenchymal traits, enhanced cell proliferation and invasion. DNAJC6 positively regulated expression of EMT-related transcription factor, also activating transforming growth factor β (TGF-β) pathway to contribute to EMT. Our findings demonstrated an important function of DNAJC6 in the progression of HCC by induction of EMT, and they implicate DNAJC6 as a marker of poor outcome in HCC.

  12. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation.

    Science.gov (United States)

    Mohanty, Sambit K; Kim, Stacey A; DeLair, Deborah F; Bose, Shikha; Laury, Anna R; Chopra, Shefali; Mertens, Richard B; Dhall, Deepti

    2016-08-01

    Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with primary mammary carcinomas, particularly those showing evidence of neuroendocrine differentiation, and may be misdiagnosed as such. Accurate distinction between these two entities is crucial for determination of appropriate clinical management. The histologic and immunohistochemical features of metastatic neuroendocrine neoplasms to the breast were studied and compared with the features of primary invasive mammary carcinomas with neuroendocrine differentiation, which served as controls. Of the metastatic neuroendocrine neoplasms, 15 were well-differentiated neuroendocrine tumors with carcinoid tumor-type morphology and 7 were poorly differentiated/high-grade neuroendocrine carcinomas with small-cell or large-cell neuroendocrine carcinoma morphology. The majority of the metastatic neoplasms originated in the lung and gastrointestinal tract. There were histologic similarities between metastatic neuroendocrine neoplasms and invasive mammary carcinomas with neuroendocrine differentiation, both of which exhibited neuroendocrine histologic features (nested and trabecular architecture, minimal tubular differentiation, and characteristic nuclear features). Only one case of the invasive mammary carcinomas with neuroendocrine differentiation was modified Bloom-Richardson grade 1 (largely due to minimal tubular differentiation on most such tumors), and the invasive mammary carcinomas with neuroendocrine differentiation were often associated with in situ carcinoma. Immunohistochemistry was helpful in distinguishing metastatic neuroendocrine neoplasms from invasive mammary carcinomas with neuroendocrine differentiation. Whereas the majority of invasive mammary carcinomas with neuroendocrine differentiation were positive for estrogen receptor and GATA3, metastatic neuroendocrine neoplasms were typically negative for estrogen receptor and GATA3, and metastatic well

  13. Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ.

    Science.gov (United States)

    Dobbs, Jessica L; Shin, Dongsuk; Krishnamurthy, Savitri; Kuerer, Henry; Yang, Wei; Richards-Kortum, Rebecca

    2016-09-01

    Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions. PMID:27116366

  14. Poorly differentiated thyroid carcinoma with sternal invasion. A case report and review of the literature

    OpenAIRE

    Quaratulain Sabih; Michael F. Spafford; Dietl, Charles A.

    2014-01-01

    INTRODUCTION: Surgical resection of poorly differentiated thyroid carcinoma with direct invasion of the sternum has not been previously reported. Only 4 cases of concomitant thyroidectomy and sternal resection and reconstruction for sternal metastases have been published. PRESENTATION OF CASE: A 66-year-old female with a poorly differentiated thyroid carcinoma and direct sternal invasion underwent total thyroidectomy and resection of the manubrium and both clavicular heads, and chest wall ...

  15. Estrogen receptor beta rs1271572 polymorphism and invasive ovarian carcinoma risk

    DEFF Research Database (Denmark)

    Lurie, Galina; Wilkens, Lynne R; Thompson, Pamela J;

    2011-01-01

    The association of ovarian carcinoma risk with the polymorphism rs1271572 in the estrogen receptor beta (ESR2) gene was examined in 4946 women with primary invasive ovarian carcinoma and 6582 controls in a pooled analysis of ten case-control studies within the Ovarian Cancer Association Consortium...

  16. Osteoradionecrosis of the skull after radiation therapy for invasive carcinoma.

    Science.gov (United States)

    Nguyen, Michaela T; Billington, Alicia; Habal, Mutaz B

    2011-09-01

    Osteoradionecrosis (ORN) of the skull is a rare but fatal complication of radiation therapy for the treatment of head and neck malignancies. The pathogenesis of ORN follows the "3Hs Theory" proposed by Marx (J Oral Maxillofac Surg 1983;41:283-288) in which radiation induces tissue injury by causing vessel thrombosis (hypovascularity), which leads to hypoxia, and results in cell death of the skin and the underlying structure of the bony element (hypocellularity) including the deep visceral structures. This note details a patient with severe and extensive ORN of the parietooccipital region of the skull because of a large dose of radiation therapy for the treatment of an invasive basal cell carcinoma of the scalp. The patient's condition was further complicated by an extensive infection with methicillin-resistant Staphylococcus aureus, which leads to meningitis and cerebral edema as well as cerebritis. The patient was successfully treated with interdisciplinary medical and surgical aggressive therapy and radical procedures involving 4 separate trips to the operating room for an 18-month period. Success was achieved because of early clinical diagnosis of ORN, aggressive eradication of infected and necrotic tissues including the brain, and restoration of functioning and viable tissues through the use of local flaps to change an open wound to a closed wound. PMID:21959411

  17. Invasive ductal carcinomas of the breast showing partial reversed cell polarity are associated with lymphatic tumor spread and may represent part of a spectrum of invasive micropapillary carcinoma.

    Science.gov (United States)

    Acs, Geza; Esposito, Nicole N; Rakosy, Zsuzsa; Laronga, Christine; Zhang, Paul J

    2010-11-01

    Invasive micropapillary carcinomas (IMPC) of the breast are aggressive tumors frequently associated with lymphatic invasion and nodal metastasis even when micropapillary (MP) differentiation is very focal within the tumors. We have noticed that some breast carcinomas showing lymphatic spread but lacking histologic features of IMPC have occasional tumor cell clusters reminiscent of those of IMPC without the characteristic prominent retraction artifact. To study the clinicopathologic significance of such features, we prospectively selected 1323 invasive ductal carcinomas and determined the presence and extent of MP differentiation and retraction artifact in the tumors. One representative tumor block per case was used for immunostaining for epithelial membrane antigen (EMA). Partial reverse cell polarity (PRCP) was defined as prominent linear EMA reactivity on at least part of the periphery of tumor cell clusters usually associated with decreased cytoplasmic staining. The clinicopathologic features of carcinomas with PRCP were compared with IMPC and invasive ductal (no special type) carcinomas without this feature. Of the 1323 cases, 96 (7.3%) and 92 (7.0%) showed MP features and the presence of PRCP, respectively. We found that the presence of both PRCP and MP features were strongly associated with decreased cytoplasmic EMA immunoreactivity and the presence of lymphatic invasion and nodal metastasis, even if such features were present only very focally. Our results suggest that breast carcinomas with PRCP may have the same implication as MP differentiation and these tumors may represent part of a spectrum of IMPC. Complete or partial reversal of cell polarity may play a significant role in lymphatic tumor spread.

  18. Assessment of vascular invasion in pancreatic carcinoma by MDCT

    Directory of Open Access Journals (Sweden)

    Omar Hassanen

    2014-06-01

    Conclusion: Assessment of vascular invasion is crucial in the evaluation of resectability for pancreatic cancer. MDCT is an accurate diagnostic tool for peripancreatic vascular invasion in cancer pancreas.

  19. Invasive ductal carcinoma of the breast in a 14-year-old girl

    International Nuclear Information System (INIS)

    Breast cancer is rare in children and adolescents. In particular, there are very few cases of invasive ductal carcinoma in childhood. We report a case of invasive ductal carcinoma of the breast in a 14-year-old girl presenting as a palpable mass. While the tumor demonstrated a relatively benign appearance on ultrasound, magnetic resonance imaging revealed typical malignant features. Several polymorphisms of single nucleotide variation were observed on gene analysis. The patient underwent breast conserving surgery and received subsequent concurrent chemo-radiation therapy. An awareness that ductal carcinoma of the breast rarely occurs in children is important to detect early stage breast cancer. (orig.)

  20. Invasive ductal carcinoma of the breast in a 14-year-old girl

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joo Yeon; Kim, Yun Ju; Kim, Sung Hun; Kang, Bong Joo [Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Department of Radiology, Seoul (Korea, Republic of); Song, Byung Joo [The Catholic University of Korea, Department of General Surgery, Seoul St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of)

    2014-11-15

    Breast cancer is rare in children and adolescents. In particular, there are very few cases of invasive ductal carcinoma in childhood. We report a case of invasive ductal carcinoma of the breast in a 14-year-old girl presenting as a palpable mass. While the tumor demonstrated a relatively benign appearance on ultrasound, magnetic resonance imaging revealed typical malignant features. Several polymorphisms of single nucleotide variation were observed on gene analysis. The patient underwent breast conserving surgery and received subsequent concurrent chemo-radiation therapy. An awareness that ductal carcinoma of the breast rarely occurs in children is important to detect early stage breast cancer. (orig.)

  1. Management of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma.

    Science.gov (United States)

    Arslanoğlu, Seçil; Eren, Erdem; Özkul, Yılmaz; Ciğer, Ejder; Kopar, Aylin; Önal, Kazım; Etit, Demet; Tütüncü, G Yazgı

    2016-02-01

    The objective of this study was to determine the incidence of thyroid gland invasion in laryngeal and hypopharyngeal squamous cell carcinoma; and the association between clinicopathological parameters and thyroid gland invasion. Medical records of 75 patients with laryngeal and hypopharyngeal squamous cell carcinoma who underwent total laryngectomy with thyroidectomy were reviewed, retrospectively. Preoperative computed tomography scans, clinical and operative findings, and histopathological data of the specimens were evaluated. There were 73 male and two female patients with an age range of 41-88 years (mean 60.4 years). Hemithyroidectomy was performed in 62 (82.7 %) and total thyroidectomy was performed in 13 patients (17.3 %). Four patients had histopathologically proven thyroid gland invasion (5.3 %). In three patients, thyroid gland involvement was by means of direct invasion. Thyroid gland invasion was significantly correlated with thyroid cartilage invasion. Therefore, prophylactic thyroidectomy should not be a part of the treatment policy for these tumors.

  2. All delays before radiotherapy risk progression of Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Prolonged waiting times for radiotherapy have resulted in many centres assigning priorities to various patient or diagnostic groups. A high risk of progression on a waiting list is one factor that would reasonably influence the priority. The present descriptive study of 27 patients with Merkel cell carcinoma (MCC) found that a median wait of 24 days for radiotherapy is associated with a high risk of progression. Eleven (41%) of 27 patients developed progressive disease, including five (45%) of 11 patients waiting for adjuvant radiotherapy. Patients treated adjuvantly also had longer waiting times prior to their initial radiotherapy consultation (median 41 days), which may have contributed to the rate of progression. Merkel cell carcinoma is an aggressive but curable malignancy and appropriate management should include efforts to minimize all potential delays prior to the commencement of radiotherapy. Copyright (2004) Blackwell Science Pty Ltd

  3. Invasive micropapillary carcinomas arising 42 years after augmentation mammoplasty: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Kikuchi Kazunori

    2008-03-01

    Full Text Available Abstract Background There has been no definitive consensus regarding the causal relationships between foreign bodies in the breast and carcinogenesis. This report describes the first case of invasive micropapillary carcinomas after augmentation mammoplasty. Multiple tumors located in immediate contact with the siliconomas suggested a causal link between the siliconomas and carcinomas. Case presentation This report presents the case of a 64-year-old female who underwent liquid silicone injections for augmentation mammoplasty 42 years previously. Eight years before admission, siliconomas of the left breast were removed due to pain and discomfort. The patient visited the hospital for further treatment of newly diagnosed carcinoma of the left breast. Images showed multiple tumors located in various areas of the left breast. The pathological findings of the left breast showed each tumor to be solitary and not continuous with the others. The tumors were diagnosed to be invasive micropapillary carcinomas, and they all came into immediate contact with the residual siliconomas. The siliconomas were therefore suspected to have played a causative role in the development of the breast cancer. Conclusion This rare case of multiple invasive micropapillary carcinomas following augmentation mammoplasty provides evidence that siliconomas may lead to carcinomas. Although a causal relationship was not established unequivocally, we review evidence that suggest silicone gel may cause cell damage responsible for carcinoma development.

  4. Aspergillus fumigatus invasion increases with progressive airway ischemia.

    Directory of Open Access Journals (Sweden)

    Joe L Hsu

    Full Text Available Despite the prevalence of Aspergillus-related disease in immune suppressed lung transplant patients, little is known of the host-pathogen interaction. Because of the mould's angiotropic nature and because of its capacity to thrive in hypoxic conditions, we hypothesized that the degree of Aspergillus invasion would increase with progressive rejection-mediated ischemia of the allograft. To study this relationship, we utilized a novel orthotopic tracheal transplant model of Aspergillus infection, in which it was possible to assess the effects of tissue hypoxia and ischemia on airway infectivity. Laser Doppler flowmetry and FITC-lectin were used to determine blood perfusion, and a fiber optic microsensor was used to measure airway tissue oxygen tension. Fungal burden and depth of invasion were graded using histopathology. We demonstrated a high efficacy (80% for producing a localized fungal tracheal infection with the majority of infection occurring at the donor-recipient anastomosis; Aspergillus was more invasive in allogeneic compared to syngeneic groups. During the study period, the overall kinetics of both non-infected and infected allografts was similar, demonstrating a progressive loss of perfusion and oxygenation, which reached a nadir by days 10-12 post-transplantation. The extent of Aspergillus invasion directly correlated with the degree of graft hypoxia and ischemia. Compared to the midtrachea, the donor-recipient anastomotic site exhibited lower perfusion and more invasive disease; a finding consistent with clinical experience. For the first time, we identify ischemia as a putative risk factor for Aspergillus invasion. Therapeutic approaches focused on preserving vascular health may play an important role in limiting Aspergillus infections.

  5. Expression of Wntless in colorectal carcinomas is associated with invasion, metastasis, and poor survival.

    Science.gov (United States)

    Xu, Hanfeng; Jiang, Wen; Zhu, Fang; Zhu, Chuandong; Wei, Juan; Wang, Jiandong

    2016-06-01

    Wntless also known as WLS, GPR177, or Evi, is a key modulator of Wnt protein secretion. Its overexpression is found in certain types of human cancers such as malignant astrocytoma and breast cancers. We hypothesized that this protein may be aberrantly expressed in colorectal carcinoma which also possesses aberrant Wnt signaling. To investigate the association between the expression of Wnt and clinicopathological parameters in colorectal carcinomas, a set of colorectal carcinoma tissue samples was analyzed for the expression of WLS using an anti-GPR177 monoclonal antibody specific for the WLS protein. High expression of WLS protein was observed in most colorectal carcinoma samples compared with nontumor mucosa in the same patients (117/201, 58.2%). High expression of WLS was associated with sex (p = 0.005), age (p = 0.009), depth of invasion (p < 0.001), lymph node metastasis (p = 0.026), and tumor-node-metastasis (TNM) stage (p = 0.003). No significant relationship between the expression of WLS and tumor location, size, and differentiation was found. The survival analyses showed WLS was an independent prognostic marker and that patients whose carcinoma exhibited high expression of WLS had a poorer outcome (p = 0.033). Our results indicate that WLS may play a role in invasion and metastasis of colorectal carcinoma. The WLS protein expression level may be used as a potential prognostic marker in colorectal carcinoma. Furthermore, the WLS gene may provide a novel target for therapy of colorectal carcinoma. PMID:27102079

  6. ARID1A immunohistochemistry improves outcome prediction in invasive urothelial carcinoma of urinary bladder.

    Science.gov (United States)

    Faraj, Sheila F; Chaux, Alcides; Gonzalez-Roibon, Nilda; Munari, Enrico; Ellis, Carla; Driscoll, Tina; Schoenberg, Mark P; Bivalacqua, Trinity J; Shih, Ie-Ming; Netto, George J

    2014-11-01

    AT-rich interactive domain 1A (ARID1A) is tumor suppressor gene that interacts with BRG1 adenosine triphosphatase to form a SWI/SNF chromatin remodeling protein complex. Inactivation of ARID1A has been described in several neoplasms, including epithelial ovarian and endometrial carcinomas, and has been correlated with prognosis. In the current study, ARID1A expression in urothelial carcinoma (UC) of the bladder and its association with clinicopathological parameters and outcome are addressed. Five tissue microarrays were constructed from 136 cystectomy specimens performed for UC at our institution. Nuclear ARID1A staining was evaluated using immunohistochemistry. An H-score was calculated as the sum of the products of intensity (0-3) multiplied by extent of expression (0%-100%). Average H-score per case was used for statistical analysis. ARID1A expression was categorized in low and high using Youden index to define the cut point. ARID1A expression significantly increased from normal to noninvasive UC to invasive UC. For both tumor progression and cancer death, Youden index yielded an H-score of 288 as the optimal cut point for ARID1A expression. Low ARID1A expression showed a tendency for lower risk of tumor progression and cancer mortality. Adding ARID1A expression to pathologic features offers a better model for predicting outcome than pathologic features alone. Low ARID1A expression was more frequently seen in earlier stage disease. There was a tendency for low ARID1A expression to predict better outcome. More importantly, the findings indicate that adding ARID1A expression to pathologic features increases the goodness of fit of the predictive model. PMID:25175170

  7. Stromal CEA immunoreactivity is correlated with lymphatic invasion of human esophageal carcinoma.

    Science.gov (United States)

    Kijima, H; Oshiba, G; Kenmochi, T; Kise, Y; Tanaka, H; Chino, O; Shimada, H; Ueyama, Y; Tanaka, M; Makuuchi, H

    2000-04-01

    Carcinoembryonic antigen (CEA) is a good marker of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathways; i.e. modulation of immune responses, facilitation of intercellular adhesion and cellular migration. However, expression patterns of CEA have not yet been established in human esophageal carcinomas. In this study, we examined CEA expression in human esophageal squamous cell carcinoma and its clinicopathological significance. CEA immunoreactivity was frequently detected in the cancer cells (cytoplasmic type; 81.1%, 43/53) as well as in the cancer stroma (stromal type; 32.1%, 17/53), regardless of the depth of tumor invasion. Lymphatic invasion of cancer cells was frequently found in the stromal CEA-positive esophageal cancer (44.4%, 16/36), compared to stromal CEA-negative cancer (5.9%, 1/17) (pCEA expression plays important roles in lymphatic invasion of human esophageal squamous cell carcinoma.

  8. Transcriptional differences of the human papillomavirus type 16 genome between precancerous lesions and invasive carcinomas

    International Nuclear Information System (INIS)

    Human papillomavirus type 16 (HPV16) genome DNA and its transcripts in biopsied cervical neoplasias were analyzed by simultaneous extraction of DNA and RNA from one biopsied sample. Southern blot analysis revealed that 5 of 20 cervical intraepithelial neoplasias (CINs) contained HPV16 DNAs existing primarily as episomes and two of seven invasive carcinomas harbored HPV16 genome sequences integrated into the host DNA. Northern (RNA) blot analysis showed that the HPV16 genome sequences were transcriptionally active in the five CINs, as well as in the two invasive carcinomas. The pattern of HPV16-specific transcripts in the CINs was uniform, and the major transcripts were 4.2, 2.2, 1.6, and 1.4 kilobases in size. However, the pattern of HPV16-specific transcripts in the invasive carcinomas was variable and different from that in CINs, suggesting that the alteration of transcriptional pattern might play a key role in the development of malignancy

  9. Invasive Cribriform Carcinoma Arising in Malignant Phyllodes Tumor of Breast: A Case Report

    OpenAIRE

    Choi, Yoomi; Lee, Kyoung Yul; Jang, Min Hye; Seol, Hyesil; Kim, Sung-Won; Park, So Yeon

    2012-01-01

    Phyllodes tumor is an uncommon fibroepithelial neoplasm of the breast. And it is characterized by expanded stroma with increased cellularity and elongated epithelium-lined clefts. Mammary carcinomas within phyllodes tumors have been rarely reported. To date, however, no reports have described the invasive cribriform carcinoma arising in malignant phyllodes tumor. Here, we report a 62-year-old woman who presented with a large breast mass. Microscopically, the mass was a typical malignant phyll...

  10. Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma.

    Science.gov (United States)

    Warszawik-Hendzel, Olga; Olszewska, Małgorzata; Maj, Małgorzata; Rakowska, Adriana; Czuwara, Joanna; Rudnicka, Lidia

    2015-12-31

    Squamous cell carcinoma is the second most common cutaneous malignancy after basal cell carcinoma. Although the gold standard of diagnosis for squamous cell carcinoma is biopsy followed by histopathology evaluation, optical non-invasive diagnostic tools have obtained increased attention. Dermoscopy has become one of the basic diagnostic methods in clinical practice. The most common dermoscopic features of squamous cell carcinoma include clustered vascular pattern, glomerular vessels and hyperkeratosis. Under reflectance confocal microscopy, squamous cell carcinoma shows an atypical honeycomb or disarranged pattern of the spinous-granular layer of the epidermis, round nucleated bright cells in the epidermis and round vessels in the dermis. High frequency ultrasound and optical coherence tomography may be helpful in predominantly in pre-surgical evaluation of tumor size. Emerging non-invasive or minimal invasive techniques with possible application in the diagnosis of squamous cell carcinoma of the skin, lip, oral mucosa, vulva or other tissues include high-definition optical coherence tomography, in vivo multiphoton tomography, direct oral microscopy, electrical impedance spectroscopy, fluorescence spectroscopy, Raman spectroscopy, elastic scattering spectroscopy, differential path-length spectroscopy, nuclear magnetic resonance spectroscopy, and angle-resolved low coherence interferometry.

  11. Analysis of alterations adjacent to invasive vulvar carcinoma and their relationship with the associated carcinoma: a study of 67 cases.

    Science.gov (United States)

    Vilmer, C; Cavelier-Balloy, B; Nogues, C; Trassard, M; Le Doussal, V

    1998-01-01

    A retrospective analysis of histological lesions adjacent to 67 invasive vulvar squamous cell carcinomas (SCC) was undertaken to analyse their nature, as well as their relationship to SCC. Patient age, clinical presentation and histological type of carcinoma, ISSVD classification of its adjacent lesions, disease-free and overall survival were reviewed. Severe undifferentiated vulvar intra-epithelial neoplasia (VIN3) was found in 19.4% of cases and vulvar lichen sclerosus (VLS) in 76.1% of cases. All VLS, except 2 cases, were associated with squamous cell hyperplasia (SCH), and a concomitant differentiated VIN was found in 76.6% of cases. Undifferentiated VIN3 was never associated with VLS. VLS was significantly associated with a keratinizing, well-differentiated SCC (98% of cases), while undifferentiated VIN3, was linked preferentially to 2 other types of SCC: in 77% of cases, a moderately-differentiated SCC with the same histological features as the so-called basaloid carcinoma and, in 23% of cases, a well-differentiated SCC with a variable extent of koilocytic atypia, similar to the so-called warty carcinoma. Carcinoma of the fourchette was more often associated with undifferentiated VIN3. Disease-free and overall survival were significantly better for carcinoma associated with undifferentiated VIN3 (p < 0.01 and p < 0.05, respectively). These findings suggest invasive vulvar SCC occurs on 2 distinct types of vulvar lesions: differentiated VIN and/or SCH associated with VLS and undifferentiated VIN3. Furthermore, the histological type of the carcinoma seems to differ according to adjacent lesions.

  12. Five-year survival following a medial pancreatectomy for an invasive ductal carcinoma from the body of the pancreas

    Institute of Scientific and Technical Information of China (English)

    Hideki Abe; Kouichi Tsuneyama; Kazuhiro Tsukada; Masatoshi Makuuchi

    2006-01-01

    We report a rare case of a patient who survived for 5years after undergoing a medial pancreatectomy for invasive ductal carcinoma originating from the body of the pancreas. A 63-year-old woman was diagnosed as a small cancer of the pancreatic body, and surgery was performed. Even though the tumor was a carcinoma, its small size prompted us to perform a medial pancreatectomy with regional lymph nodes dissection. Additional chemoradiation was performed and, five years after surgery, the patient is well with no signs of recurrence.Medial pancreatectomy for invasive ductal carcinoma has not ever been reported. Furthermore, long-term survival after a lumpectomy for invasive ductal carcinoma has never been reported in the literatures. The current case suggests that long-term survival in patients with invasive ductal carcinoma of the pancreas may be associated with the pathological or biological features of pancreatic carcinoma.

  13. Upregulation of metastasis-associated gene 2 promotes cell proliferation and invasion in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Wu MH

    2016-03-01

    Full Text Available Minhua Wu,1,2,* Xiaoxia Ye,2,* Xubin Deng,3,* Yanxia Wu,4 Xiaofang Li,4 Lin Zhang11Department of Histology and Embryology, Southern Medical University, Guangzhou, 2Department of Histology and Embryology, Guangdong Medical University, Zhanjiang, 3Affiliated Cancer Hospital of Guangzhou Medical University, Cancer Center of Guangzhou Medical University, Guangzhou, 4Pathological Diagnosis and Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China*These authors contributed equally to this workAims: Metastasis-associated gene 2 (MTA2 is reported to play an important role in tumor progression, but little is known about the role of MTA2 in nasopharyngeal carcinoma (NPC. The aim of the study was to explore the expression and function of MTA2 in NPC.Methods: Expression of MTA2 in NPC tissues and cell lines was detected by immunohistochemistry and Western blotting. Relationship between MTA2 expression and clinicopathological features was analyzed. Stable MTA2-overexpressing and MTA2-siliencing NPC cells were established by transfection with plasmids encoding MTA2 cDNA and lentivirus-mediated short hairpin RNA, respectively. Cell viability was determined by Cell Counting Kit-8 and colony formation assay. Cell migration ability was evaluated by wound healing and transwell invasion assay. The impact of MTA2 knockdown on growth and metastasis of CNE2 cells in vivo was determined by nude mouse xenograft models. Expression of several Akt pathway proteins was detected by Western blotting.Results: MTA2 was upregulated in NPC tissues and three NPC cell lines detected (CNE1, CNE2, and HNE1. MTA2 expression was related to clinical stage and lymph node metastasis of patients with NPC. MTA2 upregulation promoted proliferation and invasion of CNE1 cells, while MTA2 depletion had opposite effects on CNE2 cells. Moreover, MTA2 depletion suppressed growth and metastasis of CNE2 cells in vivo. MTA2 overexpression

  14. Basal cell carcinoma with progression to metastatic neuroendocrine carcinoma: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Volkan Adsay

    2010-03-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Merkel cell carcinoma (MCC or primary cutaneous neuroendocrine carcinoma is a malignant tumor considered to demonstrate differentiation towards Merkel cells that are present at the base of the epidermis or around the apical end of some hair follicles and are thought to play an yet uncertain role in sensory transduction. Here we present the case of a 54-year-old female with a basal cell carcinoma (BCC of the skin with neuroendocrine features (positivity for chromogranin that has evolved during multiple recurrences and radiotherapy into a high-grade neuroendocrine carcinoma with morphologic and immunohistochemical features of MCC (trabecular and nesting arrangement, positivity for chromogranin, cytokeratin 20, neuron specific enolase, and also neurosecretory granules on electron microscopy. The progression from a chromogranin positive basal cell carcinoma of the skin, to a high grade neuroendocrine carcinoma demonstrates the potential for cross differentiation among skin tumors.

  15. TGF-β1 promotes the migration and invasion of bladder carcinoma cells by increasing fascin1 expression.

    Science.gov (United States)

    Zhang, Naiwen; Bi, Xiaojun; Zeng, Yu; Zhu, Yuyan; Zhang, Zhe; Liu, Yang; Wang, Jianfeng; Li, Xuejie; Bi, Jianbin; Kong, Chuize

    2016-08-01

    Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that is reported to regulate cellular motility and invasive capability during tumor progression. Fascin1, an actin-bundling protein, increases cell motility, migration and adhesion. To investigate the function of TGF-β1 and test whether fascin1 is an important mediator of the tumor response to TGF-β1 in bladder carcinoma cells, real-time RT-PCR and western blot analysis were used to test changes in fascin1 expression after TGF-β1 (10 ng/ml) treatment in T24 and BIU87 cells. Small interfering RNA (siRNA) technique was performed to silence fascin1. Cell viability and biological behavior changes were evaluated by cell growth (MTT), wound-healing and Matrigel invasion assays. In the present study, we found that the mRNA and protein levels of fascin1 in the T24 and BIU87 cells were significantly increased after 10 ng/ml TGF-β1 treatment (pTGF-β1. The findings suggested that TGF-β1 can promote invasion and migration of T24 and BIU87 bladder carcinoma cells, and the increase in fascin1 expression may be the key point of this impact of TGF-β1.

  16. Reflectance confocal microscopy and dermoscopy for in vivo, non-invasive skin imaging of superficial basal cell carcinoma

    Science.gov (United States)

    GHITA, MIHAELA A.; CARUNTU, CONSTANTIN; ROSCA, ADRIAN E.; KALESHI, HARILLAQ; CARUNTU, ANA; MORARU, LILIANA; DOCEA, ANCA OANA; ZURAC, SABINA; BODA, DANIEL; NEAGU, MONICA; SPANDIDOS, DEMETRIOS A.; TSATSAKIS, ARISTIDIS M.

    2016-01-01

    Superficial basal cell carcinoma (sBCC) is the second most frequent histological type of basal cell carcinoma (BCC), usually requiring a skin biopsy to confirm the diagnosis. It usually appears on the upper trunk and shoulders as erythematous and squamous lesions. Although it has a slow growth and seldom metastasizes, early diagnosis and management are of crucial importance in preventing local invasion and subsequent disfigurement. Dermoscopy is nowadays an indispensable tool for the dermatologist when evaluating skin tumors. Reflectance confocal microscopy (RCM) is a novel imaging technique that allows the non-invasive, in vivo quasi-microscopic morphological and dynamic assessment of superficial skin tumors. Moreover, it offers the advantage of performing infinite repeatable determinations to monitor disease progression and non-surgical treatment for sBCC. Herein, we present three lesions of sBCC evaluated using in vivo and non-invasive imaging techniques, emphasizing the usefulness of combining RCM with dermoscopy for increasing the diagnostic accuracy of sBCC. PMID:27123056

  17. Metastatic Urothelial Carcinoma of the Prepuce and Glans Penis: Suspected Implantation of Non-Muscle-Invasive Bladder Cancer via Urine

    OpenAIRE

    Makino, Tomoyuki; Kitagawa, Yasuhide; Namiki, Mikio

    2014-01-01

    Abstract Cutaneous metastatic implantation of non-muscle-invasive urothelial carcinoma via urine is a rare finding, and only few cases have been reported in the literature. Here, we present a case of metastatic urothelial carcinoma of the prepuce and glans penis, which was suspected to be an implantation of non-muscle-invasive bladder cancer via urine. The patient had pseudophimosis of the penis, and contact with urine containing urothelial carcinoma cells was considered to be the cause of th...

  18. Macrophage Capping Protein CapG Is a Putative Oncogene Involved in Migration and Invasiveness in Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    J. Glaser

    2014-01-01

    Full Text Available The actin binding protein CapG modulates cell motility by interacting with the cytoskeleton. CapG is associated with tumor progression in different nongynecologic tumor entities and overexpression in breast cancer cell lines correlates with a more invasive phenotype in vitro. Here, we report a significant CapG overexpression in 18/47 (38% of ovarian carcinomas (OC analyzed by qRealTime-PCR analyses. Functional analyses in OC cell lines through siRNA mediated CapG knockdown and CapG overexpression showed CapG-dependent cell migration and invasiveness. A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. The minor allele frequency (MAF of SNP rs6886 (c.1004A/G was higher and the homozygous (A/A, His335 genotype was significantly more prevalent in patients with fallopian tube carcinomas (50% as in controls (10%. With OC being one of the most lethal cancer diseases, the detection of novel biomarkers such as CapG could reveal new diagnostic and therapeutic targets. Moreover, in-depth analyses of SNP rs6886 related to FTC and OC will contribute to a better understanding of carcinogenesis and progression of OC.

  19. Research Progress on Metastatic Carcinoma of the Spleen

    Institute of Scientific and Technical Information of China (English)

    Zhaoxiang Zhang

    2006-01-01

    ABSTRACT Metastatic carcinoma of the spleen (MCS) is a rare condition which is frequency misdiagnosed. Research progress on the prevalence,clinicopathological features and diagnosis of MCS from the Chinese and English medical literature was reviewed to increase understanding of all aspects related to MCS. It is hoped that a better comprehension of MCS will increase the diagnotic level and the rate of MCS detection.

  20. Significance of Epithelial-mesenchaymal Transition Phenotype in Invasive Tumor Front Cells of Lung Squamous Cell Carcinoma

    OpenAIRE

    Song, Yinghua; Caiqing ZHANG; Zhixin CAO; XU, Jiawen; Wang, Lingcheng; Lin, Xiaoyan

    2014-01-01

    Background and objective The invasive tumor front (ITF) refers to cells or invasive nests in the junctional region of a tumor and its host. The ITF contains the most invasive cells of a tumor, and has a high prognostic value in carcinoma. The aim of this study is to investigate the epithelial-mesenchymal transformation phenotype in ITF cells of lung squamous cell carcinoma (SCC), and analyze the relationship between clinicopathological features and clinical outcomes of patients. Methods Semiq...

  1. Cutaneous head and neck basal and squamous cell carcinomas with perineural invasion

    NARCIS (Netherlands)

    Mendenhall, W.M.; Ferlito, A.; Takes, R.P.; Bradford, C.R.; Corry, J.; Fagan, J.J.; Rinaldo, A.; Strojan, P.; Rodrigo, J.P.

    2012-01-01

    Perineural invasion (PNI) occurs in 2% to 6% of cutaneous head and neck basal and squamous cell carcinomas (SCCs) and is associated with mid-face location, recurrent tumors, high histologic grade, and increasing tumor size. Patients may be asymptomatic with PNI appreciated on pathologic examination

  2. Relationship between the Expression of Telomerase and Human Papillomavirus Infection in Invasive Uterine Cervical Carcinoma

    Institute of Scientific and Technical Information of China (English)

    SIMA Ni; CAI Liping; ZHU Yuanfang; WANG Wei; WANG Shixuan; MA Ding

    2007-01-01

    Telomerase activity was examined in invasive cervical carcinoma to assess whether it is activated during cervical malignant transformation and to look for its possible association with human papillomavirus (HPV) infection. Histologically confirmed invasive cervical carcinomas and benign cervices were assayed for telomerase activity by using a modified telomere repeat amplification protocol (TRAP). The same cases were subjected to polymerase chain reaction (PCR) detection of HPV by using consensus primers and type-specific (HPV types 16 and 18) primers. Telomerase activity was detected in 40 of 45 (88.9%) invasive cervical carcinomas and 2 (all chronic cervicitis) of 50 (4%) benign cervical lesions. HPV was detected in 36 (24 HPV-16 and 4 HPV-18 cases) of 45 (80%) invasive cervical carcinomas and 20 (11 HPV-16 and 1 HPV-18 cases) of 50 (40%) benign cervical changes. There was a significant correlation between the expression of telomerase with histological grade (φ=0.44, P<0.005), but no correlation was found between telomerase expression and HPV-18 (P>0.05). Although larger sample studies are needed, there seems to be a clear association between telomerase upregulation and HPV status, mainly HPV-16 infection.

  3. Intertwining of Activin A and TGFβ Signaling: Dual Roles in Cancer Progression and Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Loomans, Holli A. [Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Andl, Claudia D., E-mail: claudia.andl@vanderbilt.edu [Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Vanderbilt Digestive Disease Center, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Vanderbilt Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2014-12-30

    In recent years, a significant amount of research has examined the controversial role of activin A in cancer. Activin A, a member of the transforming growth factor β (TGFβ) superfamily, is best characterized for its function during embryogenesis in mesoderm cell fate differentiation and reproduction. During embryogenesis, TGFβ superfamily ligands, TGFβ, bone morphogenic proteins (BMPs) and activins, act as potent morphogens. Similar to TGFβs and BMPs, activin A is a protein that is highly systemically expressed during early embryogenesis; however, post-natal expression is overall reduced and remains under strict spatiotemporal regulation. Of importance, normal post-natal expression of activin A has been implicated in the migration and invasive properties of various immune cell types, as well as endometrial cells. Aberrant activin A signaling during development results in significant morphological defects and premature mortality. Interestingly, activin A has been found to have both oncogenic and tumor suppressor roles in cancer. Investigations into the role of activin A in prostate and breast cancer has demonstrated tumor suppressive effects, while in lung and head and neck squamous cell carcinoma, it has been consistently shown that activin A expression is correlated with increased proliferation, invasion and poor patient prognosis. Activin A signaling is highly context-dependent, which is demonstrated in studies of epithelial cell tumors and the microenvironment. This review discusses normal activin A signaling in comparison to TGFβ and highlights how its dysregulation contributes to cancer progression and cell invasion.

  4. S100A4 silencing blocks invasive ability of esophageal squamous cell carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Dong Chen; Xue-Feng Zheng; Ze-You Yang; Dong-Xiao Liu; Guo-You Zhang; Xue-Long Jiao; Hui Zhao

    2012-01-01

    AIM:To investigate a potential role of S100A4 in esophagus squamous cell carcinoma metastasis (ESCCs).METHODS:Expression of S100A4 and E-cadherin were analyzed in frozen sections from ESCCs (metastasis,n =28; non-metastasis,n =20) by reverse transcription-polymerase chain reaction,quantitative polymerase chain reaction and immunohistochemistry.To explore the influence of S100A4 on esophageal cancer invasion and metastasis,S100A4 was overexpressed or silenced by S100A4 siRNA in TE-13 or Eca-109 cells in vitro and in vivo.RESULTS:We found the mRNA and protein levels of S100A4 expression in ESCCs was significantly upregulated,and more importantly,that expression of S100A4 and E cadherin are strongly negatively correlated in patients who had metastasis.It was indicated that overexpression of S100A4 in TE-13 and Eca-109 cells downregulates the expression of E-cadherin,leading to increased cell migration in vitro,whereas knockdown of S100A4 inhibited cell migration and upregulation of E-cadherin expression.Moreover,the loss of cell metastatic potential was rescued by overexpression of E-cadherin completely.In addition,nude mice inoculated with S100A4 siRNA-transfected cells exhibited a significantly decreased invasion ability in vivo.CONCLUSION:S100A4 may be involved in ESCC progression by regulate E-cadherin expression,vectorbased RNA interference targeting S100A4 is a potential therapeutic method for human ESCC.

  5. Pokemon and MEF2D co-operationally promote invasion of hepatocellular carcinoma.

    Science.gov (United States)

    Hong, Xin; Hong, Xing-Yu; Li, Tao; He, Cheng-Yan

    2015-12-01

    Hepatocellular carcinoma (HCC) is one of the most deadly human malignancy, and frequent invasion and metastasis is closely associated with its poor prognosis. However, the molecular mechanism underlying HCC invasion is still not completely elucidated. Pokemon is a well-established oncogene for HCC growth, but its contribution to HCC invasion has not been studied yet. In this paper, Pokemon was found to be overexpressed in MHCC-97H HCC cell line, which possesses higher invasiveness. Downregulation of Pokemon abolished the invasion of MHCC-97H HCC cell lines. Pokemon overexpression was able to enhance the invasion of MHCC-97L cells with lower invasiveness. MEF2D, an oncogene promoting the invasion of HCC cells, was further detected to be upregulated and downregulated when Pokemon was overexpressed and silenced, respectively. Online database analysis indicated that one Pokemon recognition site was located within the promoter of MEF2D. Chromatin co-precipitation, luciferase, and qPCR assays all proved that Pokemon can promote the expression of MEF2D in HCC cells. Restoration of MEF2D expression can prevent the impaired invasion of HCC cells with Pokemon silencing, while suppression of MEF2D abolished the effect of Pokemon overexpression on HCC invasion. More interestingly, MEF2D was also found to increase the transcription of Pokemon by binding myocyte enhancer factor 2 (MEF2) sites within its promoter region, implying an auto-regulatory circuit consisting of these two oncogenes that can promote HCC invasion. Our findings can contribute to the understanding of molecular mechanism underlying HCC invasion, and provided evidence that targeting this molecular loop may be a promising strategy for anti-invasion therapy. PMID:26164003

  6. A STUDY ON THE ROLE OF MICRO NUCLEI IN ASSESSING THE PROGRESSION OF PRECANCEROUS LESIONS OF CERVIX AND THE DIAGNOSIS OF CARCINOMA OF CERVIX

    Directory of Open Access Journals (Sweden)

    Anitha

    2015-06-01

    analysed the distribution of intraepithelial neoplasia and invasive carcinoma of cervix with particular reference to age distribution. This study also demonstrated the superiority of Feulgen stain over conventional Papanicolaou stain i n elucidating nuclear features and micronuclei analysis showed a consistent increase in micronucleated cells proportional to the increase in severity of the lesions. So it is suggested that micronuclei analysis may be used as a marker of a greater potentia l for disease progression.

  7. Chromosomal imbalances exclusively detected in invasive front area are associated with poor outcome in laryngeal carcinomas from different anatomical sites

    DEFF Research Database (Denmark)

    Ambrosio, Eliane Papa; Silveira, Cássia Gisele Terrassani; Drigo, Sandra Aparecida;

    2013-01-01

    Laryngeal squamous cell carcinoma (LSCC) is a malignant neoplasm exhibiting aggressive phenotype, high recurrence rate, and risk of developing second primary tumors. Current evidence suggests that cells in the invasive front of carcinomas have different molecular profiles compared to those...... in superficial areas. This study aimed to identify candidate genes in the invasive front and superficial cells from laryngeal carcinomas that would be useful as molecular markers. Invasive front and tumor surface cells of 32 LSCC were evaluated by high-resolution comparative genomic hybridization. Both CCND1...

  8. Progress of biological invasions research in China over the last decade

    OpenAIRE

    Chengjen Shih; Bo Li; Hui Li; Ruiting Ju

    2012-01-01

    As one of the five major global environmental problems, invasive species have posed serious threats to native ecosystems, public health, and regional economies. Although much progress has been madein the field of biological invasions research in China over the last decade, there are still large knowledge gaps. This paper reviews progress in the field of biological invasions research since 2000 as it relates to China, covering the diversity, colonization and immigration patterns of invasive sp...

  9. Effect of bortezomib on migration and invasion in cervical carcinoma HeLa cell

    Institute of Scientific and Technical Information of China (English)

    Chong; Shi; Guo-Bin; Zhang; Shu-Wang; Yin

    2015-01-01

    Objective:To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism.Methods:The effect of bortezomib on the viability of HeLa cell was measured by MTT assay.The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively.The activation of Akt/mTOR signaling pathway and expression level of MMP2,MMP9 were assayed by western blot.Results:MTT assay indicated bortezomib(2.5 μM.5 μM,10 μM)could inhibit HeLa cell viability,and the inhibitory rate was highest at 48 h.Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion.Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR.and down-regulate the expression of MMP2 and MMP9.Conclusions:These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell,which might be related to Akt/mTOR signal pathway.

  10. Effect of bortezomib on migration and invasion in cervical carcinoma HeLa cell

    Institute of Scientific and Technical Information of China (English)

    Chong Shi; Guo-Bin Zhang; Shu-Wang Yin

    2015-01-01

    Objective: To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism. Methods:The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot. Results:MTT assay indicated bortezomib (2.5μM, 5μM, 10μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48 h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9. Conclusions:These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.

  11. Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast

    Institute of Scientific and Technical Information of China (English)

    Zhenhuan Zhang; Hirotaka Iwase; Hiroko Yamashita; Tatsuya Toyama; Hiroshi Sugiura; Yoshiaki Ando; Keiko Mita; Maho Hamaguchi; Yasuo Hara; Shunzo Kobayashi

    2006-01-01

    Estrogen is well-established as a mitogenic factor implicated in the tumorigenesis and progression of breast cancer via its binding to the estrogen receptor a(ERα). Recent data indicate that chromatin inactivation mediated by histone deacetylation(HDAC) and DNA methylation is a critical component of ERα silencing in human breast cancer cells. The aim of this study was to determine the expression of the HDAC1 gene in malignant human breast tissue and to correlate our observations with available clinical information. In the present study, the level of expression of HDAC1 mRNA was assessed by LightCycler-based quantitative real-time reverse transcriptase (RT)-PCR analvsis in 162 cases of invasive carcinoma of the breast. Associations between HDAC1 mRNA expression and different clinicopathological factors were sought. It was found that HDAC1 mRNA was expressed at significantly higher levels in tumors from patients over 50 years of age and in those tumors without axillary lymph node involvement, that are less than 2 cm, that are of a non-high histological grade, that are HER2 negative and that are ERα/PgR positive. Patients with tumors displaying high levels of HDAC1 mRNA expression tended to have a better prognosis in terms of both disease-free and overall survival. However, univariate and multivariate analysis did not show HDAC1 mRNA expression level to be an independent prognostic factor for either disease-free or overall survival. These results imply that HDAC1 mRNA expression could have potential as an endocrine response marker and may have prognostic implications for breast cancer progression.

  12. Preoperative Diagnosis of Extraglandular Invasion of Thyroid Papillary Carcinoma: High Resolution Sonography versus Multidetector Computed Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Jung; Hong, Hyun Pyo; Kwag, Hyon Joo; Kook, Shin Ho; Yun, Ji Sup; Kim, Dong Hoon [Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2009-03-15

    To compare the diagnostic efficacy of high-resolution sonography (HRS) and multidetector computed tomography (MDCT) in determining the presence of extraglandular invasion of thyroid papillary cancer and to define ultrasound (US) features of perithyroidal invasion that correlate with histopathological findings. We prospectively evaluated extracapsular invasion in 177 thyroid cancer patients using both HRS and MDCT. Receiver operating characteristics (ROC) were assessed with a four-point confidence scale (0 = no extracapsular invasion:1 = possible invasion:2 = probable invasion:3 = definite invasion) by two reviewers for each imaging modality. Sensitivity, specificity, and accuracy were analyzed for each modality, along with interobserver variability. MDCT had a mean area under the ROC curve larger than that of HRS (HRS = 0.733, MDCT = 0.807, p < 0.05). HRS and MDCT were significantly different with regard to diagnostic sensitivity, specificity, and accuracy for extrathyroidal extension (p < 0.05: HRS = 75.7%, 66.1%, and 69.8%, respectively: MDCT = 86.7%,69.7%, and 76%, respectively). Interobserver reliability was greater for MDCT than for HRS (kappa value, 0.861 versus 0.429). The cutoff value used in HRS for estimating the status of perithyroidal invasion was 2. Conclusion: HRS may be useful for preoperative investigation of thyroid papillary carcinoma extension, but it was inferior to MDCT because of lower diagnostic accuracy and lower interobserver reliability

  13. Morphological heterogeneity of the simultaneous ipsilateral invasive tumor foci in breast carcinoma: a retrospective study of 418 cases of carcinomas.

    Science.gov (United States)

    Boros, Monica; Marian, Cristina; Moldovan, Cosmin; Stolnicu, Simona

    2012-10-15

    The aim of this paper was to assess whether the morphological appearance (i.e. histological tumor type and histological grade) of simultaneous invasive breast carcinoma foci is heterogeneous, since it is known that adjuvant therapy is established according to these parameters. Patients with simultaneous breast tumors in which only the features of the largest neoplastic focus are reported could thus be undertreated. A retrospective study of 418 cases of breast carcinomas was conducted over a 3-year period. The histological tumor types and histological grades of multifocal/multicentric carcinomas in each tumor focus were compared, and mismatches among foci were recorded. Ninety-one of the 418 cases reviewed had multiple carcinomas (21.77%). A comparison between multiple synchronous tumor foci revealed that their histological type was different in 12.08% of the cases. Mismatches among foci were also observed in 9.89% of the cases when evaluating the histological grade, and 5 out of 9 additional tumor foci with a different grade from the largest (index) tumor (55.55%) displayed a higher grade compared to the index tumor. Since the histological tumor type and histological grade of the individual foci may vary considerably within the same tumor and the additional foci may be of higher grade than the index tumor, we believe that reporting morphologic parameters with more unfavorable characteristics in addition to the parameters of the index tumor is imperative.

  14. Progression of Hepatic Adenoma to Carcinoma in the Setting of Hepatoportal Sclerosis in HIV Patient: Case Report and Review of the Literature

    Science.gov (United States)

    Yeh, M.; Reyes, J. D.

    2016-01-01

    We report a case of hepatic adenoma progression to carcinoma in the setting of hepatoportal sclerosis in an HIV+ patient and provide a review of the scarce literature regarding hepatoportal sclerosis in HIV patients. We describe the clinical presentation, diagnostic workup, and management. This is the first case report in the literature of progression of hepatic adenoma to carcinoma in hepatoportal sclerosis in an HIV patient. This case also highlights the broad differential diagnosis that should always be included in the study of any liver disease in this patient population, including the performance of invasive and aggressive tests to arrive at the final diagnosis. PMID:27812395

  15. Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Geng-Qiu Luo; Jing-He Li; Ji-Fang Wen; Yan-Hong Zhou; Yong-Bin Hu; Jian-Hua Zhou

    2008-01-01

    AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved.METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique.RT-PCR,Western blotting, ENSA, gelatin zymography assay, and in vitro invasion and migration assays were performed.Nude mice metastasis models were established by the abdominal cavity transfer method.RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained.Compared with MKN28 and pcDNA3-MKN28 cells, adherence,migration and invasion ability of TwistS-MKN28 cells were clearly raised.The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells.Overexpression of Twist in MKN28 cells increased Tcf-4/Lef DNA binding activity, and promoted expression of Tcf-4's downstream target genes cyclin Dt and HMP-2.However, suppression of Twist (TwistAS-NKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced.The activity of MMP-2 was also decreased.CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/Tcf-4 signaling.

  16. Inhibitory effects of tanshinone Ⅱ-A on invasion and metastasis of human colon carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Yun-feng SHAN; Xian SHEN; Yuan-kang XIE; Ji-cai CHEN; Hong-qi SHI; Zheng-ping YU; Qi-tong SONG; Men-tao ZHOU; Qi-yu ZHANG

    2009-01-01

    Aim: To investigate the effects and possible mechanisms of tanshinone Ⅱ-A, an alcohol extract of the root of Salvia miltiorrhiza Bunge, on tumor invasion and metastasis of human colon carcinoma (CRC) cells.Methods: The effects of tanshinone Ⅱ-A on invasion and metastasis of CRC cell lines HT29 and SW480 were evaluated by in vitro and in vivo assays. Western blotting was used to investigate possible molecular mechanisms of tanshinone Ⅱ-A anti-cancer actions. Results: Tanshinone Ⅱ-A inhibited migration and invasion of CRC cells in a dose-dependent manner. The inhibitory effect also depended on time, with the most significant effects observed at 72 h. Tanshinone Ⅱ-A also significantly inhibited in vivo metastasis of colon carcinoma SW480 cells. It inhibited in vitro and in vivo invasion and metastasis of CRC cells by reducing levels of urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMP)-2 and MMP-9, and by increasing levels of tissue inhibitor of matrix metalloproteinase protein (TIMP)-1 and TIMP-2. Tanshinone Ⅱ-A was also shown to suppress the nuclear factor-kappaB (NF-kB) signal. Conclusion: Tanshinone Ⅱ-A inhibited in vitro and in vivo invasion and metastasis of CRC cells. The effect resulted from changes in the levels of uPA, MMP-2, MMP-9, TIMP-1, and TIMP-2, and apparent inhibition of the NF-kB signal transduction pathway.

  17. Incidence of invasive cancers following carcinoma in situ of the cervix.

    OpenAIRE

    Levi, F; Randimbison, L.; La Vecchia, C; Franceschi, S.

    1996-01-01

    Women with carcinoma in situ (CIS) of the cervix uteri, notified to the population-based Cancer Registry of the Swiss Canton of Vaud between 1974 and 1993, were actively followed up to 31 December 1993 for the occurrence of subsequent invasive neoplasms. Among 2190 incident cases of CIS, followed for a total of 22,225 person-years, 95 metachronous cancers were observed vs 77.9 expected, corresponding to a significant standardised incidence ratio (SIR) of 1.2. Ten cases of invasive cervical ca...

  18. Recurrent invasive squamous cell carcinoma of the ocular surface requiring penetrating therapeutic sclerokeratoplasty

    Directory of Open Access Journals (Sweden)

    Mark J. Mannis

    2012-12-01

    Full Text Available Purpose: We review a case of invasive squamous cell carcinoma invading the cornea to discuss optimal management. Methods:  Observational case report with histopathologic analysis. Results: Histopathology demonstrates corneal invasion by the tumor that appears to have been completely excised with a large therapeutic keratoplasty and adjuvant cryotherapy. Conclusions: Successful management of ocular surface squamous neoplasia (OSSN requires removal of identifiably abnormal tissue without disruption of normal protective architecture, careful histopathologic analysis, and the employment of adjuvant therapy at the time of or subsequent to surgical excision.

  19. Invasiveness and Ploidy of Human Mammary Carcinomas in Short-Term Culture

    Science.gov (United States)

    Smith, Helene S.; Liotta, Lance A.; Hancock, Miriam C.; Wolman, Sandra R.; Hackett, Adeline J.

    1985-03-01

    Invasiveness and ploidy were examined in cultures of human epithelial cells derived from nonmalignant breast tissue, primary breast carcinomas, and breast cancer effusion metastases. Successful short-term culture was achieved from approximately 70% of the primary breast cancers. These primary cancers were essentially diploid by flow cytometry and karyotype in contrast to the effusion metastases, which were mostly aneuploid. The diploid tumor cells retained their malignant phenotype in culture as demonstrated by invasion into a denuded human amnion basement membrane. In contrast, epithelial cells cultured from nonmalignant mammary tissue did not invade the amnion. We suggest that the diploid carcinoma cultures may be useful for investigating the essential differences between normal and malignant cells and may complement information derived from studies of tumor cell lines with grossly aberrant karyotypes.

  20. Malignant Mesothelioma Mimicking Invasive Mammary Carcinoma in a Male Breast

    Directory of Open Access Journals (Sweden)

    Mohamed Mokhtar Desouki

    2015-01-01

    Full Text Available Malignant mesothelioma is an uncommon tumor with strong association with asbestos exposure. Few cases of malignant pleural mesothelioma metastatic to the female breast have been reported. Herein, we presented, for the first time, a case of locally infiltrating malignant pleural mesothelioma forming a mass in the breast of a male as the first pathologically confirmed manifestation of the disease. Breast ultrasound revealed an irregular mass in the right breast which involves the pectoralis muscle. Breast core biopsy revealed a proliferation of neoplastic epithelioid cells mimicking an infiltrating pleomorphic lobular carcinoma. IHC studies showed the cells to be positive for calretinin, CK5/6, WT1, and CK7. The cells were negative for MOC-31, BerEp4, ER, and PR. A final diagnosis of malignant mesothelioma, epithelioid type, was rendered. This case demonstrates the importance of considering a broad differential diagnosis in the setting of atypical presentation with application of a panel of IHC markers.

  1. Characterization of human papillomavirus type 66 from an invasive carcinoma of the uterine cervix.

    OpenAIRE

    Tawheed, A R; Beaudenon, S; Favre, M; Orth, G

    1991-01-01

    Human papillomavirus (HPV) DNA sequences coexisting with HPV16 and HPV45 were cloned from an invasive cervical carcinoma. The cloned HPV was shown to be a novel type, named HPV66, and is related to HPV56 (an HPV detected in cervical cancer). After screening 160 anogenital biopsies, four specimens exhibited histological features of intraepithelial neoplasia and contained HPV66 sequences. Of these, three were found to be associated with another HPV type.

  2. Evaluation of Helical CT Scanning in Judging the Invasion and Metastasis of Gastric Carcinoma

    Institute of Scientific and Technical Information of China (English)

    GAOJianbo; KONGXiangquan; GUOHua; LIShuxin; YANGXuehua; LIYintai; ZHANGZhixu

    2004-01-01

    To determine the accuracy of triphase enhanced helical CT in judging the invasion and metastasis of gastric carcinoma, and to discuss the relation between imaging signs and pathological findings. Methods: Triphase enhanced helical CT scanning was performed in 46 patients with gastric carcinoma. Imaging findings were compared with postoperative pathologic results. Results: (1) The accuracy of helical CT for diagnosing involvement of tunica serosa, lymph node metastasis and distant metastasis was 84.8%, 87.0% and 100~ respectively. (2) CT signs of serosal involvement, lymph node metastasis and distant metastasis were in good accordance with pathological findings (P<0.05). Conclusion: Triphase enhanced helical CT scans can comprehensively and precisely reflect the pathologic characteristics of gastric carcinoma, thus it is a reliable technique for the diagnosis of this disease.

  3. Expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas

    Institute of Scientific and Technical Information of China (English)

    LIU Qun; LI Ji-guang; ZHENG Xin-yu; JIN Feng; DONG Hui-ting

    2009-01-01

    Background Biomarkers in breast neoplasms provide invaluable information regarding prognosis and help determining the optimal treatment. We have examined the possible correlation between cancer stem cell (CSC)-Iike markers (CD133,paired box gene 2 protein (PAX2), epithelial specific antigen (ESA)), and a new membrane estrogen receptor (G-protein coupled receptor 30 (GPR30)) in invasive ductal breast carcinomas with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers.Methods In 74 invasive ductal breast carcinomas, we investigated the protein expression of these molecular markers by immunohistochemistry, and their associations with known clinicopathological parameters, tumor recurrence, and expression of some known biomarkers. We studied the interrelationship between the expressions of these proteins.Results CD133, a putative CSC marker, was positively related to tumor size, tumor stage, and lymph node metastasis.PAX2 was negatively correlated with tumor recurrence. ESA, one of the breast CSC markers, was an indicator of tumor recurrence. GPR30 was associated with hormone receptors. Despite the correlation between GPR30 and the nuclear estrogen receptor, the expression was dependent. Positive staining of GPR30 in tumors displayed a significant association with high C-erbB2 expression and a tendency for tumor recurrence. A positive relationship between GPR30 and CD133 existed.Conclusion Detecting the expression of CD133, PAX2, ESA, and GPR30 in invasive ductal breast carcinomas may be of help in more accurately predicting the aggressive properties of breast cancer and determining the optimal treatment.

  4. Expression of altered retinoblastoma protein inversely correlates with tumor invasion in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Nan-Hua Chou; Hui-Chun Chen; Nan-Song Chou; Ping-I Hsu; Hui-Hwa Tseng

    2006-01-01

    AIM: To investigate the clinical and pathological significance of altered retinoblastoma (Rb) encoding protein (pRb) in gastric carcinoma.METHODS: Expression of altered pRb was analyzed in 91 patients with gastric adenocarcinoma by immunohistochemistry.RESULTS: Sixty-five percent (59/91) of the tumors were positively stained and the staining in tumor nuclei of gastric carcinoma ranged 0%-90%. Moreover, strong expression of altered pRb was found in 35% (6/17),24% (5/21), 17% (8/46) and 0% (0/7) of T1, T2, T3 and T4 gastric carcinomas, respectively. Altered pRb expression was inversely correlated with the depth of tumor invasion (P = 0.047). Degree of immunoreactivity had no significant correlation with tumor grade, node metastasis and distant metastasis. In terms of prognostic significance, univariate analysis showed that poor differentiation [41 (66.1%) vs 34 (42.5%) P = 0.051],advanced tumor stage (P < 0.001) and weakly altered pRb expression [17 (80.5%) vs 58 (49.6%) P = 0.044]were associated with worse prognosis in these patients.However, multivariate analysis revealed that advanced tumor stage was the only independent poor prognostic factor (P < 0.001).CONCLUSION: The mutation of Rb gene is frequent in gastric carcinoma. The expression of altered pRb inversely correlates with tumor invasion and is not an independent prognostic marker in gastric adenocarcinoma

  5. Diagnostic value of multidetector computed tomography for renal sinus fat invasion in renal cell carcinoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Cherry, E-mail: cherrykim0505@gmail.com; Choi, Hyuck Jae, E-mail: choihj@amc.seoul.kr; Cho, Kyoung-Sik, E-mail: kscho@amc.seoul.kr

    2014-06-15

    Objective: Although renal sinus fat invasion has prognostic significance in patients with renal cell carcinomas (RCCs), there are no previous studies about the value of multidetector computed tomography (MDCT) about this issue in the current literature. Materials and methods: A total of 863 consecutive patients (renal sinus fat invasion in 110 patients (12.7%)) from single institutions with surgically-confirmed renal cell carcinoma who underwent MDCT between 2010 and 2012 were included in this study. The area under the curves (AUCs) of the receiver operating characteristic (ROC) analysis was used to compare diagnostic performance. Reference standard was pathologic examination. Weighted κ statistics were used to measure the level of interobserver agreement. Multivariate logistic regression model was used to find the predictors for renal sinus fat invasion. Image analysis was first performed with axial-only CT images. A second analysis was then performed with both axial and coronal CT images. A qualitative analysis was then conducted by two reviewers who reached consensus regarding tumor size, decreased perfusion, tumor margin, vessel displacement, and lymph node metastasis. The reference standard was pathologic evaluation. Results: The AUCs of the ROC analysis were 0.881 and 0.922 for axial-only images and 0.889 and 0.902 for combined images in both readers. The AUC of tumor size was 0.884, a similar value to that of the reviewers. In multivariate analysis, tumor size, a linear-nodular or nodular type of fat infiltration, and an irregular tumor margin were independent predicting factors for perinephric fat invasion. Conclusion: MDCT shows relatively high diagnostic performance in detecting perinephric fat invasion of RCC but suffers from a relatively low PPV related to low prevalence of renal sinus fat invasion. Applying tumor size alone we could get similar diagnostic performance to those of radiologists. Tumor size, fat infiltration with a nodular appearance, and

  6. Clinico-pathological correlation of E-cadherin expression at the invasive tumor front of Indian oral squamous cell carcinomas: An immunohistochemical study

    Science.gov (United States)

    Mehendiratta, Monica; Solomon, Monica Charlotte; Boaz, Karen; Guddattu, Vasudeva; Mohindra, Aashima

    2014-01-01

    Background: Recent studies have indicated that although malignant cells at the invasive tumor front, bare morphological resemblance to the cells at central portion of the tumor, their molecular character differs significantly. E-cadherin is a cell-cell adhesion molecule that connects epithelial cells. This study attempts to correlate the E-cadherin expression at the invasive tumor front with tumor differentiation along with its clinico-pathological parameters. Materials and Methods: Immunohistochemical staining with E-cadherin was carried out on archival cases of primary oral squamous cell carcinomas (n = 30). The E-cadherin expression at the invasive tumor front was analyzed and was linked to clinico-pathological parameters including patient prognosis. Results: The downregulation of E-cadherin expression at the invasive tumor edge when compared with patient's prognosis yielded a significant correlation (P = 0.041) but its correlation with the degree of differentiation determined was not significant (P = 0.27). Also, its association with tumor size and lymph node status was negative. Conclusions: Loss of E-cadherin expression at the invasive tumor front is an important event in the progression of oral squamous cell carcinomas. Tumors with a loss of expression of E-cadherin are those which had a poor prognosis PMID:25328302

  7. Effects of an Engineered Anti-HER2 Antibody chA21 on Invasion of Human Ovarian Carcinoma Cell In Vitro

    Institute of Scientific and Technical Information of China (English)

    Yi Gao; Qiang Wu; Zheng-sheng Wu; Gui-hong Zhang; An-Li Zhang

    2011-01-01

    Objective: HER-2 plays an important role in the development and progression of ovarian carcinoma. A number of monoclonal antibodies (MAbs) and engineered antibody fragments (such as scFvs) against the subdomain Ⅱ or Ⅳ of HER-2 extracellular domain (ECD) have been developed. We investigated the effect of chA21, an engineered anti-HER-2 antibody that bind primarily to subdomain I, on ovarian carcinoma cell invasion in vitro, and explored its possible mechanisms. Methods: Growth inhibition of SK-OV-3 cells was assessed using a Methyl thiazolyl tetrazolium (MTT) assay. The invasion ability of SK-OV-3 was determined by a Transwell invasion assay. The expression of matrix metalloproteinase-2 (MMP-2) and its tissue inhibitors (TIMP-2) was detected by immunocytochemical staining, and the expression of p38 and the phosphorylation of p38 were assayed by both immunocytochemistry and Western blot. Results: After treatment with chA21, the invasion of human ovarian cancer SK-OV-3 cells was inhibited in doseand time-dependent manners. Simultaneously the expression of p38, phospho-p38, MMP-2 and the MMP-2/TIMP-2 ratio decreased, while TIMP-2 expression increased. Additionally, the decrease in phospho-p38 was much greater than that of p38. Conclusion: chA21 may inhibit SK-OV-3 cell invasion via the signal transduction pathway involving MMP-2,TIMP-2, p38 and the activation of p38MAPK.

  8. Slug down-regulation by RNA interference inhibits invasion growth in human esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang Shaoyan

    2011-05-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is one of the most aggressive carcinomas of the gastrointestinal tract. We assessed the relevance of Slug in measuring the invasive potential of ESCC cells in vitro and in vivo in immunodeficient mice. Methods We utilized RNA interference to knockdown Slug gene expression, and effects on survival and invasive carcinoma were evaluated using a Boyden chamber transwell assay in vitro. We evaluated the effect of Slug siRNA-transfection and Slug cDNA-transfection on E-cadherin and Bcl-2 expression in ESCC cells. A pseudometastatic model of ESCC in immunodeficient mice was used to assess the effects of Slug siRNA transfection on tumor metastasis development. Results The EC109 cell line was transfected with Slug-siRNA to knockdown Slug expression. The TE13 cell line was transfected with Slug-cDNA to increase Slug expression. EC109 and TE13 cell lines were tested for the expression of apoptosis-related genes bcl-2 and metastasis-related gene E-cadherin identified previously as Slug targets. Bcl-2 expression was increased and E-cadherin was decreased in Slug siRNA-transfected EC109 cells. Bcl-2 expression was increased and E-cadherin was decreased in Slug cDNA-transfected TE13 cells. Invasion of Slug siRNA-transfected EC109 cells was reduced and apoptosis was increased whereas invasion was greater in Slug cDNA-transfected cells. Animals injected with Slug siRNA-transfected EC109 cells exhihited fewer seeded nodes and demonstrated more apoptosis. Conclusions Slug down-regulation promotes cell apoptosis and decreases invasion capability in vitro and in vivo. Slug inhibition may represent a novel strategy for treatment of metastatic ESCC.

  9. Relations of proliferative activities of gastric carcinoma cells to lymphatic involvement, venous invasion and prognosis

    Institute of Scientific and Technical Information of China (English)

    吴云飞; 徐惠绵; 陈峻青

    2004-01-01

    Background This study was to evaluate bivariate bromodeoxyuridine(BrdUrd)/DNA flow cytometric analysis in detection of gastric carcinoma and to study the relations of cellular BrdUrd labeling indices (LI), G2/M-phase fraction(G2/MPF) and DNA ploidy pattern to lymphatic involvement, venous invasion and prognosis.Methods Fresh tumor samples from 60 patients with gastric carcinoma were analyzed by bivariate BrdUrd/DNA flow cytometry. The results were correlated with lymphatic vessel invasion, lymphatic node metastasis, the number of matastatic lymphatic nodes, and venous invasion. Propidium iodide (PI) was used as a fluorescent probe for total cellular DNA, and a monoclonal antibody against BrdUrd was used as a probe for BrdUrd incorporated into DNA. Fluorescent-labeled goat anti-mouse antibody was used as a second antibody. S-phase fractions were measured by in vitro BrdUrd labeling, and DNA ploidy and G2/MPF were also measured. Comparison of survival was performed with the log-rank test, the Chi-square test for qualitative data, and Student's t test for quantu data. Results BrdUrd LI and G2/MPF values were significantly higher in tumors with lymphatic vessel invasion than in those without invasion respectively (P<0.01); the patients who had tumors with lymphatic vessel invasion showed a significantly poor prognosis (P<0.01). Both BrdUrd LI and G2/MPF values were significantly higher in tumors with lymphatic node metastasis than in those without metastasis (P<0.01). A statistical significant difference was noted in the 5-year survival rates between the patients with lymph node metastasis and those without metastasis. Compared with diploid carcinoma, the incidence of lymph node metastasis was significantly higher in aneuploid carcinoma (P<0.05), and the patients with aneuploid carcinoma showed a significantly poor prognosis (P<0.05). BrdUrd LI was significantly higher in patients with more than 5 metastatic lymph nodes than those with 1-4 metastatic lymph nodes (P<0

  10. Metastatic Urothelial Carcinoma of the Prepuce and Glans Penis: Suspected Implantation of Non-Muscle-Invasive Bladder Cancer via Urine

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    Tomoyuki Makino

    2014-07-01

    Full Text Available Cutaneous metastatic implantation of non-muscle-invasive urothelial carcinoma via urine is a rare finding, and only few cases have been reported in the literature. Here, we present a case of metastatic urothelial carcinoma of the prepuce and glans penis, which was suspected to be an implantation of non-muscle-invasive bladder cancer via urine. The patient had pseudophimosis of the penis, and contact with urine containing urothelial carcinoma cells was considered to be the cause of the metastatic implantation.

  11. Whole-range studies on alien plant invasion: recent progress and future prospects

    OpenAIRE

    Hongyu Niu; Hao Shen; Wanhui Ye

    2010-01-01

    The regions invaded by alien species are normally disjunct from their native ranges, so it is difficult to understand the reasons for successful invasion through studies conducted only in native or invasive ranges. Many researchers have engaged in whole-range studies of invasive species, i.e. studying the exotics both in their introduced and native ranges, in order to explain the present geographical patterns and invasion mechanisms of alien plants. Here, we review progress in whole-range stu...

  12. Three-dimensional reconstruction and quantification of cervical carcinoma invasion fronts from histological serial sections.

    Science.gov (United States)

    Braumann, Ulf-Dietrich; Kuska, Jens-Peer; Einenkel, Jens; Horn, Lars-Christian; Löffler, Markus; Höckel, Michael

    2005-10-01

    The analysis of the three-dimensional (3-D) structure of tumoral invasion fronts of carcinoma of the uterine cervix is the prerequisite for understanding their architectural-functional relationship. The variation range of the invasion patterns known so far reaches from a smooth tumor-host boundary surface to more diffusely spreading patterns, which all are supposed to have a different prognostic relevance. As a very decisive limitation of previous studies, all morphological assessments just could be done verbally referring to single histological sections. Therefore, the intention of this paper is to get an objective quantification of tumor invasion based on 3-D reconstructed tumoral tissue data. The image processing chain introduced here is capable to reconstruct selected parts of tumor invasion fronts from histological serial sections of remarkable extent (90-500 slices). While potentially gaining good accuracy and reasonably high resolution, microtome cutting of large serial sections especially may induce severe artifacts like distortions, folds, fissures or gaps. Starting from stacks of digitized transmitted light color images, an overall of three registration steps are the main parts of the presented algorithm. By this, we achieved the most detailed 3-D reconstruction of the invasion of solid tumors so far. Once reconstructed, the invasion front of the segmented tumor is quantified using discrete compactness.

  13. N-cadherin knock-down decreases invasiveness of esophageal squamous cell carcinoma in vitro

    Institute of Scientific and Technical Information of China (English)

    Ke Li; Wei He; Na Lin; Xin Wang; Qing-Xia Fan

    2009-01-01

    AIM: To examine the expressions of N-cadherin and E-cadherin in specimens of 62 normal esophageal epithela, 31 adjacent atypical hyperplastic epithelia and 62 esophageal squamous cell carcinomas (ESCCs), and to investigate the roles of N-cadherin in the invasiveness of ESCC cell line EC9706 transfected by N-cadherin shRNA. METHODS: PV immunohistochemistry was used to detect the expression pattern of N-cadherin and E-cadherin in specimens of 62 normal esophageal epithelia, 31 adjacent atypical hyperplastic epithelia and 62 ESCCs. The invasiveness of ESCC line EC9706 was determined by transwell assay after EC9706 was transfected by N-cadherin shRNA. RESULTS: The positive rates of N-cadherin decreased in the carcinoma, adjacent atypical hyperplastic and normal esophageal tissues (75.8%, 61.3% and 29.0%, P < 0.05), respectively, while those of E-cadherin increased (40.3%, 71.0% and 95.2%, P < 0.05). The increased expression of N-cadherin and decreased expression of E-cadherin were related to invasion, differentiation, and lymph node metastasis ( P < 0.05). The expression level of N-cadherin decreased in the N-cadherin knocked down cells, and the invasiveness of those cells decreased significantly as well. The number of cells which crossed the basement membrane filter 0.05). CONCLUSION: E-cadherin and N-cadherin expression is correlated with the invasion and aggravation of ESCC. The down-regulation of N-cadherin lowers the invasiveness of EC9706 cell line.

  14. Etiology and pathogenesis of precancerous lesions and invasive cervical carcinoma

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    Panjković Milana

    2008-01-01

    Full Text Available Cervical cancer is the second most common gynecological malignancy in the world. Human papilloma virus (HPV infection is the leading ethiologic agent in the development of premalignant and malignant cervical diseases. HPV is a member of the Papovaviridae family and until now over 100 types have been recognized. There are two types of viral infection: latent and productive. Virus induced oncogenesis is the result of interaction between virus oncoproteins E6 and E7 and tumor supresor host genes p53 and Rb. Many cofactors such as immunosuppression, early sexual relationship, multiple sexual partners, other sexualy transsmited infections and smooking are contributing factors of the precancerous and invasive cervical lesions. According to the oncogenic potential HPV are divided into three groups: low, intermediate and high oncogenic risk viruses. Molecular technics which are used for the virus detection are: In situ hibridisation,, Hybrid capture test and polymerasa chain reaction. Human papilloma virus testing has an important role in the follow up and treatment of women with 'atypical squamous cells of unknown significant' changes in cervical smears and low-grade squamous intraepithelial lesions, changes in punch biopsy.

  15. Radiation therapy for portal venous invasion by hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Keiichi Nakagawa; Masatoshi Makuuchi; Kuni Ohtomo; Hideomi Yamashita; Kenshiro Shiraishi; Naoki Nakamura; Masao Tago; Hiroshi Igaki; Yoshio Hosoi; Shuichiro Shiina; Masao Omata

    2005-01-01

    AIM: To clarify the efficacy and safety of three-dimensional conformal radiotherapy (3-D CRT) for this disease and to specify patient subgroups suitable for this treatment.METHODS: Fifty-two patients with HCC received PVI-targeted radiation therapy from January 1995 through December 2003. Portal venous invasion (PVI) was found in the second or lower order branches of the portal vein in 6 patients, in the first branch in 24 patients and in the main trunk in 22 patients. Child classifications of liver function before radiation therapy were A, B, and C for 19, 24 and 2 patients, respectively. All patients received three-dimensional conformal radiotherapy with a total dose ranging from 39 to 60 Gy (57.0 Gy in average).RESULTS: Overall survival rates at 1, 2, 3, 4, and 5 years were 45.1%, 25.3%, 15.2%, 10.1%, and 5.1%, respectively. Univariate analysis revealed that Child status, the number of tumor foci, tumor type,transcatheter arterial embolization (TAE) after radiation therapy were statistically significant prognostic factors.Multivariate analysis showed that the number of tumor foci and TAE after radiation therapy were statistically significant.CONCLUSION: The results of this study strongly suggest the efficacy of 3-D CRT as treatment for PVI in HCC. 3-D CRT is recommended in combination with postradiation TAE for PVI of HCC with 5 tumor foci or less in the liver and with Child A liver function.

  16. β-catenin is required for prostate development and cooperates with Pten loss to drive invasive carcinoma.

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    Jeffrey C Francis

    Full Text Available Prostate cancer is a major cause of male death in the Western world, but few frequent genetic alterations that drive prostate cancer initiation and progression have been identified. β-Catenin is essential for many developmental processes and has been implicated in tumorigenesis in many tissues, including prostate cancer. However, expression studies on human prostate cancer samples are unclear on the role this protein plays in this disease. We have used in vivo genetic studies in the embryo and adult to extend our understanding of the role of β-Catenin in the normal and neoplastic prostate. Our gene deletion analysis revealed that prostate epithelial β-Catenin is required for embryonic prostate growth and branching but is dispensable in the normal adult organ. During development, β-Catenin controls the number of progenitors in the epithelial buds and regulates a discrete network of genes, including c-Myc and Nkx3.1. Deletion of β-Catenin in a Pten deleted model of castration-resistant prostate cancer demonstrated it is dispensable for disease progression in this setting. Complementary overexpression experiments, through in vivo protein stabilization, showed that β-Catenin promotes the formation of squamous epithelia during prostate development, even in the absence of androgens. β-Catenin overexpression in combination with Pten loss was able to drive progression to invasive carcinoma together with squamous metaplasia. These studies demonstrate that β-Catenin is essential for prostate development and that an inherent property of high levels of this protein in prostate epithelia is to drive squamous fate differentiation. In addition, they show that β-Catenin overexpression can promote invasive prostate cancer in a clinically relevant model of this disease. These data provide novel information on cancer progression pathways that give rise to lethal prostate disease in humans.

  17. Central carbon metabolism in the progression of mammary carcinoma

    Science.gov (United States)

    Richardson, Adam D.; Yang, Chen; Osterman, Andrei

    2007-01-01

    There is a growing belief that the metabolic program of breast tumor cells could be a therapeutic target. Yet, without detailed information on central carbon metabolism in breast tumors it is impossible to know which metabolic pathways to target, and how their inhibition might influence different stages of breast tumor progression. Here we perform the first comprehensive profiling of central metabolism in the MCF10 model of mammary carcinoma, where the steps of breast tumor progression (transformation, tumorigenicity and metastasis) can all be examined in the context of the same genetic background. The metabolism of [U-13C]-glucose by a series of progressively more aggressive MCF10 cell lines was tracked by 2D NMR and mass spectrometry. From this analysis the flux of carbon through distinct metabolic reactions was quantified by isotopomer modeling. The results indicate widespread changes to central metabolism upon cellular transformation including increased carbon flux through the pentose phosphate pathway (PPP), the TCA cycle, as well as increased synthesis of glutamate, glutathione and fatty acids (including elongation and desaturation). The de novo synthesis of glycine increased upon transformation as well as at each subsequent step of breast tumor cell progression. Interestingly, the major metabolic shift in metastatic cells is a large increase in the de novo synthesis of proline. This work provides the first comprehensive view of changes to central metabolism as a result of breast tumor progression. Electronic supplementary material The online version of this article (doi:10.1007/s10549-007-9732-3) contains supplementary material, which is available to authorized users. PMID:17879159

  18. MiR-145 expression accelerates esophageal adenocarcinoma progression by enhancing cell invasion and anoikis resistance.

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    Mathieu Francois Derouet

    Full Text Available BACKGROUND: Carcinoma of the esophagus has a high case fatality ratio and is now the 6th most common cause of cancer deaths in the world. We previously conducted a study to profile the expression of miRNAs in esophageal adenocarcinoma (EAC pre and post induction therapy. Of the miRNAs differentially expressed post induction chemoradiation, miR-145, a known tumor suppressor miRNA, was upregulated 8-fold following induction therapy, however, its expression was associated with shorter disease-free survival. This unexpected result was explored in this current study. METHODS: In order to study the role of miR-145 in EAC, miRNA-145 was overexpressed in 3 EAC cell lines (OE33, FLO-1, SK-GT-4 and one ESCC cell line (KYSE-410. After validation of the expression of miR-145, hallmarks of cancer such as cell proliferation, resistance to chemotherapy drugs or anoikis, and cell invasion were analyzed. RESULTS: There were no differences in cell proliferation and 5 FU resistance between miR145 cell lines and the control cell lines. miR-145 expression also had no effect on cisplatin resistance in two of three cell lines (OE33 and FLO-1, but miR-145 appeared to protect SK-GT-4 cells against cisplatin treatment. However, there was a significant difference in cell invasion, cell adhesion and resistance to anoikis. All three EAC miR-145 cell lines invaded more than their respective controls. Similarly, OE33 and SK-GT-4 miR-145 cell lines were able to survive longer in a suspension state. DISCUSSION: While expression of miR-145 in ESCC stopped proliferation and invasion, expression of miR-145 in EAC cells enhanced invasion and anoikis resistance. Although more work is required to understand how miR-145 conveys these effects, expression of miR-145 appears to promote EAC progression by enhancing invasion and protection against anoikis, which could in turn facilitate distant metastasis.

  19. A novel antagonist of CXCR4 prevents bone marrow-derived mesenchymal stem cell-mediated osteosarcoma and hepatocellular carcinoma cell migration and invasion.

    Science.gov (United States)

    Fontanella, Raffaela; Pelagalli, Alessandra; Nardelli, Anna; D'Alterio, Crescenzo; Ieranò, Caterina; Cerchia, Laura; Lucarelli, Enrico; Scala, Stefania; Zannetti, Antonella

    2016-01-01

    Recent findings suggest that bone marrow-derived mesenchymal stem cells (BM-MSCs) are recruited into the microenvironment of developing tumors, where they contribute to metastatic processes. The aim of this study was to investigate the role of BM-MSCs in promoting osteosarcoma and hepatocellular carcinoma cell progression in vitro and the possible mechanisms involved in these processes. U2OS and SNU-398 are osteosarcoma and hepatocellular carcinoma cell lines, respectively, that can be induced to proliferate when cultured in the presence of BM-MSCs. To determine the effect of BM-MSCs on U2OS and SNU-398 cells, the AKT and ERK signaling pathways were investigated, and increases were observed in active P-Akt and P-Erk forms. Moreover, BM-MSCs caused an increase in tumor cell migration and invasion that was derived from the enhancement of CXCR4 levels. Thus, when tumor cells were treated with the CXCR4 antagonist AMD3100, a reduction in their migration and invasion was observed. Furthermore, a new CXCR4 inhibitor, Peptide R, which was recently developed as an anticancer agent, was used to inhibit BM-MSC-mediated tumor invasion and to overcome AMD3100 toxicity. Taken together, these results suggest that inhibiting CXCR4 impairs the cross-talk between tumor cells and BM-MSCs, resulting in reduced metastatic potential in osteosarcoma and hepatocellular carcinoma cells. PMID:26517945

  20. Armc8 regulates the invasive ability of hepatocellular carcinoma through E-cadherin/catenin complex.

    Science.gov (United States)

    Zhao, Yang; Peng, Songlin; Jia, Changjun; Xu, Feng; Xu, Yongqing; Dai, Chaoliu

    2016-08-01

    Armc8 (armadillo-repeat-containing protein 8) was proved to promote disruption of E-cadherin complex through regulating α-catenin degradation. In this study, we investigated Armc8 expression in hepatocellular carcinoma using immunohistochemistry (IHC). The positive rate of Armc8 expression in hepatocellular carcinoma was 53.9 % and higher than that in normal hepatic tissues (9.2 %) (p < 0.05). Clinicopathological analysis shows that Armc8 expression in hepatocellular carcinoma was significantly associated with larger tumor size (≥5 cm), multiple tumor numbers, higher pathological grade (media and poor), advanced TNM stages (II/III), and advanced BCLC stages (B/C). Western blot study also detected higher Armc8 expression in hepatocellular carcinoma cells including HepG2, HCC97L, and SMMC-7721 than in human hepatic cell Bel-7402. We further use specific small interfering RNAs (siRNAs) to knock down Armc8 expression in HepG2 cells and found that knockdown of Armc8 expression significantly inhibited the invasive ability of HepG2 cells. Downregulation of Armc8 expression significantly upregulated α-catenin, β-catenin, and E-cadherin expression in HepG2 cells. Immunofluorescent study shows that knockdown of Armc8 expression restored E-cadherin expression in membrane of HepG2 cells. These results indicate that Armc8 may be a potential cancer marker in hepatocellular carcinoma and may regulate cancer invasion through E-cadherin/catenin complex. PMID:26944057

  1. CT-scan prediction of thyroid cartilage invasion for early laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Hartl, Dana M; Landry, Guillaume; Bidault, François; Hans, Stéphane; Julieron, Morbize; Mamelle, Gérard; Janot, François; Brasnu, Daniel F

    2013-01-01

    Treatment choice for laryngeal cancer may be influenced by the diagnosis of thyroid cartilage invasion on preoperative computed tomography (CT). Our objective was to determine the predictive value of CT for thyroid cartilage invasion in early- to mid-stage laryngeal cancer. Retrospective study (1992-2008) of laryngeal squamous cell carcinoma treated with open partial laryngectomy and resection of at least part of the thyroid cartilage. Previous laser surgery, radiation therapy, chemotherapy and second primaries were excluded. CT prediction of thyroid cartilage invasion was determined by specialized radiologists. Tumor characteristics and pathologic thyroid cartilage invasion were compared to the radiologic assessment. 236 patients were treated by vertical (20 %), supracricoid (67 %) or supraglottic partial laryngectomy (13 %) for tumors staged cT1 (26 %), cT2 (55 %), and cT3 (19 %). The thyroid cartilage was invaded on pathology in 19 cases (8 %). CT's sensitivity was 10.5 %, specificity 94 %, positive predictive value 13 %, and negative predictive value 92 %. CT correctly predicted thyroid cartilage invasion in only two cases for an overall accuracy of 87 %. Among the false-positive CT's, tumors involving the anterior commissure were significantly over-represented (61.5 % vs. 27 %, p = .004). Tumors with decreased vocal fold (VF) mobility were significantly over-represented in the group of false-negatives (41 vs. 13 %, p = .0035). Preoperative CT was not effective in predicting thyroid cartilage invasion in these early- to mid-stage lesions, overestimating cartilage invasion for AC lesions and underestimating invasion for lesions with decreased VF mobility.

  2. Submucosal Invasive Micropapillary Carcinoma of the Colon with Massive Lymph Node Metastases: A Case Report

    Directory of Open Access Journals (Sweden)

    Shoichiro Mukai

    2012-11-01

    Full Text Available Micropapillary carcinoma was originally reported to be an aggressive variant of breast carcinoma, and it is associated with frequent lymphovascular invasion and a dismal clinical outcome. It has subsequently been found in other organs; however, at present, only a limited number of cases of colorectal micropapillary carcinoma have been reported. We present a case of early colon cancer with extensive nodal metastases in a Japanese patient. An 82-year-old man was found by colonoscopy to have a 20-mm pedunculated polyp in his sigmoid colon. Endoscopic resection of the sigmoid colon tumor was performed, and pathological examination of the resected specimen revealed a poorly differentiated adenocarcinoma component and a micropapillary component. Despite the tumor being confined within the submucosa, massive lymphatic invasion was noted. Thereafter, the patient underwent laparoscopic sigmoidectomy with lymph node dissection, and multiple lymph node metastases were observed. Our case suggests that when a micropapillary component is identified in a pre-operative biopsy specimen, even for early colorectal cancer, surgical resection with adequate lymph node dissection would be required because of the high potential for nodal metastases.

  3. Intratumoral metabolic heterogeneity predicts invasive components in breast ductal carcinoma in situ

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    Yoon, Hai-Jeon [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Kim, Yemi [Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of); Kim, Bom Sahn [Ewha Womans University School of Medicine, Department of Nuclear Medicine, Yangchun-Ku, Seoul (Korea, Republic of); Ewha Womans University, Clinical Research Institute, Seoul (Korea, Republic of)

    2015-12-15

    This study investigated whether texture-based imaging parameters could identify invasive components of ductal carcinoma in situ (DCIS). We enrolled 65 biopsy-confirmed DCIS patients (62 unilateral, 3 bilateral) who underwent {sup 18}F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV{sub max} and intratumoral metabolic heterogeneity by the area under the curve (AUC) of cumulative SUV histograms (CSH) on PET, tumour-to-normal ratio (TNR) and coefficient of variation (COV) as an index of heterogeneity on BSGI, minimum ADC (ADC{sub min}) and ADC difference (ADC{sub diff}) as an index of heterogeneity on DWI. After surgery, final pathology was categorized as pure-DCIS (DCIS-P), DCIS with microinvasion (DCIS-MI), or invasive ductal carcinoma (IDC). Clinicopathologic features of DCIS were correlated with final classification. Final pathology confirmed 44 DCIS-P, 14 DCIS-MI, and 10 IDC. The invasive component of DCIS was significantly correlated with higher SUV{sub max} (p = 0.017) and lower AUC-CSH (p < 0.001) on PET, higher TNR (p = 0.008) and COV (p = 0.035) on BSGI, lower ADC{sub min} (p = 0.016) and higher ADC{sub diff} (p = 0.009) on DWI, and larger pathologic size (p = 0.018). On multiple regression analysis, AUC-CSH was the only significant predictor of invasive components (p = 0.044). The intratumoral metabolic heterogeneity of {sup 18}F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

  4. Gas6/Axl pathway promotes tumor invasion through the transcriptional activation of Slug in hepatocellular carcinoma.

    Science.gov (United States)

    Lee, Hsin-Jung; Jeng, Yung-Ming; Chen, Yu-Ling; Chung, Ling; Yuan, Ray-Hwang

    2014-04-01

    Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide. Other than the sorafenib treatment, no effective systemic therapy has been available thus far. Most targets in molecularly targeted therapy for cancer are receptor tyrosine kinases (RTKs). Therefore, identifying activated RTKs in HCC is critical for developing new molecularly targeted therapies. Using a phospho-RTK array, we found that Axl is one of the most frequently activated RTKs in liver cancer cell lines. The knockdown of Axl by RNA interference significantly reduced cell migration and invasion in the HCC cell lines HA22T and Mahlavu. Stimulation of HCC cell lines by Axl ligand growth arrest-specific 6 (Gas6) enhanced cell migration and invasion. The Gas6/Axl pathway enhanced the expression of the epithelial-mesenchymal transition-inducing transcription factor Slug, which is essential for the invasion-promoting activity of Axl. Treating HCC cells with the Axl inhibitor bosutinib suppressed Slug expression and decreased the invasiveness of HCC cell lines. These findings indicate that Gas6/Axl regulates tumor invasion through the transcriptional activation of Slug.

  5. Three-Dimensional Reconstruction of Oral Tongue Squamous Cell Carcinoma at Invasion Front

    Directory of Open Access Journals (Sweden)

    Tomoo Kudo

    2013-01-01

    Full Text Available We conducted three-dimensional (3D reconstruction of oral tongue squamous cell carcinoma (OTSCC using serial histological sections to visualize the architecture of invasive tumors. Fourteen OTSCC cases were collected from archival paraffin-embedded specimens. Based on a pathodiagnostic survey of whole cancer lesions, a core tissue specimen (3 mm in diameter was dissected out from the deep invasion front using a paraffin tissue microarray. Serial sections (4 μm thick were double immunostained with pan-cytokeratin and Ki67 antibodies and digitized images were acquired using virtual microscopy. For 3D reconstruction, image registration and RGB color segmentation were automated using ImageJ software to avoid operator-dependent subjective errors. Based on the 3D tumor architecture, we classified the mode of invasion into four types: pushing and bulky architecture; trabecular architecture; diffuse spreading; and special forms. Direct visualization and quantitative assessment of the parenchymal-stromal border provide a new dimension in our understanding of OTSCC architecture. These 3D morphometric analyses also ascertained that cell invasion (individually and collectively occurs at the deep invasive front of the OTSCC. These results demonstrate the advantages of histology-based 3D reconstruction for evaluating tumor architecture and its potential for a wide range of applications.

  6. Effects of Roundabout 5 on adhesion, invasion and potential motility of human tongue carcinoma Tb cells

    Institute of Scientific and Technical Information of China (English)

    XIAO Rui; ZHAO yuan; WANG Li-jing; LI Wei-ping

    2011-01-01

    Background Roundabout 5 (R5) is a monoclonal antibody which can neutralize the binding of Roundabout 1 (Robo1)to Slit2. Oral squamous cell carcinoma angiogenesis was significantly inhibited when R5 blocked slit-robo signaling pathway. However, the effect of R5 on the invasion of tongue cancer cells has not been investigated clearly. Methods In this study, we treated human brain metastasis of tongue cancer cell lines (Tb cells) with R5 at different concentrations, and the control Tb cells were treated with 10 mg/ml immunoglobin G 2b (lgG2b). The effect of R5 on the proliferation, adhension, invasion and motility of Tb cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cell attachment assay on fibronectin (FN), wound assay and chemotaxis assay,respectively. And gelatin-incorporated sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to investigate the activity of matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9). Results R5 had no effect on the proliferation of Tb cells. However, R5 could significantly inhibit the motility, attachment and chemotaxis of Tb cells to FN, and it could also significantly inhibit the activity of MMP2 and MMP9 in Tb cells. Conclusion R5 can inhibit the adhesion, invasion and motility of human tongue carcinoma Tb cells.

  7. Classification of progression free survival with nasopharyngeal carcinoma tumors

    Science.gov (United States)

    Farhidzadeh, Hamidreza; Kim, Joo Y.; Scott, Jacob G.; Goldgof, Dmitry B.; Hall, Lawrence O.; Harrison, Louis B.

    2016-03-01

    Nasopharyngeal carcinoma (NPC) is an abnormal growth of tissue which arises from the back of the nose. At the time of diagnosis, detection of tumor features with prognostic significance, including patient demographics, imaging characteristics and molecular characteristics, can enable the treating clinician to select a treatment that is optimized for the individual patient. At present, the analysis of tumor imaging features is limited to size criteria and macroscopic textural semantic descriptors, but computerized quantification of intratumoral heterogeneity and their temporal evolution may provide another metric for predicting prognosis. We propose medical imaging feature analysis methods and radiomics machine learning methods to predict failure of treatment. NPC tumors on contrast-enhanced T1 (T1Gd) sequences of 25 NPC patients' diagnostic magnetic resonance images (MRI) were manually contoured. Otsu segmentation was applied to segment the tumor into highly enhancing vs. weakly enhancing signal intensity subregions. Within these subregions, texture features were extracted to numerically quantify the intraregional heterogeneity. Patients were divided into two prognostic groups; a progression-freesurvival group (those without locoregional recurrence or distant metastases), and the disease progression group (those with locoregional recurrence or distant metastases). We used Support Vector Machines (SVM) to perform classification (prediction of prognosis). The features from the highly enhancing subregion classify prognosis with 80% predictive accuracy with AUC=0.60, while the captured features from the weakly enhancing subregion classify prognosis with 76% accuracy with AUC= 0.76.

  8. Protein p 16INK4A expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of uterine cervix

    Directory of Open Access Journals (Sweden)

    Gupta Ruchi

    2010-01-01

    Full Text Available The association of human papilloma virus (HPV infection and cervical intraepithelial neoplasia (CIN is well recognized. Interaction of HPV oncogenic proteins with cellular regulatory proteins leads to up regulation of p16 INK4A , a CDK inhibitor, which is a biomarker for HPV infection. We investigated p16 expression in CIN and invasive squamous cell carcinoma (SCC which has not been reported in the Indian population previously. Materials and Methods: Retrospective analysis of 100 cases with 20 cases each of histologically normal cervical epithelium, CIN1, 2, 3 and invasive SCC for p16 expression was performed by immunohistochemistry using commercially available mouse monoclonal antibody to p16 (clone 6H12. Statistical Analysis: For differences in expression among groups, statistical analysis was carried out using ANOVA and post hoc test of Scheffe. Results: p16 immunoreactivity was found to be both nuclear and/or cytoplasmic. The normal cervical epithelium was predominantly negative for p16 (18/20. There was a progressive increase of p16 expression with the grade of CIN. In CIN 1, two cases (20% showed nuclear and nucleocytoplasmic positivity respectively. In contrast, diffuse strong nuclear or nucleocytoplasmic expression was observed in 45 and 55% cases of CIN 2 and CIN 3 respectively. All except one squamous cell carcinoma stained strongly positive for p16. The difference in expression between CIN 2/3 and SCC versus normal cervix was found highly significant (p is equal to 0.008 and p less than 0.001. Conclusions: p16 expression correlates excellently with the grade of CIN and is a sensitive marker of cervical intraepithelial neoplasia.

  9. miR-208-3p promotes hepatocellular carcinoma cell proliferation and invasion through regulating ARID2 expression

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    Yu, Peng; Wu, Dingguo; You, Yu; Sun, Jing; Lu, Lele; Tan, Jiaxing; Bie, Ping, E-mail: bieping2010@163.com

    2015-08-15

    MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at post-transcriptional level. miRNA dysregulation plays a causal role in cancer progression. In this study, miR-208-3p was highly expressed and directly repressed ARID2 expression. As a result, ARID2 expression in hepatocellular carcinoma (HCC) was decreased. In vitro, miR-208-3p down-regulation and ARID2 over-expression elicited similar inhibitory effects on HCC cell proliferation and invasion. In vivo test results revealed that miR-208-3p down-regulation inhibited HCC tumorigenesis in Hep3B cells. Moreover, ARID2 was possibly a downstream element of transforming growth factor beta1 (TGFβ1)/miR-208-3p/ARID2 regulatory pathway. These findings suggested that miR-208-3p up-regulation is associated with HCC cell progression and may provide a new target for liver cancer treatment. - Highlights: • miR-208-3p was highly expressed and directly repressed the expression of ARID2 in HCC. • miR-208-3p contributed to HCC cell progression both in vitro and in vivo. • Over-expression of ARID2 inhibited the HCC cell proliferation and invasion. • Restoration of ARID2 partly reversed the the effect of miR-208-3p down-regulation on HCC cells. • Newly regulatory pathway: miR-208-3p mediated the repression of ARID2 by TGFβ1 in HCC cells.

  10. EphA2 silencing in nasopharyngeal carcinoma leads to decreased proliferation, invasion and increased sensitization to paclitaxel.

    Science.gov (United States)

    Tan, Pingqing; Liu, Yong; Yu, Changyun; Su, Zhongwu; Li, Guo; Zhou, Xiaojuan; Huang, Donghai; Zhang, Xin; Qiu, Yuanzheng; Tian, Yongquan

    2012-09-01

    EphA2 is frequently overexpressed and functionally altered in a variety of human cancers. However, its roles in human nasopharyngeal carcinoma (NPC) remain unclear. To investigate the roles of EphA2 in the development and progression of NPC, we initially evaluated the expression pattern of EphA2 protein in NPC tissues using western blotting and CCK-8 assay. Fluorescence-activated cell sorting analysis and invasion assay were conducted to observe the effects of EphA2 inhibition in vivo. Our results demonstrated that EphA2 was overexpressed in NPC specimens and the expression of EphA2 was significantly associated with T classification, advanced clinical stage and lymph node metastasis. Moreover, human NPC 5-8F cells were infected with lentiviral vector-mediated EphA2-specific shRNA, which resulted in the significant inhibition of cell growth, invasion of 5-8F cells and markedly enhanced the sensitivity of 5-8F cells to the chemotherapeutic agent paclitaxel in vitro. Collectively, our results demonstrate that EphA2 is involved in malignant cell behavior and is a potential therapeutic target in human NPC. PMID:23741245

  11. Expression of the alpha 6 beta 4 integrin by squamous cell carcinomas and basal cell carcinomas: possible relation to invasive potential?

    DEFF Research Database (Denmark)

    Rossen, K; Dahlstrøm, K K; Mercurio, A M;

    1994-01-01

    We have studied the expression of alpha 6 beta 4 integrin, a carcinoma laminin receptor in ten squamous cell carcinomas (SCCs) and ten basal cell carcinomas (BCCs) of the skin in order to examine whether changes in alpha 6 beta 4 integrin expression may be related to invasive and metastatic...... potential. Monoclonal antibodies specific for each subunit were applied on cryosections, using a three step indirect peroxidase technique. In normal epidermis the basal cells expressed both the alpha 6 and the beta 4 subunits, and the expression was polarized against the basement membrane. In SCCs the...

  12. Analysis of P53 Mutation and Invasion Front Grading in Oral Squamous Cell Carcinomas

    Institute of Scientific and Technical Information of China (English)

    唐三保; 徐东选; 周彬

    2010-01-01

    We examined P53 mutation and invasion front grading (IFG) in 30 cases of oral squamous cell carcinomas (OSCCs). The association of P53 mutation and IFG scores with clinicopa-thological parameters was evaluated. P53 mutation existed in exon 5-8 in 15 out of the 30 OSCCs (50%). The incidence of P53 mutation was not associated with age, gender, N value and TNM stage. However, there was a significant correlation between P53 mutation and T value (P=0.046). There were no statistically significant correlations amo...

  13. siRNA targeting RBP2 inhibits expression, proliferation, tumorigenicity and invasion in thyroid carcinoma cells

    OpenAIRE

    KONG, LING-LING; MAN, DONG-MEI; Wang, Tian; ZHANG, GUO-AN; Cui, Wen

    2015-01-01

    In order to estimate the effects of small interfering RNA (siRNA) targeting retinoblastoma binding protein 2 (RBP2) on the proliferation, expression, invasion, migration and tumorigenicity abilities of papillary thyroid carcinoma K1 cells, siRNA targeting RBP2 (RBP2-siRNA) and negative control siRNA were transfected into K1 cells. The mRNA levels of RBP2 in the transfected cells were estimated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the protein levels of...

  14. Management of Locally Advanced Renal Cell Carcinoma with Invasion of the Duodenum

    Directory of Open Access Journals (Sweden)

    Andrew T. Schlussel

    2013-01-01

    Full Text Available Renal cell carcinoma (RCC is rare but aggressive, with greater than 20% of patients presenting with stage III or IV, disease. Surgical resection of the primary tumor regardless of stage is the treatment of choice, and en bloc resection of involved organs provides the only potential chance for cure. This case report describes a patient with metastatic right-sided RCC with invasion of the inferior vena cava and duodenum managed by en block resection and pancreaticoduodenectomy. This report will review the workup and treatment of locally advanced RCC, as well as the role of cytoreductive nephrectomy in the setting of metastatic disease.

  15. Novel Use for DOG1 in Discriminating Breast Invasive Carcinoma from Noninvasive Breast Lesions

    OpenAIRE

    Henghui Cheng; Shouhua Yang; Zhiling Qu; Sheng Zhou; Qiurong Ruan

    2016-01-01

    Aims. DOG1 has proven to be a useful marker of gastrointestinal stromal tumors (GISTs). Recently, DOG1 expression has also been reported in some non-GIST malignant tumors, but the details related to DOG1 expression in breast tissue remain unclear. The aim of this study was to detect the expression of DOG1 in the human breast and to evaluate the feasibility of using DOG1 to discriminate between invasive breast carcinoma and noninvasive breast lesions. Methods and Results. A total of 210 cases,...

  16. The Roles of the Epithelial-Mesenchymal Transition Marker PRRX1 and miR-146b-5p in Papillary Thyroid Carcinoma Progression

    Science.gov (United States)

    Hardin, Heather; Guo, Zhenying; Shan, Weihua; Montemayor-Garcia, Celina; Asioli, Sofia; Yu, Xiao-Min; Harrison, April D.; Chen, Herbert; Lloyd, Ricardo V.

    2015-01-01

    Thyroid carcinoma is the most common endocrine malignancy, and papillary thyroid carcinoma represents the most common thyroid cancer. Papillary thyroid carcinomas that invade locally or metastasize are associated with a poor prognosis. We found that, during epithelial–mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1), papillary thyroid carcinoma cells acquired increased cancer stem cell-like features and the transcription factor paired-related homeobox protein 1 (PRRX1; alias PRX-1), a newly identified EMT inducer, was markedly up-regulated. miR-146b-5p was also transiently up-regulated during EMT, and in siRNA experiments miR-146b-5p had an inhibitory role on cell proliferation and invasion during TGF-β1–induced EMT. We conclude that papillary thyroid carcinoma tumor cells exhibit increased cancer stem cell-like features during TGF-β1–induced EMT, that miR-146b-5p has a role in cell proliferation and invasion, and that PRRX1 plays an important role in papillary thyroid carcinoma EMT and disease progression. PMID:24946010

  17. Overexpression of VCC-1 gene in human hepatocellular carcinoma cells promotes cell proliferation and invasion

    Institute of Scientific and Technical Information of China (English)

    Xia Mu; Yao Chen; Shuihai Wang; Xiang Huang; Huazhen Pan; Ming Li

    2009-01-01

    Vascular endothelial growth factor-correlated chemo-kine 1 (VCC-1), a novel chemokine, is hypothesized to be associated with carcinogenesis. VCC-1 is expressed in hepatocellular carcinoma (HCC) cells, but its func-tion remains unknown. To investigate the molecular effects of VCC-1 on HCC cells, the HCC cell line SMMC7721 was stably transfected with the recombi-nant plasmid pcDNA3.1/VCC-1. Our data demonstrated that overexpression of VCC-1 in SMMC7721 cells sig-nificantly enhanced the cellular proliferation, invasive ability, and tumor growth, when compared with both empty vector control cells and parental cells. These results strongly suggest that VCC-1 plays an important role in SMMC7721 invasion and tumor growth, and indicate that VCC-1 may serve as a potential biomarker for anti-HCC therapies.

  18. [A case of partial hepatectomy and gastrectomy for hepatocellular carcinoma with direct invasion to the stomach].

    Science.gov (United States)

    Yoshida, Yuta; Murakami, Masahiro; Shimizu, Junzo; Kawada, Masahiro; Yasuyama, Akinobu; Yoshikawa, Yukihiro; Watase, Chikashi; Nishigaki, Takahiko; Kim, Ho Min; Hitora, Toshiki; Oda, Naofumi; Hirota, Masaki; Yoshikawa, Masato; Morishima, Hirotaka; Ikenaga, Masakazu; Mikata, Shoki; Matsunami, Nobuteru; Hasegawa, Junichi

    2014-11-01

    An 81-year-old man treated with chronic hepatitis C virus (HCV)-related hepatitis and hepatocellular carcinoma (HCC) was diagnosed in 2010 with HCC recurrence (subclass S2) on computed tomography (CT). He refused surgery and was followed up without treatment. In 2012, he was admitted to our hospital because of hematemesis. Gastrointestinal endoscopy revealed a large tumor in the upper gastric corpus, and pathological examination of the tumor revealed HCC; hence, we diagnosed the patient with direct HCC invasion to the stomach. Although active bleeding from the tumor was controlled, he experienced repeated episodes of hematemesis, and the tumor increased in size. Therefore, partial hepatectomy and gastrectomy were performed. It was confirmed that the tumor invaded the stomach wall. Although surgery was effective for gastrointestinal bleeding caused by HCC invasion, the patient died 12 months after surgery because of multiple liver metastases and exacerbated liver failure.

  19. Baicalein mediates inhibition of migration and invasiveness of skin carcinoma through Ezrin in A431 cells

    International Nuclear Information System (INIS)

    Ezrin is highly expressed in skin cancer and promotes tumor metastasis. Ezrin serves as a promising target for anti-metastasis therapy. The aim of this study is to determine if the flavonoid bacailein inhibits the metastasis of skin cancer cells through Ezrin. Cells from a cutaneous squamous carcinoma cell line, A431, were treated with baicalein at 0-60 μM to establish the non-cytotoxic concentration (NCC) range for baicalein. Following treatment with baicalein within this range, total Ezrin protein (both phosphorylated and unphosphorylated forms) and phosphorylated-Ezrin (phos-Ezrin) were detected by western blotting, and Ezrin RNA was detected in A431 cells using reverse transcription-polymerase chain reaction (RT-PCR). Thereafter, the motility and invasiveness of A431 cells following baicalein treatment were determined using wound-healing and Boyden chamber invasion assays. Short-interfering RNA (si-RNA) specifically targeting Ezrin was transfected into A431 cells, and a si-RNA Ezrin-A431 cell line was established by G418 selection. This stable cell line was transiently transfected with Ezrin and mutant Ezrin plasmids, and its motilityand invasiveness was subsequently determined to clarify whether bacailein inhibits these processes through Ezrin. We determined the range of NCCs for baicalein to be 2.5-40 μM in A431 cells. Baicalein displayed a dose- and time-dependent inhibition of expressions of total Ezrin and phos-Ezrin within this range NCCs. In addition, it exerted this inhibitory effect through the reduction of Ezrin RNA transcript. Baicalein also inhibited the motility and invasiveness of A431 skin carcinoma cells within the range of NCCs, in a dose- and time-dependent manner. A431 cell motility and invasiveness were inhibited by 73% and 80% respectively when cells were treated with 20 μM baicalein. However, the motility and invasiveness of A431 cells containing the Ezrin mutant were not effectively inhibited by baicalein. Baicalein reduces the

  20. Rab25 upregulation correlates with the proliferation, migration, and invasion of renal cell carcinoma

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is a common urological cancer with a poor prognosis. A recent cohort study revealed that the median survival of RCC patients was only 1.5 years and that <10% of the patients in the study survived up to 5 years. In tumor development, Rab GTPase are known to play potential roles such as regulation of cell proliferation, migration, invasion, communication, and drug resistance in multiple tumors. However, the correlation between Rabs expression and the occurrence, development, and metastasis of RCC remains unclear. In this study, we analyzed the transcriptional levels of 52 Rab GTPases in RCC patients. Our results showed that high levels of Rab25 expression were significantly correlated with RCC invasion classification (P < 0.01), lymph-node metastasis (P < 0.001), and pathological stage (P < 0.01). Conversely, in 786-O and A-498 cells, knocking down Rab25 protein expression inhibited cell proliferation, migration, and invasion. Our results also demonstrated that Rab25 is a target gene of let-7d, and further suggested that Rab25 upregulation in RCC is due to diminished expression of let-7d. These findings indicate that Rab25 might be a novel candidate molecule involved in RCC development, thus identifying a potential biological therapeutic target for RCC. - Highlights: • The transcriptional levels of 52 Rab GTPases were analyzed in renal cell carcinoma (RCC). • High levels of Rab25 expression were significantly correlated with clinicopathological factors of RCC. • Knockdown of Rab25 protein expression reduced RCC cells proliferation, migration, and invasion. • Rab25 is a target gene of let-7d in RCC

  1. Rab25 upregulation correlates with the proliferation, migration, and invasion of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuanyuan; Jia, Qingzhu [Biomedical Analysis Center, Third Military Medical University, Chongqing (China); Chongqing Key Laboratory of Cytomics, Chongqing (China); Zhang, Qian [Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing (China); Wan, Ying, E-mail: wanying_cn@163.com [Biomedical Analysis Center, Third Military Medical University, Chongqing (China); Chongqing Key Laboratory of Cytomics, Chongqing (China)

    2015-03-20

    Renal cell carcinoma (RCC) is a common urological cancer with a poor prognosis. A recent cohort study revealed that the median survival of RCC patients was only 1.5 years and that <10% of the patients in the study survived up to 5 years. In tumor development, Rab GTPase are known to play potential roles such as regulation of cell proliferation, migration, invasion, communication, and drug resistance in multiple tumors. However, the correlation between Rabs expression and the occurrence, development, and metastasis of RCC remains unclear. In this study, we analyzed the transcriptional levels of 52 Rab GTPases in RCC patients. Our results showed that high levels of Rab25 expression were significantly correlated with RCC invasion classification (P < 0.01), lymph-node metastasis (P < 0.001), and pathological stage (P < 0.01). Conversely, in 786-O and A-498 cells, knocking down Rab25 protein expression inhibited cell proliferation, migration, and invasion. Our results also demonstrated that Rab25 is a target gene of let-7d, and further suggested that Rab25 upregulation in RCC is due to diminished expression of let-7d. These findings indicate that Rab25 might be a novel candidate molecule involved in RCC development, thus identifying a potential biological therapeutic target for RCC. - Highlights: • The transcriptional levels of 52 Rab GTPases were analyzed in renal cell carcinoma (RCC). • High levels of Rab25 expression were significantly correlated with clinicopathological factors of RCC. • Knockdown of Rab25 protein expression reduced RCC cells proliferation, migration, and invasion. • Rab25 is a target gene of let-7d in RCC.

  2. Deletion of inositol hexakisphosphate kinase 1 (IP6K1) reduces cell migration and invasion, conferring protection from aerodigestive tract carcinoma in mice.

    Science.gov (United States)

    Jadav, Rathan S; Kumar, Dharmika; Buwa, Natasha; Ganguli, Shubhra; Thampatty, Sitalakshmi R; Balasubramanian, Nagaraj; Bhandari, Rashna

    2016-08-01

    Inositol hexakisphosphate kinases (IP6Ks), a family of enzymes found in all eukaryotes, are responsible for the synthesis of 5-diphosphoinositol pentakisphosphate (5-IP7) from inositol hexakisphosphate (IP6). Three isoforms of IP6Ks are found in mammals, and gene deletions of each isoform lead to diverse, non-overlapping phenotypes in mice. Previous studies show a facilitatory role for IP6K2 in cell migration and invasion, properties that are essential for the early stages of tumorigenesis. However, IP6K2 also has an essential role in cancer cell apoptosis, and mice lacking this protein are more susceptible to the development of aerodigestive tract carcinoma upon treatment with the oral carcinogen 4-nitroquinoline-1-oxide (4NQO). Not much is known about the functions of the equally abundant and ubiquitously expressed IP6K1 isoform in cell migration, invasion and cancer progression. We conducted a gene expression analysis on mouse embryonic fibroblasts (MEFs) lacking IP6K1, revealing a role for this protein in cell receptor-extracellular matrix interactions that regulate actin cytoskeleton dynamics. Consequently, cells lacking IP6K1 manifest defects in adhesion-dependent signaling, evident by lower FAK and Paxillin activation, leading to reduced cell spreading and migration. Expression of active, but not inactive IP6K1 reverses migration defects in IP6K1 knockout MEFs, suggesting that 5-IP7 synthesis by IP6K1 promotes cell locomotion. Actin cytoskeleton remodeling and cell migration support the ability of cancer cells to achieve their complete oncogenic potential. Cancer cells with lower IP6K1 levels display reduced migration, invasion, and anchorage-independent growth. When fed an oral carcinogen, mice lacking IP6K1 show reduced progression from epithelial dysplasia to invasive carcinoma. Thus, our data reveal that like IP6K2, IP6K1 is also involved in early cytoskeleton remodeling events during cancer progression. However, unlike IP6K2, IP6K1 is essential for 4NQO

  3. Deletion of inositol hexakisphosphate kinase 1 (IP6K1) reduces cell migration and invasion, conferring protection from aerodigestive tract carcinoma in mice.

    Science.gov (United States)

    Jadav, Rathan S; Kumar, Dharmika; Buwa, Natasha; Ganguli, Shubhra; Thampatty, Sitalakshmi R; Balasubramanian, Nagaraj; Bhandari, Rashna

    2016-08-01

    Inositol hexakisphosphate kinases (IP6Ks), a family of enzymes found in all eukaryotes, are responsible for the synthesis of 5-diphosphoinositol pentakisphosphate (5-IP7) from inositol hexakisphosphate (IP6). Three isoforms of IP6Ks are found in mammals, and gene deletions of each isoform lead to diverse, non-overlapping phenotypes in mice. Previous studies show a facilitatory role for IP6K2 in cell migration and invasion, properties that are essential for the early stages of tumorigenesis. However, IP6K2 also has an essential role in cancer cell apoptosis, and mice lacking this protein are more susceptible to the development of aerodigestive tract carcinoma upon treatment with the oral carcinogen 4-nitroquinoline-1-oxide (4NQO). Not much is known about the functions of the equally abundant and ubiquitously expressed IP6K1 isoform in cell migration, invasion and cancer progression. We conducted a gene expression analysis on mouse embryonic fibroblasts (MEFs) lacking IP6K1, revealing a role for this protein in cell receptor-extracellular matrix interactions that regulate actin cytoskeleton dynamics. Consequently, cells lacking IP6K1 manifest defects in adhesion-dependent signaling, evident by lower FAK and Paxillin activation, leading to reduced cell spreading and migration. Expression of active, but not inactive IP6K1 reverses migration defects in IP6K1 knockout MEFs, suggesting that 5-IP7 synthesis by IP6K1 promotes cell locomotion. Actin cytoskeleton remodeling and cell migration support the ability of cancer cells to achieve their complete oncogenic potential. Cancer cells with lower IP6K1 levels display reduced migration, invasion, and anchorage-independent growth. When fed an oral carcinogen, mice lacking IP6K1 show reduced progression from epithelial dysplasia to invasive carcinoma. Thus, our data reveal that like IP6K2, IP6K1 is also involved in early cytoskeleton remodeling events during cancer progression. However, unlike IP6K2, IP6K1 is essential for 4NQO

  4. Anatomic Invasive Depth Predicts Delayed Cervical Lymph Node Metastasis of Tongue Squamous Cell Carcinoma.

    Science.gov (United States)

    Mitani, Sohei; Tomioka, Toshifumi; Hayashi, Ryuichi; Ugumori, Toru; Hato, Naohito; Fujii, Satoshi

    2016-07-01

    Delayed cervical lymph node metastasis (CLNM) is the most negative prognostic factor of tongue squamous cell carcinoma (SCC). This study analyzed the relationship between clinicopathologic factors, including anatomic invasive depth (AID), and CLNM. A total of 212 patients with clinically node-negative (cN0) tongue SCC who had undergone partial glossectomy through the mouth were eligible for this retrospective study. The deepest portions where tongue SCC cells invaded as determined by microscopic analyses were classified into 5 categories, including epithelial and submucosal tissue, lateral extrinsic tongue muscle (ETM), intrinsic tongue muscles (ITM), paralingual and sublingual spaces, and medial ETM according to AID. We examined the relationship between clinicopathologic factors including AID and delayed CLNM. Multivariate analysis demonstrated that AID was an independent predictive factor for delayed CLNM (P=0.0022; odds ratio=7.1). Deeper invasion than ITM, including ITM, paralingual and sublingual spaces, and medial ETM, had high sensitivity and negative predictive value for delayed CLNM (94.4% and 95.7%, respectively). Precise elucidation of AID may be useful for the preoperative decision for performing elective neck dissection. None of 11 patients in whom the deepest portion where tumor invaded to lateral ETM (according to AID) showed delayed CLNM, although tongue SCC T4a tumor is defined by the presence of invasion of cancer cells to ETM. Tumors with invasion to lateral ETM might have to be excluded from the pathologic T4a category. PMID:27186852

  5. [A Case of Invasive Intraductal Papillary Mucinous Carcinoma, Penetrating the Stomach, Colon, and Jejunum].

    Science.gov (United States)

    Goto, Tadahiro; Toyama, Hirochika; Asari, Sadaki; Terai, Sachio; Kinoshita, Hisoka; Matsumoto, Taku; Kuramitsu, Kaori; Tanaka, Motofumi; Takebe, Atsushi; Kido, Masahiro; Matsumoto, Ippei; Ajiki, Tetsuo; Fukumoto, Takumi; Ku, Yonson

    2015-11-01

    A 69-year-old woman was admitted to a nearby clinic complaining of abdominal pain. Abdominal CT showed a 10 cm diameter huge cystic lesion in the body and tail of the pancreas. The patient was referred to our institution for treatment. Endoscopic ultrasonography (EUS) revealed a cystic mass with a solid lesion. Endoscopic retrograde pancreatography(ERP) demonstrated mucous at the opening of the papilla of Vater and dilatation of the pancreatic duct with a solid nodule. Contrast radiography revealed a fistula from the tumor to the jejunum. A biopsy specimen from the lesion showed adenocarcinoma. Intraoperative findings showed a tumor occupying the pancreas body and tail with suspected invasion to the stomach, jejunum, and transverse colon. We performed distal pancreatectomy with partial resection of stomach, jejunum, and colon. Pathological findings showed an invasive type of IPMC, with invasion to the subserosal layer of the stomach and colon and the mucous layer of the jejunum. While IPMC is recognized as a slow growing malignancy, some cases of invasive carcinoma with fistulation into adjacent organs have been reported. To our knowledge, a case of IPMC penetrating to 3 adjacent organs is rare.

  6. Positive association of RhoC gene overexpression with tumour invasion and lymphatic metastasis in gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Zhen-ning; XU Hui-mian; JIANG Li; ZHOU Xin; LU Chong; ZHANG Xue

    2005-01-01

    @@ Worldwide estimates establish gastric carcinoma as the second most frequent cause of cancer deaths. Tumour invasion and metastasis is the biggest impediment to gastric carcinoma cure. Active migration of tumour cells is now considered as the pivotal step in cancer invasion and metastasis. RhoC is a member of the Ras-superfamily of small guanosine triphosphatases that can regulate many cellular functions, especially cytoskeletal organization and cell locomotion. Overexpressing RhoC in vitro in the poorly metastatic cell line from human melanoma may induce a highly metastatic phenotype.1 The recent development of laser capture microdissection (LCM) affords the opportunity to further evaluate the role RhoC plays in the invasion and metastasis of gastric carcinoma cells in their native tissue environment.

  7. Invasive aspergillosis causing small bowel infarction in a patient of carcinoma breast undergoing chemotherapy

    Directory of Open Access Journals (Sweden)

    Jain Vinod

    2006-01-01

    Full Text Available Abstract Background To report a 45 year old lady presenting with proximal jejunal gangrene due to invasive Aspergillosis. The patient was undergoing adjuvant chemotherapy for advance carcinoma of breast (Stage IV. Methods The patient was referred to our surgical emergency for acute abdominal symptoms for 6 hours. Histopathology revealed bowel wall necrosis and vascular invasion by Aspergillus Fumigatus. Postoperative recovery was uneventful and the patient received Amphotericin-B (1 mg/kg/day for invasive aspergillosis. Invasive pulmonary aspergillosis was confirmed by isolating Aspergillus Fumigatus from bronchoalveolar lavage and by a positive circulating galactomannan test (ELISA Assay. Results Detailed history revealed dry cough and two episodes of haemoptesis for 2 weeks. Haemogram and counts revealed anemia and neutropenia. Plain X – ray of the abdomen showed multiple air fluid levels and ultrasound of the abdomen revealed distended bowel loops. On exploration small bowel was found to be gangrenous. The patient was successfully managed by supportive treatment and conventional intravenous Amphotericin-B for 2 weeks. The lady was discharged one week after completion of antifungal therapy and one month later she underwent toilet mastectomy. The lady came to follow up for 1 year and she is currently under hormone therapy. Conclusion With the emergence of new and powerful immunosuppressive, anticancer drugs and potent antibiotics the survival of transplant and critically ill patients has remarkably increased but it has shown a significant rise in the incidence of invasive opportunistic fungal infections. We conclude hat the diagnosis of invasive gastrointestinal aspergillosis may be considered in a neutropenic patient with acute abdominal symptoms.

  8. KL-6 mucin expression in carcinoma of the ampulla of Vater: Association with cancer progression

    Institute of Scientific and Technical Information of China (English)

    Wei Tang; Masatoshi Makuuchi; Yoshinori Inagaki; Norihiro Kokudo; Qian Guo; Yasuji Seyama; Munehiro Nakata; Hiroshi Imamura; Keiji Sano; Yasuhiko Sugawara

    2005-01-01

    AIM: To assess histochemical expression of KL-6 and its clinicopathological significance in carcinoma of the ampulla of Vater.METHODS: Ampullary carcinoma tissues were collected from 38 patients who underwent pancreatoduodenectomy or local resection. Tissues were subjected to immunohistochemical analysis using KL-6 antibody.RESULTS: Positive staining of ampullary carcinoma cells was observed in 26 (68.4%) cases. Staining was not found in the surrounding non-cancer regions of the ampullary tissues. Remarkable KL-6 expression was observed in invasive carcinoma cells in pancreatic and duodenal tissues and in metastatic carcinoma cells in lymph nodes. Positive KL-6 expression was related to lymph node metastasis (P = 0.020), pancreatic invasion (P = 0.016), duodenal invasion (P = 0.034), and advanced stage of TNM clinical classification (P = 0.010). Survival analysis showed that positive expression of KL-6 was related to a poorer prognosis (P = 0.029).CONCLUSION: The aberrant expression of KL-6 mucin is significantly related to unfavorable behaviors of carcinoma of the ampulla of Vater.

  9. MicroRNA-638 inhibits cell proliferation, invasion and regulates cell cycle by targeting tetraspanin 1 in human colorectal carcinoma

    Science.gov (United States)

    Wang, Qifeng; Song, Mingxu; Yin, Yuan; Zhang, Binbin; Ni, Shujuan; Guo, Weijie; Bian, Zehua; Quan, Chao; Liu, Zhihui; Wang, Yugang; Yu, Jian; Du, Xiang; Hua, Dong; Huang, Zhaohui

    2014-01-01

    The expression of miR-638 was found downregulated in colorectal carcinoma (CRC) in our previous study. However, the role of miR-638 in CRC remains unknown. The aim of this study was to determine the function and mechanism of miR-638 in CRC. Here, we verified that miR-638 was frequently downregulated in CRC tissues compared with corresponding noncancerous tissues (NCTs) in an expanded CRC cohort, and survival analysis showed that the downregulation of miR-638 in CRC was associated with poor prognoses. The ectopic expression of miR-638 inhibited CRC cell proliferation, invasion and arrest the cell cycle in G1 phase, whereas the repression of miR-638 significantly promoted CRC cell growth, invasion and cell cycle G1/S transition. Subsequent mechanism analyses revealed that miR-638 inhibited CRC cell growth, invasion and cell cycle progression by targeting TSPAN1. TSPAN1 protein levels were upregulated in CRC samples and were inversely correlated with miR-638 levels. More importantly, high TSPAN1 expression levels in CRC tissues predicted poor overall survival, and appears to be an independent prognostic factor for CRC survival. Furthermore, CpG island methylation analyses revealed that the miR-638 promoter was hypermethylated in CRC and that attenuating promoter methylation was sufficient to restore miR-638 expression in CRC cells. Taken together, our current data demonstrate that miR-638 functions as a tumor suppressor in human CRC by inhibiting TSPAN1, and that TSPAN1 is a potential prognostic factor for CRC. PMID:25301729

  10. Epigenetic regulation of proliferation and invasion in hepatocellular carcinoma cells by CBP/p300 histone acetyltransferase activity.

    Science.gov (United States)

    Inagaki, Yuji; Shiraki, Katsuya; Sugimoto, Kazushi; Yada, Takazumi; Tameda, Masahiko; Ogura, Suguru; Yamamoto, Norihiko; Takei, Yoshiyuki; Ito, Masaaki

    2016-02-01

    Altered epigenetic control of gene expression plays a substantial role in tumor development and progression. Accumulating studies suggest that somatic mutations of CREB binding proteins (CBP)/p300 occur in some cancer cells. CBP/p300 possess histone acetyltransferase (HAT) activity, and are involved in many cellular processes. In this study, we investigated the expression and functional role of CBP/p300 in hepatocellular carcinoma (HCC) using the specific inhibitor C646 of CBP/p300 HAT activity. We examined its effect on several apoptosis-related proteins and invasion-related genes. The results showed that CBP/p300 were highly expressed in HCC tissues and that expression of p300, but not of CBP, was strongly correlated with the malignant character of HCC. C646 inhibited proliferation of HCC cell lines in a dose dependent manner. C646 significantly augmented TRAIL-induced apoptotic sensitivity, which was accompanied by reduced levels of survivin, in HepG2, HLE and SK-HEP1 cells. C646 significantly inhibited invasion of Huh7, HLE and SK-HEP1 cells. The level of matrix metallopeptidase 15 (MMP15) mRNA expression was significantly reduced, whereas the level of laminin alpha 3 (LAMA3) and secreted phosphoprotein 1 (SPP1) mRNA expression was significantly increased in Huh7 cells following exposure to C646. In conclusion, our results suggest that CBP/p300 HAT activity has an important role in malignant transformation, proliferation, apoptotic sensitivity and invasion in HCC. CBP/p300 could be a promising therapeutic target in HCC. PMID:26676548

  11. Ultrasound-Guided Laser-Induced Thermal Therapy for Small Palpable Invasive Breast Carcinomas: A Feasibility Study

    OpenAIRE

    Esser, S; Stapper, G.; van Diest, P J; van den Bosch, M.A.A.J.; Klaessens, J. H. G. M.; Mali, W P Th M; Borel Rinkes, I. H. M.; van Hillegersberg, R.

    2009-01-01

    Background The next step in breast-conserving surgery for small breast carcinomas could be local ablation. In this study, the feasibility of ultrasound-guided laser-induced thermal therapy (LITT) is evaluated. Methods Patients with large-core needle biopsy-proven invasive, palpable breast carcinoma (clinically ≤2 cm) underwent ultrasound-guided LITT, followed by surgical excision. Completeness of ablation was determined by both hematoxylin and eosin staining and nicotinamide adenosine diaphor...

  12. Immunohistochemical localization of Bcl-2 and Bax proteins in in situ and invasive duct breast carcinomas.

    Science.gov (United States)

    Kapucuoglu, N; Losi, L; Eusebi, V

    1997-01-01

    Bcl-2 and Bax proteins are coded by a family of genes that take part in the manteinance of the balance between cell proliferation rate and programmed cell death in multicellular organisms. The Bax gene acts as promoter of cell death by opposing the death protector effect of the Bcl-2 gene. Expression of the Bcl-2 and Bax proteins has been investigated in 58 cases of duct carcinoma in situ (DCIS) and duct invasive and invasive lobular carcinomas (IC) of the breast. While both proteins were expressed at the same time in normal and benign epithelium, different staining patterns were observed according to the degree of differentiation of the neoplastic epithelium. In well-differentiated DCIS and grade I IC there was a predominance of Bcl-2 protein staining. Grade II lesions co-expressed both proteins. Poorly differentiated DCIS displayed a predominantly Bax protein staining pattern. Therefore, it appears that Bax protein expression, especially in DCIS, relates to more aggressive neoplasms while Bcl-2 protein expression is associated with less aggressive malignant lesions.

  13. SEMA6D Expression and Patient Survival in Breast Invasive Carcinoma

    Directory of Open Access Journals (Sweden)

    Dongquan Chen

    2015-01-01

    Full Text Available Breast cancer (BC is the second most common cancer diagnosed in American women and is also the second leading cause of cancer death in women. Research has focused heavily on BC metastasis. Multiple signaling pathways have been implicated in regulating BC metastasis. Our knowledge of regulation of BC metastasis is, however, far from complete. Identification of new factors during metastasis is an essential step towards future therapy. Our labs have focused on Semaphorin 6D (SEMA6D, which was implicated in immune responses, heart development, and neurogenesis. It will be interesting to know SEMA6D-related genomic expression profile and its implications in clinical outcome. In this study, we examined the public datasets of breast invasive carcinoma from The Cancer Genome Atlas (TCGA. We analyzed the expression of SEMA6D along with its related genes, their functions, pathways, and potential as copredictors for BC patients’ survival. We found 6-gene expression profile that can be used as such predictors. Our study provides evidences for the first time that breast invasive carcinoma may contain a subtype based on SEMA6D expression. The expression of SEMA6D gene may play an important role in promoting patient survival, especially among triple negative breast cancer patients.

  14. Invasive neuroendocrine carcinoma of the breast: a population-based study from the surveillance, epidemiology and end results (SEER) database

    International Nuclear Information System (INIS)

    Neuroendocrine carcinoma (NEC) of the breast is a rare type of carcinoma that has not been well studied or characterized. Of the limited number of studies reported in the literature, most are case reports. A few small retrospective series studies have been reported. We reviewed data on 142 cases of mammary NEC recorded in the surveillance, epidemiology, and end results (SEER) database during 2003–2009 and evaluated disease incidence and patient age, sex, and race/ethnicity; clinicopathologic characteristics; and survival in comparison to invasive mammary carcinoma, not otherwise specified. We also performed univariate and multivariate analyses to identify prognostic factors in this disease. Review of the 142 SEER cases revealed that NEC is an aggressive variant of invasive mammary carcinoma. It generally occurred in older women (>60 years); present with larger tumor size (>20 mm), higher histologic grade, and higher clinical stage; and result in shorter overall survival and disease-specific survival than invasive mammary carcinoma, not otherwise specified (IMC-NOS). Overall survival and disease-specific survival were shorter in NEC at each stage than in IMC-NOS of the same stage. Furthermore, when all NEC and IMC-NOS cases were pooled together, neuroendocrine differentiation itself was an adverse prognostic factor independent of other known prognostic factors, including age, tumor size, nodal status, histologic grade, estrogen/progesterone receptor status, and therapy. NEC is a rare but aggressive type of mammary carcinoma. Novel therapeutic approaches should be explored for this uniquely clinical entity

  15. Comparison of intraoperative frozen section analysis for sentinel lymph node biopsy during breast cancer surgery for invasive lobular carcinoma and invasive ductal carcinoma

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    Povoski Stephen P

    2009-03-01

    Full Text Available Abstract Background Sentinel lymph node (SLN biopsy is the standard of care for the surgical assessment of the axilla during breast cancer surgery. However, the diagnostic accuracy of intraoperative frozen section analysis for confirming metastatic involvement of SLNs in cases of invasive lobular carcinoma (ILC versus that of invasive ductal carcinoma (IDC has generated controversy secondary to a frequently low-grade cytologic appearance and an often discohesive pattern displayed by metastatic lymph nodes in ILC. In the current report, we present a comparison of intraoperative frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC. Methods We evaluated the results of 131 consecutive cases of ILC from 1997 to 2008 and 133 cases of IDC (selected by a random sequence generator program from amongst 1163 consecutive cases of IDC from the same time period. All cases had at least one SLN that had both intraoperative frozen section analysis and confirmatory permanent section analysis performed. Results No statistically significant difference was found in the sensitivity (67% vs. 75%, P = 0.385, specificity (100% vs. 100%, accuracy (86% vs. 92%, P = 0.172, false negative rate (33% vs. 25%, P = 0.385, negative predictive value (81% vs. 89%, P = 0.158, and positive predictive value (100% vs. 100% for frozen section analysis for confirming the presence of metastatic disease within SLNs during breast cancer surgery for ILC and IDC. Conclusion Since there was no statistically significant difference in sensitivity, specificity, accuracy, false negative rate, negative predictive value, and positive predictive value between frozen section analysis of SLNs for patients with ILC and IDC, the clinical accuracy of confirming metastatic involvement of SLNs on frozen section analysis for ILC should not be considered inferior to the clinical accuracy for IDC. Therefore, frozen section analysis

  16. Activation of H-Ras and Rac1 correlates with epidermal growth factor-induced invasion in Hs578T and MDA-MB-231 breast carcinoma cells.

    Science.gov (United States)

    Koh, Min-Soo; Moon, Aree

    2011-03-01

    There is considerable experimental evidence that hyperactive Ras proteins promote breast cancer growth and development including invasiveness, despite the low frequency of mutated forms of Ras in breast cancer. We have previously shown that H-Ras, but not N-Ras, induces an invasive phenotype mediated by small GTPase Rac1 in MCF10A human breast epithelial cells. Epidermal growth factor (EGF) plays an important role in aberrant growth and metastasis formation of many tumor types including breast cancer. The present study aims to investigate the correlation between EGF-induced invasiveness and Ras activation in four widely used breast cancer cell lines. Upon EGF stimulation, invasive abilities and H-Ras activation were significantly increased in Hs578T and MDA-MB-231 cell lines, but not in MDA-MB-453 and T47D cell lines. Using small interfering RNA (siRNA) to target H-Ras, we showed a crucial role of H-Ras in the invasive phenotype induced by EGF in Hs578T and MDA-MB-231 cells. Moreover, siRNA-knockdown of Rac1 significantly inhibited the EGF-induced invasiveness in these cells. Taken together, this study characterized human breast cancer cell lines with regard to the relationship between H-Ras activation and the invasive phenotype induced by EGF. Our data demonstrate that the activation of H-Ras and the downstream molecule Rac1 correlates with EGF-induced breast cancer cell invasion, providing important information on the regulation of malignant progression in mammary carcinoma cells.

  17. Correlation between 3 T apparent diffusion coefficient values and grading of invasive breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cipolla, Valentina, E-mail: valentina.cipolla@yahoo.it [Department of Radiological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy); Santucci, Domiziana; Guerrieri, Daniele; Drudi, Francesco Maria [Department of Radiological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy); Meggiorini, Maria Letizia [Department of Gynaecological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy); Felice, Carlo de [Department of Radiological Sciences, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome (Italy)

    2014-12-15

    Highlights: • Apparent diffusion coefficient is a quantitative parameter which reflects molecular water movement. • Grading is an independent prognostic factor which correlates with other histopathological features. • Apparent diffusion coefficient values were significantly different between G1 and G3 classes. - Abstract: Purpose: The aim of this study was to evaluate whether the apparent diffusion coefficient (ADC) provided by 3.0 T (3 T) magnetic resonance diffusion-weighted imaging (DWI) varied according to the grading of invasive breast carcinoma. Materials and methods: A total of 92 patients with 96 invasive breast cancer lesions were enrolled; all had undergone 3 T magnetic resonance imaging (MRI) for local staging. All lesions were confirmed by histological analysis, and tumor grade was established according to the Nottingham Grading System (NGS). MRI included both dynamic contrast-enhanced and DWI sequences, and ADC value was calculated for each lesion. ADC values were compared with NGS classification using the Mann–Whitney U and the Kruskal–Wallis H tests. Grading was considered as a comprehensive prognostic factor, and Rho Spearman test was performed to determine correlation between grading and tumor size, hormonal receptor status, HER2 expression and Ki67 index. Pearson's Chi square test was carried out to compare grading with the other prognostic factors. Results: ADC values were significantly higher in G1 than in G3 tumors. No significant difference was observed when G1 and G3 were compared with G2. Tumor size, hormonal receptor status, HER2 expression and Ki67 index correlated significantly with grading but there was a significant difference only between G1 and G3 related to the ER and PR status, HER2 expression and Ki67 index. There was no statistically significant difference in lesion size between the two groups. Conclusion: ADC values obtained on 3 T DWI correlated with low-grade (G1) and high-grade (G3) invasive breast carcinoma. 3

  18. The relationship between histologic grades of invasive carcinoma of breast ducts and mast cell infiltration

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    Ashraf Fakhrjou

    2016-01-01

    Full Text Available Introduction: Breast carcinoma is the most prevalent tumors among women. Transformation of inflated cells in immune response leads to increase in inflammatory cells such as macrophages, mast cells (MC and fibroblasts. The aim of this study was to determine the relationship between grades of invasive carcinoma of the breast ducts and MC infiltration around tumoral cells. Methods: During the present study, 75 female patients suffering from invasive ductal carcinoma who underwent surgery or diagnostic biopsy during 2010 and 2013 in Educational-Medical centers of Tabriz University of Medical Sciences, were included in the study. Based on Bloom-Richardson grading system, 25 cases were selected from each grade. To better observe of MCs, samples were stained by Toluidine blue and MCs were counted in 10 40 × 10 fields. Results: The mean age was 47.56 ± 10.84 and the number of MCs was between 6 and 96 and their overall average was 43.01. Average count of MCs in grade 1, 2 and 3 were 15.92 ± 10.07, 45.32 ± 10.47, and 67.8 ± 20.70, respectively. There was a significant relationship between the number of MCs and increase in disease grade (P < 0.001. With increasing grade of malignancy, the number of MCs had grown. No significant relationship was observed between age and grade of disease or age and number of MC. Conclusion: According to obtained results, number of MC around tumoral cells increased significantly with an increase in the grade of disease. In order to treat in thefirst stages of the disease, recognizing primary changes in the stroma of cells could be helpful.

  19. NDRG2 inhibits hepatocellular carcinoma adhesion, migration and invasion by regulating CD24 expression

    International Nuclear Information System (INIS)

    The prognosis of most hepatocellular carcinoma (HCC) patients is poor due to the high metastatic rate of the disease. Understanding the molecular mechanisms underlying HCC metastasis is extremely urgent. The role of CD24 and NDRG2 (N-myc downstream-regulated gene 2), a candidate tumor suppressor gene, has not yet been explored in HCC. The mRNA and protein expression of CD24 and NDRG2 was analyzed in MHCC97H, Huh7 and L-02 cells. Changes in cell adhesion, migration and invasion were detected by up- or down-regulating NDRG2 by adenovirus or siRNA. The expression pattern of NDRG2 and CD24 in HCC tissues and the relationship between NDRG2 and HCC clinical features was analyzed by immunohistochemical and western blotting analysis. NDRG2 expression was negatively correlated with malignancy in HCC. NDRG2 exerted anti-tumor activity by regulating CD24, a molecule that mediates cell-cell interaction, tumor proliferation and adhesion. NDRG2 up-regulation decreased CD24 expression and cell adhesion, migration and invasion. By contrast, NDRG2 down-regulation enhanced CD24 expression and cell adhesion, migration and invasion. Immunohistochemical analysis of 50 human HCC clinical specimens showed a strong correlation between NDRG2 down-regulation and CD24 overexpression (P = 0.04). In addition, increased frequency of NDRG2 down-regulation was observed in patients with elevated AFP serum level (P = 0.006), late TNM stage (P = 0.009), poor differentiation grade (P = 0.002), tumor invasion (P = 0.004) and recurrence (P = 0.024). Our findings indicate that NDRG2 and CD24 regulate HCC adhesion, migration and invasion. The expression level of NDRG2 is closely related to the clinical features of HCC. Thus, NDRG2 plays an important physiological role in HCC metastasis

  20. NDRG2 inhibits hepatocellular carcinoma adhesion, migration and invasion by regulating CD24 expression

    Directory of Open Access Journals (Sweden)

    Tao Yurong

    2011-06-01

    Full Text Available Abstract Background The prognosis of most hepatocellular carcinoma (HCC patients is poor due to the high metastatic rate of the disease. Understanding the molecular mechanisms underlying HCC metastasis is extremely urgent. The role of CD24 and NDRG2 (N-myc downstream-regulated gene 2, a candidate tumor suppressor gene, has not yet been explored in HCC. Methods The mRNA and protein expression of CD24 and NDRG2 was analyzed in MHCC97H, Huh7 and L-02 cells. Changes in cell adhesion, migration and invasion were detected by up- or down-regulating NDRG2 by adenovirus or siRNA. The expression pattern of NDRG2 and CD24 in HCC tissues and the relationship between NDRG2 and HCC clinical features was analyzed by immunohistochemical and western blotting analysis. Results NDRG2 expression was negatively correlated with malignancy in HCC. NDRG2 exerted anti-tumor activity by regulating CD24, a molecule that mediates cell-cell interaction, tumor proliferation and adhesion. NDRG2 up-regulation decreased CD24 expression and cell adhesion, migration and invasion. By contrast, NDRG2 down-regulation enhanced CD24 expression and cell adhesion, migration and invasion. Immunohistochemical analysis of 50 human HCC clinical specimens showed a strong correlation between NDRG2 down-regulation and CD24 overexpression (P = 0.04. In addition, increased frequency of NDRG2 down-regulation was observed in patients with elevated AFP serum level (P = 0.006, late TNM stage (P = 0.009, poor differentiation grade (P = 0.002, tumor invasion (P = 0.004 and recurrence (P = 0.024. Conclusions Our findings indicate that NDRG2 and CD24 regulate HCC adhesion, migration and invasion. The expression level of NDRG2 is closely related to the clinical features of HCC. Thus, NDRG2 plays an important physiological role in HCC metastasis.

  1. Transarterial Chemoembolization for Hepatocellular Carcinomas with Central Bile Duct Invasion: Safety, Prognosis, and Predictive Factors

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jin Woo; Chung, Jin Wook, E-mail: chungjw@snu.ac.kr [Seoul National University Hospital, Department of Radiology (Korea, Republic of); Cho, Yun Ku [VHS Medical Center, Department of Radiology (Korea, Republic of); Kim, Yoon Jun; Yoon, Jung-Hwan [Seoul National University Hospital, Department of Internal Medicine (Korea, Republic of); Kim, Hyo-Cheol; Jae, Hwan Jun [Seoul National University Hospital, Department of Radiology (Korea, Republic of)

    2015-08-15

    PurposeTo assess the safety and effectiveness of transarterial chemoembolization (TACE) of patients who have hepatocellular carcinomas (HCCs) with central bile duct invasion.Materials and MethodsThe institutional review board approved this retrospective study and waived informed consent. Fifty-three patients, initially treated with TACE for HCCs with central bile duct invasion from January 1999 to September 2012, were included. Clinical, laboratory, and survival data were reviewed. Complications and hospitalization length were evaluated using the χ{sup 2} test, Fisher’s exact test, and logistic regression analysis. Survival was analyzed using the Kaplan–Meier method with log-rank test and Cox proportional hazard model.ResultsSeven patients experienced TACE-related major complications (severe post-embolization syndrome in 3, non-fatal sepsis in 3, and secondary bacterial peritonitis in 1). The overall major complication rate was 13.2 %, but there were no permanent adverse sequelae or deaths within 30 days. Serum total bilirubin ≥3.0 mg/dL was the only significant risk factor for long hospitalization [hazard ratio (HR) = 4.341, p = .022]. The median survival was 12.2 months. Extrahepatic metastasis (HR = 6.145, p < .001), international normalized ratio (PT-INR) ≥1.20 (HR = 4.564, p < .001), vascular invasion (HR = 3.484, p = .001), and intermediate tumor enhancement (HR = 2.417, p = .019) were significantly associated with shorter survival.ConclusionTACE can be a safe and effective treatment for patients who have HCCs with central bile duct invasion. In particular, long-term survival can be expected if patients have strongly enhancing tumors without poor prognostic factors such as extrahepatic metastasis, PT-INR prolongation, and vascular invasion.

  2. Transarterial Chemoembolization for Hepatocellular Carcinomas with Central Bile Duct Invasion: Safety, Prognosis, and Predictive Factors

    International Nuclear Information System (INIS)

    PurposeTo assess the safety and effectiveness of transarterial chemoembolization (TACE) of patients who have hepatocellular carcinomas (HCCs) with central bile duct invasion.Materials and MethodsThe institutional review board approved this retrospective study and waived informed consent. Fifty-three patients, initially treated with TACE for HCCs with central bile duct invasion from January 1999 to September 2012, were included. Clinical, laboratory, and survival data were reviewed. Complications and hospitalization length were evaluated using the χ2 test, Fisher’s exact test, and logistic regression analysis. Survival was analyzed using the Kaplan–Meier method with log-rank test and Cox proportional hazard model.ResultsSeven patients experienced TACE-related major complications (severe post-embolization syndrome in 3, non-fatal sepsis in 3, and secondary bacterial peritonitis in 1). The overall major complication rate was 13.2 %, but there were no permanent adverse sequelae or deaths within 30 days. Serum total bilirubin ≥3.0 mg/dL was the only significant risk factor for long hospitalization [hazard ratio (HR) = 4.341, p = .022]. The median survival was 12.2 months. Extrahepatic metastasis (HR = 6.145, p < .001), international normalized ratio (PT-INR) ≥1.20 (HR = 4.564, p < .001), vascular invasion (HR = 3.484, p = .001), and intermediate tumor enhancement (HR = 2.417, p = .019) were significantly associated with shorter survival.ConclusionTACE can be a safe and effective treatment for patients who have HCCs with central bile duct invasion. In particular, long-term survival can be expected if patients have strongly enhancing tumors without poor prognostic factors such as extrahepatic metastasis, PT-INR prolongation, and vascular invasion

  3. Stat3 promotes invasion of esophageal squamous cell carcinoma through up-regulation of MMP2.

    Science.gov (United States)

    Xuan, Xaioyan; Li, Shanshan; Lou, Xi; Zheng, Xianzhao; Li, Yunyun; Wang, Feng; Gao, Yuan; Zhang, Hongyan; He, Hongliu; Zeng, Qingru

    2015-05-01

    Stat3 alters the expression of its downstream genes and is associated with tumor invasion and metastasis in several human cancers. Its role in esophageal squamous cell carcinoma (ESCC) has not been well characterized. We examined the tumor sections of 100 cases of ESCC by immunohistochemistry and observed significant overexpression of Stat3 in the cytoplasm of 89% of ESCC cells and of phosphorylated Stat3 (p-Stat3) in the nuclei of 71% of ESCC when compare with normal esophageal mucosa (72%, p = 0.02; and 31%, p = 0.001). Overexpression of Stat3 and p-Stat3 positively correlated with that of matrix metalloproteinase-2 (MMP2), a known regulator for cell migration, in 65% of ESCC while only 26% shown in benign esophageal mucosa. To further investigate the association of Stat3 with tumor metastasis in vitro, invasion of EC-1 cells (a human ESCC cell line) were investigated with Boyden chambers. The results showed that transfection of Stat3 not only promoted invasion of EC-1 cells but also significantly induced MMP2 expression in a dose-dependent manner. In contrast, suppressing expression of endogenous Stat3 mRNA and protein by Stat3 siRNA significantly reduced EC-1 cell invasion and MMP2 expression. A high-affinity Stat3-binding element was localized to the positions of 648-641 bp (TTCTCGAA) in the MMP2 promoter with electrophoretic mobility shift assay. Our results suggest that Stat3, p-Stat3, and MMP2 were overexpressed in ESCC and associated with invasion of ESCC; and Stat3 up-regulated expression of MMP2 in ESCC through directly binding to the MMP2 promoter.

  4. Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma

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    Dai W

    2016-04-01

    Full Text Available Wei Dai,1,2 Changfu Sun,1,2 Shaohui Huang,1,2 Qing Zhou1,21Department of Oromaxillofacial-Head and Neck Surgery, 2Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaAbstract: Carvacrol, a component of thyme oil, as a novel antitumor agent, has been implicated in several types of cancer cells. However, the mechanisms underlying the effect of carvacrol in human oral squamous cell carcinoma (OSCC remain unclear. Here, we report that carvacrol significantly inhibits tumor cell proliferation, metastasis and invasion, and induces apoptosis in OSCC. Our results demonstrated that the molecular mechanisms of the effect of carvacrol in Tca-8113 induces G1/S cell cycle arrest through downregulation of CDK regulator CCND1 and CDK4, and upregulation of CDK inhibitor P21. Further analysis demonstrated that carvacrol also inhibited Tca-8113 cells’ clone formation in clonogenic cell survival assay. Student’s t-test (two-tailed was used to compare differences between groups, and the significance level was P<0.01. Then, treatment of Tca-8113 cells with carvacrol resulted in downregulation of Bcl-2, Cox2, and upregulation of Bax. Carvacrol significantly inhibited the migration and invasion of human OSCC cells by blocking the phosphorylation of FAK and MMP-9 and MMP-2, transcription factor ZEB1, and β-catenin proteins’ expression. Taken together, these results provide novel insights into the mechanism of carvacrol and suggest potential therapeutic strategies for human OSCC.Keywords: carvacrol, proliferation, metastasis and invasion, oral squamous cell carcinoma

  5. A Case Report: Lobular Carcinoma In Situ in a Male Patient with Subsequent Invasive Ductal Carcinoma Identified on Screening Breast MRI

    Directory of Open Access Journals (Sweden)

    Linda Kao, Yekaterina Bulkin, Susan Fineberg, Leslie Montgomery, Tova Koenigsberg

    2012-01-01

    Full Text Available Lobular carcinoma in situ is a form of in situ neoplasia that develops within the terminal lobules of the breast. It is an extremely rare finding in males due to the lack of lobular development in the male breast. The authors herein report an unusual case of incidentally discovered lobular carcinoma in situ in a male patient with recurrent bilateral gynecomastia who was subsequently diagnosed with invasive ductal carcinoma of the left breast. The pathology of lobular carcinoma in situ in a male as well as screening MRI surveillance of male patients at high risk for breast cancer are discussed, emphasizing the importance of screening and imaging follow up in men who are at high risk for breast cancer.

  6. Matrine inhibits the migratory and invasive properties of nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Sun, Bin; Xu, Min

    2015-06-01

    Matrine is a widely used Chinese herbal medicine that has historically been used in the treatment of inflammation and cancer. However, the antimetastatic effects and associated molecular mechanisms of matrine on nasopharyngeal carcinoma (NPC) remain to be elucidated. Therefore, the aims of the present study were to assess the antimetastatic effects of matrine on NPC, and identify the underlying mechanisms. Matrine inhibited the proliferation of NPC cells in vitro and in vivo. Furthermore, matrine inhibited the migration and invasion of NPC tumor cells at doses below the toxic range. Following treatment with matrine for 24 h, there was a decrease in the protein expression levels and activities of matrix metalloproteinase (MMP)‑2 and MMP‑9 in NPC‑039 cells. In addition, matrine markedly reduced the expression levels of p65 and p50 in the nuclei. Combined treatment of matrine with helenalin, a nuclear factor‑κB (NF‑κB) inhibitor resulted in a synergistic reduction in MMP‑2 and MMP‑9 expression levels, and the invasive capabilities of the NPC‑039 cells were also reduced. In conclusion, matrine inhibits NPC cell migration and invasion by suppressing the NF‑κB pathway. These results suggest that matrine may be a potential therapeutic agent for NPC.

  7. Direct invasion to the colon by hepatocellular carcinoma: Report of two cases

    Institute of Scientific and Technical Information of China (English)

    Teijiro Hirashita; Masayuki Ohta; Kentaro Iwaki; Seiichiro Kai; Kohei Shibata; Atsushi Sasaki; Kimihiro Nakashima; Seigo Kitano

    2008-01-01

    Although hepatocellular carcinoma (HCC) is a common tumor, direct invasion of the gastrointestinal tract by HCC is uncommon. Recently, we encountered two cases of HCC with direct invasion to the colon. The first patient was a 79-year-old man who underwent transarterial chemo-embolization (TACE) for HCC 1.5 years prior to admission to our hospital. Computed tornography (CT) showed a 7.5-cm liver tumor directly invading the transverse colon. Partial resection of the liver and transverse colon was performed. The patient survived 6 mo after surgery, but died of recurrent HCC. The second patient was a 69-year-old man who underwent TACE and ablation for HCC 2 years and 7 months prior to being admitted to our hospital for melena and abdominal distension. CT revealed a 6-cm liver tumor with direct invasion to the colon. The patient underwent partial resection of the liver and right hemicolectomy. The patient recovered from the surgery. But, unfortunately, he died of liver failure due to liver cirrhosis one month later. Although the prognosis of HCC that has invaded the colon is generally poor due to the advanced stage of the disease, surgical resection may be a favorable treatment option in patients with a good general condition.

  8. Progression of Intravesical Condyloma Acuminata to Locally Advanced Poorly Differentiated Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    A. Khambati

    2016-07-01

    Full Text Available Condyloma acuminata (CA is a common sexually transmitted disease caused by Human Papilloma Virus (HPV infection. CA of the bladder, however, is an exceedingly rare lesion. We present a rare case of poorly differentiated locally invasive squamous cell carcinoma (SCC arising from recurrent CA of the bladder in an immunocompetent patient and discuss pathophysiology and management of this unusual condition.

  9. Progress in surgical and nonsurgical approaches for hepatocellular carcinoma treatment

    Institute of Scientific and Technical Information of China (English)

    Ender Gunes Yegin; Erkan Oymaci; Emrah Karatay; Ahmet Coker

    2016-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a com-plex and heterogeneous malignancy, frequently occurs in the setting of a chronically diseased organ, with multiple con-founding factors making its management challenging. HCC represents one of the leading causes of cancer-related mortal-ity globally with a rising trend of incidence in some of the de-veloped countries, which indicates the need for better surgical and nonsurgical management strategies. DATA SOURCES: PubMed database was searched for relevant articles in English on the issue of HCC management. RESULTS: Surgical resection represents a potentially cura-tive option for appropriate candidates with tumors detected at earlier stages and with well-preserved liver function. The long-term outcome of surgery is impaired by a high rate of recurrence. Surgical approaches are being challenged by local ablative therapies such as radiofrequency ablation and micro-wave ablation in selected patients. Liver transplantation offers potential cure for HCC and also correction of underlying liver disease, and minimizes the risk of recurrence, but is reserved for patients within a set of criteria proposed for a prudent allocation in the shortage of donor organs. Transcatheter locoregional therapies have become the palliative standard allowing local control for intermediate stage patients with noninvasive multinodular or large HCC who are beyond the potentially curative options. The signiifcant survival beneift with the multikinase inhibitor sorafenib for advanced HCC has shifted the direction of research regarding systemic treat-ment toward molecular therapies targeting the disregulated pathways of hepatocarcinogenesis. Potential beneift is sug-gested from simultaneous or sequential multimodal therapies, and optimal combinations are being investigated. Despite the striking progress in preclinical studies of HCC immuno-therapy and gene therapy, extensive clinical trials are required to achieve successful clinical applications

  10. Progress in surgical and nonsurgical approaches for hepatocellular carcinoma treatment

    Institute of Scientific and Technical Information of China (English)

    Ender Gunes Yegin; Erkan Oymaci; Emrah Karatay; Ahmet Coker

    2015-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a com-plex and heterogeneous malignancy, frequently occurs in the setting of a chronically diseased organ, with multiple con-founding factors making its management challenging. HCC represents one of the leading causes of cancer-related mortal-ity globally with a rising trend of incidence in some of the de-veloped countries, which indicates the need for better surgical and nonsurgical management strategies. DATA SOURCES: PubMed database was searched for relevant articles in English on the issue of HCC management. RESULTS: Surgical resection represents a potentially cura-tive option for appropriate candidates with tumors detected at earlier stages and with well-preserved liver function. The long-term outcome of surgery is impaired by a high rate of recurrence. Surgical approaches are being challenged by local ablative therapies such as radiofrequency ablation and micro-wave ablation in selected patients. Liver transplantation offers potential cure for HCC and also correction of underlying liver disease, and minimizes the risk of recurrence, but is reserved for patients within a set of criteria proposed for a prudent allocation in the shortage of donor organs. Transcatheter locoregional therapies have become the palliative standard allowing local control for intermediate stage patients with noninvasive multinodular or large HCC who are beyond the potentially curative options. The signiifcant survival beneift with the multikinase inhibitor sorafenib for advanced HCC has shifted the direction of research regarding systemic treat-ment toward molecular therapies targeting the disregulated pathways of hepatocarcinogenesis. Potential beneift is sug-gested from simultaneous or sequential multimodal therapies, and optimal combinations are being investigated. Despite the striking progress in preclinical studies of HCC immuno-therapy and gene therapy, extensive clinical trials are required to achieve successful clinical applications

  11. Expression of YY1 correlates with progression and metastasis in esophageal squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Luo J

    2014-09-01

    Full Text Available Judong Luo,1,* Xin Jiang,1,* LiLi Cao,2,* Kejun Dai,1 Shuyu Zhang,3,4 Xin Ge,3,4 Xifa Zhou,1 Xujing Lu1 1Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou, People's Republic of China; 2Department of Molecular Radiobiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan; 3School of Radiation Medicine and Protection and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, 4Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X, Soochow University, Suzhou, People's Republic of China  *These authors contributed equally to this work Objective: Esophageal squamous cell carcinoma (ESCC is one of the deadliest cancers worldwide. Yin Yang 1 (YY1 is a ubiquitous and multifunctional zinc-finger transcription factor that plays important biological functions in cell homeostasis and tumorigenesis. The purpose of this study was to investigate the expression of YY1 in different ESCC tissues and the potential relationship with clinicopathological features. Methods: One hundred and four ESCC tissues were collected in this study. The protein levels of YY1 were measured by immunohistochemistry. TE-1 cell invasion in vitro was assessed using the Transwell assay. Results: There were no obvious differences between expression levels in patients over age 64 and those younger than 64, and no noticeable distinction was observed between males and females. However, the YY1 protein level was significantly higher in ESCC tissues with lymph node metastasis than those without lymph node metastasis (P=0.042. Furthermore, the expression of the YY1 protein was stronger in stage III–IV patients than in stage I–II patients (P=0.002, but the protein levels between different histological grades (well, moderate, or poor showed no statistical significance. Similarly, there was no

  12. 胃癌局部神经侵犯的临床研究%Clinical Study of Perineural Invasion of Gastric Carcinoma

    Institute of Scientific and Technical Information of China (English)

    高杰; 邓为民

    2014-01-01

    目的:探讨胃癌局部神经侵犯(PNI)的临床意义。方法:对110例胃癌根治手术的病理组织行苏木素-伊红染色,肿瘤细胞侵犯神经束或神经束膜为PNI阳性。结果:110例中PNI阳性49例,PNI与肿瘤大小、浸润深度、区域淋巴结转移、TNM分期、脉管癌栓、断端阳性有显著相关性,与性别、年龄、肿瘤部位及远处转移无相关性。结论:胃癌周围神经侵犯与肿瘤的进展密切相关,但不是影响预后的独立因素。%Objective To determine the clinical significance of perineural invasion (PNI) in patients with gastric carcinoma who underwent curative resection. Methods One hundred and ten patients with gastric car-cinoma who had undergone curative gastrectomy were retrospectively analyzed. Paraffin sections of gastric carci-noma tissues from all patients were stained with hematoxylin and eosin. PNI was assessed as positive when can-cer cells were seen in the perineurium or neural fascicles. The relationship between PNI and the other clinico-pathologic features of gastric carcinoma was studied. Results PNI was detected as positive in 49 of the 110 patients. PNI was closely related to tumor size, depth of invasion, lymph node metastasis, TNM stage, lymphatic vessel and blood vessel invasion, positive surgical margins; However, PNI showed no correlation to age, gender, tumor location, and distant metastasis. Conclusion PNI was closely related to the progression of gastric carci-noma, and it may improve accuracy of the staging of gastric carcinoma. However, PNI is not an independent prognostic factor.

  13. The prediction of mandibular invasion by squamous cell carcinomas with the expression of osteoclast-related cytokines in biopsy specimens.

    NARCIS (Netherlands)

    Cann, E.M. van; Slootweg, P.J.; Wilde, P.C.M. de; Otte-Holler, I.; Koole, R.; Stoelinga, P.J.W.; Merkx, M.A.W.

    2009-01-01

    Destruction of bone by tumour is caused by osteoclasts rather than by tumour cells directly. Tumour cells of invasive oral squamous cell carcinomas (SCC) release osteoclast-related cytokines and cytokines activate osteoclasts. The purpose of this study was to investigate the possibility of predictin

  14. Reproducibility and prognostic value of pattern of invasion scoring in low-stage oral squamous cell carcinoma

    NARCIS (Netherlands)

    Heerema, Marjolein G. J.; Melchers, Lieuwe J.; Roodenburg, Jan L. N.; Schuuring, Ed; de Bock, Geertruida H.; van der Vegt, Bert

    2016-01-01

    AimsTo evaluate and compare the prognostic value and reproducibility of different methods of pattern of invasion scoring in oral squamous cell carcinomas. The additional prognostic value to established histopathological prognostic factors was also analysed. Methods and resultsThe study group was con

  15. An novel role of sphingosine kinase-1 (SPHK1 in the invasion and metastasis of esophageal carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang Yan-Lan

    2011-09-01

    Full Text Available Abstract Background Treatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells in vitro and in vivo. Methods A metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting. Results We identified sphingosine kinase 1 (SPHK1 as an invasion and metastasis-related gene of esophageal cancer. SPHK1 was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest SPHK1 mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%, SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%, SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC. Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (P P = 0.016. By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (P SPHK1 overexpression significantly increased the invasiveness of EC9706 cells in vitro and also increased EC9706 cell growth and spontaneous metastasis in vivo, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. SPHK1 expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR

  16. Glucocorticoids Suppress Renal Cell Carcinoma Progression by Enhancing Na,K-ATPase Beta-1 Subunit Expression

    Science.gov (United States)

    Huynh, Thu P.; Barwe, Sonali P.; Lee, Seung J.; McSpadden, Ryan; Franco, Omar E.; Hayward, Simon W.; Damoiseaux, Robert; Grubbs, Stephen S.; Petrelli, Nicholas J.; Rajasekaran, Ayyappan K.

    2015-01-01

    Glucocorticoids are commonly used as palliative or chemotherapeutic clinical agents for treatment of a variety of cancers. Although steroid treatment is beneficial, the mechanisms by which steroids improve outcome in cancer patients are not well understood. Na,K-ATPase beta-subunit isoform 1 (NaK-β1) is a cell-cell adhesion molecule, and its expression is down-regulated in cancer cells undergoing epithelial-to mesenchymal-transition (EMT), a key event associated with cancer progression to metastatic disease. In this study, we performed high-throughput screening to identify small molecules that could up-regulate NaK-β1 expression in cancer cells. Compounds related to the glucocorticoids were identified as drug candidates enhancing NaK-β1 expression. Of these compounds, triamcinolone, dexamethasone, and fluorometholone were validated to increase NaK-β1 expression at the cell surface, enhance cell-cell adhesion, attenuate motility and invasiveness and induce mesenchymal to epithelial like transition of renal cell carcinoma (RCC) cells in vitro. Treatment of NaK-β1 knockdown cells with these drug candidates confirmed that these compounds mediate their effects through up-regulating NaK-β1. Furthermore, we demonstrated that these compounds attenuate tumor growth in subcutaneous RCC xenografts and reduce local invasiveness in orthotopically-implanted tumors. Our results strongly indicate that the addition of glucocorticoids in the treatment of RCC may improve outcome for RCC patients by augmenting NaK-β1 cell-cell adhesion function. PMID:25836370

  17. Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: an intricate pathway.

    Science.gov (United States)

    Cardin, Romilda; Piciocchi, Marika; Bortolami, Marina; Kotsafti, Andromachi; Barzon, Luisa; Lavezzo, Enrico; Sinigaglia, Alessandro; Rodriguez-Castro, Kryssia Isabel; Rugge, Massimo; Farinati, Fabio

    2014-03-28

    The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma (HCC) are still ill-defined; however, there is increasing evidence that the gradual accumulation of mutations, genetic and epigenetic changes which occur in preneoplastic hepatocytes results in the development of dysplastic foci, nodules, and finally, overt HCC. As well as many other neoplasias, liver cancer is considered an "inflammatory cancer", arising from a context of inflammation, and characterized by inflammation-related mechanisms that favor tumor cell survival, proliferation, and invasion. Molecular mechanisms that link inflammation and neoplasia have been widely investigated, and it has been well established that inflammatory cells recruited at these sites with ongoing inflammatory activity release chemokines that enhance the production of reactive oxygen species. The latter, in turn, probably have a major pathogenic role in the continuum starting from hepatitis followed by chronic inflammation, and ultimately leading to cancer. The relationship amongst chronic liver injury, free radical production, and development of HCC is explored in the present review, particularly in the light of the complex network that involves oxidative DNA damage, cytokine synthesis, telomere dysfunction, and microRNA regulation. PMID:24696595

  18. Effects of Hydroxyapatite Nanoparticles on Apoptosis and Invasion of Human Renal Cell Carcinoma 786-0 Cells

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-xin; KONG Xiang-bo; ZHAO Xu; ZHANG Ling; HOU Yi; HAN Wei; WANG Kai-chen; GUO Bao-feng; LIU Ying; CHANG Xi-hua; WANG Wei-hua; NA Wan-li

    2011-01-01

    Renal cell carcinoma is the most common cancer of the kidney, and resistant to traditional therapies. The aim of this study is to investigate the effects of hydroxyapatite nanoparticles on human renal cell carcinoma 786-0 cells. Cell proliferation was assessed with an 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide(MTT)staining kit. The apoptosis assay was assessed with an FITC Annexin V Apoptosis Detection Kit. Caspase-3 and caspase-12 were detected by immunocytochemical staining and semi-quantitative RT-PCR. Cell wound healing assay was used to ensure cell motility. Matrigel invasion assay was analysed via transwell chambers. Our results showed that hydroxyapatite nanoparticles significantly reduced cell proliferation, invasion and induced apoptosis of 786-0 cells. The inhibiting action may have relation with up-regulated caspase-12, leading the cells to apoptosis. This study suggests that hydroxyapatite nanoparticles may be an effective and delivery system for renal cell carcinoma therapy.

  19. Targeting EMP3 suppresses proliferation and invasion of hepatocellular carcinoma cells through inactivation of PI3K/Akt pathway.

    Science.gov (United States)

    Hsieh, Yi-Hsien; Hsieh, Shu-Ching; Lee, Chien-Hsing; Yang, Shun-Fa; Cheng, Chun-Wen; Tang, Meng-Ju; Lin, Chia-Liang; Lin, Chu-Liang; Chou, Ruey-Hwang

    2015-10-27

    Epithelial membrane protein-3 (EMP3), a typical member of the epithelial membrane protein (EMP) family, is epigenetically silenced in some cancer types, and has been proposed to be a tumor suppressor gene. However, its effects on tumor suppression are controversial and its roles in development and malignancy of hepatocellular carcinoma (HCC) remain unclear. In the present study, we found that EMP3 was highly expressed in the tumorous tissues comparing to the matched normal tissues, and negatively correlated with differentiated degree of HCC patients. Knockdown of EMP3 significantly reduced cell proliferation, arrested cell cycle at G1 phase, and inhibited the motility and invasiveness in accordance with the decreased expression and activity of urokinase plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9) in HCC cells. The in vivo tumor growth of HCC was effectively suppressed by knockdown of EMP3 in a xenograft mouse model. The EMP3 knockdown-reduced cell proliferation and invasion were attenuated by inhibition of phosphatidylinositol 3-kinase (PI3K) or knockdown of Akt, and rescued by overexpression of Akt in HCC cells. Clinical positive correlations of EMP3 with p85 regulatory subunit of PI3K, p-Akt, uPA, as well as MMP-9 were observed in the tissue sections from HCC patients. Here, we elucidated the tumor progressive effects of EMP3 through PI3K/Akt pathway and uPA/MMP-9 cascade in HCC cells. The findings provided a new insight into EMP3, which might be a potential molecular target for diagnosis and treatment of HCC. PMID:26472188

  20. Inherent phenotypic plasticity facilitates progression of head and neck cancer: Endotheliod characteristics enable angiogenesis and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Meng, E-mail: tong.59@osu.edu [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States); Han, Byungdo B.; Holpuch, Andrew S.; Pei, Ping; He, Lingli; Mallery, Susan R. [Division of Oral Pathology and Radiology, The Ohio State University College of Dentistry, Columbus, OH 43210 (United States)

    2013-04-15

    The presence of the EMT (epithelial-mesenchymal transition), EndMT (endothelial-mesenchymal transition) and VM (vasculogenic mimicry) demonstrates the multidirectional extent of phenotypic plasticity in cancers. Previous findings demonstrating the crosstalk between head and neck squamous cell carcinoma (HNSCC) and vascular endothelial growth factor (VEGF) imply that HNSCC cells share some functional commonalities with endothelial cells. Our current results reveal that cultured HNSCC cells not only possess endothelial-specific markers, but also display endotheliod functional features including low density lipoprotein uptake, formation of tube-like structures on Matrigel and growth state responsiveness to VEGF and endostatin. HNSCC cell subpopulations are also highly responsive to transforming growth factor-β1 and express its auxiliary receptor, endoglin. Furthermore, the endotheliod characteristics observed in vitro recapitulate phenotypic features observed in human HNSCC tumors. Conversely, cultured normal human oral keratinocytes and intact or ulcerated human oral epithelia do not express comparable endotheliod characteristics, which imply that assumption of endotheliod features is restricted to transformed keratinocytes. In addition, this phenotypic state reciprocity facilitates HNSCC progression by increasing production of factors that are concurrently pro-proliferative and pro-angiogenic, conserving cell energy stores by LDL internalization and enhancing cell mobility. Finally, recognition of this endotheliod phenotypic transition provides a solid rationale to evaluate the antitumorigenic potential of therapeutic agents formerly regarded as exclusively angiostatic in scope. - Highlights: ► HNSCC tumor cells express endothelial specific markers VE-cadherin, CD31 and vimentin. ► Similarly, cultured HNSCC cells retain expression of these markers. ► HNSCC cells demonstrate functional endotheliod characteristics i.e. AcLDL uptake. ► HNSCC cell

  1. Chromosomal aberrations detected by comparative genomic hybridization technique (CGH in invasive ductal carcinoma of breast

    Directory of Open Access Journals (Sweden)

    Nooshiravanpour P

    2007-10-01

    Full Text Available Background: Nonlethal genetic damage is the basis for carcinogenesis. As various gene aberrations accumulate, malignant tumors are formed, regardless of whether the genetic damage is subtle or large enough to be distinguished in a karyotype. The study of chromosomal changes in tumor cells is important in the identification of oncogenes and tumor suppressor genes by molecular cloning of genes in the vicinity of chromosomal aberrations. Furthermore, some specific aberrations can be of great diagnostic and prognostic value. Comparative genomic hybridization (CGH is used to screen the entire genome for the detection and/or location chromosomal copy number changes.Methods: In this study, frozen sections of 20 primary breast tumors diagnosed as invasive ductal carcinoma from the Cancer Institute of Imam Khomeini Hospital, Tehran, Iran, were studied by CGH to detect chromosomal aberrations. We compared histopathological and immunohistochemical findings.Results: Hybridization in four of the cases was not optimal for CGH analysis and they were excluded from the study. DNA copy number changes were detected in 12 (75% of the remaining 16 cases. Twenty-one instances of chromosomal aberrations were detected in total, including: +1q, +17q, +8q, +20q, -13q, -11q, -22q, -1p, -16q, -8p. The most frequent were +1q, +17q, +8q, -13q, similar to other studies. In three cases, we detected -13q, which is associated with axillary lymph node metastasis and was reported in one previous study. The mean numbers of chromosomal aberrations per tumor in metastatic and nonmetastatic tumors was 1.5 and 1, respectively. No other association between detected chromosomal aberrations and histopathological and immunohistochemical findings were seen.Conclusion: Since intermediately to widely invasive carcinomas are more likely to have chromosomal aberrations, CGH can be a valuable prognostic tool. Furthermore, CGH can be used to detect targeting molecules within novel amplifications

  2. Peritumoral lymphatic invasion in patients with node-negative mammary duct carcinoma.

    Science.gov (United States)

    Clemente, C G; Boracchi, P; Andreola, S; Del Vecchio, M; Veronesi, P; Rilke, F O

    1992-03-15

    Five hundred six consecutive cases of ductal infiltrating carcinoma of the breast (T1-T2,N0,M0) were evaluated to define the frequency of peritumoral lymphatic invasion (PLI) and verify its possible prognostic significance. Histologically, PLI was characterized by the presence of neoplastic emboli within vascular lumina lined by recognizable endothelial cells, adjacent to but outside the margins of the carcinoma. In routine histopathologic assessment the frequency of PLI was 68% whereas in a randomly selected group of 234 reviewed cases the frequency rose to 20%. Patients with routinely evaluated PLI had a worse prognosis than those without PLI with reference both to disease-free survival (P = 0.0001) and total survival rates (P = 0.0001). The difference for local recurrences was prognostically highly significant (P = 0.0001) and also significant for the development of metastases (P = 0.0576). In the reviewed material the difference in prognosis between PLI-positive and PLI-negative cases was not confirmed for total survival whereas the significance for the disease-free interval persisted. The assessment of PLI, carried out following strict histopathologic criteria, appears to select a group of node-negative breast cancer patients who have an increased risk of recurrences and might benefit from a treatment different from that reserved for node-negative and PLI-negative patients.

  3. Preliminary study for non – invasive optical detection of squamous and basal cell carcinomas

    Directory of Open Access Journals (Sweden)

    Ali Ahmed Mohammed

    2012-11-01

    Full Text Available Abstract Background The early detection of skin cancer may highly increase the chances of its healing. One of the non-invasive methods of such detection based on the Oblique- Incidence Diffuse Reflectance (OIDR measurements of the reflected diode laser light from the skin. In this research we designed and implemented the OIDR reflectometry measuring system with a 650 nm diode laser source to aid physicians in diagnosing both squamous cell carcinomas (SCC and basal cell carcinomas(BCC. Method The laser is delivered obliquely to the skin surface by an optical fiber fitted through a tube holder of CCD camera. The diffused reflected laser light from the skin is captured by the CCD camera and sent to a computer, which is supplied by a specially prepared Matlab program to analyze these images in order to decide in a time whether the lesion is malignant or benign. Fifty cases were diagnosed under supervision of the consultant section of The Governmental Specialized Marjan Teaching Hospital – MOH – Iraq. Result The fifty diagnosed cases by this technique, the results were 90% accurate. Conclusion The method of laser oblique-incidence diffuse reflectance (OIDR combined with using the developed algorithms that have high classification rates may prove useful in the clinic as the process is fast, noninvasive and accurate.

  4. Relationship between Lymphatic Vessel Density and Lymph Node Metastasis of Invasive Micropapillary Carcinoma of the Breast

    Institute of Scientific and Technical Information of China (English)

    Xiaojing Guo; Ling Chen; Ronggang Lang; Yu Fan; Li Fu

    2006-01-01

    OBJECTIVE To investigate the relationship between lymphatic vessel density and lymph node metastasis of invasive micropapillary carcinoma (IMPC) of the breast.METHODS The immunohistochemical study for vascular endothelial growth factor-c (VEGF-C), VEGF Receptor-3 (VEGFR-3) and lymphatic vessel density of 51 cases of IMPC were performed, and lymph node metastases were examined by microscopic analysis of these cases.RESULTS In IMPC, VEGF-C was expressed in the cytoplasm and/or on the membrane of the tumor cells, and the expression of VEGF-C showed a positive correlation with lymph node metastasis (P<0.01). Lymphatic vessel density was determined by the number of micro-lymphatic vessels with VEGFR-3 positive staining. Lymphatic vessel density was positively correlated with VEGF-C expression (P<0.01) and lymph node metastasis (P<0.01). The percentage of IMPC in the tumor was not associated with the incidence of lymph node metastasis. The metastatic foci in lymph nodes were either pure or predominant micropapillary carcinoma.CONCLUSION The results suggested that VEGF-C overexpression stimulated tumor lymphangiogenesis, and the increased lymphatic vessel density may be the key factor that influenced lymph node metastasis of IMPC.

  5. Correlation of Beta-2 Adrenergic Receptor Expression in Tumor-Free Surgical Margin and at the Invasive Front of Oral Squamous Cell Carcinoma

    Science.gov (United States)

    Bravo-Calderón, Diego Mauricio; Lauand, Gustavo Amaral; Assao, Agnes; Suárez-Peñaranda, José-Manuel; Pérez-Sayáns, Mario; García-García, Abel; Marana, Aparecido Nilceu; Nonogaki, Suely; Lauris, José Roberto Pereira; Kowalski, Luiz Paulo

    2016-01-01

    Background. The beta-2 adrenergic receptor is expressed by neoplastic cells and is correlated with a wide spectrum of tumor cell mechanisms including proliferation, apoptosis, angiogenesis, migration, and metastasis. Objectives. The present study aimed to analyze the expression of the beta-2 adrenergic receptor (β2-AR) in tumor-free surgical margins of oral squamous cell carcinomas (OSCC) and at the invasive front. Sixty-two patients diagnosed with OSCC, confirmed by biopsy, were selected for the study. The clinicopathological data and clinical follow-up were obtained from medical records and their association with β2-AR expression was verified by the chi-square test or Fischer's exact test. To verify the correlation of β2-AR expression in tumor-free surgical margins and at the invasive front of OSCCs, Pearson's correlation coefficient test was applied. Results. The expression of β2-AR presented a statistically significant correlation between the tumor-free surgical margins and the invasive front of OSCC (r = 0.383; p = 0.002). The immunohistochemical distribution of β2-AR at the invasive front of OSCC was also statistically significant associated with alcohol (p = 0.038), simultaneous alcohol and tobacco consumption (p = 0.010), and T stage (p = 0.014). Conclusions. The correlation of β2-AR expression in OSCC and tumor-free surgical margins suggests a role of this receptor in tumor progression and its expression in normal oral epithelium seems to be constitutive. PMID:27042179

  6. Correlation of Beta-2 Adrenergic Receptor Expression in Tumor-Free Surgical Margin and at the Invasive Front of Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Denise Tostes Oliveira

    2016-01-01

    Full Text Available Background. The beta-2 adrenergic receptor is expressed by neoplastic cells and is correlated with a wide spectrum of tumor cell mechanisms including proliferation, apoptosis, angiogenesis, migration, and metastasis. Objectives. The present study aimed to analyze the expression of the beta-2 adrenergic receptor (β2-AR in tumor-free surgical margins of oral squamous cell carcinomas (OSCC and at the invasive front. Sixty-two patients diagnosed with OSCC, confirmed by biopsy, were selected for the study. The clinicopathological data and clinical follow-up were obtained from medical records and their association with β2-AR expression was verified by the chi-square test or Fischer’s exact test. To verify the correlation of β2-AR expression in tumor-free surgical margins and at the invasive front of OSCCs, Pearson’s correlation coefficient test was applied. Results. The expression of β2-AR presented a statistically significant correlation between the tumor-free surgical margins and the invasive front of OSCC (r=0.383; p=0.002. The immunohistochemical distribution of β2-AR at the invasive front of OSCC was also statistically significant associated with alcohol (p=0.038, simultaneous alcohol and tobacco consumption (p=0.010, and T stage (p=0.014. Conclusions. The correlation of β2-AR expression in OSCC and tumor-free surgical margins suggests a role of this receptor in tumor progression and its expression in normal oral epithelium seems to be constitutive.

  7. Long Non-Coding RNA HOTAIR Promotes Cell Migration and Invasion via Down-Regulation of RNA Binding Motif Protein 38 in Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chaofeng Ding

    2014-03-01

    Full Text Available Long non-coding RNA HOTAIR exerts regulatory functions in various biological processes in cancer cells, such as proliferation, apoptosis, mobility, and invasion. We previously found that HOX transcript antisense RNA (HOTAIR is a negative prognostic factor and exhibits oncogenic activity in hepatocellular carcinoma (HCC. In this study, we aimed to investigate the role and molecular mechanism of HOTAIR in promoting HCC cell migration and invasion. Firstly, we profiled its gene expression pattern by microarray analysis of HOTAIR loss in Bel-7402 HCC cell line. The results showed that 129 genes were significantly down-regulated, while 167 genes were significantly up-regulated (fold change >2, p < 0.05. Bioinformatics analysis indicated that RNA binding proteins were involved in this biological process. HOTAIR suppression using RNAi strategy with HepG2 and Bel-7402 cells increased the mRNA and protein expression levels of RNA binding motif protein 38 (RBM38. Moreover, the expression levels of RBM38 in HCC specimens were significantly lower than paired adjacent noncancerous tissues. In addition, knockdown of HOTAIR resulted in a decrease of cell migration and invasion, which could be specifically rescued by down-regulation of RBM38. Taken together, HOTAIR could promote migration and invasion of HCC cells by inhibiting RBM38, which indicated critical roles of HOTAIR and RBM38 in HCC progression.

  8. Endostatin induces proliferation of oral carcinoma cells but its effect on invasion is modified by the tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Alahuhta, Ilkka [Research Group of Cancer and Translational Medicine, Faculty of Medicine, University of Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland); Aikio, Mari [Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu (Finland); Oulu Center for Cell-Matrix Research, University of Oulu (Finland); Väyrynen, Otto; Nurmenniemi, Sini [Research Group of Cancer and Translational Medicine, Faculty of Medicine, University of Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland); Suojanen, Juho [Department of Oral and Maxillo-facial Diseases, University of Helsinki, Helsinki University Central Hospital (Finland); Teppo, Susanna [Research Group of Cancer and Translational Medicine, Faculty of Medicine, University of Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland); Pihlajaniemi, Taina; Heljasvaara, Ritva [Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu (Finland); Oulu Center for Cell-Matrix Research, University of Oulu (Finland); Salo, Tuula [Research Group of Cancer and Translational Medicine, Faculty of Medicine, University of Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland); Department of Oral and Maxillo-facial Diseases, University of Helsinki, Helsinki University Central Hospital (Finland); Department of Oral Diagnosis, School of Dentistry, State University of Campinas, Piracicaba, Sao Paolo (Brazil); Nyberg, Pia, E-mail: pia.nyberg@oulu.fi [Research Group of Cancer and Translational Medicine, Faculty of Medicine, University of Oulu (Finland); Medical Research Center, Oulu University Hospital, Oulu (Finland)

    2015-08-01

    The turnover of extracellular matrix liberates various cryptic molecules with novel biological activities. Endostatin is an endogenous angiogenesis inhibitor that is derived from the non-collagenous domain of collagen XVIII. Although there are a large number of studies on its anti-tumor effects, the molecular mechanisms are not yet completely understood, and the reasons why endostatin has not been successful in clinical trials are unclear. Research has mostly focused on its anti-angiogenic effect in tumors. Here, we aimed to elucidate how endostatin affects the behavior of aggressive tongue HSC-3 carcinoma cells that were transfected to overproduce endostatin. Endostatin inhibited the invasion of HSC-3 cells in a 3D collagen–fibroblast model. However, it had no effect on invasion in a human myoma organotypic model, which lacks vital fibroblasts. Recombinant endostatin was able to reduce the Transwell migration of normal fibroblasts, but had no effect on carcinoma associated fibroblasts. Surprisingly, endostatin increased the proliferation and decreased the apoptosis of cancer cells in organotypic models. Also subcutaneous tumors overproducing endostatin grew bigger, but showed less local invasion in nude mice xenografts. We conclude that endostatin affects directly to HSC-3 cells increasing their proliferation, but its net effect on cancer invasion seem to depend on the cellular composition and interactions of tumor microenvironment. - Highlights: • Endostatin affects not only angiogenesis, but also carcinoma cells and fibroblasts. • Endostatin increased carcinoma cell proliferation, but decreased 3D invasion. • The invasion inhibitory effect was sensitive to the microenvironment composition. • Fibroblasts may be a factor regulating the fluctuating roles of endostatin.

  9. Progress of biological invasions research in China over the last decade

    Directory of Open Access Journals (Sweden)

    Chengjen Shih

    2012-09-01

    Full Text Available As one of the five major global environmental problems, invasive species have posed serious threats to native ecosystems, public health, and regional economies. Although much progress has been madein the field of biological invasions research in China over the last decade, there are still large knowledge gaps. This paper reviews progress in the field of biological invasions research since 2000 as it relates to China, covering the diversity, colonization and immigration patterns of invasive species, mechanisms and ecological effects of biological invasions, and management and control of invasive species. In China, 529 invasive alien species have been identified, which originated primarily from South and North America, and the major taxa included terrestrial plants, terrestrial invertebrates, and microorganisms. We found a higher prevalence of invasive species in the eastern and southern provinces, compared to the western and northern provinces in China. This pattern is likely due to the differences in the level of economic development and environmental suitability between the two regions. Moreover, with further economic development, China may face more serious biological invasions in the future. These invasions of alien species are largely the combined results of the interactions between the intrinsic traits of these species along with resource opportunities and disturbances by human beings. Many mechanisms are responsible for successful invasionsof alien species, but phenotypic plasticity, adaptive evolution, enemy release, interspecific mutualism or commensalism, and new allelochemicals may be primary causative factors. Biological invasions in China have caused serious impacts on native ecosystems, including biodiversity and ecosystem services, alteration of biogeochemical cycles, threats to agricultural and forestry production, traffic and shipping, environmental safety, and public facilities. China has also made progress in the detection and

  10. Expression of SRSF3 is Correlated with Carcinogenesis and Progression of Oral Squamous Cell Carcinoma

    OpenAIRE

    Peiqi, Liu; Zhaozhong, Guo; Yaotian, Yin; Jun, Jia; Jihua, Guo; Rong, Jia

    2016-01-01

    Objective: Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck with high mortality rates. The mechanisms of initiation and development of OSCC remain largely unknown. Dysregulated alternative splicing of pre-mRNA has been associated with OSCC. Splicing factor SRSF3 is a proto-oncogene and overexpressed in multiple cancers. The aim of this study was to uncover the relationship between SRSF3 and carcinogenesis and progression of oral squamous cell carcinoma. Desig...

  11. Prognostic factors in invasive squamous cell carcinoma of the vulva treated with surgery and irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Malmstroem, H.; Janson, H.; Simonsen, E.; Stenson, S.; Stendahl, U. (Linkoeping Univ. Hospital (Sweden). Dept. of Gynaecological Oncology Uppsala Univ. Hospital (Sweden). Dept. of Gynaecological Oncology Umeaa Univ. Hospital (Sweden). Dept. of Gynaecological Oncology Uppsala Univ. Hospital (Sweden). Dept. of Radiophysics)

    1990-01-01

    From 1958 through 1980, 113 women with invasive squamous cell carcinoma of the vulva were treated with vulvectomy. Postoperative irradiation was given with cobalt-60 beam or 10 MV photons from a linear accelerator from anterior fields including the vulva and groins, with the intention of delivering 40-52 Gy with 2-4 Gy/day at a depth of 0.5 cm or 2 cm. The overall corrected five-year survival rate was 68%. The prognosis was shown to worsen significantly with advancing stages (I/96%, II/75%, III/62% and IV/19%), increasing grades (G1/78%, G2/70% and G3/22%) and increasing size of the tumor (T1/90%, T2/71% and T3/37%), as it also did when there were signs of vascular invasion, multifocal tumors or positive nodes in the inguinal regions. Recurrences were diagnoses in 32% of the patients. With the less aggressive surgical approach used, combined with radiation therapy to eradicate subclinical disease, the morbidity rate was acceptable and the survival rate comparable to that reported after more aggressive surgery. (orig.).

  12. Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma.

    Science.gov (United States)

    Dai, Wei; Sun, Changfu; Huang, Shaohui; Zhou, Qing

    2016-01-01

    Carvacrol, a component of thyme oil, as a novel antitumor agent, has been implicated in several types of cancer cells. However, the mechanisms underlying the effect of carvacrol in human oral squamous cell carcinoma (OSCC) remain unclear. Here, we report that carvacrol significantly inhibits tumor cell proliferation, metastasis and invasion, and induces apoptosis in OSCC. Our results demonstrated that the molecular mechanisms of the effect of carvacrol in Tca-8113 induces G1/S cell cycle arrest through downregulation of CDK regulator CCND1 and CDK4, and upregulation of CDK inhibitor P21. Further analysis demonstrated that carvacrol also inhibited Tca-8113 cells' clone formation in clonogenic cell survival assay. Student's t-test (two-tailed) was used to compare differences between groups, and the significance level was P<0.01. Then, treatment of Tca-8113 cells with carvacrol resulted in downregulation of Bcl-2, Cox2, and upregulation of Bax. Carvacrol significantly inhibited the migration and invasion of human OSCC cells by blocking the phosphorylation of FAK and MMP-9 and MMP-2, transcription factor ZEB1, and β-catenin proteins' expression. Taken together, these results provide novel insights into the mechanism of carvacrol and suggest potential therapeutic strategies for human OSCC. PMID:27143925

  13. Prognostic factors in invasive squamous cell carcinoma of the vulva treated with surgery and irradiation

    International Nuclear Information System (INIS)

    From 1958 through 1980, 113 women with invasive squamous cell carcinoma of the vulva were treated with vulvectomy. Postoperative irradiation was given with cobalt-60 beam or 10 MV photons from a linear accelerator from anterior fields including the vulva and groins, with the intention of delivering 40-52 Gy with 2-4 Gy/day at a depth of 0.5 cm or 2 cm. The overall corrected five-year survival rate was 68%. The prognosis was shown to worsen significantly with advancing stages (I/96%, II/75%, III/62% and IV/19%), increasing grades (G1/78%, G2/70% and G3/22%) and increasing size of the tumor (T1/90%, T2/71% and T3/37%), as it also did when there were signs of vascular invasion, multifocal tumors or positive nodes in the inguinal regions. Recurrences were diagnoses in 32% of the patients. With the less aggressive surgical approach used, combined with radiation therapy to eradicate subclinical disease, the morbidity rate was acceptable and the survival rate comparable to that reported after more aggressive surgery. (orig.)

  14. Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

    Science.gov (United States)

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos; Brook, Mark N; Nowinski, Salpie; Papouli, Efterpi; Fletcher, Olivia; Pinder, Sarah; Hanby, Andrew; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Peto, Julian; Dos Santos Silva, Isabel; Johnson, Nichola; Swann, Ruth; Dwek, Miriam; Perkins, Katherine-Anne; Gillett, Cheryl; Houlston, Richard; Ross, Gillian; De Ieso, Paolo; Southey, Melissa C; Hopper, John L; Provenzano, Elena; Apicella, Carmel; Wesseling, Jelle; Cornelissen, Sten; Keeman, Renske; Fasching, Peter A; Jud, Sebastian M; Ekici, Arif B; Beckmann, Matthias W; Kerin, Michael J; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Benitez, Javier; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K; Lochmann, Magdalena; Brauch, Hiltrud; Fischer, Hans-Peter; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Chenevix-Trench, Georgia; Investigators, Kconfab; Lambrechts, Diether; Weltens, Caroline; Van Limbergen, Erik; Hatse, Sigrid; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Volorio, Sara; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; McLean, Catriona A; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Devillee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline M; Kriege, Mieke; Figueroa, Jonine; Chanock, Stephen J; Sherman, Mark E; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Li, Jingmei; Czene, Kamila; Humphreys, Keith; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Shah, Mitul; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Couch, Fergus J; Hallberg, Emily; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Dunning, Alison M; Hall, Per; Easton, Doug; Pharoah, Paul; Schmidt, Marjanka K; Tomlinson, Ian; Garcia-Closas, Montserrat

    2014-04-01

    Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity

  15. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    Science.gov (United States)

    Petridis, Christos; Brook, Mark N.; Nowinski, Salpie; Papouli, Efterpi; Fletcher, Olivia; Pinder, Sarah; Hanby, Andrew; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Swann, Ruth; Dwek, Miriam; Perkins, Katherine-Anne; Gillett, Cheryl; Houlston, Richard; Ross, Gillian; De Ieso, Paolo; Southey, Melissa C.; Hopper, John L.; Provenzano, Elena; Apicella, Carmel; Wesseling, Jelle; Cornelissen, Sten; Keeman, Renske; Fasching, Peter A.; Jud, Sebastian M.; Ekici, Arif B.; Beckmann, Matthias W.; Kerin, Michael J.; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Benitez, Javier; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Lochmann, Magdalena; Brauch, Hiltrud; Fischer, Hans-Peter; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Investigators, kConFab; Lambrechts, Diether; Weltens, Caroline; Van Limbergen, Erik; Hatse, Sigrid; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Volorio, Sara; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona A.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Devillee, Peter; Tollenaar, Rob A. E. M.; Seynaeve, Caroline M.; Kriege, Mieke; Figueroa, Jonine; Chanock, Stephen J.; Sherman, Mark E.; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; van Deurzen, Carolien H. M.; Li, Jingmei; Czene, Kamila; Humphreys, Keith; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Shah, Mitul; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Couch, Fergus J.; Hallberg, Emily; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Dunning, Alison M.; Hall, Per; Easton, Doug; Pharoah, Paul; Schmidt, Marjanka K.; Tomlinson, Ian; Garcia-Closas, Montserrat

    2014-01-01

    Invasive lobular breast cancer (ILC) accounts for 10–15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09–1.18), P = 6.0×10−10; P-het for ILC vs IDC ER+ tumors = 1.8×10−4). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there

  16. Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

    Directory of Open Access Journals (Sweden)

    Elinor Sawyer

    2014-04-01

    Full Text Available Invasive lobular breast cancer (ILC accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+ and often associated with lobular carcinoma in situ (LCIS. Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI for ILC = 1.13 (1.09-1.18, P = 6.0 × 10(-10; P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4. Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03; and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04. In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365 and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7. In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity

  17. Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway

    Institute of Scientific and Technical Information of China (English)

    Jing-tao LU; Wen-di ZHAO; Wei HE; Wei WEI

    2012-01-01

    To investigate the role of Hedgehog (Hh) signaling pathway in the invasion and metastasis of human hepatocellular carcinoma (HCC).Methods:Eighty six HCC tissues samples and HCC cell line Bel-7402 were examined.The protein expression of sonic hedgehog (Shh),nuclear glioma-associated oncogene-1 (Gli1),MMP-9 and p-ERK1/2 in HCC was analyzed using immunohistochemistry and Western blot analysis.Boyden chamber assay and wound-healing assay were used to quantify the invasion and metastasis of Bel-7402 cells.Results:In 86 HCC tissue samples,the positive ratio of Shh and nucleus Gli1 was 67.44% (58/86) and 60.47% (52/86),respectively;the expression of nucleus Gli1 was correlated with the tumor pathological grade (P=0.034),and with the ability of the tumor to invade and metastasize (P=0.001); the expression of nucleus Gli1 was also correlated with p-ERK1/2 (P=0.031) and with MMP-9 (P=0.034).Neither Shh,nor nucleus Gli1 was observed in normal liver tissue.KAAD-cyclopamine (KAAD-cyc),a specific inhibitor of the Hh pathway,at the concentrations of 1 and 4 μmol/L inhibited the invasion and migration of Bel-7402 cells and decreased the expression of Gli1 in nucleus and MMP-9,p-ERK1/2 proteins in Bel-7402 cells,On the other hand,Shh,a ligand of the Hh pathway,at the concentration of 0.5 μg/mL produced opposite effects.The MAPK pathway inhibitors U0126 and PD98059 at the concentrations of 5 and 10μmol/L inhibited invasion and metastasis of Bel-7402 cells induced by Shh,and decreased the expression of p-ERK1/2 and MMP-9.However,U0126 and PD98059 had no effect on the expression of Gii1.Conclusion:Hh signaling pathway mediates invasion and metastasis of human HCC by up-regulating the protein expression of MMP-9via ERK pathway.

  18. Expression analysis of E-cadherin, Slug and GSK3β in invasive ductal carcinoma of breast

    Directory of Open Access Journals (Sweden)

    Bhatnagar Dinesh

    2009-09-01

    Full Text Available Abstract Background Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-β and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT. Recent findings from our laboratory confirm that active Wnt/β-catenin signaling is critically involved in invasive ductal carcinomas (IDCs of breast. Methods In the current study, we analyzed the expression patterns and relationships between the key Wnt/β-catenin signaling components- E-cadherin, Slug and GSK3β in IDCs of breast. Results Of the 98 IDCs analyzed, 53 (54% showed loss/or reduced membranous staining of E-cadherin in tumor cells. Nuclear accumulation of Slug was observed in 33 (34% IDCs examined. Loss or reduced level of cytoplasmic GSK3β expression was observed in 52/98 (53% cases; while 34/98 (35% tumors showed nuclear accumulation of GSK3β. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001; nuclear β-catenin (p = 0.001, and cytoplasmic β-catenin (p = 0.005, suggesting Slug mediated E-cadherin suppression via the activation of Wnt/β-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3β nuclear localization and tumor grade (p = 0.02, suggesting its association with tumor progression. Conclusion The present study for the first time provided the clinical evidence in support of Wnt/β-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3β with β-catenin in implementing EMT in these cells.

  19. The Combination of Periostin Overexpression and Microvascular Invasion Is Related to a Poor Prognosis for Hepatocellular Carcinoma

    Science.gov (United States)

    Jang, Se Young; Park, Soo Young; Lee, Hye Won; Choi, Yeon-Kyung; Park, Keun-Gyu; Yoon, Ghil Suk; Tak, Won Young; Kweon, Young Oh; Hur, Keun; Lee, Won Kee

    2016-01-01

    Background/Aims Periostin is an extracellular matrix protein and is known to be related to the metastatic potential and prognosis of cancer. However, few studies have investigated the expression level of periostin and its association with prognoses in hepatocellular carcinoma. Therefore, we analyzed periostin overexpression in hepatocellular carcinoma and its implication for prognoses. Methods We evaluated 149 patients who underwent surgical resection between 2006 and 2010. Tissue microarrays were constructed from hepatocellular carcinoma tissue and adjacent nontumor tissue, and immunohistochemistry was performed. Results A high periostin level was observed more frequently in cases of multiple tumors (odds ratio [OR], 2.826; 95% confidence interval [CI], 1.224 to 6.527; p=0.013), positive microvascular invasion (OR, 2.974; 95% CI, 1.431 to 6.181; p=0.003), and advanced stage disease (OR, 3.032; 95% CI, 1.424 to 6.452; p=0.003). Patients with high periostin expression had significantly (p=0.002) lower overall survival rates than those with low periostin expression (90.3%, 66.1%, and 56.2% vs 97.7%, 85.1%, and 77.5% at 1, 3, and 5 years). Conclusions We found that a combination of periostin overexpression and microvascular invasion in hepatocellular carcinoma was correlated with a poor prognosis and can be a good prognostic marker for hepatocellular carcinoma. PMID:27458178

  20. Downregulation of LSD1 suppresses the proliferation, tumorigenicity and invasion of papillary thyroid carcinoma K1 cells

    OpenAIRE

    KONG, LING-LING; MAN, DONG-MEI; Wang, Tian; ZHANG, GUO-AN; Cui, Wen

    2016-01-01

    The present study aimed to evaluate the effects of lysine-specific demethylase 1 (LSD1) downregulation, induced by small interfering RNA (siRNA) transfection, on the proliferation, colony formation, migration and invasion of the papillary thyroid carcinoma K1 cell line. The siRNA targeting LSD1 and scrambled non-targeting siRNA were each transfected into papillary thyroid carcinoma K1 cells. Downregulation of LSD1 mRNA and protein level was evaluated by reverse transcription-quantitative poly...

  1. Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    He Zu-gen

    2006-12-01

    Full Text Available Abstract Background The development of esophageal squamous cell carcinoma (ESCC progresses a multistage process, collectively known as precursor lesions, also called dysplasia (DYS and carcinoma in situ (CIS, subsequent invasive lesions and final metastasis. In this study, we are interested in investigating the expression of a variety of functional classes of proteins in ESCC and its precursor lesions and characterizing the correlation of these proteins with ESCC malignant progression. Methods Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5γ2 and SPARC were analyzed using immunohistochemistry on tissue microarray containing 205 ESCC and 173 adjacent precursor lesions as well as corresponding normal mucosa. To confirm the immunohistochemical results, three proteins, fascin, CK14 and laminin-5γ2, which were overexpressed in ESCC on tissue microarray, were detected in 12 ESCC cell lines by Western blot assay. Results In ESCC and its precursor lesions, FADD, CDC25B, fascin, CK14, laminin-5γ2 and SPARC were overexpressed, while Fas, caspase 8, CK4 and annexin I were underexpressed. The abnormalities of these proteins could be classified into different groups in relation to the stages of ESCC development. They were "early" corresponding to mild and moderate DYS with overexpression of fascin, FADD and CDC25B and underexpression of Fas, caspase 8, CK4 and annexin I, "intermediate" to severe DYS and CIS with overexpression of FADD and CK14, and "late" to invasive lesions (ESCC and to advanced pTNM stage ESCC lesions with overexpression of CK14, laminin-5γ2 and SPARC. Conclusion Analyzing the protein expression patterns of Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4, annexin I, laminin-5γ2 and SPARC would be valuable to develop rational strategies for early detection of lesions at risk in advance as well as for prevention and treatment of ESCC.

  2. Clinical experience of MRI in two dogs with muscle-invasive transitional cell carcinoma of the urinary bladder.

    Science.gov (United States)

    Lee, Kija; Choi, Sooyoung; Choi, Hojung; Lee, Youngwon

    2016-09-01

    This study described high-field magnetic resonance imaging (MRI) and computed tomography (CT) characteristics of muscle-invasive bladder transitional cell carcinoma (TCC) in two dogs. Ultrasonography revealed a urinary bladder mass with ambiguous result about invasion to the muscular layer. Contrast-enhanced CT showed that the bladder wall in which the mass was attached was more intensely enhanced than the normal bladder walls, supporting invasion to the muscular layer. The mass revealed an intermediate signal intensity with interruption of the hypointense muscular layer on T2-weighted MRI and showed greater enhancement compared with the normal bladder wall on postcontrast T1-weighted images. T2-weighted MRI, postcontrast T1-weighted MRI and contrast-enhanced dual-phasic CT were useful for evaluating muscle-invasive bladder TCC in dogs. PMID:27149892

  3. The prognostic role of lymphovascular invasion in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Mathieu, Romain; Lucca, Ilaria; Rouprêt, Morgan; Briganti, Alberto; Shariat, Shahrokh F

    2016-08-01

    Outcome prediction in patients with bladder cancer has improved through the development of nomograms and predictive models. However, integration of further characteristics such as lymphovascular invasion (LVI) might increase the accuracy and clinical utility of these instruments. Assessment and reporting of LVI in specimens from transurethral resection of the bladder tumour (TURBT) or biopsy in patients with non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC) might enable improved staging, prognostication and clinical decision-making. In NMIBC, presence of LVI in TURBT and biopsy samples seems to be associated with understaging and increased risks of disease recurrence and progression. In MIBC, presence of LVI is associated with features of aggressive disease and predicts recurrence and survival. Integration of LVI status into predictive models might aid clinical decision-making regarding intravesical instillation schedules and regimens, early radical cystectomy in patients with high-grade T1 disease and perioperative chemotherapy. However, LVI assessment is hampered by insufficient reproducibility and reliability, lack of routine evaluation and limited concordance between findings in TURBT and radical cystectomy specimens. Standardization of the pathological criteria defining LVI is warranted to improve its reporting in routine clinical practice and its utility as a care-changing prognostic marker. PMID:27431340

  4. Parameter estimates for invasive breast cancer progression in the Canadian National Breast Screening Study

    OpenAIRE

    Taghipour, S.; Banjevic, D; Miller, A.B.; Montgomery, N; A K S Jardine; Harvey, B. J.

    2013-01-01

    Background: The aim of screening is to detect a cancer in the preclinical state. However, a false-positive or a false-negative test result is a real possibility. Methods: We describe invasive breast cancer progression in the Canadian National Breast Screening Study and construct progression models with and without covariates. The effect of risk factors on transition intensities and false-negative probability is investigated. We estimate the transition rates, the sojourn time and sensitivity o...

  5. Assessing tumor progression factors by somatic gene transfer into a mouse model: Bcl-xL promotes islet tumor cell invasion.

    Directory of Open Access Journals (Sweden)

    Yi-Chieh Nancy Du

    2007-10-01

    Full Text Available Tumors develop through multiple stages, implicating multiple effectors, but the tools to assess how candidate genes contribute to stepwise tumor progression have been limited. We have developed a novel system in which progression of phenotypes in a mouse model of pancreatic islet cell tumorigenesis can be used to measure the effects of genes introduced by cell-type-specific infection with retroviral vectors. In this system, bitransgenic mice, in which the rat insulin promoter (RIP drives expression of both the SV40 T antigen (RIP-Tag and the receptor for subgroup A avian leukosis virus (RIP-tva, are infected with avian viral vectors carrying cDNAs encoding candidate progression factors. Like RIP-Tag mice, RIP-Tag; RIP-tva bitransgenic mice develop isolated carcinomas by approximately 14 wk of age, after progression through well-defined stages that are similar to aspects of human tumor progression, including hyperplasia, angiogenesis, adenoma, and invasive carcinoma. When avian retroviral vectors carrying a green fluorescent protein marker were introduced into RIP-Tag; RIP-tva mice by intra-cardiac injection at the hyperplastic or early dysplastic stage of tumorigenesis, approximately 20% of the TVA-positive cells were infected and expressed green fluorescent proteins as measured by flow cytometry. Similar infection with vectors carrying cDNA encoding either of two progression factors, a dominant-negative version of cadherin 1 (dnE-cad or Bcl-xL, accelerated the formation of islet tumors with invasive properties and pancreatic lymph node metastasis. To begin studying the mechanism by which Bcl-xL, an anti-apoptotic protein, promotes invasion and metastasis, RIP-Tag; RIP-tva pancreatic islet tumor cells were infected in vitro with RCASBP-Bcl-xL. Although no changes were observed in rates of proliferation or apoptosis, Bcl-xL altered cell morphology, remodeled the actin cytoskeleton, and down-regulated cadherin 1; it also induced cell migration and

  6. Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

    Directory of Open Access Journals (Sweden)

    Yung Hyun Choi

    2013-10-01

    Full Text Available Diallyl trisulfide (DATS, an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637 cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer.

  7. A quantitative assessment of standard vs. customized midline shield construction for invasive cervical carcinoma

    International Nuclear Information System (INIS)

    Purpose: An individualized midline shield (MLS) has been advocated for delivering homogeneous radiotherapy for patients with invasive cervical carcinoma. Yet, many radiation oncologists continue to employ a standard block. In the latter instance, any deviation of the cranial-caudal central axis of the tandem from the patient's midline could result in dose inhomogeneity to tumor. A retrospective review of a single university medical center's experience with constructing the MLS was initiated to determine the outcome of using a standard block vs. a customized block that conforms to the 'Point A' isodose line. In addition, participating radiation oncologists associated with the Gynecologic Oncology Group (GOG) were polled to assess if there exists a consensus regarding midline block utilization in the management of cervical cancer patients which could be compared to the institutional study. Methods and Materials: From January 1, 1990 through December 31, 1992, 32 patients with invasive cervical carcinoma who underwent low dose rate brachytherapy at a single institution were identified. Patients were grouped as having a standard block (18 cases), customized block (5 cases), or no block (9 cases). The 'Point A' isodose distribution from the implant was superimposed onto the whole pelvic simulation film and quantitatively compared to the actual or a hypothetical standard block outlined on the same radiograph. In September of 1995, 56 member and affiliated institutions in the GOG were surveyed concerning their use of a MLS, and the results were tabulated in December of 1995. Results: Approximately 72% of all cases 923 out of 32) at the single institution had tandem deviation ranging from 0-230 with a median of 50. This translated into a median percent overdosage to 'Point A' Right of 15% and 'Point A' Left of 12.5%. Although overall survival and incidence of chronic complications have not been affected by type of shielding, patient follow-up is limited with a median of 17

  8. Distribution analysis of the putative cancer marker S100A4 across invasive squamous cell carcinoma penile tissue

    Directory of Open Access Journals (Sweden)

    Brian Flatley

    2015-06-01

    Full Text Available MS-based proteomic methods were utilised for the first time in the discovery of novel penile cancer biomarkers. MALDI MS imaging was used to obtain the in situ biomolecular MS profile of squamous cell carcinoma of the penis which was then compared to benign epithelial MS profiles. Spectra from cancerous and benign tissue areas were examined to identify MS peaks that best distinguished normal epithelial cells from invasive squamous epithelial cells, providing crucial evidence to suggest S100A4 to be differentially expressed. Verification by immunohistochemistry resulted in positive staining for S100A4 in a sub-population of invasive but not benign epithelial cells.

  9. The invasive lobular carcinoma as a prototype luminal A breast cancer: A retrospective cohort study

    International Nuclear Information System (INIS)

    Although the invasive lobular carcinoma (ILC) is the second most frequent histologic subtype in Western countries, its incidence is much lower in Asia, and its characteristics are less well known. We assessed the clinical characteristics and outcomes of 83 Korean patients (2.8%) with ILC for comparison with 2,833 (97.2%) with the invasive ductal carcinoma (IDC), including 1,088 (37.3%) with the luminal A subtype (LA-IDC). The mean age of all patients was 48.2 years, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥T2, 59.8% vs. 38.8%, P = 0.001), a lower histologic grade (HG 1/2, 90.4% vs. 64.4%, P < 0.001), more frequent estrogen receptor positive (90.4% vs. 64.4%, P < 0.001), progesterone receptor positive (71.1% vs. 50.1%, P < 0.001) and HER2 negative (97.5% vs. 74.6%, P < 0.001) status, and lower Ki-67 expression (10.3% ± 10.6% vs. 20.6% ± 19.8%, P < 0.001), as well as being more likely to be of the luminal A subtype (91.4% vs. 51.2%, P < 0.001). Six (7.2%) ILC and 359 (12.7%) IDC patients developed disease recurrence, with a median follow-up of 56.4 (range 4.9-136.6) months. The outcome of ILC was close to LA-IDC (HR 0.77 for recurrence, 95% CI 0.31-1.90, P = 0.57; HR 0.75 for death, 95% CI 0.18-3.09, P = 0.70) and significantly better than for the non-LA-IDC (HR 1.69 for recurrence, 95% CI 1.23-2.33, P = 0.001; HR 1.50 for death, 95% CI 0.97-2.33, P = 0.07). ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC

  10. Development and Evaluation of a Prediction Model for Underestimated Invasive Breast Cancer in Women with Ductal Carcinoma In Situ at Stereotactic Large Core Needle Biopsy

    OpenAIRE

    Suzanne C E Diepstraten; van de Ven, Stephanie M. W. Y.; Pijnappel, Ruud M; Peeters, Petra H. M.; van den Bosch, Maurice A. A. J.; Helena M Verkooijen; Elias, Sjoerd G

    2013-01-01

    BACKGROUND: We aimed to develop a multivariable model for prediction of underestimated invasiveness in women with ductal carcinoma in situ at stereotactic large core needle biopsy, that can be used to select patients for sentinel node biopsy at primary surgery. METHODS: From the literature, we selected potential preoperative predictors of underestimated invasive breast cancer. Data of patients with nonpalpable breast lesions who were diagnosed with ductal carcinoma in situ at stereotactic lar...

  11. Defining progression in nonmuscle invasive bladder cancer: it is time for a new, standard definition

    NARCIS (Netherlands)

    Lamm, D.; Persad, R.; Brausi, M.; Buckley, R.; Witjes, J.A.; Palou, J.; Bohle, A.; Kamat, A.M.; Colombel, M.; Soloway, M.

    2014-01-01

    PURPOSE: Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A stand

  12. Mesenchymal stem cell-derived exosomes facilitate nasopharyngeal carcinoma progression

    OpenAIRE

    Shi, Si; Zhang, Qicheng; Xia, Yunfei; You, Bo; Shan, Ying; Bao, Lili; Li, Li; You, Yiwen; Gu, Zhifeng

    2016-01-01

    Mesenchymal stem cells (MSCs), which are capable of differentiating into multiple cell types, are reported to exert multiple effects on tumor development. However, the relationship between MSCs and nasopharyngeal carcinoma (NPC) cells remains unclear. Exosomes are small membrane vesicles that can be released by several cell types, including MSCs. Exosomes, which can carry membrane and cytoplasmic constituents, have been described as participants in a novel mechanism of cell-to-cell communicat...

  13. Loss of the α2β1 integrin alters human papilloma virus-induced squamous carcinoma progression in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Thuy Tran

    Full Text Available Expression of the α2β1 integrin, a receptor for collagens and laminin, is altered during tumor progression. Recent studies have linked polymorphisms in the α2 integrin gene with oral, squamous cell carcinoma (SCC. To determine the α2β1 integrin's role in SCC progression, we crossed α2-null mice with K14-HPV16 transgenic animals. Pathological progression to invasive carcinoma was evaluated in HPV-positive, α2-null (HPV/KO and HPV-positive, wild-type (HPV/WT animals. α2β1 integrin expression stimulated progression from hyperplasia and papillomatosis to dysplasia with concomitant dermal mast cell infiltration. Moreover, lymph node metastasis was decreased by 31.3% in HPV/KO, compared to HPV/WT, animals. To evaluate the integrin-specific impact on the malignant epithelium versus the microenvironment, we developed primary tumor cell lines. Although transition from dysplasia to carcinoma was unaltered during spontaneous tumor development, isolated primary HPV/KO SCC cell lines demonstrated decreased migration and invasion, compared to HPV/WT cells. When HPV/WT and HPV/KO SCC cells were orthotopically injected into WT or KO hosts, tumor α2β1 integrin expression resulted in decreased tumor latency, regardless of host integrin status. HPV/WT SCC lines failed to demonstrate a proliferative advantage in vitro, however, the HPV/WT tumors demonstrated increased growth compared to HPV/KO SCC lines in vivo. Although contributions of the integrin to the microenvironment cannot be excluded, our studies indicate that α2β1 integrin expression by HPV-transformed keratinocytes modulates SCC growth and progression.

  14. Effect of the combined thoracoscopic and laparoscopic minimally invasive esophagectomy for the treatment of esophageal carcinoma on pulmonary function

    Institute of Scientific and Technical Information of China (English)

    Xin-Hui Rao; Han-Yun Liu; Jin-Song Liang; Zi-Zheng Zhang; Huan-Rong Zhang

    2015-01-01

    Objective: To explore the effect of the combined thoracoscopic and laparoscopic minimally invasive esophagectomy for the treatment of esophageal carcinoma on pulmonary function and its clinical efficacy. Methods: A total of 200 esophageal carcinoma patients with complete medical materials, admitted in our hospital from January, 2011 to December, 2014 were included in the study and divided into the observation group and the control group with 100 cases in each group. The patients in the observation group were undergoing the combined thoracoscopic and laparoscopic minimally invasive esophagectomy for the treatment of esophageal carcinoma, while the patients in the control group were undergoing open esophagectomy for the treatment of esophageal carcinoma. The operation indicators, postoperative complications, short-term efficacy, and the effect of operation on pulmonary function in the two groups were compared. Results: The comparison of operation time, lymph node dissection number, and the occurrence rate of postoperative complications between the two groups was not statistically significant. The intraoperative amount of bleeding, thoracic duct indwelling time, and hospitalization time in the observation group were significantly lower than those in the control group. FEV1 the 5th day after operation in the observation group was not statistically different from that before operation, while in the control group it was statistically different from that before operation. FEV1/FVC after treatment in the observation group was significantly higher than that in the control group. PaO2 and SaO2 after operation in the observation group were not statistically different from those before operation, while PaO2 and SaO2 after operation in the control group were significantly lower than those before operation. Conclusions: The combined thoracoscopic and laparoscopic minimally invasive esophagectomy for the treatment of esophageal carcinoma has an accurate efficacy with no obvious

  15. Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP

    OpenAIRE

    Chen, Yong; Liu, Ju Mei; Xiong, Xin Xin; Qiu, Xin Yao; Pan, Feng; Liu, Di; Lan, Shu Jue; Jin, Si; Yu, Shang Bin; Chen, Xiao Qian

    2015-01-01

    Hepatocellular carcinomas (HCC) are highly malignant and aggressive tumors lack of effective therapeutic drugs. Piperlongumine (PL), a natural product isolated from longer pepper plants, is recently identified as a potent cytotoxic compound highly selective to cancer cells. Here, we reported that PL specifically suppressed HCC cell migration/invasion via endoplasmic reticulum (ER)-MAPKs-CHOP signaling pathway. PL selectively killed HCC cells but not normal hepatocytes with an IC50 of 10-20 μM...

  16. Hypoxia-inducible factor-2a is associated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma

    Directory of Open Access Journals (Sweden)

    Xiang Lei

    2012-03-01

    Full Text Available Abstract Background Breast cancer is the most common cancer and the leading cause of cancer mortality in women worldwide. Hypoxia is an important factor involved in the progression of solid tumors and has been associated with various indicators of tumor metabolism, angiogenesis and metastasis. But little is known about the contribution of Hypoxia-Inducible Factor-2a (HIF-2a to the drug resistance and the clinicopathological characteristics in breast cancer. Methods Immunohistochemistry was employed on the tissue microarray paraffin sections of surgically removed samples from 196 invasive breast cancer patients with clinicopathological data. The correlations between the expression of HIF-2a and ABCG2 as well as other patients' clinicopathological data were investigated. Results The results showed that HIF-2a was expressed in different intensities and distributions in the tumor cells of the breast invasive ductal carcinoma. A positive staining for HIF-2a was defined as a brown staining observed mainly in the nucleus. A statistically significant correlation was demonstrated between HIF-2a expression and ABCG2 expression (p = 0.001, histology-grade (p = 0.029, and Ki67 (p = 0. 043 respectively. Conclusion HIF-2a was correlated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma. HIF-2a could regulate ABCG2 in breast cancer cells, and could be a novel potential bio-marker to predict chemotherapy effectiveness. The hypoxia/HIF-2a/ABCG2 pathway could be a new mechanism of breast cancer multidrug-resistance. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2965948166714795

  17. Spiclomazine induces apoptosis associated with the suppression of cell viability, migration and invasion in pancreatic carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Wenjing Zhao

    Full Text Available The effective treatment for pancreatic carcinoma remains critically needed. Herein, this current study showed that spiclomazine treatment caused a reduction in viability in pancreatic carcinoma cell lines CFPAC-1 and MIA PaCa-2 in vitro. It was notable in this regard that, compared with pancreatic carcinoma cells, normal human embryonic kidney (HEK-293 and liver (HL-7702 cells were more resistant to the antigrowth effect of spiclomazine. Biochemically, spiclomazine treatment regulated the expression of protein levels in the apoptosis related pathways. Consistent with this effect, spiclomazine reduced the mitochondria membrane potential, elevated reactive oxygen species, and activated caspase-3/9. In addition, a key finding from this study was that spiclomazine suppressed migration and invasion of cancer cells through down-regulation of MMP-2/9. Collectively, the proposed studies did shed light on the antiproliferation effect of spiclomazine on pancreatic carcinoma cell lines, and further clarified the mechanisms that spiclomazine induced apoptosis associated with the suppression of migration and invasion.

  18. Automatic detection of invasive ductal carcinoma in whole slide images with convolutional neural networks

    Science.gov (United States)

    Cruz-Roa, Angel; Basavanhally, Ajay; González, Fabio; Gilmore, Hannah; Feldman, Michael; Ganesan, Shridar; Shih, Natalie; Tomaszewski, John; Madabhushi, Anant

    2014-03-01

    This paper presents a deep learning approach for automatic detection and visual analysis of invasive ductal carcinoma (IDC) tissue regions in whole slide images (WSI) of breast cancer (BCa). Deep learning approaches are learn-from-data methods involving computational modeling of the learning process. This approach is similar to how human brain works using different interpretation levels or layers of most representative and useful features resulting into a hierarchical learned representation. These methods have been shown to outpace traditional approaches of most challenging problems in several areas such as speech recognition and object detection. Invasive breast cancer detection is a time consuming and challenging task primarily because it involves a pathologist scanning large swathes of benign regions to ultimately identify the areas of malignancy. Precise delineation of IDC in WSI is crucial to the subsequent estimation of grading tumor aggressiveness and predicting patient outcome. DL approaches are particularly adept at handling these types of problems, especially if a large number of samples are available for training, which would also ensure the generalizability of the learned features and classifier. The DL framework in this paper extends a number of convolutional neural networks (CNN) for visual semantic analysis of tumor regions for diagnosis support. The CNN is trained over a large amount of image patches (tissue regions) from WSI to learn a hierarchical part-based representation. The method was evaluated over a WSI dataset from 162 patients diagnosed with IDC. 113 slides were selected for training and 49 slides were held out for independent testing. Ground truth for quantitative evaluation was provided via expert delineation of the region of cancer by an expert pathologist on the digitized slides. The experimental evaluation was designed to measure classifier accuracy in detecting IDC tissue regions in WSI. Our method yielded the best quantitative

  19. Tri-modal confocal mosaics detect residual invasive squamous cell carcinoma in Mohs surgical excisions

    Science.gov (United States)

    Gareau, Dan; Bar, Anna; Snaveley, Nicholas; Lee, Ken; Chen, Nathaniel; Swanson, Neil; Simpson, Eric; Jacques, Steve

    2012-06-01

    For rapid, intra-operative pathological margin assessment to guide staged cancer excisions, multimodal confocal mosaic scan image wide surgical margins (approximately 1 cm) with sub-cellular resolution and mimic the appearance of conventional hematoxylin and eosin histopathology (H&E). The goal of this work is to combine three confocal imaging modes: acridine orange fluorescence (AO) for labeling nuclei, eosin fluorescence (Eo) for labeling cytoplasm, and endogenous reflectance (R) for marking collagen and keratin. Absorption contrast is achieved by alternating the excitation wavelength: 488 nm (AO fluorescence) and 532 nm (Eo fluorescence). Superposition and false-coloring of these modes mimics H&E, enabling detection of cutaneous squamous cell carcinomas (SCC). The sum of mosaic Eo+R is false-colored pink to mimic the appearance of eosin, while the AO mosaic is false-colored purple to mimic the appearance of hematoxylin in H&E. In this study, mosaics of 10 Mohs surgical excisions containing invasive SCC, and five containing only normal tissue were subdivided for digital presentation equivalent to 4× histology. Of the total 50 SCC and 25 normal sub-mosaics presented, two reviewers made two and three type-2 errors (false positives), respectively. Limitations to precisely mimic H&E included occasional elastin staining by AO. These results suggest that confocal mosaics may effectively guide staged SCC excisions in skin and other tissues.

  20. Treatments for invasive carcinoma of the cervix: what are their impacts on the pelvic floor functions?

    Directory of Open Access Journals (Sweden)

    Alessandra Ferreira de Noronha

    2013-01-01

    Full Text Available Aims: Describe the impact of surgery, radiotherapy and chemoradiation in the pelvic floor functions in cervical cancer patients. Materials and Methods: A prospective study with women submitted to radical hysterectomy (RH (n = 20, exclusive radiotherapy (RT (n = 20 or chemoradiation (CT/RT (n = 20 for invasive cervical cancer. Urinary, intestinal and sexual function, as well as vaginal length and pelvic floor muscle contraction were evaluated. Comparisons between groups were performed by Kruskal-Wallis and Chi-square tests (p < 0.05. Results: The groups were similar in stress urinary incontinence incidence (p = 0.56, urinary urgency (p = 0.44, urge incontinence (p = 0.54, nocturia (p = 0.53, incomplete bowel emptying (p = 0.76, bowel urgency (p = 0.12 and soilage (p = 0.43. The CT/RT group presented a higher urinary frequency (p < 0.001 and diarrhea (p = 0.025. Patients in the RH group were more sexually active (p = 0.01 and experienced less dyspareunia (p = 0.021. Vaginal length was shorter in RT group (5.5 ± 1.9cm and CT/RT(5.3 ± 1.5 cm than in the RH group (7.4 ± 1.1 cm (p < 0.001. Pelvic floor muscle contraction was similar (p = 0.302. Conclusions: RT and CT/RT treatment for cervical carcinoma are more associated to sexual and intestinal dysfunctions.

  1. Neuroendocrine carcinoma of the pancreas with similar genetic alterations to invasive ductal adenocarcinoma.

    Science.gov (United States)

    Kimura, Tetsuo; Miyamoto, Hiroshi; Fukuya, Akira; Kitamura, Shinji; Okamoto, Koichi; Kimura, Masako; Muguruma, Naoki; Ikemoto, Tetsuya; Shimada, Mitsuo; Yoneda, Akiko; Bando, Yoshimi; Takishita, Makoto; Takayama, Tetsuji

    2016-08-01

    Neuroendocrine carcinoma (NEC) of the pancreas is very rare, and its origin is not fully elucidated. Here, we present a case of a small-size NEC of the pancreas that is genetically similar to invasive ductal adenocarcinoma (IDA). A 65-year-old man was referred to our hospital due to obstructive jaundice and found to have a 12-mm solid tumor in the pancreas head. The tumor exhibited low vascularity on enhanced computed tomography, and endoscopic retrograde pancreatographic imaging revealed an irregular obstruction in a branch duct of the pancreas. The patient was thereby diagnosed with a pancreatic ductal cancer, and stomach-preserving pancreaticoduodenectomy with regional lymph node resection was performed. Histochemical analysis of the resected tumor showed that the neoplastic cells with scanty cytoplasm and hyperchromatic nuclei strongly expressed chromogranin A and synaptophysin. The Ki-67 index was 40 % in the most proliferative tumor regions, and the tumor was diagnosed as a NEC of the pancreas. However, in the analysis of genetic alterations of the tumor tissue, the neoplastic cells showed altered KRAS, TP53, and SMAD4/DPC4, suggesting that the NEC in our case is genetically related to IDA. Our data suggest that poorly differentiated IDAs may transform into NECs. PMID:27262570

  2. Inhibition of invasiveness and expression of epidermal growth factor receptor in human colorectal carcinoma cells induced by retinoic acid

    Institute of Scientific and Technical Information of China (English)

    SUNBAODONG; JINDANSONG

    1995-01-01

    Human amniotic basement membrane (HABM) model and agarose drop explant method were used to investigate the effects of retinoic acid(RA) on the invasive ness and adhesiveness to the basement membrane,and the migration of a highly invasive human colorectal cancer cell line CCL229.Results showed that 5×106 MRA markedly reduced the in vitro invasiveness and adhesiveness to the HABM,and the migration of the CCL229 cells.In addition,to elucidate the relation between expression of epidermal growth factor receptor(EGFR) and the invasiveness of the colorectal carcinoma cells,two well-differentiated,but with different invasiveness colorectal cancer cell lines were compared at mRNA level for expression of EGFR by using EGFR cDNA probe labeled with digoxigenin(DIG). Expression of EGFR was shown to be markedly higher in the highly invassive CCL229 cells than that in the low invasive CX-1 cells.Furthermore,expression of EGFR in RA treated CCL229 cells gradually decreased with time,the level being the lowest on day 6 of the RA treatment.

  3. MDCT findings of extrapancreatic nerve plexus invasion by pancreas head carcinoma: correlation with en bloc pathological specimens and diagnostic accuracy

    International Nuclear Information System (INIS)

    To elucidate the multi-detector row computed tomography (MDCT) findings of extrapancreatic nerve plexus (PLX) invasion by pancreas head carcinoma (PhC) by ''point-by-point'' correlation with en bloc pathological specimens and to assess their diagnostic accuracy. Each pathological section of PhC and adjusted double oblique multiplanar reconstruction MDCT images were correlated in 554 sections from 37 patients. The diagnostic accuracy of the MDCT patterns derived was assessed by blind reading. PLX invasion with fibrosis showed mass or strand shape (85.6%) or coarse reticula (13.3%). The CT findings were divided into fine reticular and linear, coarse reticular, mass and strand, and nodular patterns. PLX invasion was revealed pathologically in 92% of the regions of investigation showing the mass and strand pattern and 63% of the coarse reticular pattern (all continuous with PhC), and they were highly suggestive of PLX invasion by PhC on MDCT images (p < 0.001). Sensitivity, specificity, accuracy, and positive and negative predictive values of these MDCT findings in the diagnosis of PLX invasion were 100% (25/25), 83.3% (10/12), 94.6% (35/37), 92.6% (25/27) and 100% (10/10), respectively. The mass and strand pattern and the coarse reticular pattern continuous with PhC on MDCT images were highly suggestive of PLX invasion by PhC. (orig.)

  4. Akt Inhibitor MK2206 in Treating Patients With Progressive, Recurrent, or Metastatic Adenoid Cyst Carcinoma

    Science.gov (United States)

    2016-06-14

    Recurrent Oral Cavity Adenoid Cystic Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Adenoid Cystic Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Oral Cavity Adenoid Cystic Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Oral Cavity Adenoid Cystic Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Oral Cavity Adenoid Cystic Carcinoma

  5. Aggressiveness of 'true' interval invasive ductal carcinomas of the breast in postmenopausal women

    NARCIS (Netherlands)

    van der Vegt, Bert; Wesseling, J.; Pijnappel, R.M.; Dorrius, M.D.; den Heeten, G.J.; de Roos, M.A.J.; de Bock, G.H.

    2010-01-01

    There is debate whether interval carcinomas differ from screen-detected tumours biologically. In this study, clinico-pathological parameters and the expression of well-validated biological markers were compared between 'true' interval carcinomas and screen-detected/missed carcinomas hypothesising th

  6. BOLD-MRI of breast invasive ductal carcinoma: correlation of R2* value and the expression of HIF-1α

    International Nuclear Information System (INIS)

    To explore the reliability and feasibility of blood oxygenation level-dependent-based functional magnetic resonance imaging (BOLD-fMRI) to depict hypoxia in breast invasive ductal carcinoma. A total of 103 women with 104 invasive ductal carcinomas (IDCs) underwent breast BOLD-fMRI at 3.0 T. Histological specimens were analysed for tumour size, grade, axillary lymph nodes and expression of oestrogen receptors, progesterone receptors, human epidermal growth factor receptor 2, p53, Ki-67 and hypoxia inducible factor 1α (HIF-1α). The distribution and reliability of R2* were analysed. Correlations of the R2* value with the prognostic factors and HIF-1α were respectively analysed. The R2* map of IDC demonstrated a relatively heterogeneous signal. The mean R2* value was (53.4 ± 18.2) Hz. The Shapiro-Wilk test (W = 0.971, P = 0.020) suggested that the sample did not follow a normal distribution. The inter-rater and intrarater correlation coefficient was 0.967 and 0.959, respectively. The R2* values of IDCs were significantly lower in patients without axillary lymph nodes metastasis. The R2* value had a weak correlation with Ki67 expression (r = 0.208, P = 0.038). The mean R2* value correlated moderately with the level of HIF-1α (r = 0.516, P = 0.000). BOLD-fMRI is a simple and non-invasive technique that yields hypoxia information on breast invasive ductal carcinomas. (orig.)

  7. BOLD-MRI of breast invasive ductal carcinoma: correlation of R2* value and the expression of HIF-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Min; Guo, Xiaojuan; Wang, Shuangkun [Capital Medical University, Department of Radiology, Beijing Chao Yang Hospital, Beijing (China); Jin, Mulan; Wang, Ying [Capital Medical University Beijing, Department of Pathology, Beijing Chaoyang Hospital, Beijing (China); Li, Jie; Liu, Jun [Capital Medical University Beijing, Department of Breast Surgery, Beijing Chaoyang Hospital, Beijing (China)

    2013-12-15

    To explore the reliability and feasibility of blood oxygenation level-dependent-based functional magnetic resonance imaging (BOLD-fMRI) to depict hypoxia in breast invasive ductal carcinoma. A total of 103 women with 104 invasive ductal carcinomas (IDCs) underwent breast BOLD-fMRI at 3.0 T. Histological specimens were analysed for tumour size, grade, axillary lymph nodes and expression of oestrogen receptors, progesterone receptors, human epidermal growth factor receptor 2, p53, Ki-67 and hypoxia inducible factor 1{alpha} (HIF-1{alpha}). The distribution and reliability of R2* were analysed. Correlations of the R2* value with the prognostic factors and HIF-1{alpha} were respectively analysed. The R2* map of IDC demonstrated a relatively heterogeneous signal. The mean R2* value was (53.4 {+-} 18.2) Hz. The Shapiro-Wilk test (W = 0.971, P = 0.020) suggested that the sample did not follow a normal distribution. The inter-rater and intrarater correlation coefficient was 0.967 and 0.959, respectively. The R2* values of IDCs were significantly lower in patients without axillary lymph nodes metastasis. The R2* value had a weak correlation with Ki67 expression (r = 0.208, P = 0.038). The mean R2* value correlated moderately with the level of HIF-1{alpha} (r = 0.516, P = 0.000). BOLD-fMRI is a simple and non-invasive technique that yields hypoxia information on breast invasive ductal carcinomas. (orig.)

  8. Correlation of HER2 overexpression with gene amplification and its relation to chromosome 17 aneuploidy: a 5-year experience with invasive ductal and lobular carcinomas.

    Science.gov (United States)

    Nassar, Aziza; Khoor, Andras; Radhakrishnan, Reshmitha; Radhakrishnan, Anu; Cohen, Cynthia

    2014-01-01

    The HER2 oncogene shows expression or amplification, or both, in approximately 15% to 20% of breast cancers and has been associated with poor prognosis and a response to trastuzumab therapy. HER2 gene status determines the eligibility of breast cancer patients for trastuzumab therapy and a large fraction (41-56%) of these patients respond to targeted therapy. Several studies have related the increased expression of HER2 to an increased copy number of chromosome 17, rather than amplification of the HER2 gene. We compared the results of immunohistochemistry and fluorescence in situ hybridization in both invasive ductal and invasive lobular carcinomas, to determine the frequency of chromosome 17 aneuploidy associated with discordant results. In total, 390 invasive ductal carcinomas and 180 invasive lobular carcinomas diagnosed from January 2000 to December 2005 were included in the study only if results were available for immunohistochemistry (HercepTest; DAKO, Carpinteria, California) and fluorescence in situ hybridization (PathVysion HER2 DNA Probe Kit; Abbott Laboratories, Des Plaines, Illinois). Tumors classified as invasive ductal carcinomas were graded according to the Bloom-Richardson grading system. Correlation between the results of immunohistochemistry and fluorescence in situ hybridization was performed for all categories. Among invasive ductal carcinomas, 29% (115/390) showed chromosome 17 aneuploidy, mostly associated with grade 3/HER2 2+ (45%) or grade 2/HER2 3+ (55%) that were not amplified. Also, 34% (12/35) of invasive lobular carcinomas showed chromosome 17 aneuploidy; approximately one-third of these cases were HER2 2+ (33%) and HER2 3+ (37%) that were not amplified. Discordance between the results of immunohistochemistry and fluorescence in situ hybridization in both ductal and lobular carcinomas is largely associated with chromosome 17 aneuploidy.

  9. The association of the microcystic, elongated and fragmented (MELF) invasion pattern in endometrial carcinomas with deep myometrial invasion, lymphovascular space invasion and lymph node metastasis.

    Science.gov (United States)

    Dogan Altunpulluk, M; Kir, G; Topal, C S; Cetiner, H; Gocmen, A

    2015-05-01

    The purpose of this study was to investigate the frequency of microcystic, elongated and fragmented (MELF) pattern of invasion in endometrioid endometrial adenocarcinomas (EA) and its association with prognostic factors. Stained tissue sections from 121 cases of EA (total hysterectomy and pelvic, with or without para-aortic, lymphadenectomy specimens) were reviewed to identify cases showing MELF-type invasion. The prognostic factors of low tumour grade, deep myometrial invasion (MI), cervical stromal involvement, lymphovascular space invasion (LVSI), lymph node (LN) metastasis and advanced clinical stage were more frequently observed in MELF-positive cases (p deep MI, cervical stroma involvement and LVSI were significantly related to LN metastasis (p < 0.05). However, in multivariate analysis, only MELF pattern invasion and cervical stroma involvement were independent factors for LN metastasis. Nevertheless, further studies are needed to evaluate the clinical significance of MELF pattern of invasion in endometrial adenocarcinoma.

  10. Human beta-defensin-1 suppresses tumor migration and invasion and is an independent predictor for survival of oral squamous cell carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Qi Han

    Full Text Available BACKGROUND: Human beta-defensin-1 (hBD-1 has recently been considered as a candidate tumor suppressor in renal and prostate cancer. The aim of this study was to investigate the role of hBD-1 in the progression of oral squamous cell carcinoma (OSCC and its potential as diagnostic/prognostic biomarker and therapeutic target for OSCC. METHODS: HBD-1 expression in tissues at different stages of oral carcinogenesis, as well as OSCC cell lines was examined. HBD-1 was overexpressed in HSC-3, UM1, SCC-9 and SCC-25 cells and subjected to cell growth, apoptosis, migration and invasion assays. Tissue microarray constructed with tissues from 175 patients was used to examine clinicopathological significance of hBD-1 expression in OSCC. RESULTS: HBD-1 expression decreased from oral precancerous lesions to OSCC and was lower in OSCC with lymph node metastasis than those without metastasis. In vitro, the expression of hBD-1 was related to the invasive potential of OSCC cell lines. Induction of exogenous expression of hBD-1 inhibited migration and invasion of OSCC cells, probably by regulation of RhoA, RhoC and MMP-2; but had no significant effect on proliferation or apoptosis. In a cohort of patients with primary OSCC, cases with no expression of hBD-1 had more chance to be involved in lymph node metastasis. Eventually, the positive expression of hBD-1 was associated with longer survival of patients with OSCC, and multivariate analysis and ROC curve analysis confirmed hBD-1 positivity to be an independent prognostic factor of OSCC, especially OSCC at early stage. CONCLUSIONS: Overall, these data indicated that hBD-1 suppressed tumor migration and invasion of OSCC and was likely to be a prognostic biomarker and a potential target for treatment of OSCC.

  11. Topotecan Monotherapy in Heavily Pretreated Patients with Progressive Advanced Stage Neuroendocrine Carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Knigge, Ulrich; Federspiel, Birgitte;

    2014-01-01

    BACKGROUND: Neuroendocrine carcinomas (WHO grade 3) are highly aggressive tumors with an immense tendency to metastasize and with a poor prognosis. In advanced disease, there is no standard treatment beyond first-line platin/etoposide-based chemotherapy. Topotecan is widely used as second......-line treatment in small cell lung cancer, which also responds markedly on first-line platin/etoposide. Hence, we investigated the feasibility of topotecan in previously treated patients with neuroendocrine carcinomas. MATERIAL AND METHODS: Retrospective analysis of 22 patients with disseminated and progressive...... neuroendocrine carcinomas (Ki67>20%, G3) successively treated with oral topotecan 2.3 mg/m(2) d1-5 every 3 weeks. All patients had previously received treatment with carboplatin/etoposide. Demographic, clinical and pathological features were recorded. CT-evaluations according to RECIST 1.1 were performed after...

  12. Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection

    Science.gov (United States)

    Lambros, Maryou B; Campion-Flora, Adriana; Rodrigues, Daniel Nava; Gauthier, Arnaud; Cabral, Cecilia; Pawar, Vidya; Mackay, Alan; A’Hern, Roger; Marchiò, Caterina; Palacios, Jose; Natrajan, Rachael; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    The mechanisms underlying the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast are yet to be fully elucidated. Several hypotheses have been put forward to explain the progression from DCIS to IDC, including the selection of a subpopulation of cancer cells with specific genetic aberrations, the acquisition of new genetic aberrations or non-genetic mechanisms mediated by the tumour microenvironment. To determine whether synchronously diagnosed ipsilateral DCIS and IDCs have modal populations with distinct repertoires of gene copy number aberrations and mutations in common oncogenes, matched frozen samples of DCIS and IDCs were retrieved from 13 patients and subjected to microarray-based comparative genomic hybridisation (aCGH), and Sequenom MassARRAY (Oncocarta v1.0 panel). Fluorescence in situ hybridisation and Sanger sequencing were employed to validate the aCGH and Sequenom findings, respectively. Although the genomic profiles of matched DCIS and IDCs were similar, in three of 13 matched pairs amplification of distinct loci (i.e. 1q41, 2q24.2, 6q22.31, 7q11.21, 8q21.2 and 9p13.3) was either restricted to, or more prevalent in, the modal population of cancer cells of one of the components. Sequenom MassARRAY identified PIK3CA mutations restricted to the DCIS component in two cases, and in a third case, the frequency of the PIK3CA mutant allele reduced from 49% in the DCIS to 25% in the IDC component. Despite the genomic similarities between synchronous DCIS and IDC, our data provide strong circumstantial evidence to suggest that in some cases the progression from DCIS to IDC is driven by the selection of non-modal clones that harbour a specific repertoire of genetic aberrations. PMID:22252965

  13. Micro-PIXE analysis in invasive ductal carcinoma tissues after treatment of astaxanthin

    International Nuclear Information System (INIS)

    Trace elements play an important role in a number of biological processes. Astaxanthin, a carotoid pigment found in certain marine plant and animals, has shown anti cancer and anti free radical properties. This work intended to understand the effect of Astaxanthin in breast cancer (invasive ductal carcinoma) by using micro-PIXE method. For this aim the concentration of trace elements were compared in healthy, cancerous and cancer treated with astaxanthin in the breast and liver tissues of breast cancer bearing mice, using proton induced X-ray emission. Materials and Methods: Proton induced X-ray emission was used In a study intending to compare the concentration of trace elements in breast and liver tissues of mice bearing tumor, three groups of mice: healthy, cancerous, and cancerous treated by astaxanthin, were considered. Astaxanthin was supplied from Research Institute of women, Alzahra University. Results: Comparing the untreated tumor tissue, treatment with Astaxanthm significantly decreased the amount Fe, P, S, and Ca elements level in tumor tissue of the breast cancer. It is also found that the concentrations of those elements in liver of the untreated mice and the liver of treated mice with astaxanthin were fairly equal. Astaxanthln significantly decrease the accumulation of elements in the site of tumor, and caused the breast cancer cell membrane to lose their desire to collect the elements from healthy tissues. Conclusion: The micro -PIXE technique could calculate elemental concentrations in tissues. Changes in metallic elements may affect microenvironment and cell functions, which might led lead to cell degeneration or death, the results shows that astaxanthin reduces vital element concentration in tumor site, thus it could be used as an anti tumor agent.

  14. Marriage, cohabitation and incidence trends of invasive penile squamous cell carcinoma in Denmark 1978-2010.

    Science.gov (United States)

    Ulff-Møller, Constance J; Simonsen, Jacob; Frisch, Morten

    2013-09-01

    Few population-based studies have investigated the relation between living arrangements and risk of invasive penile squamous cell carcinoma (iP-SCC). Using long-term national cancer registry data in Denmark we examined incidence trends of iP-SCC. Furthermore, we examined the relation between marital status, cohabitation status and risk of iP-SCC using hazard ratios (HRs) with 95% confidence intervals (CIs) obtained in Cox proportional hazards regression analyses as our measure of relative risk. Overall, 1,292 cases of iP-SCC were identified during 65.6 million person-years of observation between 1978 and 2010. During this period, the WHO world age-standardized incidence remained relatively stable (p-trend = 0.41) with an average incidence of 1.05 cases per 100,000 person-years. When compared to married men, those who were unmarried (HR 1.37; 95% CI: 1.13-1.66), divorced (HR 1.49; 95% CI: 1.24-1.79) or widowed (HR 1.36; 95% CI: 1.13-1.63) were at increased risk of iP-SCC. Regarding cohabitation status, single-living men were at increased risk of iP-SCC compared to men in opposite-sex cohabitation (HR 1.43; 95% CI: 1.26-1.62). Risk increased with increasing numbers of prior opposite-sex (p-trend = 0.02) and same-sex (p-trend cohabitations. In conclusion, single-living Danish men and men who are not currently married are at increased risk of iP-SCC, and the risk increases with the number of prior cohabitations, perhaps reflecting less stable sexual relations in these subgroups.

  15. Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status

    Science.gov (United States)

    Farquharson, M. J.; Al-Ebraheem, A.; Geraki, K.; Leek, R.; Jubb, A.; Harris, A. L.

    2009-07-01

    Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01).

  16. Mitotic figure counts are significantly overestimated in resection specimens of invasive breast carcinomas.

    Science.gov (United States)

    Lehr, Hans-Anton; Rochat, Candice; Schaper, Cornelia; Nobile, Antoine; Shanouda, Sherien; Vijgen, Sandrine; Gauthier, Arnaud; Obermann, Ellen; Leuba, Susana; Schmidt, Marcus; C, Curzio Ruegg; Delaloye, Jean-Francois; Simiantonaki, Nectaria; Schaefer, Stephan C

    2013-03-01

    Several authors have demonstrated an increased number of mitotic figures in breast cancer resection specimen when compared with biopsy material. This has been ascribed to a sampling artifact where biopsies are (i) either too small to allow formal mitotic figure counting or (ii) not necessarily taken form the proliferating tumor periphery. Herein, we propose a different explanation for this phenomenon. Biopsy and resection material of 52 invasive ductal carcinomas was studied. We counted mitotic figures in 10 representative high power fields and quantified MIB-1 immunohistochemistry by visual estimation, counting and image analysis. We found that mitotic figures were elevated by more than three-fold on average in resection specimen over biopsy material from the same tumors (20±6 vs 6±2 mitoses per 10 high power fields, P=0.008), and that this resulted in a relative diminution of post-metaphase figures (anaphase/telophase), which made up 7% of all mitotic figures in biopsies but only 3% in resection specimen (Pmitotic figures in resection specimen. We propose that the increase in mitotic figures in resection specimen and the significant shift towards metaphase figures is not due to a sampling artifact, but reflects ongoing cell cycle activity in the resected tumor tissue due to fixation delay. The dwindling energy supply will eventually arrest tumor cells in metaphase, where they are readily identified by the diagnostic pathologist. Taken together, we suggest that the rapidly fixed biopsy material better represents true tumor biology and should be privileged as predictive marker of putative response to cytotoxic chemotherapy.

  17. No-Touch Pancreatectomy for Invasive Ductal Carcinoma of the Pancreas

    Directory of Open Access Journals (Sweden)

    Masahiko Hirota

    2014-05-01

    Full Text Available Background Pancreatectomy is the only effective treatment for cancers of the pancreas. Surgeons usually grasp tumors duringpancreatectomy, however, this procedure may increase the risk of squeezing and shedding of the cancer cells into the portal vein, retroperitoneum, and/or peritoneal cavity. In an effort to overcome these problems, we have developed surgical techniques for no-touch pancreatectomy. Methods From April 2008 through September 2013, 52 patients have been operated on no-touch pancreatectomy for invasive ductal carcinoma of the pancreas by a single operator (M.H.. Among them, 40 received pancreatoduodenectomy (PD, and 12 did distal pancreatectomy (DP. Twenty two cases (42% required SMV-PV resection. This is a study to see if pancreatectomy can be technically done using a no-touch surgical technique without deteriorating the post-operative prognosis. During the procedure, the pancreatic tumor is neither grasped nor squeezed by the surgeon. Furthermore, for improved dissection of the retroperitoneal tissue (leftward and posterior margins for PD and rightward and posterior margins for DP, we use a hanging and clamping maneuver and dissection behind Gerota fascia. Results Overall 2- and 5-year survival rates were 64 and 42% with mean follow-up periods of 34.4 months (range: 6-68 months. Recurrence free 2- and 5-year survival rates were 49 and 31%, respectively. The 5-year survival rates of patients with JPS-stage ? andthose with JPS-stage ? were 57 and 20%, respectively. The 5-year survival rates of patients with UICC-stage ?A and those with UICCstage ?B were 49 and 39%, respectively. Patients with UICC-stage ? or ? did not survive for more than 2 years. Conclusions No-touch pancreatectomy has many theoretic advantages that merit further investigation in future randomized controlled trials.

  18. Continuous taurocholic acid exposure promotes esophageal squamous cell carcinoma progression due to reduced cell loss resulting from enhanced vascular development.

    Directory of Open Access Journals (Sweden)

    Sho Sato

    Full Text Available BACKGROUND: Refluxogenic effects of smoking and alcohol abuse may be related to the risk of esophageal squamous cell carcinoma (ESCC. The present study attempts to clarify the effects of continuous taurocholic acid (TCA exposure, which is neither mutagenic nor genotoxic, on ESCC progression. METHODS: A squamous carcinoma cell line (ESCC-DR was established from a tumor induced in a rat model of gastroduodenal reflux. ESCC-DR cells were incubated with 2 mM TCA for ≥2 months. The effects of continuous TCA exposure were evaluated in vitro on cell morphology, growth, and invasion and in vivo on xenograft tumor growth in nude mice. Moreover, the mean level of secreted transforming growth factor (TGF-β1 and vascular endothelial growth factor (VEGF proteins in cell culture supernatants and mRNA synthesis of TGF-β1 and VEGF-A of ESCC cells were measured. The angiogenic potential was further examined by a migration assay using human umbilical vein endothelial cells (HUVECs. RESULTS: Continuous TCA exposure induced marked formation of filopodia in vitro. Expression levels of angiogenic factors were significantly higher in the cells treated with TCA than in control cells. Tumor xenografts derived from cells pre-exposed to TCA were larger and more vascularized than those derived from control cells. In addition, TCA exposure increased HUVEC migration. CONCLUSION: Continuous TCA exposure enhanced ESCC progression due to reduced cell loss in vivo. Cell loss was inhibited by TCA-induced vascular endothelial cell migration, which was mediated by TGF-β1 and VEGF-A released from ESCC cells.

  19. Piperlongumine selectively kills hepatocellular carcinoma cells and preferentially inhibits their invasion via ROS-ER-MAPKs-CHOP.

    Science.gov (United States)

    Chen, Yong; Liu, Ju Mei; Xiong, Xin Xin; Qiu, Xin Yao; Pan, Feng; Liu, Di; Lan, Shu Jue; Jin, Si; Yu, Shang Bin; Chen, Xiao Qian

    2015-03-20

    Hepatocellular carcinomas (HCC) are highly malignant and aggressive tumors lack of effective therapeutic drugs. Piperlongumine (PL), a natural product isolated from longer pepper plants, is recently identified as a potent cytotoxic compound highly selective to cancer cells. Here, we reported that PL specifically suppressed HCC cell migration/invasion via endoplasmic reticulum (ER)-MAPKs-CHOP signaling pathway. PL selectively killed HCC cells but not normal hepatocytes with an IC50 of 10-20 µM while PL at much lower concentrations only suppressed HCC cell migration/invasion. PL selectively elevated reactive oxygen species (ROS) in HCC cells, which activated or up-regulated downstream PERK/Ire 1α/Grp78, p38/JNK/Erk and CHOP subsequently. Administration of antioxidants completely abolished PL's effects on cell death and migration/invasion. However, pharmacological inhibition of ER stress-responses or MAPKs signaling pathways with corresponding specific inhibitors only reversed PL's effect on cell migration/invasion but not on cell death. Consistently, knocking-down of CHOP by RNA interference only reversed PL-suppressed HCC cell migration. Finally, PL significantly suppressed HCC development and activated the ER-MAPKs-CHOP signaling pathway in HCC xenografts in vivo. Taken together, PL selectively killed HCC cells and preferentially inhibited HCC cell migration/invasion via ROS-ER-MAPKs-CHOP axis, suggesting a novel therapeutic strategy for the highly malignant and aggressive HCC clinically. PMID:25788268

  20. Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-08-01

    Full Text Available Yuanyuan Zhao,1,* Jing Zhang,2,* Ying Tian,1,* Cong Xue,1 Zhihuang Hu,1 Li Zhang1,3 1Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, the First Affiliated Hospital of Guang Zhou Traditional Chinese Medicine University, 3National Anti-Cancer Drug Research Centre, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this work Purpose: We explored the effect of hepatocyte growth factor (HGF/Met signaling pathway on nasopharyngeal carcinoma (NPC cells in vitro and in vivo, and investigated the ability of Met tyrosine kinase inhibitor (TKI to block HGF-induced biological signaling.Experimental design: Met TKI inhibitor PF-2341066 alone, or in combination with cisplatin, was investigated for its ability to block HGF-induced signaling and biological effects in vitro and in vivo. HGF/Met expression and activation of signaling in NPC cells were detected by using Western blot and immunohistochemistry. Biological evaluation, including wound healing, cell proliferation, and invasion of NPC cells, was also examined, and the correlation between HGF/Met expression of primary and metastatic tumor in NPC patients and clinical prognosis were also analyzed.Results: Met TKI inhibitor, PF-2341066, inhibited growth of NPC cells in vivo with half maximal inhibitory concentration of 0.79±0.21 µmol/L, and suppressed invasion and migration of NPC cells; also, the inhibition of PF-2341066 was synergized with cisplatin treatment. Compared with the control group, Met TKI inhibited metastasis of transplanted NPC in nude mice (the number of live metastases [mean ± SD]: 5.8±2.2 versus 11.8±2.2, P=0.03; the number of lung metastases: 2.3±1.5 versus

  1. Aberrant methylation of Glutathione S-transferase P1 and E-cadherin in invasive ductal breast carcinoma and fibroadenoma

    Institute of Scientific and Technical Information of China (English)

    Wings Tjing Yung Loo; Mary Ngan Bing Cheung; Louis Wing Cheong Chow

    2010-01-01

    Objective To investigate the hypermethylation status of glutathione transferase P1(GSTP1) and E cadherin (ECAD), TSGs (tumor suppressor genes) in our breast cancer samples and explore their correlation with clinicopathological features of corresponding cancer patients. Methods One hundred and thirty six IDC (invasive ductal carcinoma) patients were recruited for analysis and 16 fibroadenoma patients acted as control. DNA extraction and methylation specific PCR (MSP) were subsequently performed preceded by pathological examination. Results The percentage of hypermethylated GSTP1 in carcinoma and fibroadenoma groups was 34.92% and 15.79% respectively and the percentage of hypermethylated ECAD in carcinomas and fibroadenomas was 18.00% and 0.00% respectively. Carcinoma had the highest percentage of c erbB2 overexpression being 54.55% among the clinicopathological parameters. Conclusion Hypermethylation patterns are frequent in IDC and seem to relate to c erbB2 overexpression, and such epigenetic change should not be neglected in fibroadenoma. Tumor methylation status in cancer patients can be determined at early stage and it may be a reference for better treatment planning.

  2. Anti-CSF-1 treatment is effective to prevent carcinoma invasion induced by monocyte-derived cells but scarcely by microglia

    Science.gov (United States)

    Rietkötter, Eva; Bleckmann, Annalen; Bayerlová, Michaela; Menck, Kerstin; Chuang, Han-Ning; Wenske, Britta; Schwartz, Hila; Erez, Neta; Binder, Claudia; Hanisch, Uwe-Karsten; Pukrop, Tobias

    2015-01-01

    The mononuclear phagocytic system is categorized in three major groups: monocyte-derived cells (MCs), dendritic cells and resident macrophages. During breast cancer progression the colony stimulating factor 1 (CSF-1) can reprogram MCs into tumor-promoting macrophages in the primary tumor. However, the effect of CSF-1 during colonization of the brain parenchyma is largely unknown. Thus, we analyzed the outcome of anti-CSF-1 treatment on the resident macrophage population of the brain, the microglia, in comparison to MCs, alone and in different in vitro co-culture models. Our results underline the addiction of MCs to CSF-1 while surprisingly, microglia were not affected. Furthermore, in contrast to the brain, the bone marrow did not express the alternative ligand, IL-34. Yet treatment with IL-34 and co-culture with carcinoma cells partially rescued the anti-CSF-1 effects on MCs. Further, MC-induced invasion was significantly reduced by anti-CSF-1 treatment while microglia-induced invasion was reduced to a lower extend. Moreover, analysis of lung and breast cancer brain metastasis revealed significant differences of CSF-1 and CSF-1R expression. Taken together, our findings demonstrate not only differences of anti-CSF-1 treatment on MCs and microglia but also in the CSF-1 receptor and ligand expression in brain and bone marrow as well as in brain metastasis. PMID:26098772

  3. MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma.

    Science.gov (United States)

    Chen, Jing-Song; Li, Hua-Shu; Huang, Jiong-Qiang; Dong, Shi-Hao; Huang, Zhi-Jie; Yi, Wei; Zhan, Gao-Fang; Feng, Ju-Tao; Sun, Jian-Cong; Huang, Xiao-Hui

    2016-05-28

    Some microRNAs (miRNAs) have been implicated in hepatocellular carcinoma (HCC) development and progression. However, the roles and mechanisms of several miRNAs in HCC remain poorly understood. Here, we report that miR-379-5p, which is down-regulated in HCC tissues and cell lines, is associated with advanced TNM stage and metastasis in HCC. The ectopic overexpression of miR-379-5p inhibited HCC cell migration, invasion, epithelial-to-mesenchymal transition (EMT) and metastasis both in vitro and in vivo. Conversely, miR-379 knockdown increased migration, invasion and EMT in HCC cells. Moreover, miR-379-5p exerted this function by directly targeting focal adhesion kinase (FAK) 3'-UTR and repressing FAK expression, thus leading to suppression of AKT signaling. Furthermore, the tumor suppressive effects of miR-379-5p in HCC cells were reversed by activating AKT signaling or restoring FAK expression. In clinical samples of HCC, miR-379-5p negatively correlated with FAK, which was up-regulated in HCC. Taken together, our findings highlight the important role of miR-379-5p in regulating the EMT and metastasis of HCC by targeting FAK/AKT signaling, suggesting that miR-379-5p may represent a novel potential therapeutic target and prognostic marker for HCC. PMID:26944318

  4. Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: An intricate pathway

    OpenAIRE

    Cardin, Romilda; Piciocchi, Marika; Bortolami, Marina; Kotsafti, Andromachi; Barzon, Luisa; Lavezzo, Enrico; Sinigaglia, Alessandro; Rodriguez-Castro, Kryssia Isabel; Rugge, Massimo; Farinati, Fabio

    2014-01-01

    The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma (HCC) are still ill-defined; however, there is increasing evidence that the gradual accumulation of mutations, genetic and epigenetic changes which occur in preneoplastic hepatocytes results in the development of dysplastic foci, nodules, and finally, overt HCC. As well as many other neoplasias, liver cancer is considered an “inflammatory cancer”, arising from a context of inflammat...

  5. Importance of Serum IL-18 and RANTES as Markers for Breast Carcinoma Progression

    International Nuclear Information System (INIS)

    Interleukin-18 (IL-18), a cytokine that plays an important role in the T-cell-helper response, acts as an angiogenic factor and a tumor suppressor. RANTES (regulated upon activation normal T-cells expressed and secreted) is a member of the C-C chemokine family with chemo attractant activity for a variety of cell types. High incidence and intensity of RANTES were noted in advanced breast carcinoma. Aim of tile Study: To correlate the levels of RANTES and IL- 18 in serum of breast cancer patients with bone or other organ metastasis compared to breast cancer patients without metastasis and healthy controls and to estimate the role of each of them as a prognostic marker for the progression of the disease. Patients and Methods: The study was conducted on 60 breast cancer patients (25 cases with no metastasis and 35 cases with metastasis) who were admitted to the outpatient clinic of the NCI, Cairo University during the period from March 2004 to September 2004 and 30 apparently healthy controls who were volunteers at the blood bank of the NCI, Cairo University. Showed that there was a statistically significant difference between the level of IL- 18 in breast cancer patients without metastasis and the control group (ρ< 0.05) while there was a highly significant difference between the metastatic group and the control group (ρ<0.0001). There was a significant increase in IL-18 levels between metastatic and non-metastatic cases (ρ<0.01). RANTES showed a significant increase in breast cancer cases with no metastasis and the control group (ρ<0.05) and it showed a highly significant increase in metastatic patients compared to controls (ρ<0.0001). There was no significant increase in the level of RANTES in metastatic compared to non-metastatic patients (ρ<0.05). IL-18 is an important non invasive marker suspecting metastasis. Even though RANTES levels were higher in cancer patients compared to controls, its role in staging of breast cancer was not clear in this study

  6. Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Skakkebaek, N E

    1994-01-01

    Carcinoma-in-situ of the testis (CIS) is the precursor of invasive germ cell tumours. It is believed that CIS cells may originate from early fetal gonocytes. Recently, the proto-oncogene c-kit has been implicated as crucial for the development and migration of primordial germ cells. In this study......, CIS and overtly invasive human male germ cell tumours were analysed immunohistochemically for expression of the c-kit proto-oncogene protein product. Testicular tissue samples from 36 patients with various types of testicular germ cell neoplasia and 19 control specimens were stained using an indirect...... in 61% of the samples while focal expression was observed in 39% of the samples studied. No expression of c-kit was detected in non-seminomas or in normal testicular germ cells. High expression of the proto-oncogene in CIS cells supports the hypothesis of their origin from primordial germ cells...

  7. Significance of Epithelial-mesenchaymal Transition Phenotype in Invasive Tumor Front Cells of Lung Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Yinghua SONG

    2014-04-01

    Full Text Available Background and objective The invasive tumor front (ITF refers to cells or invasive nests in the junctional region of a tumor and its host. The ITF contains the most invasive cells of a tumor, and has a high prognostic value in carcinoma. The aim of this study is to investigate the epithelial-mesenchymal transformation phenotype in ITF cells of lung squamous cell carcinoma (SCC, and analyze the relationship between clinicopathological features and clinical outcomes of patients. Methods Semiquantitative immunohistochemistry was used to examine the expression of epithelial markers (E-cadherin and β-catenin and mesenchymal marker (vimentin in 104 lung SCC tumor tissues. Results A decrease in E-cadherin expression in ITF cells was observed in 56 of 104 (53.8% tumors from patients. This result was markedly lower than that of non-ITF cells, which eventually developed metastatic tumors and were also associated with death (P=0.04. Vimentin expression was observed in 44 of 104 (42.3% ITF cells, which was much higher than that of non-ITF cells. The downregulation of E-cadherin and overexpression of vimentin were associated with tumor invasive pattern, lymphatic metastasis, and poor prognosis (P<0.01. The expression of β-catenin was 67.3% (70/104 in ITF cells. Moreover, ITF cells showed more nuclear and plasma-positive cells, which were closely associated with metastasis (P<0.01. Conclusion The loss in expression of E-cadherin/β-catenin and overexpression of vimentin in ITF cells may be associated with poor prognosis of lung SCC patients.

  8. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Lin Yang; Li-Ge Kuang; Hua-Chuan Zheng; Jin-Yi Li; Dong-Ying Wu; Su-Min Zhang; Yan Xin

    2003-01-01

    AIM: To detect the expression of PTEN encoding productin normal mucosa, intestinal metaplasia (IM), dysplasia andcarcinoma of the stomach, and to investigate its clinicalimplication in tumorigenesis and progression of gastriccarcinoma.METHODS: Formalin-fixed paraffin embedded specimens from184 cases of gastric carcinoma, their adjacent normal mucosa,IM and dysplasia were evaluated for PTEN protein expressionby SABC immunohistochemistry. PTEN expression wascompared with tumor stage, lymph node metastasis, Lauren'sand WHO's histological classification of gastric carcinoma.Expression of VEGF was also detected in 60 cases of gastriccarcinoma and its correlation with PTEN was concerned.RESULTS: The positive rates of PTEN protein were 100 %(102/102), 98.5 %(65/66), 66.7 % (4/6) and 47.8 %(88/184)in normal mucosa, IM, dysplasia and carcinoma of the stomach,respectively. The positive rates in dysplasia and carcinomawere lower than in normal mucosa and IM (P<0.01).Advanced gastric cancers expressed less frequent PTEN thanearly gastric cancer (42.9 % v567.6 %, P<0.01). The positiverate of PTEN protein was lower in gastric cancer with thanwithout lymph node metastasis (40.3 % v563.3 %, P<0.01).PTEN was less expressed in diffuse-type than in intestinal-type gastric cancer (41.5 % v557.8 %,P<0.05). Signet ringcell carcinoma showed the expression of PTEN at the lowestlevel (25.0 %, 7/28); less than well and moderatelydifferentiated ones (P<0.01). Expression of PTEN was notcorrelated with expression of VEGF (P>0.05).CONCLUSION: Loss or reduced expression of PTEN proteinoccures commonly in tumorigenesis and progression of gastriccarcinoma. It is suggested that PTEN can be an objective markerfor pathologically biological behaviors of gastric carcinoma.

  9. Tumor cyclooxygenase-2 levels correlate with tumor invasiveness in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Terence C. Tang; Ronnie T. Poon; Cecilia P. Lau; Dan Xie; Sheung Tat Fan

    2005-01-01

    AIM: Recent studies suggested that cyclooxygenase-2(COX-2) enhances tumor angiogenesis via upregulationof vascular endothelial growth factor (VEGF). AlthoughCOX-2 expression has been demonstrated in hepatocellularcarcinoma (HCC), the significance of COX-2 in progressionof HCC remains unclear. This study evaluated the clinico-pathological correlation of COX-2 level and its relationshipwith VEGF level in HCC.METHODS: Fresh tumor tissues were obtained from 100patients who underwent resection of HCC. COX-2 proteinexpression was examined by immunohistochemistry, andquantitatively by an enzyme immunometric assay (EIA)of tumor cytosolic COX-2 levels. Tumor cytosolic VEGFlevels were measured by an ELISA.RESULTS: Immunostaining showed expression of COX-2in tumor cells. Tumor cytosolic COX-2 levels correlatedwith VEGF levels (r = 0.469, P<0.001). Correlation withclinicopathological features showed significantly highertumor cytosolic COX-2 levels in the presence of multipletumors (P = 0.027), venous invasion (P = 0.030),microsatellite lesions (P = 0.037) and advanced tumorstage (P = 0.008). Higher tumor cytosolic COX-2 levelswere associated with worse patient survival.CONCLUSION: This study shows that elevated tumorCOX-2 levels correlate with elevated VEGF levels andinvasiveness in HCC, suggesting that COX-2 plays a significantrole in the progression of HCC.

  10. The lipid-reactive oxygen species phenotype of breast cancer. Raman spectroscopy and mapping, PCA and PLSDA for invasive ductal carcinoma and invasive lobular carcinoma. Molecular tumorigenic mechanisms beyond Warburg effect.

    Science.gov (United States)

    Surmacki, Jakub; Brozek-Pluska, Beata; Kordek, Radzislaw; Abramczyk, Halina

    2015-04-01

    Vibrational signatures of human breast tissue (invasive ductal carcinoma and invasive lobular carcinoma) were used to identify, characterize and discriminate structures in normal (noncancerous) and cancerous tissues by confocal Raman imaging, Raman spectroscopy and IR spectroscopy. The most important differences between normal and cancerous tissues were found in regions characteristic for vibrations of carotenoids, fatty acids, proteins, and interfacial water. Particular attention was paid to the role played by unsaturated fatty acids and their derivatives. K-means clustering and basis analysis followed by PCA and PLSDA is employed to analyze Raman spectroscopic maps of human breast tissue and for a statistical analysis of the samples (82 patients, 164 samples). Raman maps successfully identify regions of carotenoids, fatty acids, and proteins. The intensities, frequencies and profiles of the average Raman spectra differentiate the biochemical composition of normal and cancerous tissues. The paper demonstrates that Raman imaging has reached a clinically relevant level in regard to breast cancer diagnosis applications. The sensitivity and specificity obtained directly from PLSLD and cross validation are equal to 90.5% and 84.8% for calibration and 84.7% and 71.9% for cross-validation respectively.

  11. Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis

    Directory of Open Access Journals (Sweden)

    Srovnal Josef

    2007-03-01

    Full Text Available Abstract Background Invasive ductal and lobular carcinomas (IDC and ILC are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells. Methods We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17 was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR. Results Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1 distinguished large sets of IDC from ILC. Conclusion IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN and collagen triple helix repeat containing 1 (CTHRC1 which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue

  12. Effects of 5-aza-2′deoxycytidine on RECK gene expression and tumor invasion in salivary adenoid cystic carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, X.Q. [Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan (China); Department of Oral and Maxillofacial Surgery, The First People' s Hospital of Jining, Shandong (China); Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan (China); Huang, S.Y. [Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan (China); Zhang, D.S. [Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan (China); Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan (China); Zhang, S.Z.; Li, W.G.; Chen, Z.W.; Wu, H.W. [Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital, Affiliated to Shandong University, Jinan (China)

    2014-12-12

    Reversion-inducing cysteine-rich protein with kazal motifs (RECK), a novel tumor suppressor gene that negatively regulates matrix metalloproteinases (MMPs), is expressed in various normal human tissues but downregulated in several types of human tumors. The molecular mechanism for this downregulation and its biological significance in salivary adenoid cystic carcinoma (SACC) are unclear. In the present study, we investigated the effects of a DNA methyltransferase (DNMT) inhibitor, 5-aza-2′deoxycytidine (5-aza-dC), on the methylation status of the RECK gene and tumor invasion in SACC cell lines. Methylation-specific PCR (MSP), Western blot analysis, and quantitative real-time PCR were used to investigate the methylation status of the RECK gene and expression of RECK mRNA and protein in SACC cell lines. The invasive ability of SACC cells was examined by the Transwell migration assay. Promoter methylation was only found in the ACC-M cell line. Treatment of ACC-M cells with 5-aza-dC partially reversed the hypermethylation status of the RECK gene and significantly enhanced the expression of mRNA and protein, and 5-aza-dC significantly suppressed ACC-M cell invasive ability. Our findings showed that 5-aza-dC inhibited cancer cell invasion through the reversal of RECK gene hypermethylation, which might be a promising chemotherapy approach in SACC treatment.

  13. miR-940 Suppresses Tumor Cell Invasion and Migration via Regulation of CXCR2 in Hepatocellular Carcinoma

    Science.gov (United States)

    Ding, Dong; Zhang, Yaodong; Yang, Renjie; Wang, Xing; Ji, Guwei; Huo, Liqun; Shao, Zicheng

    2016-01-01

    Aim. To investigate the expression of miR-940 in the hepatocellular carcinoma (HCC) and its impact on function and biological mechanism in the HCC cells. Methods. Quantitative RT-PCR analysis was used to quantify miR-940 expression in 46 cases of tissues and cells. Transfection of HCC cell lines was performed by miR-940 mimics; the abilities of invasion and migration were assessed through Transwell array. Western blot represents the alteration in expression of CXCR2 by miR-940 mimics. Results. miR-940 expression was decreased significantly in the HCC tissues and the relevant cell lines. miR-940 upregulation suppressed the invasion and migration of HCC cells in vitro. Furthermore, the CXCR2 was downregulated to suppress invasion and migration after miR-940 mimics. Moreover, decreased miR-940 expression was negatively correlated with Edmondson grade (P = 0.008), tumor microsatellite or multiple tumors (P = 0.04), vascular invasion (P = 0.035), and recurrence and metastasis (P = 0.038). Kaplan-Meier analysis demonstrated that decreased miR-940 expression contributed to poor overall survival (P migration in vitro. Our study suggests that miR-940 may be a novel poor prognostic biomarker for HCC.

  14. Epidemiology and patterns of care for invasive breast carcinoma at a community hospital in Southern India

    Directory of Open Access Journals (Sweden)

    Venkata Phanindra

    2007-05-01

    Full Text Available Abstract Background Breast cancer incidence in India is on rise. We report epidemiological, clinical and survival patterns of breast cancer patients from community perspective. Methods All breast cancer patients treated at this hospital from July 2000 to July 2005 were included. All had cytological or histological confirmation of breast cancer. TNM guidelines for staging and Immunohistochemistry to assess the receptor status were used. Either lumpectomy with axillary lymph node dissection or Modified radical mastectomy (MRM was done for operable breast cancer, followed by 6 cycles of adjuvant chemotherapy with FAC or CMF regimens to patients with pT >1 cm or lymph node positive or estrogen receptor negative and radiotherapy to patients after breast conservation surgery, pT size > 5 cm, 4 or more positive nodes and stage IIIB disease. Patients with positive Estrogen receptor or Progesterone receptor were advised Tamoxifene 20 mg per day for 3 years. Descriptive analysis was performed. Independent T test and Chi-square test were used. Overall survival time was computed by Kaplan – Meier method. Results Of 1488 cancer patients, 122 (8.2% had breast cancer. Of 122 patients, 96.7% had invasive breast carcinoma and 3.3% had sarcoma. 94% came from the rural and semi urban areas. Premenopausal women were 27%. The median age was 50 years. Stage I-6.8%, II-45.8%, III-22%, IV-6.8%, Bilateral breast cancer – 2.5%. The mean pT size was 3.9 cm. ER and PR were positive in 31.6% and 28.1% respectively. MRM was done in 93.8%, while 6.3% patients underwent breast conservation surgery. The mean of the lymph nodes dissected were 3. CMF and FAC regimens were used in 48.8% and 51.2% of patients respectively. FAC group were younger than the CMF group (43.6 yr vs. 54 yrs, P = 0.000. Toxicities were more in FAC than CMF group, alopecia (100% vs. 26.2%, grade2 or more emesis (31.8% vs. 9.2%, grade2 or more fatigue (40.9% vs.19%, anemia (43.1% vs. 16.6%. Median

  15. Prognostic value of immunohistochemical stratification of invasive duct carcinoma of the breast

    Institute of Scientific and Technical Information of China (English)

    Asmaa Salama; Habiba El-Fendy; Sahar Talaat; Badaweya Bayomi; Amr Amin

    2013-01-01

    Objective: Gene expression profiling of breast cancer has identified five molecularly distinct subtypes of breast cancer that have different biological behavior and clinical outcomes. These subtypes are termed luminal A, luminal B, luminal HER2, HER2-enriched and triple negative breast cancers (TNBC). We aimed at identification of breast cancer subtypes among Egyptian population and their clinicopathologic features using ER, PR and HER2, Ki-67 and CK5/6. Methods: Tumors from 100 patients with invasive duct carcinoma were subtyped by immunohistochemistry using ER, PR, HER2, Ki-67 and CK5/6. The prognostic value of the immunohistochemical assignment for breast cancer disease-specific survival was investigated by using Kaplan-Meier curves. Results: Immunohistochemical profiling classified 22 cases as luminal A, 33 cases as luminal B, 9 cases as luminal HER2, 26 cases as HER2-enriched and 10 cases as TNBC. Tumors that measured more than 3.5 cm, showed predominance of HER2-enriched subtype. HER2-enriched and luminal B subtypes dominated the node positive cases (35.4% and 33.8%; respectively). Large tumor size (> 3.5 cm), hormone receptor negative state and HER2 positive state were associated with poor prognosis. Disease free survivals (DFSs) were significantly different (P < 0.0001) among different breast subtypes with worst 2-year DFS for HER2-enriched subtype (40.77%) followed by luminal A (63.56%). DFS was almost similar in the remaining other subtypes, and luminal B, luminal HER2 and TNBC which were 86.85%, 87.5% and 88.89%; respectively. Conclusion: ER, PR, HER2 and Ki-67 constituted a strong surrogate for molecular breast cancer subtypes and can be easily applied. HER2-enriched subtype carries worse features being associated with large tumor size, nodal metastasis and is associated with poor outcome. Luminal A is a heterogeneous subtype with underlying several factors that can turn its prognosis adversely. TNBC subtype may behave unexpected in a favorable way.

  16. Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status

    Energy Technology Data Exchange (ETDEWEB)

    Farquharson, M J [Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main St W Hamilton, Ontario, L8S 4L8 (Canada); Al-Ebraheem, A [Department of Radiography, City Community and Health Sciences, City University, London, EC1V 0HB (United Kingdom); Geraki, K [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxon, OX11 0DE (United Kingdom); Leek, R; Jubb, A; Harris, A L [Cancer Research UK, Oxford Cancer Centre, Molecular Oncology Laboratories, University of Oxford, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, 0X3 9DS (United Kingdom)], E-mail: farquhm@mcmaster.ca

    2009-07-07

    Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P < 0.001) and a non-significant increase in the ER-ve samples. When comparing the increase in zinc in the tumour regions expressed as a percentage of the surrounding non-tumour tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01)

  17. The Role of Epithelial Mesenchymal Transition Markers in Thyroid Carcinoma Progression

    Science.gov (United States)

    Montemayor-Garcia, Celina; Hardin, Heather; Guo, Zhenying; Larrain, Carolina; Buehler, Darya; Asioli, Sofia; Chen, Herbert; Lloyd, Ricardo V.

    2013-01-01

    Understanding the molecular mechanisms involved in thyroid cancer progression may provide targets for more effective treatment of aggressive thyroid cancers. Epithelial-mesenchymal transition (EMT) is a major pathologic mechanism in tumor progression and is linked to the acquisition of stem-like properties of cancer cells. We examined expression of ZEB1 which activates EMT by binding to the E-box elements in the E-cadherin promoter, and expression of E-cadherin in normal and neoplastic thyroid tissues in a tissue microarray (TMA) which included 127 neoplasms and 10 normal thyroid specimens. Thyroid follicular adenomas (FA, n=32), follicular thyroid carcinomas (FTC, n=28), and papillary thyroid carcinomas (PTC, n=57) all expressed E-cadherin and were mostly negative for ZEB1 while most anaplastic thyroid carcinomas (ATC, n=10) were negative for E-cadherin, but positive for ZEB1. A validation set of 10 whole sections of ATCs showed 90% of cases positive for ZEB1 and all cases were negative for E-cadherin. Analysis of three cell lines (normal thyroid, NTHY-OR13-1; PTC, TPC-1 and ATC, THJ-21T) showed that the ATC cell line expressed the highest levels of ZEB1 while the normal thyroid cell line expressed the highest levels of E-Cadherin. Quantitative RT-PCR analyses showed that Smad7 mRNA was significantly higher in ATC than in any other group (p<0.05). These results indicate that ATCs show evidence of EMT including decreased expression of E-cadherin and increased expression of ZEB1 compared to well differentiated thyroid carcinomas and that increased expression of Smad7 may be associated with thyroid tumor progression. PMID:24126800

  18. Perfil imuno-histoquímico de carcinomas mamários invasores em homens Immunohistochemical profile of invasive male breast carcinomas

    Directory of Open Access Journals (Sweden)

    Alexandra Medeiros Souza de Freitas

    2008-10-01

    phenotypes of male breast carcinomas is little known. We analyzed the clinical and immunohistochemical data of a sample comprising 20 cases of invasive male breast tumor. We used a panel of five antibodies that encompasses estrogen receptor, cytokeratins 5/6, cytokeratins 8/18, HER1 and HER2. Among these 20 cases, 19 were non-special ductal carcinomas (95% and one was a lobular carcinoma (5%. Most cases were mastectomies (65% and the average size of the neoplasias was 2.8 cm. The most frequent histological grade was II (60%. Axillary lymph node metastases were presented by 86.6% of the total cases. The average number of affected lymph nodes was 5.2 in the samples with positive nodes. Fourteen tumors corresponded to ER+/luminal phenotype (70%, two were classified as undetermined (10%, one (5% belonged to the basal phenotype and three breast tumors (15% corresponded to HER2-positive phenotype. The immunohistochemical results of the male breast carcinomas allow us to make comparisons with female breast tumors, what may elucidate the intrinsic factors of the disease in each gender.

  19. Role of CDH12 siRNA on invasiveness of salivary adenoid cystic carcinoma cells%CDH12基因siRNA对涎腺腺样囊性癌细胞侵袭力的影响

    Institute of Scientific and Technical Information of China (English)

    苏柏华; 王锦锋; 佘林; 郑斐斐; 丁林灿; 卢友光

    2011-01-01

    目的:探讨钙粘素12(Cadherin 12,CDH12)对涎腺腺样囊性癌(Salivary adenoid cystic carcinoma,SACC)细胞侵袭和转移能力的影响.方法:以人涎腺腺样囊性癌高转移细胞株(Salivary adenoid cystic carcinoma cell line with high metastatic ability,SACC-M)为研究对象,利用CDH12小分子干扰RNA(Small interfering RNA,siRNA)对CDH12基因进行沉默,Western blot检测转染前后CDH12的表达变化.Cell Counting Kit-8法检测转染前后细胞的生长速度,体外侵袭实验比较细胞侵袭能力变化,体外迁移运动实验比较细胞运动能力的改变.结果:CDH12 siRNA明显下调CDH12基因的表达.CDH12表达下调后,SACC-M细胞体外侵袭能力显著降低,体外迁移运动能力明显降低.结论:CDH12明显地促进了SACC细胞的体外侵袭和迁移运动,提示CDH12可能在SACC的恶性进展中起着重要作用.%Objective:To study the effect of CDH12 on invasion and migration of human salivary adenoid cystic carcinoma cells in vitro. Methods:The highly metastatic human salivary adenoid cystic carcinoma cell line SACC-M was transfected by CDH12 siRNA to silence CDH12 gene. The protein expression of CDH12,before and after siRNA transfection,was examined by Western blot. Cell growth rate was determined with Cell Counting Kit-8.At the same time,the invasive capability and migration capability were evaluated by tumour invasion assay and migration assay, respectively. Results CDH 12 siRNA transfection specifically down-regulated the CDH 12 protein in SACC-M cells. The downregulation of CDH12 supressed the invasive capability and migration capability of SACC-M cells. Conclusion:CDH12 obviously promotes the invasion and migration of SACC cells in vitro. These results suggest that CDH12 may play an important role in the malignant progression in salivary adenoid cystic carcinoma.

  20. Integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

    Energy Technology Data Exchange (ETDEWEB)

    Sansing, Hope A. [Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center-New Orleans, School of Dentistry, New Orleans, LA (United States); Sarkeshik, Ali; Yates, John R. [Department of Chemical Physiology, Scripps Research Institute, La Jolla, CA (United States); Patel, Vyomesh; Gutkind, J. Silvio [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Yamada, Kenneth M. [Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Berrier, Allison L., E-mail: allison.berrier@gmail.com [Department of Oral and Craniofacial Biology, Louisiana State University Health Sciences Center-New Orleans, School of Dentistry, New Orleans, LA (United States)

    2011-03-11

    Research highlights: {yields} Proteomics of clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} receptors in oral carcinoma. {yields} p130Cas, Dek, Src and talin regulate oral carcinoma invasion. {yields} p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomics screen of proteins recruited to clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta} or {alpha}{sub 6}{beta} receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.

  1. Patients without hepatocellular carcinoma progression after transarterial chemoembolization benefit from liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Aiman Obed; Alexander Beham; Kerstin Püllmann; Heinz Becker; Hans J Schlitt; Thomas Loft

    2007-01-01

    AIM: To assess the outcome of patients, who underwent transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) and subsequently liver transplantation (OLT) irrespective of tumor size when no tumor progression was observed.METHODS: Records, imaging studies and pathology of 84 patients with HCC were reviewed. Ten patients were not treated at all, 67 patients had TACE and 35 of them were listed for OLT. Tumor progression was monitored by ultrasound and AFP level every 6 wk. Fifteen patients showed signs of tumor progression without transplantation. The remaining 20 patients underwent OLT. Further records of 7 patients with HCC seen in histological examination after OLT were included.RESULTS: The patients after TACE without tumor progression underwent transplantation and had a median survival of 92.3 mo. Patients, who did not qualify for liver transplantation or had signs of tumor progression had a median survival of 8.4 mo. The patients without treatment had a median survival of 3.8 mo. Independent of International Union Against Cancer (UICC) stages, the patients without tumor progression and subsequent OLT had longer median survival. No significant difference was seen in the OLT treated patients if they did not fulfill the Mlilan criteria.CONCLUSION: Selection of patients for OLT based on tumor progression results in good survival. The evaluation of HCC patients should not only be based on tumor size and number of foci but also on tumor progression and growth behavior under therapy.

  2. Identification of the boundary between normal breast tissue and invasive ductal carcinoma during breast-conserving surgery using multiphoton microscopy

    Science.gov (United States)

    Deng, Tongxin; Nie, Yuting; Lian, Yuane; Wu, Yan; Fu, Fangmeng; Wang, Chuan; Zhuo, Shuangmu; Chen, Jianxin

    2014-11-01

    Breast-conserving surgery has become an important way of surgical treatment for breast cancer worldwide nowadays. Multiphoton microscopy (MPM) has the ability to noninvasively visualize tissue architectures at the cellular level using intrinsic fluorescent molecules in biological tissues without the need for fluorescent dye. In this study, MPM is used to image the microstructures of terminal duct lobular unit (TDLU), invasive ductal carcinoma and the boundary region between normal and cancerous breast tissues. Our study demonstrates that MPM has the ability to not only reveal the morphological changes of the cuboidal epithelium, basement membrane and interlobular stroma but also identify the boundary between normal breast tissue and invasive ductal carcinoma, which correspond well to the Hematoxylin and Eosin (H and E) images. Predictably, MPM can monitor surgical margins in real time and provide considerable accuracy for resection of breast cancerous tissues intraoperatively. With the development of miniature, real-time MPM imaging technology, MPM should have great application prospects during breast-conserving surgery.

  3. Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland.

    Science.gov (United States)

    Annunziato, Stefano; Kas, Sjors M; Nethe, Micha; Yücel, Hatice; Del Bravo, Jessica; Pritchard, Colin; Bin Ali, Rahmen; van Gerwen, Bas; Siteur, Bjørn; Drenth, Anne Paulien; Schut, Eva; van de Ven, Marieke; Boelens, Mirjam C; Klarenbeek, Sjoerd; Huijbers, Ivo J; van Miltenburg, Martine H; Jonkers, Jos

    2016-06-15

    Large-scale sequencing studies are rapidly identifying putative oncogenic mutations in human tumors. However, discrimination between passenger and driver events in tumorigenesis remains challenging and requires in vivo validation studies in reliable animal models of human cancer. In this study, we describe a novel strategy for in vivo validation of candidate tumor suppressors implicated in invasive lobular breast carcinoma (ILC), which is hallmarked by loss of the cell-cell adhesion molecule E-cadherin. We describe an approach to model ILC by intraductal injection of lentiviral vectors encoding Cre recombinase, the CRISPR/Cas9 system, or both in female mice carrying conditional alleles of the Cdh1 gene, encoding for E-cadherin. Using this approach, we were able to target ILC-initiating cells and induce specific gene disruption of Pten by CRISPR/Cas9-mediated somatic gene editing. Whereas intraductal injection of Cas9-encoding lentiviruses induced Cas9-specific immune responses and development of tumors that did not resemble ILC, lentiviral delivery of a Pten targeting single-guide RNA (sgRNA) in mice with mammary gland-specific loss of E-cadherin and expression of Cas9 efficiently induced ILC development. This versatile platform can be used for rapid in vivo testing of putative tumor suppressor genes implicated in ILC, providing new opportunities for modeling invasive lobular breast carcinoma in mice. PMID:27340177

  4. Differential Effects of Leptin on the Invasive Potential of Androgen-Dependent and -Independent Prostate Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Dayanand D. Deo

    2008-01-01

    Full Text Available Obesity has been linked with an increased risk of prostate cancer. The formation of toxic free oxygen radicals has been implicated in obesity mediated disease processes. Leptin is one of the major cytokines produced by adipocytes and controls body weight homeostasis through food intake and energy expenditure. The rationale of the study was to determine the impact of leptin on the metastatic potential of androgen-sensitive (LNCaP cells as well as androgen-insensitive (PC-3 and DU-145 cells. At a concentration of 200_nm, LNCaP cells showed a significant increase (20% above control; P<.0001 in cellular proliferation without any effect on androgen-insensitive cells. Furthermore, exposure to leptin caused a significant (P<.01 to P<.0001 dose-dependent decrease in migration and invasion of PC3 and Du-145 prostate carcinoma cell lines. At the molecular level, exposure of androgen-independent prostate cancer cells to leptin stimulates the phosphorylation of MAPK at early time point as well as the transcription factor STAT3, suggesting the activation of the intracellular signaling cascade upon leptin binding to its cognate receptor. Taken together, these results suggest that leptin mediates the invasive potential of prostate carcinoma cells, and that this effect is dependent on their androgen sensitivity.

  5. Clinicopathologic features of sentinel node metastases predictive of positive axillary clearance in grade 1 invasive breast carcinoma.

    LENUS (Irish Health Repository)

    Hayes, B

    2012-02-01

    BACKGROUND: Sentinel node (SN) biopsy is widely used to stage breast carcinoma and, when positive, typically leads to axillary clearance (AC). AIMS: This study assesses clinicopathologic features of grade 1 breast carcinoma SNs with the aim of identifying a group of patients, who are likely to have a negative AC and can, therefore, safely be spared further surgery. RESULTS: Two hundred and forty-seven patients with grade 1 invasive carcinoma were identified, of whom 29 had a positive SN. Four patients (13.8%) had a positive AC. Positive AC occurred in 3 of 6 (50%) patients whose SN showed extranodal extension (EE), but in only 1 of 23 (4.3%) patients without EE. All patients were staged as pN1(sn) following SN biopsy: only one, who had a 5.27 mm metastasis with EE, was pN2 following AC. CONCLUSIONS: Extranodal extension is a significant predictor of a positive AC in this group. In its absence, AC did not alter the post-SN biopsy pN stage.

  6. Invasive lobular carcinoma of the breast with extracellular mucin: A case report

    Directory of Open Access Journals (Sweden)

    G.S. Gómez Macías

    2016-01-01

    Conclusion: It is important to know that extracellular mucin production is not exclusive of ductal lesions and keep in mind the lobular carcinomas with extracellular mucin as a differential diagnosis.

  7. The Pattern of Myometrial Invasion As a Predictor of Lymph Node Metastasis or Extrauterine Disease in Low Grade Endometrial Carcinoma

    Science.gov (United States)

    Euscher, Elizabeth; Fox, Patricia; Bassett, Roland; Al-Ghawi, Hayma; Ali-Fehmi, Rouba; Barbuto, Denise; Djordjevic, Bojana; Frauenhoffer, Elizabeth; Kim, Insun; Hong, Sun Rang; Montiel, Delia; Moschiano, Elizabeth; Roma, Andres; Silva, Elvio; Malpica, Anais

    2013-01-01

    The purpose of this study was to examine predictors of lymph node metastases (LN+) or extrauterine disease (ED) in low grade (FIGO grades 1 or 2) endometrioid carcinoma (LGEC) in a multi institutional setting. For LGEC with and without LNM or ED, each of the 9 participating institutions evaluated patients age, tumor size, myometrial invasion (MI), FIGO grade, % solid component, the presence or absence of papillary architecture, microcystic elongated and fragmented glands (MELF) and single cell/cell cluster invasion (SCI), lymphovascular invasion (LVI), lower uterine segment (LUS) and cervical stromal (CX) involvement and numbers of pelvic (PLN) and para-aortic (PALN) LNs sampled.302 cases were reviewed: LN+ or ED +, 96; LN-/ED-, 208. Patients' ages ranged from 23-91 yrs (median 61). Table 1 summarizes the histopathologic variables that were noted for the LN+ or ED+ group: tumor size ≥2cm, 93/96 (97%), MI >50%, 54/96 (56%), MELF, 67/96 (70%), SCI, 33/96 (34%), LVI, 79/96 (82%), >20% solid, 65/96 (68%), papillary architecture present, 68/96 (72%), LUS involved, 64/96 (67%) and CX involved, 31/96 (32%). For the LN-/ED- group, the results were as follows: tumor size ≥2cm, 152/208 (73%), MI >50%, 56/208 (27%), MELF, 79/208 (38%), single cell invasion, 19/208 (9%) , LVI, 56/208 (27%), >20% solid, 160/208 (77%), papillary architecture present, 122/208 (59%), LUS involved, 77/208 (37%), CX involved, 31/208 (15%). There was no evidence of a difference in the number of pelvic or para-aortic LNs sampled between groups (p=0.9 and 0.1, respectively). Following multivariate analysis, depth of myometrial invasion, cervical stromal involvement, lymphovascular space invasion, and the single cell pattern of invasion emerged as significant predictors of advanced stage disease. Although univariate analysis pointed to LUS involvement, MELF pattern of invasion, and papillary architecture as possible predictors of advanced stage disease, these were not shown to be significant by

  8. Development and Validation of Web-Based Nomograms to Predict Postoperative Invasive Component in Ductal Carcinoma in Situ at Needle Breast Biopsy

    OpenAIRE

    Lee, Seong Cheol; Chang, Myung-Chul

    2014-01-01

    Objectives Although sonography-guided core needle biopsy is a highly targeted method, there is a possibility of an invasive component after surgical excision of ductal carcinoma in situ (DCIS) of the breast. This study was performed to develop and validate nomograms to predict the postoperative invasive component in DCIS at core needle biopsy. Methods Two nomograms were developed using the data of previous meta-analysis and multivariate analysis. Nomograms were validated externally using the ...

  9. Interferon-alpha restrains growth and invasive potential of hepatocellular carcinoma induced by hepatitis B virus X protein

    Institute of Scientific and Technical Information of China (English)

    Jian-Qing Yang; Guang-Dong Pan; Guang-Ping Chu; Zhen Liu; Qiang Liu; Yi Xiao; Lin Yuan

    2008-01-01

    AIM: To investigate the effects of interferon-alpha (IFN-α) to restrain the growth and invasive potential of hepatocellular carcinoma (HCC) induced by hepatitis B virus (HBV) X protein.METHODS: The pcDNA3.1-HBx plasmid was transfected into Chang cells by Lipofectamine In vitro,and Chang/HBx was co-cultured with IFN-α.Cell survival growth curve and donogenicity assay were used to test the growth potential of Chang/pcDNA3.1,Chang/Hbxand IFN-a-Chang/HBx in vitro.Growth assay in nude mice was used to detect the growth potential of Chang/pcDNA3.1,Chang/HBx and IFN-α-Chang/HBx in vivo.Wound healing and transwell migration assays were used to detect the invasive ability of Chang/pcDNA3.1,Chang/HBx and IFN-α-Chang/HBx.RESULTS: Compared with CCL13 cells transfected with pcDNA3.1,CCL13 with stable expression of hepatitis B virus X protein showed the characteristics of malignant cells with high capability of growth and invasion by detecting their growth curves,colony forming efficiency,wound healing,transwell migration assays and growth assays in nude mice.Its capability of growth and invasion could be controlled by IFN-α.CONCLUSION: IFN-α can restrain the growth and invasive potential of HCC cells induced by HBx protein,which has provided an experimental basis for IFN-αtherapy of HCC.

  10. miR-4295 promotes cell proliferation and invasion in anaplastic thyroid carcinoma via CDKN1A

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Mingchen; Geng, Yiwei [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Xi, Ying [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Wei, Sidong [Liver Transplantation Hepatobiliary Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Wang, Liuxing; Fan, Qingxia [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China); Ma, Wang, E-mail: doctormawang@126.com [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Laboratory of Tumor Biology, Zhengzhou University, Zhengzhou (China)

    2015-09-04

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in anaplastic thyroid carcinoma (ATC), has remained elusive. Here, we identified that miR-4295 promotes ATC cell proliferation by negatively regulates its target gene CDKN1A. In ATC cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-4295, while miR-4295 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-4295 mimics significantly promoted the migration and invasion of ATC cells, whereas miR-4295 inhibitors significantly reduced cell migration and invasion. luciferase assays confirmed that miR-4295 directly bound to the 3'untranslated region of CDKN1A, and western blotting showed that miR-4295 suppressed the expression of CDKN1A at the protein levels. This study indicated that miR-4295 negatively regulates CDKN1A and promotes proliferation and invasion of ATC cell lines. Thus, miR-4295 may represent a potential therapeutic target for ATC intervention. - Highlights: • miR-4295 mimics promote the proliferation and invasion of ATC cells. • miR-4295 inhibitors inhibit the proliferation and invasion of ATC cells. • miR-4295 targets 3′UTR of CDKN1A in ATC cells. • miR-4295 negatively regulates CDKN1A in ATC cells.

  11. Axillary fine needle aspiration cytology for pre-operative staging of patients with screen-detected invasive breast carcinoma.

    LENUS (Irish Health Repository)

    Hayes, Brian D

    2012-02-01

    INTRODUCTION: Fine needle aspiration cytology (FNAC) of radiologically abnormal axillary lymph nodes in patients with breast cancer can identify patients suitable for primary axillary clearance (AC) rather than sentinel node biopsy, enabling surgical axillary staging by a single operation. This study assessed the accuracy of FNAC in predicting positive axillary lymph nodes. METHODS: 161 patients with screen-detected invasive carcinoma and who had pre-operative FNAC of a radiologically abnormal axillary lymph node were identified from two screening units, The axillary FNAC reports were correlated with sentinel node biopsy and AC reports, and sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. RESULTS: FNAC had a moderate sensitivity (66.3%) and NPV (71.8%), and a high specificity (98.7%) and PPV (98.3%). Most patients (86%) had a single axillary operation. The sensitivity was highest in grade 3 (81.8%) and ductal type (77.8%) tumours. The sensitivity was lower in tumours of special type (34.8%), grade 1 tumours (50%) and those without lymphovascular invasion (LVI) (55.9%). The NPV was highest in pT1 (86.7%) and in grade 1 (84.5%) tumours, and lowest (44%) in tumours with LVI. The PPV was 100% in grade 1 and 3 tumours, stage pT2 and pT3 tumours and those without LVI, and was high (>96%) in all other groups. In lymph-node-positive patients, the mean number of lymph nodes involved was higher in the case of a positive (6.4) than negative FNAC (4.4). CONCLUSIONS: FNAC of ultrasonically abnormal axillary lymph nodes achieved surgical staging by a single operation in most patients with screen-detected invasive breast carcinoma, with moderate sensitivity and high specificity.

  12. Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Xue Yi-Jun

    2012-09-01

    Full Text Available Abstract Background Fork head box M1 (FoxM1 is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FoxM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. The present study was conducted to investigate the expression of FoxM1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC. Meanwhile, the function of FoxM1 in human ccRCC was further investigated in cell culture models. Methods Real-time quantitative PCR, western blot and immunohistochemistry were used to explore FoxM1 expression in ccRCC cell lines and primary ccRCC clinical specimens. FoxM1 expression was knocked down by small interfering RNA (siRNA in Caki-1 and 786-O cells; proliferation, colony formation, cell cycle, migration, invasion, and angiogenesis were assayed. Results FoxM1 expression was up-regulated in the majority of the ccRCC clinical tissue specimens at both mRNA and protein levels. Clinic pathological analysis showed that FoxM1 expression was significantly correlated with primary tumor stage (P P = 0.01, distant metastasis (P = 0.01, TNM stage (P P = 0.003. The Kaplan–Meier survival curves revealed that high FoxM1 expression was associated with poor prognosis in ccRCC patients (P P = 0.008. Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation and induced cell cycle arrest with reduced expression of cyclin B1, cyclin D1, and Cdk2, and increased expression of p21 and p27. Also, down-regulation of FoxM1 reduced expression and activity of matrix metalloproteinase-2 (MMP-2, MMP-9 and vascular endothelial growth factor (VEGF, resulting in the inhibition of migration, invasion, and angiogenesis. Conclusions These results suggest that FoxM1 expression is likely to play important roles in ccRCC development and progression, and that FoxM1 is a prognostic biomarker and a

  13. Epithelial-Mesenchymal Transition in Pancreatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Thomas Wirth

    2010-12-01

    Full Text Available Pancreatic carcinoma is the fourth-leading cause of cancer death and is characterized by early invasion and metastasis. The developmental program of epithelial-mesenchymal transition (EMT is of potential importance for this rapid tumor progression. During EMT, tumor cells lose their epithelial characteristics and gain properties of mesenchymal cells, such as enhanced motility and invasive features. This review will discuss recent findings pertinent to EMT in pancreatic carcinoma. Evidence for and molecular characteristics of EMT in pancreatic carcinoma will be outlined, as well as the connection of EMT to related topics, e.g., cancer stem cells and drug resistance.

  14. miR-182 targets CHL1 and controls tumor growth and invasion in papillary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Hongling [Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai (China); Fang, Jin [Department of Endocrine, The 118th Hospital of Chinese PLA, Wenzhou, Zhejiang (China); Zhang, Jichen; Zhao, Zefei; Liu, Lianyong; Wang, Jingnan; Xi, Qian [Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai (China); Gu, Mingjun, E-mail: mjgugonglihos@yeah.net [Department of Endocrine, Shanghai Pudong New Area Gongli Hospital, Shanghai (China)

    2014-07-18

    Highlights: • miR-182 and CHL1 expression patterns are negatively correlated. • CHL1 is a direct target of miR-182 in PTC cells. • miR-182 suppression inhibits PTC cell growth and invasion. • CHL1 is involved in miR-182-mediated cell behavior. - Abstract: In this study, we investigated the role and underlying mechanism of action of miR-182 in papillary thyroid carcinoma (PTC). Bioinformatics analysis revealed close homolog of LI (CHL1) as a potential target of miR-182. Upregulation of miR-182 was significantly correlated with CHL1 downregulation in human PTC tissues and cell lines. miR-182 suppressed the expression of CHL1 mRNA through direct targeting of the 3′-untranslated region (3′-UTR). Downregulation of miR-182 suppressed growth and invasion of PTC cells. Silencing of CHL1 counteracted the effects of miR-182 suppression, while its overexpression mimicked these effects. Our data collectively indicate that miR-182 in PTC promotes cell proliferation and invasion through direct suppression of CHL1, supporting the potential utility of miR-182 inhibition as a novel therapeutic strategy against PTC.

  15. miR-1179 promotes cell invasion through SLIT2/ROBO1 axis in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Jiang, Lixin; Wang, Yongfang; Rong, Yaxiong; Xu, Lianhong; Chu, Ying; Zhang, Ying; Yao, Yonghua

    2015-01-01

    MiR-1179, a new identified miRNA highly associated with metastasis of colorectal cancer which was never reported in esophageal squamous cell carcinoma (ESCC). Here we measured the expression levels of miR-1179 and the candidate target gene in tissues from 40 patients with ESCC. Transwell, Dual-luciferase reporter assay and immunocytochemistry assay were employed to detect the function role of miR-1179 in vitro. We found that miR-1179 was up-regulated in human ESCC tumor tissues. Bioinformatics analysis indicated that SLIT2 acting as a new potential target of miR-1179 which was confirmed by luciferase reporter assay. Down-regulation of miR-1179 suppressed cell invasion in vitro with an increasing level of SLIT2 and ROBO1, besides, the up-regulation of SLIT2 decreased cell invasion through ROBO1. Taken together, these findings will shed light the role to mechanism of miR-1179 in regulating cell invasion via SLIT2/ROBO1 axis.

  16. Long noncoding RNA SPRY4-IT1 promotes esophageal squamous cell carcinoma cell proliferation, invasion, and epithelial-mesenchymal transition.

    Science.gov (United States)

    Cui, Fei; Wu, Duoguang; He, Xiaotian; Wang, Wenjian; Xi, Jingle; Wang, Minghui

    2016-08-01

    The biology of esophageal squamous cell carcinoma (ESCC) remains poorly understood. Long noncoding RNAs (lncRNAs) are found to be dysregulated in a variety of cancers, including ESCC. SPRY4-IT1 has been recently revealed as oncogenic regulator or tumor suppressors in different cancers; however, whether SPRY4-IT1 is involved in ESCC remains poorly understood. To investigate the role of SPRY4-IT1 in ESCC, we evaluated the SPRY4-IT1 expression levels in a series of ESCC patients and a panel of ESCC cell line using qRT-PCR. CCK8 and colony formation assay were performed to assess the effect of SPRY4-IT1siRNA on cell proliferation, migration, and invasion of ESCC cell lines. SPRY4-IT1 expression was upregulated in ESCC tissues and the higher expression of SPRY4-IT1 was significantly correlated with tumor grade, depth of invasion, and lymph node metastasis. Moreover, silencing of SPRY4-IT1 expression inhibited ESCC cell proliferation, colony formation, migration, and invasion. Therefore, our study indicates that SPRY4-IT1 promotes proliferation and migration of ESCC cells and is a potential oncogene of ESCC.

  17. Recombinant Human Bone Morphogenetic Protein-2 in Development and Progression of Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Zaid, Khaled Waleed; Chantiri, Mansour; Bassit, Ghassan

    2016-01-01

    Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor-β superfamily, regulate many cellular activities including cell migration, differentiation, adhesion, proliferation and apoptosis. Use of recombinant human bone morphogenic protein?2 (rhBMP?2) in oral and maxillofacial surgery has seen a tremendous increase. Due to its role in many cellular pathways, the influence of this protein on carcinogenesis in different organs has been intensively studied over the past decade. BMPs also have been detected to have a role in the development and progression of many tumors, particularly disease-specific bone metastasis. In oral squamous cell carcinoma - the tumor type accounting for more than 90% of head and neck malignancies- aberrations of both BMP expression and associated signaling pathways have a certain relation with the development and progression of the disease by regulating a range of biological functions in the altered cells. In the current review, we discuss the influence of BMPs -especially rhBMP-2- in the development and progression of oral squamous cell carcinoma. PMID:27039814

  18. A Multifaceted Role for Myd88-Dependent Signaling in Progression of Murine Mammary Carcinoma

    Science.gov (United States)

    Higgins, Mary J.; Serrano, Antonio; Boateng, Kofi Y.; Parsons, Victoria A.; Phuong, Tiffany; Seifert, Alyssa; Ricca, Jacob M.; Tucker, Kyle C.; Eidelman, Alec S.; Carey, Maureen A.; Kurt, Robert A.

    2016-01-01

    Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent signaling cascade in murine mammary carcinoma. Here, we extended these findings by showing that, in the absence of an added Toll-like receptor (TLR) agonist, the myddosome complex was preformed in 4T1 tumor cells, and that Myd88 influenced cytoplasmic extracellular signal–regulated kinase (Erk)1/Erk2 levels, nuclear levels of nuclear factor-kappaB (NFκB) and signal transducer and activator of transcription 5 (STAT5), tumor-derived chemokine (C–C motif) ligand 2 (CCL2) expression, and in vitro and in vivo tumor growth. In addition, RNA-sequencing revealed that Myd88-dependent signaling enhanced the expression of genes that could contribute to breast cancer progression and genes previously associated with poor outcome for patients with breast cancer, in addition to suppressing the expression of genes capable of inhibiting breast cancer progression. Yet, Myd88-dependent signaling in tumor cells also suppressed expression of genes that could contribute to tumor progression. Collectively, these data revealed a multifaceted role for Myd88-dependent signaling in murine mammary carcinoma. PMID:27812285

  19. The Progress and Prospects of Putative Biomarkers for Liver Cancer Stem Cells in Hepatocellular Carcinoma.

    Science.gov (United States)

    Xiang, Yan; Yang, Ting; Pang, Bing-Yao; Zhu, Ying; Liu, Yong-Ning

    2016-01-01

    Accumulating evidence suggests that hepatocellular carcinoma (HCC) is organized by liver cancer stem cells (LCSCs), which are a subset of cells with "stem-like" characteristics. Identification of the LCSCs is a fundamental and important problem in HCC research. LCSCs have been investigated by various stem cell biomarkers. There is still lack of consensus regarding the existence of a "global" marker for LCSCs in HCC. In this review article, we summarize the progress and prospects of putative biomarkers for LCSCs in the past decades, which is essential to develop future therapies targeting CSCs and to predict prognosis and curative effect of these therapies. PMID:27610139

  20. Progressive dysphagia in a dog caused by a scirrhous, poorly differentiated perioesophageal carcinoma.

    Science.gov (United States)

    Wray, J D; Blunden, A S

    2006-01-01

    Investigation of canine dysphagia is performed by a combination of diagnostic imaging, direct visualisation of the upper gastrointestinal tract, and ancillary diagnostic testing to differentiate between structural and functional causes. Video fluoroscopy may be especially helpful. The case of a seven-year-old Border collie that presented with a history of progressive pharyngeal dysphagia is described. Fluoroscopic investigation was initially suggestive of functional pharyngeal disease, but magnetic resonance imaging and surgical exploration demonstrated the presence of a diffuse, scirrhous, poorly differentiated carcinoma with extensive oesophageal involvement. This case highlights that, in some circumstances, fluoroscopy may occasionally be of limited use in the investigation of dysphagia in the dog. PMID:16417607

  1. Progression after spontaneous regression in lung large cell neuroendocrine carcinoma: Report of a curative resection

    OpenAIRE

    Tomizawa, Kenji; Suda, Kenichi; Takemoto, Toshiki; Iwasaki, Takuya; Sakaguchi, Masahiro; Kuwano, Hiroyuki; Mitsudomi, Tetsuya

    2015-01-01

    We present the first reported case of lung large cell neuroendocrine carcinoma (LCNEC) with spontaneous regression followed by progression. An 85-year-old woman presented with a 2.8-cm nodule in the right upper lung lobe on chest computed tomography. After four months, the tumor decreased to 1.8 cm and remained unchanged in size for the next three months, but it grew to 8.6 cm and invaded the mediastinal fat tissue after approximately one year. Ultrasound echo-guided percutaneous biopsy revea...

  2. 63 Patients and cytokeratin 8/18 expression in breast, atypical ductal hyperplasia, ductal carcinoma in situ and invasive Duct Carcinoma

    International Nuclear Information System (INIS)

    Background and Purpose: The pattern and distribution of 63 Patients expression as a myoepithelia/basal stem cell marker can be different between atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and may denote basal phenotype of breast ductal carcinoma. CK8/18 is a luminal marker and may indicate a luminal phenotype of IDC and its expression in ADH and DCIS may refer to a possible precursor lesion to IDC. This work was designed to study and compare the expression of 63 Patients and cytokeratin 8/18 (CK8/l8) in some cases of ADH, DC IS and IDC. Materials and Methods: Histopathological evaluation and immunohistochemical study of anti- 63 Patients and anti-CK8/l8 was performed on selected archival cases of 7 ADH, 12 DCIS, 30 IDC of known clinico pathological data and previous estrogen receptor status (ER) for IDe. Confirmatory anti-smooth muscle actin (ASMA) expression for positive 63 Patients cases was performed. Results: 63 Patients was expressed in the peripheral rim of the myoepithelial cell layer in ADH and DCIS with occasional gabs in DCrS. It was positive and stained occasional malignant cells in 3/30 (10%) of IDC cases. Confirmatory ASMA staining decorated the same peripheral rim of cells in ADH and DCIS, but was negative in 63 Patients positive IDC cases. CK8/l8 was positive in 100% of ADH, 8/12 (66.7%) of DC IS and 22/30 (73%) of IDC cases. Combined 63 Patients and CK8/ 18 expression was noticed in 3/30 (10%) of IDe. Conclusion: It is concluded from this study that 63 Patients is specific and valuable in differentiating myoepithelial cells and is more specific and valuable than other myoepithelial markers, as ASMA and can differentiate between ADH, DCIS, IDC as it stains peripheral myoepithelial cells in ADH and DCIS with gabs in the latter and does not stain any neoplastic cells. In IDC, it is positive in malignant cells in a minority of cases which may indicate basal/stem cell/myoepithelial cell origin

  3. Trimodality Therapy for an Advanced Thymic Carcinoma With Both Aorta and Vena Cava Invasion.

    Science.gov (United States)

    Momozane, Tohru; Inoue, Masayoshi; Shintani, Yasushi; Funaki, Soichiro; Kawamura, Tomohiro; Minami, Masato; Shirakawa, Yukitoshi; Kuratani, Toru; Sawa, Yoshiki; Okumura, Meinoshin

    2016-08-01

    A case of locally advanced thymic carcinoma that was successfully resected with the great vessels after chemoradiation therapy is reported. A 57-year-old man with Masaoka stage III thymic carcinoma received two cycles of cisplatin/docetaxel and 60 Gy irradiation. The response was stable disease with 19% size reduction, and a radical resection with the ascending aorta and superior vena cava with the patient under circulatory arrest with the use of cardiopulmonary bypass was performed. The postoperative course was uneventful, and the patient has been free of disease for 28 months. Trimodality therapy with use of a cardiovascular surgical procedure might be a valuable option in locally advanced thymic carcinoma. PMID:27449450

  4. Relationship between expression of CD44v6 and nm23-H1 and tumor invasion and metastasis in hepatocellular carcinoma

    OpenAIRE

    Xiao, Cheng-Zhi; Dai, Yi-Min; Yu, Hong-Yu; Wang, Jian-Jun; Ni, Can-Rong

    1998-01-01

    AIM: To detect the expression of CD44v6 mRNA and nm23-H1 mRNA in hepatocellular carcinoma (HCC) by in situ hybridization, and to evaluate the relationship between their expression and also relationship between their expressions and tumor invasion and metastasis.

  5. A case report of symptomatic gallbladder disease in the setting of peritoneal carcinomatosis originating from invasive lobular carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    David Brinkman

    2016-01-01

    Conclusion: Symptomatic gallbladder disease in the setting of peritoneal carcinomatosis secondary to invasive lobular carcinoma is an uncommon presentation to surgeons. A diagnostic laparoscopy is the preferred initial evaluation. If deemed feasible, and if the surgeon has the required experience, a laparoscopic cholecystectomy can be undertaken selectively.

  6. Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: pooled analysis in five studies within the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Lurie, Galina; Wilkens, Lynne R; Thompson, Pamela J;

    2011-01-01

    The association of invasive ovarian carcinoma risk with the functional polymorphism rs2228570 (aka rs10735810; FokI polymorphism) in the vitamin D receptor (VDR) gene was examined in 1820 white non-Hispanic cases and 3479 controls in a pooled analysis of five population-based case-control studies...

  7. Transition of high-grade cervical intraepithelial neoplasia to micro-invasive carcinoma is characterized by integration of HPV 16/18 and numerical chromosome abnormalities.

    NARCIS (Netherlands)

    Hopman, A.H.N.; Smedts, F.; Dignef, W.; Ummelen, M.; Sonke, G.; Mravunac, M.; Vooijs, G.P.; Speel, E.J.; Ramaekers, F.C.S.

    2004-01-01

    Cervical intraepithelial neoplasia (CIN I, II, and III) and cases of CIN III associated with micro-invasive cervical carcinoma (CIN III & mCA) were analysed for evidence of episomal or integrated human papillomavirus (HPV) 16/18 DNA by fluorescence in situ hybridization (FISH). In parallel, numerica

  8. Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma

    NARCIS (Netherlands)

    Qi, Liqiang; Bart, Joost; Tan, Lu Ping; Platteel, Inge; van der Sluis, Tineke; Huitema, Sippie; Harms, Geert; Fu, Li; Hollema, Harry; van den Berg, Anke

    2009-01-01

    Background: Flat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells. Genetic changes found in ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDC) are also found in FEA, albeit at a lower concentration. So far, miRNA

  9. Prevalence of high-risk human papillomavirus types in Mexican women with cervical intraepithelial neoplasia and invasive carcinoma

    Directory of Open Access Journals (Sweden)

    Sánchez-Garza Mireya

    2008-02-01

    Full Text Available Abstract Background Prevalence of high risk (HR human papillomavirus (HPV types in the states of San Luis Potosí (SLP and Guanajuato (Gto, Mexico, was determined by restriction fragment length-polymorphism (RFLP analysis on the E6 ~250 bp (E6-250 HR-HPV products amplified from cervical scrapings of 442 women with cervical intraepithelial neoplasia and invasive carcinoma (280 from SLP and 192 from Gto. Fresh cervical scrapings for HPV detection and typing were obtained from all of them and cytological and/or histological diagnoses were performed on 383. Results Low grade intraepithelial squamous lesions (LSIL were diagnosed in 280 cases (73.1%, high grade intraepithelial squamous lesions (HSIL in 64 cases (16.7% and invasive carcinoma in 39 cases (10.2%. In the 437 cervical scrapings containing amplifiable DNA, only four (0.9% were not infected by HPV, whereas 402 (92.0% were infected HR-HPV and 31 (7.1% by low-risk HPV. RFLP analysis of the amplifiable samples identified infections by one HR-HPV type in 71.4%, by two types in 25.9% and by three types in 2.7%. The overall prevalence of HR-HPV types was, in descending order: 16 (53.4% > 31 (15.6% > 18 (8.9% > 35 (5.6 > 52 (5.4% > 33 (1.2% > 58 (0.7% = unidentified types (0.7%; in double infections (type 58 absent in Gto it was 16 (88.5% > 31 (57.7% > 35 (19.2% > 18 (16.3% = 52 (16.3% > 33 (2.8% = 58 (2.8% > unidentified types (1.0%; in triple infections (types 33 and 58 absent in both states it was 16 (100.0% > 35 (54.5% > 31 (45.5% = 52 (45.5% > 18 (27.3%. Overall frequency of cervical lesions was LSIL (73.1% > HSIL (16.7% > invasive cancer (10.2%. The ratio of single to multiple infections was inversely proportional to the severity of the lesions: 2.46 for LSIL, 2.37 for HSIL and 2.15 for invasive cancer. The frequency of HR-HPV types in HSIL and invasive cancer lesions was 16 (55.0% > 31 (18.6% > 35 (7.9% > 52 (7.1% > 18 (4.3% > unidentified types (3.6% > 33 (2.9% > 58 (0.7%. Conclusion Ninety

  10. Synchronous presentation of invasive ductal carcinoma and mantle cell lymphoma: a diagnostic challenge in menopausal patients

    OpenAIRE

    Woo, Edward J.; Baugh, Aaron D.; Ching, Karen

    2016-01-01

    Synchronous presentation of breast carcinoma and non-Hodgkin lymphoma (NHL) is a rare occurrence (Bradford PT, Freedman DM, Goldstein AM, Tucker MA. Increased risk of second primary cancers after a diagnosis of melanoma. Arch Dermatol 2010;146:265–72; Dutta Roy S, Stafford JA, Scally J, Selvachandran SN. A rare case of breast carcinoma co-existing with axillary mantle cell lymphoma. World J Surg Oncol 2003;1:27; Suresh Attili VS, Dadhich HK, Rao CR, Bapsy PP, Batra U, Anupama G et al. A case ...

  11. Genistein sensitizes ovarian carcinoma cells to chemotherapy by switching the cell cycle progression in vitro

    Institute of Scientific and Technical Information of China (English)

    Huang Yanhong; Yuan Peng; Zhang Qinghong; Xin Xiaoyan

    2009-01-01

    Objective: To address how genistein sensitizes the chemotherapy-resistant ovarian carcinoma cells and promotes apoptosis in the respect of cell cycle and the regulation of survivin expression in the process. Methods: Ovarian SKOV-3 carcinoma cell line was treated with genistein or cisplatin either alone or in combination. Cell viability was showed by MTT method. Cell cycle and apoptosis were detected by flow cytometry. Survivin mRNA and protein were revealed by RT-PCR and immunocytochemistry, respectively. Results: Genistein could reduce the cell viability in a dose-dependent manner, while cisplatin did so at a much higher level. In contrast, if the two agents were treated in combination, half growth inhibition (IC50) value for cisplatin was reduced remarkably and the effect was synergistic as analyzed by isobologram. In particular, the reduced cell viability was exhibited by a switch in cell cycle progression, as the cells were arrested in G2/M phase and the G0/G1 phase-fraction was significantly decreased. The reduced cell viability appeared to involve apoptosis, based on our results from flow cytometry and Hoechst 33258 staining. In the meanwhile, genistein performed the inhibitory effect on cisplatin-induced survivin expression. Conclusion: Genistein can sensitize ovarian carcinoma cells to cisplatin therapy with the inhibition of survivin expression as the potential mechanism.

  12. Role of B7-H4 siRNA in Proliferation, Migration, and Invasion of LOVO Colorectal Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Hai-xia Peng

    2015-01-01

    Full Text Available Objectives. Colorectal cancer is one of the most common malignancies. Recent studies investigated that B7-H4 is highly expressed in various cancers. We aimed at exploring the effect of B7-H4 siRNA on proliferation, invasion, and migration of LOVO cells which expressed B7-H4 notably. Design and Methods. Colon adenocarcinoma dataset was downloaded from The Cancer Genome Atlas. 35 colorectal cancer patients admitted to Shanghai Tongren Hospital were enrolled in this study. Cell proliferation and cell cycle distribution were identified by CCK8 and flow cytometry, respectively. Transwell assay was performed to detect the invasion and migration of LOVO cells. CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were determined by real-time PCR and western blot. Results. B7-H4 expressed is elevated in colorectal cancer tissues than in the adjacent normal tissues. B7-H4 siRNA effectively inhibited the proliferation at 24 h and 48 h, arrested cell cycle at G0/G1, and suppressed cell invasion and migration. Gene set enrichment analysis showed that CXCL12/CXCR4 and JAK/STAT were correlative with the B7-H4 expression. Additionally, CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were reduced. Conclusions. B7-H4 siRNA can effectively inhibit proliferation, invasion, and migration of LOVO cells by targeting CXCL12/CXCR4 and JAK2/STAT3 signaling, which can serve as a new target for colorectal carcinoma treatment.

  13. UROKINASE-TYPE PLASMINOGEN ACTIVATOR, ITS RECEPTOR AND INHIBITOR EXPRESSION IN HEPATOCELLULAR CARCINOMA RELATION TO CANCER INVASIVENESS AND PROGNOSIS

    Institute of Scientific and Technical Information of China (English)

    Zheng Qi; Tang Zhaoyou; Wu Zhiquan; Shi Daren; Tang Huibin; Zhu Yunsong; Song Houyan

    1998-01-01

    Objective:To study the relevance of uPA, uPAR and PAI-1 to hepatocellular carcinoma (HCC). Methods:The expression at protein level of uPA, uPAR and PAI-1was determined in 48 cases of HCC and 12 cases of benign tumors of liver (as control) by immunohistochemistry.Results: When compared to cancer-adjacent liver tissue and the control, positive rate of immune staining for uPA,uPAR and PAI-1 on cell membrane were significantly higher in HCC cells (P<0.05). Positive staining of uPA and uPAR was seen in 16 of 22 and 19 of 22 cases of HCC with invasion, respectively (P<0.01 and P<0.001). In 8 of 8cases with cancer embolus, and in 6 of 6 cases with lymph node metastasis was the expression of positive uPAR.Compared with 2 of 17 cases without recurrence, uPAR was positive in 15 of 17 recurrent cases (P<0.01). In 36cases who survived, 17 was positive uPAR and 15 positive PAI-1, while in 12 cases who died 2 years after surgery, 12were positive for uPAR and 9 positive PAI-1, respectively (P<0.01 and P<0.05). In 15 positive cases for all three parameters, 11 had cancer invasion and 7 died within 2 years, while in negative cases, 2 had invasion and none died within 2 years (P<0.05). Conclusion: Expression of.uPA, uPAR and PAI-1 is increased in HCC, uPA and uPAR may contribute significantly to HCC invasion and metastasis. uPAR and PAI-1 are associated with poor prognosis of HCC.

  14. Regulation of Motility, Invasion and Metastatic Potential of Squamous Cell Carcinoma by 1,25D3

    Science.gov (United States)

    Ma, Yingyu; Yu, Wei-Dong; Su, Bing; Seshadri, Mukund; Luo, Wei; Trump, Donald L.; Johnson, Candace S.

    2012-01-01

    BACKGROUND 1,25D3, the active metabolite of vitamin D, has been shown to exhibit broad spectrum anti-tumor activity in xenograft animal models. However, its activity against metastatic disease has not been extensively investigated. METHODS Squamous cell carcinoma (SCC) or 1,25D3-resistant variant SCC-DR cells were treated with 1,25D3. Actin organization was examined by immunofluorescence assay. Cell migration was assessed by “wound” healing and chemotactic migration assay. Cell invasion was assessed by Matrigel-based invasion assay and in situ zymography. MMP-2 and MMP-9 expression and secretion was examined by immunoblot analysis and ELISA, respectively. E-cadherin expression was assessed by flow cytometry, immunoblot analysis and immunohistochemistry. Knockdown of E-cadherin was achieved by siRNA. Experimental metastasis mouse model was done by intravenous injection of tumor cells. Lung tumor development was assessed by magnetic resonance imaging, gross observation and histology. RESULTS SCC cellular morphology and actin organization were altered by 10 nM of 1,25D3. 1,25D3 inhibited SCC cell motility and invasion, which was associated with reduced expression and secretion of MMP-2 and MMP-9. 1,25D3 promoted the expression of E-cadherin. These findings were not observed in SCC-DR cells. Knock down of E-cadherin rescued 1,25D3-inhibited cell migration. Intravenous injection of SCC or SCC-DR cells resulted in the establishment of extensive pulmonary lesions in saline-treated C3H mice. Treatment with 1,25D3 resulted in a marked reduction in the formation of lung tumor colonies in animals injected with SCC but not SCC-DR cells. CONCLUSIONS 1,25D3 suppresses SCC cell motility, invasion and metastasis, partially through the promotion of E-cadherin-mediated cell-cell adhesion. PMID:22833444

  15. DJ-1 Is Upregulated in Oral Squamous Cell Carcinoma and Promotes Oral Cancer Cell Proliferation and Invasion

    Science.gov (United States)

    Xu, Shuaimei; Ma, Dandan; Zhuang, Rui; Sun, Wenjuan; Liu, Ying; Wen, Jun; Cui, Li

    2016-01-01

    Background: The development of oral squamous cell carcinoma (OSCC) is a multistep process that involves in both genetic alterations and epigenetic modifications. DJ-1, a negative regulator of tumor suppressor PTEN, functions as an oncogene in many types of cancers. However, its role in OSCC is poorly known. Methods: Immunohistochemical staining and Western blotting were performed to evaluate the expression level of DJ-1 in oral leukoplakia (OLK) and OSCC tissues respectively. Then lentiviral mediated DJ-1 shRNA was constructed and used to infect the OSCC cell lines (Tca8113 and CAL-27). MTT, cell counting, and Matrigel invasion assay were utilized to examine the effects of DJ-1 down-regulation on proliferation and invasion capacity of oral cancer cells. Results: The immunoreactivity and expression level of DJ-1 protein was significantly increased in OLK and OSCC tissues compared with the controls. Lentiviral-delivered shRNA targeting DJ-1 could effectively knock down DJ-1 at mRNA and protein level (P<0.01). The proliferative and invasion ability of OSCC cell lines was significantly suppressed following DJ-1 inhibition (P<0.01). Conclusions: Our study indicated that DJ-1 is over-expressed in both oral precancer and cancer tissues and shRNA inhibition of DJ-1 expression led to decreased proliferation and invasion capability of oral cancer cells. These findings suggest that DJ-1 might be actively involved in the development of OSCC. Future studies will investigate the potential of DJ-1 as a biomarker for early detection of OSCC. PMID:27313793

  16. Downregulation of VEGFA inhibits proliferation, promotes apoptosis, and suppresses migration and invasion of renal clear cell carcinoma

    Science.gov (United States)

    Zeng, Fan-Chang; Zeng, Ming-Qiang; Huang, Liang; Li, Yong-Lin; Gao, Ben-Min; Chen, Jun-Jie; Xue, Rui-Zhi; Tang, Zheng-Yan

    2016-01-01

    Objective The aim of this study was to investigate the effects of vascular endothelial growth factor A (VEGFA) on cell proliferation, apoptosis, migration, and invasion in renal clear cell carcinoma (RCCC). Methods Between June 2012 and June 2015, RCCC tissues were obtained for the experimental group, and RCCC adjacent tumor-free kidney parenchyma tissues were obtained for the control group. VEGFA mRNA and protein expressions and phosphoinositide 3-kinase, serine/threonine-specific protein kinase (AKT), and phosphorylated-AKT protein expressions were detected. The chemically synthesized specific siRNA using RNA interference technology was used to inhibit VEGFA gene expression in human RCCC 786-O cells. The negative control (NC) group was transfected with NC sequence, and the blank group was transfected with no sequence. Flow cytometry, scratch test, and cell-penetrating experiment were used to detect cell proliferation, apoptosis, migration, and invasion of 786-O cells. Results Positive expression of VEGFA protein was 60.62% in RCCC tissue and 18.34% in adjacent tissue with statistically significant difference (P<0.001). VEGFA protein and mRNA expressions were higher in RCCC tissue than those in adjacent tissue (both P<0.01). VEGF expression in RCCC tissue was associated with Fuhrman grading and American Joint Committee on Cancer staging (both P<0.05). After RCCC 786-O cells transfecting the VEGFA siRNA, the VEGFA mRNA and protein expressions and phosphoinositide 3-kinase and phosphorylated-AKT protein expressions were significantly decreased, cell proliferation was remarkably inhibited, cell apoptotic ratio was obviously increased, and migration distance and invasive cell number were markedly decreased compared to those in the NC group and the blank group (all P<0.05). Conclusion Inhibition of VEGFA inhibited proliferation, promoted apoptosis, and suppressed migration and invasion of RCCC 786-O cells. VEGF has a potential role in diagnosis and therapy of RCCC

  17. Epb41l3 suppresses esophageal squamous cell carcinoma invasion and inhibits MMP2 and MMP9 expression.

    Science.gov (United States)

    Zeng, Rong; Huang, Jun-Peng; Li, Xu Feng; Xiong, Wei-Bin; Wu, Gang; Jiang, Zhao-Jing; Song, Shu-Jie; Li, Ji-Qiang; Zheng, Yan-Fang; Zhang, Ji-Ren

    2016-04-01

    EPB41L3 may play a role as a metastasis suppressor by supporting regular arrangements of actin stress fibres and alleviating the increase in cell motility associated with enhanced metastatic potential. Downregulation of epb41l3 has been observed in many cancers, but the role of this gene in esophageal squamous cell carcinoma (ESCC) remains unclear. Our study aimed to determine the effect of epb41l3 on ESCC cell migration and invasion. We investigated epb41l3 protein expression in tumour and non-tumour tissues by immunohistochemical staining. Expression in the non-neoplastic human esophageal cell line Het-1a and four ESCC cell lines - Kyse150, Kyse510, Kyse450 and Caes17 - was assessed by quantitative Polymerase Chain Reaction (qPCR) and Western blotting. Furthermore, an EPB41L3 overexpression plasmid and EPB41L3-specific small interfering RNA were used to upregulate EPB41L3 expression in Kyse150 cells and to downregulate EPB41L3 expression in Kyse450 cells, respectively. Cell migration and invasion were evaluated by wound healing and transwell assays, respectively. The expression levels of p-AKT, matrix metalloproteinase (MMP)2 and MMP9 were evaluated. Expression of epb41l3 was significantly lower in tumour tissues than in non-tumour tissues and in ESCC cell lines compared with the Het-1a cell line. Kyse450 and Caes17 cells exhibited higher expression of epb41l3 than Kyse150 and Kyse510 cells. Overexpressing epb41l3 decreased Kyse150 cell migration and invasion, whereas EPB41L3-specific small interfering RNA silencing increased these functions in Kyse450 cells. Furthermore, overexpressing epb41l3 led to downregulation of MMP2 and MMP9 in Kyse150 and Kyse510 cells. Our findings reveal that EPB41L3 suppresses tumour cell invasion and inhibits MMP2 and MMP9 expression in ESCC cells.

  18. miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Jian [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Qu, Shuping [Department II of Special Medical Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Li, Xiaowei; Zhong, Jiaming; Chen, Xiaoxia [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Qu, Zengqiang, E-mail: drquzengqiang@163.com [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Wu, Dong, E-mail: wudongstc@126.com [Department II of Special Medical Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China)

    2015-08-14

    Emerging evidence suggests that microRNAs (miRNAs) play important roles in regulating HCC development and progression; however, the mechanisms by which their specific functions and mechanisms remained to be further explored. miR-129 has been reported in gastric cancers, lung cancer and colon cancer. In this study, we disclosed a new tumor suppresser function of miR-129 in HCC. We also found the downregulation of miR-129 occurred in nearly 3/4 of the tumors examined (56/76) compared with adjacent nontumorous tissues, which was more importantly, correlated to the advanced stage and vascular invasion. We then demonstrated that miR-129 overexpression attenuated HCC cells proliferation and invasion, inducing apoptosis in vitro. Moreover, we used miR-129 antagonist and found that anti-miR-129 promoted HCC cells malignant phenotypes. Mechanistically, our further investigations revealed that miR-129 suppressed cell proliferation and invasion by targeting the 3’-untranslated region of PAK5, as well as miR-129 silencing up-regulated PAK5 expression. Moreover, miR-129 expression was inversely correlated with PAK5 expression in 76 cases of HCC samples. RNA interference of PAK5 attenuated anti-miR-129 mediated cell proliferation and invasion in HCC cells. Taken together, these results demonstrated that miR-129 suppressed tumorigenesis and progression by directly targeting PAK5, defining miR-129 as a potential treatment target for HCC. - Highlights: • Decreased of miR-129 is found in HCC and associated with advanced stage and metastasis. • miR-129 suppresses proliferation and invasion of HCC cells. • miR-129 directly targets the 3′ UTR of PAK5 and diminishes PAK5 expression. • PAK5 is involved in miR-129 mediated suppression functions.

  19. Tumor characteristics and the clinical outcome of invasive lobular carcinoma compared to infiltrating ductal carcinoma in a Chinese population

    Directory of Open Access Journals (Sweden)

    Cao A-Yong

    2012-07-01

    Full Text Available Abstract Background We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between ILC and infiltrating ductal carcinoma (IDC using a large database. Methods Clinicopathologic features, overall survival (OS, and recurrence/metastasis-free survival (RFS were compared between 2,202 patients with IDC and 215 patients with ILC. Results ILC was significantly more likely to be associated with a favorable phenotype, but the incidence of contralateral breast cancer was higher for ILC patients than for IDC patients (8.4% vs. 3.9%; P =0.001. The frequencies of recurrence/metastasis (P = 0.980 and death (P = 0.064 were similar among patients with IDC and patients with ILC after adjustment for tumor size and nodal status. The median follow-up was 42.8 months. Conclusions Chinese women with ILCs do not have better clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics, and not on lobular histology.

  20. MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma.

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    Lu-Kai Wang

    Full Text Available Non-small cell lung cancers (NSCLCs cause high mortality worldwide, and the cancer progression can be activated by several genetic events causing receptor dysregulation, including mutation or amplification. MicroRNAs are a group of small non-coding RNA molecules that function in gene silencing and have emerged as the fine-tuning regulators during cancer progression. MiR-133a is known as a key regulator in skeletal and cardiac myogenesis, and it acts as a tumor suppressor in various cancers. This study demonstrates that miR-133a expression negatively correlates with cell invasiveness in both transformed normal bronchial epithelial cells and lung cancer cell lines. The oncogenic receptors in lung cancer cells, including insulin-like growth factor 1 receptor (IGF-1R, TGF-beta receptor type-1 (TGFBR1, and epidermal growth factor receptor (EGFR, are direct targets of miR-133a. MiR-133a can inhibit cell invasiveness and cell growth through suppressing the expressions of IGF-1R, TGFBR1 and EGFR, which then influences the downstream signaling in lung cancer cell lines. The cell invasive ability is suppressed in IGF-1R- and TGFBR1-repressed cells and this phenomenon is mediated through AKT signaling in highly invasive cell lines. In addition, by using the in vivo animal model, we find that ectopically-expressing miR-133a dramatically suppresses the metastatic ability of lung cancer cells. Accordingly, patients with NSCLCs who have higher expression levels of miR-133a have longer survival rates compared with those who have lower miR-133a expression levels. In summary, we identified the tumor suppressor role of miR-133a in lung cancer outcome prognosis, and we demonstrated that it targets several membrane receptors, which generally produce an activating signaling network during the progression of lung cancer.

  1. Contrast-enhanced computed tomography of the primary tumor in muscle invasive carcinoma of the urinary bladder

    International Nuclear Information System (INIS)

    Patients with muscle invasive carcinoma of the urinary bladder were examined with contrast-enhanced CT of the primary tumor. A specially designed technique was developed to increase the diagnostic potential of CT. The most important points about the technique were controlled filling of the bladder, the use of thin slices, series of scans before and after intravenous injection of contrast medium, and long scanning times in the precontrast series. The absorbed dose to the patient resulting from the new technique was found to be within the range of the dose from urography or barium enema. This dose was considered to be acceptable given the diagnostic gain of the procedure. Features of irradiated bladder tumors were analysed to find which parameter correlated with persistent malignancy. High contrast enhancement of a tumor relative to the bladder wall was found to be the best indicator of a malignant tumour after irradiation. 127 refs

  2. Rho signaling inhibitor,Y-27632,inhibits invasiveness of metastastic hepatocellular carcinoma in a mouse model

    Institute of Scientific and Technical Information of China (English)

    XUE Feng; ZHANG Jian-jun; QIU Feng; ZHANG Ming; CHEN Xiao-song; LI Qi-gen; HAN Long-zhi; XI Zhi-feng; XIA Qiang

    2007-01-01

    @@ Hepatocellular carcinoma(HCC)is among the most common tumors worldwide.Despite extensive exploration of novel therapies,the prognosis of HCC patients with intrahepatic metastasis is still poor,and no treatment is effective against metastases.Therefore,more effective therapeutic strategies for treatment of metastasis are urgently needed.

  3. Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma

    DEFF Research Database (Denmark)

    Canevari, Renata A; Marchi, Fabio A; Domingues, Maria A C;

    2016-01-01

    Breast carcinoma (BC) corresponds to 23 % of all cancers in women, with 1.38 million new cases and 460,000 deaths worldwide annually. Despite the significant advances in the identification of molecular markers and different modalities of treatment for primary BC, the ability to predict its metast...

  4. Eukaryotic translation initiation factor 5A2 regulates the migration and invasion of hepatocellular carcinoma cells via pathways involving reactive oxygen species.

    Science.gov (United States)

    Liu, Rong-Rong; Lv, Ya-Su; Tang, Yue-Xiao; Wang, Yan-Fang; Chen, Xiao-Ling; Zheng, Xiao-Xiao; Xie, Shang-Zhi; Cai, Ying; Yu, Jun; Zhang, Xian-Ning

    2016-04-26

    Eukaryotic translation initiation factor 5A2 (eIF5A2) has been identified as a critical gene in tumor metastasis. Research has suggested that reactive oxygen species (ROS) serve as signaling molecules in cancer cell proliferation and migration. However, the mechanisms linking eIF5A2 and ROS are not fully understood. Here, we investigated the effects of ROS on the eIF5A2-induced epithelial-mesenchymal transition (EMT) and migration in six hepatocellular carcinoma (HCC) cell lines. Western hybridization, siRNA transfection, transwell migration assays, wound-healing assays, and immunofluorescence analysis were used. The protein levels of eIF5A2 in tumor and adjacent tissue samples from 90 HCC patients with detailed clinical, pathological, and clinical follow-up data were evaluated. Overexpression of eIF5A2 was found in cancerous tissues compared with adjacent tissues. We found that eIF5A2 overexpression in HCC was associated with reduced overall survival. Knockdown of eIF5A2 and intracellular reduction of ROS significantly suppressed the invasion and metastasis of HCC cells. Interestingly, N1-guanyl-1, 7-diaminoheptane (GC7) suppressed the intracellular ROS levels. After blocking the EMT, administration of GC7 or N-acetyl-L-cysteine did not reduce cell migration further. Based on the experimental data, we concluded that inhibition of eIF5A2 alters progression of the EMT to decrease the invasion and metastasis of HCC cells via ROS-related pathways. PMID:27028999

  5. Eukaryotic translation initiation factor 5A2 regulates the migration and invasion of hepatocellular carcinoma cells via pathways involving reactive oxygen species

    Science.gov (United States)

    Tang, Yue-Xiao; Wang, Yan-Fang; Chen, Xiao-Ling; Zheng, Xiao-Xiao; Xie, Shang-Zhi; Cai, Ying; Yu, Jun; Zhang, Xian-Ning

    2016-01-01

    Eukaryotic translation initiation factor 5A2 (eIF5A2) has been identified as a critical gene in tumor metastasis. Research has suggested that reactive oxygen species (ROS) serve as signaling molecules in cancer cell proliferation and migration. However, the mechanisms linking eIF5A2 and ROS are not fully understood. Here, we investigated the effects of ROS on the eIF5A2-induced epithelial-mesenchymal transition (EMT) and migration in six hepatocellular carcinoma (HCC) cell lines. Western hybridization, siRNA transfection, transwell migration assays, wound-healing assays, and immunofluorescence analysis were used. The protein levels of eIF5A2 in tumor and adjacent tissue samples from 90 HCC patients with detailed clinical, pathological, and clinical follow-up data were evaluated. Overexpression of eIF5A2 was found in cancerous tissues compared with adjacent tissues. We found that eIF5A2 overexpression in HCC was associated with reduced overall survival. Knockdown of eIF5A2 and intracellular reduction of ROS significantly suppressed the invasion and metastasis of HCC cells. Interestingly, N1-guanyl-1, 7-diaminoheptane (GC7) suppressed the intracellular ROS levels. After blocking the EMT, administration of GC7 or N-acetyl-L-cysteine did not reduce cell migration further. Based on the experimental data, we concluded that inhibition of eIF5A2 alters progression of the EMT to decrease the invasion and metastasis of HCC cells via ROS-related pathways. PMID:27028999

  6. [THE MODE OF CLARIFYING DIAGNOSTIC OF PROGRESSING FORMS OF OVARIAN CARCINOMA].

    Science.gov (United States)

    Dolgova, D R; Gening, T P; Abakumova, T V; Antoneeva, I I; Butov, A A; Korchagina, I A; Tuzeeva, A Yu; Fomina, A V

    2015-10-01

    The ovarian carcinoma is the most frequent cause of death because of malignant neoplasins in women. At that, there is no pathognomonic symptoms permitting diagnosing stage of process with sufficient degree of confidence. This is a determinative not only for choosing treatment regimen but also for correlation of expected results of treatments with economic factors with purpose to evaluate cost effectiveness under monitoring of these patients. The study was carried out to develop mode of clarifying diagnostic of progressing forms of ovarian carcinoma on the basis of evaluation of oxidative modification of proteins in blood plasma. In 100 female patients with primary ovarian carcinoma (stage III and IV according FIGO,) in blood plasma 21 indicators were determined in blood plasma using standardized techniques: absolute number of leukocytes, absolute and relative number of neutrophils, products of oxidative modification of proteins of basic and ketonic character (under wavelength of 356, 370, 430, 530 nm), Her-2/neu CA-125, matrix metalloproteinase 2 and 9 in blood serum and neutrophils, interleukin-6, interleukin-10, interleukin-1β, interferon-γ, tumor necrosis factor-α, malonic dialdehyde, catalase, glutaihione transferase, glutathione reductase. The least squares method was applied to every parameter to appmximnate relative rates by density of Rayleigh distribution. For every indicator likelihood ratio functions of likelihood ratio were constructed and intervals at every stage were determined. The reliability of approximation was proved under testing with Pirson criterion hypothesis of compliance of practical values of parameters to theoretical law of density of distribution. The results permit to assert that level of oxidative modification of proteins cab be used as a reliable indicator for differentiated diagnostic of stage III and IV of ovarian carcinoma. PMID:26841670

  7. Immunohistochemical and Proteomic Evaluation of Nuclear Ubiquitous Casein and Cyclin-Dependent Kinases Substrate in Invasive Ductal Carcinoma of the Breast

    Directory of Open Access Journals (Sweden)

    Piotr Ziółkowski

    2009-01-01

    Full Text Available Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS is 27 kDa chromosomal protein of unknown function. Its amino acid composition as well as structure of its DNA binding domain resembles that of high-mobility group A, HMGA proteins. HMGA proteins are associated with various malignancies. Since changes in expression of HMGA are considered as marker of tumor progression, it is possible that similar changes in expression of NUCKS could be useful tool in diagnosis and prognosis of breast cancer. For identification and analysis of NUCKS we used proteomic and histochemical methods. Analysis of patient-matched samples of normal and breast cancer by mass spectrometry revealed elevated levels of NUCKS in protein extracts from ductal breast cancers. We elicited specific antibodies against NUCKS and used them for immunohistochemistry in invasive ductal carcinoma of breast. We found high expression of NUCKS in 84.3% of cancer cells. We suggest that such overexpression of NUCKS can play significant role in breast cancer biology.

  8. Recurrent High-Grade Invasive Mucoepidermoid Carcinoma of Larynx: A Case Report and Review of the Literature.

    Science.gov (United States)

    King, Whitney; Ko, Stephen; Miller, Daniel

    2016-06-28

    Recurrent invasive high-grade mucoepidermoid carcinoma of the larynx and hypopharynx is a rare occurrence. These tumors have been commonly associated with salivary gland tumors, most commonly the parotid gland. The patient usually presents with the following symptoms: hoarseness (if larynx is involved), or changes in voice character, sore throat, cough, odynophagia, dysphagia, otalgia, difficulty breathing, weight loss, lymphadenopathy. Here we present a case of a recurrent invasive high-grade mucoepidermoid carcinoma of larynx and hypopharynx. The patient was a 67-year-old male that originally presented in 2006. At that time he underwent a wide field laryngectomy, right thyroid lobectomy, and biopsy of the right digastric node. He was a clinical stage III, pT3N0M0. No adjuvant radiation therapy was given at that time. The patient remained asymptomatic until February 2014, when he presented with dysphagia and neck swelling. Positron emission tomography/computed tomography showed evidence of recurrence. The patient was treated with definitive intensity modulated radiation therapy (IMRT) with concurrent chemotherapy. Treatment for this disease is gathered by scattered case reports. If surgery is a possibility it is considered as first line therapy. Post-surgical radiation is then offered. However, in this case the recurrent tumor was located near the carotid artery, and thus surgery was not a possibility. Therefore, concurrent chemotherapy and radiation with IMRT and weekly cis-platinum was given. While the optimum combination of treatment has not yet been established because of the rarity of this cancer's location site, the current patient appeared to have an excellent response from the definitive IMRT and chemotherapy treatment. PMID:27441076

  9. Recurrent high-grade invasive mucoepidermoid carcinoma of larynx: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Whitney King

    2016-06-01

    Full Text Available Recurrent invasive high-grade mucoepidermoid carcinoma of the larynx and hypopharynx is a rare occurrence. These tumors have been commonly associated with salivary gland tumors, most commonly the parotid gland. The patient usually presents with the following symptoms: hoarseness (if larynx is involved, or changes in voice character, sore throat, cough, odynophagia, dysphagia, otalgia, difficulty breathing, weight loss, lymphadenopathy. Here we present a case of a recurrent invasive high-grade mucoepidermoid carcinoma of larynx and hypopharynx. The patient was a 67- year-old male that originally presented in 2006. At that time he underwent a wide field laryngectomy, right thyroid lobectomy, and biopsy of the right digastric node. He was a clinical stage III, pT3N0M0. No adjuvant radiation therapy was given at that time. The patient remained asymptomatic until February 2014, when he presented with dysphagia and neck swelling. Positron emission tomography/computed tomography showed evidence of recurrence. The patient was treated with definitive intensity modulated radiation therapy (IMRT with concurrent chemotherapy. Treatment for this disease is gathered by scattered case reports. If surgery is a possibility it is considered as first line therapy. Post-surgical radiation is then offered. However, in this case the recurrent tumor was located near the carotid artery, and thus surgery was not a possibility. Therefore, concurrent chemotherapy and radiation with IMRT and weekly cis-platinum was given. While the optimum combination of treatment has not yet been established because of the rarity of this cancer’s location site, the current patient appeared to have an excellent response from the definitive IMRT and chemotherapy treatment.

  10. Clinicopathological Characteristics and Survival Outcomes of Invasive Cribriform Carcinoma of Breast: A SEER Population-Based Study.

    Science.gov (United States)

    Liu, Xi-Yu; Jiang, Yi-Zhou; Liu, Yi-Rong; Zuo, Wen-Jia; Shao, Zhi-Ming

    2015-08-01

    Invasive cribriform carcinoma (ICC) is a rare histologic subtype of breast cancer. We aimed to investigate the clinicopathological characteristics and survival outcomes of ICC.Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 233,337 female patients diagnosed with ICC (n = 618) or infiltrating ductal carcinoma (IDC) (n = 232,719). Univariate and multivariate survival analyses were utilized to calculate and compare disease-specific survival (DSS) and overall survival (OS). A 1:1 paired match was carried out on age, tumor stage, tumor grade, estrogen receptor (ER) status, and progesterone receptor (PR) status. Baseline characteristics and survival outcomes were also analyzed in ER-positive tumors. Subgroup analyses summarized the hazard ratio (HR) of IDC versus ICC using a forest plot.ICCs presented smaller size, lower grade, higher ER and PR positive rate, less nodal metastasis, and were less likely to be treated with mastectomy compared to IDCs. Five-year DSS rates were significantly better for patients with ICC than for patients with IDC (98.8% vs. 93%, P understanding of ICC might lead to more individualized and tailored therapy for breast cancer patients. PMID:26252312

  11. Clinicopathological Characteristics and Survival Outcomes in Invasive Papillary Carcinoma of the Breast: A SEER Population-Based Study.

    Science.gov (United States)

    Zheng, Yi-Zi; Hu, Xin; Shao, Zhi-Ming

    2016-01-01

    To investigate the clinicopathological characteristics and survival outcomes of invasive papillary carcinoma (IPC), we identified 233,171 female patients in the Surveillance, Epidemiology, and End Results (SEER) database who had IPC (n = 524) or infiltrating ductal carcinoma (IDC) (n = 232,647). Generally, IPCs occurred in older women (≥ 50 years old) and presented with smaller sizes, lower grades, higher rates of oestrogen receptor (ER) and progesterone receptor (PR) positivity, and reduced lymph node (LN) involvement and were less likely to be treated with mastectomy than patients with IDC. The five-year disease-specific survival (DSS) rates were significantly better in IPC than in IDC (97.5% vs. 93%, respectively; P hazard ratio = 0.556, 95% confidence interval 0.289-1.070, P = 0.079). No significant difference was observed in DSS between matched IPC and IDC groups (P = 0.085). Differences in outcomes may be partially explained by differences in tumour grade, LN status, and ER and PR status between the 2 groups. Gaining an improved clinical and biological understanding of IPC might result in more tailored and effective therapies in breast cancer patients. PMID:27053333

  12. Estrogen receptor beta rs1271572 polymorphism and invasive ovarian carcinoma risk: pooled analysis within the Ovarian Cancer Association Consortium.

    Directory of Open Access Journals (Sweden)

    Galina Lurie

    Full Text Available The association of ovarian carcinoma risk with the polymorphism rs1271572 in the estrogen receptor beta (ESR2 gene was examined in 4946 women with primary invasive ovarian carcinoma and 6582 controls in a pooled analysis of ten case-control studies within the Ovarian Cancer Association Consortium (OCAC. All participants were non-Hispanic white women. Odds ratios (ORs and 95% confidence intervals (CIs were estimated using unconditional logistic regression adjusted for site and age. Women with the TT genotype were at increased risk of ovarian carcinoma compared to carriers of the G allele (OR = 1.10; 95%; CI: 1.01-1.21; p = 0.04; the OR was 1.09 (CI: 0.99-1.20; p = 0.07 after excluding data from the center (Hawaii that nominated this SNP for OCAC genotyping A stronger association of rs1271572 TT versus GT/GG with risk was observed among women aged ≤50 years versus older women (OR = 1.35; CI: 1.12-1.62; p = 0.002; p for interaction = 0.02 that remained statistically significant after excluding Hawaii data (OR = 1.34; CI: 1.11-1.61; p = 0.009. No heterogeneity of the association was observed by study, menopausal status, gravidity, parity, use of contraceptive or menopausal hormones, tumor histological type, or stage at diagnosis. This pooled analysis suggests that rs1271572 might influence the risk of ovarian cancer, in particular among younger women.

  13. Platelet extracts induce growth, migration and invasion in human hepatocellular carcinoma in vitro

    International Nuclear Information System (INIS)

    Thrombocytopenia has been reported to be associated with small size HCCs, and thrombocytosis to be associated with large size HCCs. The aim was to examine the effects of platelets in relation to HCC cell growth. The effects of time-expired pooled normal human platelets were examined on human HCC cell line growth and invasion. Blood platelet numbers increased with increasing HCC tumor size and portal vein invasion. Platelet extracts enhanced cell growth in 4 human HCC cell lines, as well as cell migration, medium AFP levels and decreased apoptosis. Cell invasion was significantly enhanced, using a Matrigel-coated trans-well membrane and3D (Real-Time Imaging) invasion assay. Western blots showed that platelets caused enhanced phospho-ERK and phospho–JNK signaling and anti-apoptotic effect with increase of Bcl-xL (anti-apoptotic marker) and decrease of Bid (pro-apoptotic marker) levels. Their growth effects were blocked by a JNK inhibitor. Platelets stimulated growth and invasion of several HCC cell lines in vitro, suggesting that platelets or platelet growth factors could be a potential pharmacological target

  14. Comparison of nuclear grade and immunohistochemical features in situ and invasive components of ductal carcinoma of breast Comparação do grau nuclear e perfil imunoistoquímico nos componentes in situ e invasivo de carcinoma mamário

    OpenAIRE

    Fernando Nalesso Aguiar; Henrique Nogueira Mendes; Bacchi, Carlos E.; Filomena Marino Carvalho

    2013-01-01

    PURPOSE:To compare the prognostic and predictive features between in situ and invasive components of ductal breast carcinomas. METHODS:We selected 146 consecutive breast samples with ductal carcinoma in situ (DCIS) associated with adjacent invasive breast carcinoma (IBC). We evaluated nuclear grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor recep...

  15. Profiling of the tetraspanin CD151 web and conspiracy of CD151/integrin β1 complex in the progression of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Ranjan Prasad Devbhandari

    Full Text Available Tetraspanin CD151 has been implicated in metastasis through forming complexes with different molecular partners. In this study, we mapped tetraspanin web proteins centered on CD151, in order to explore the role of CD151 complexes in the progression of hepatocellular carcinoma (HCC. Immunoprecipitation was used to isolate tetraspanin complexes from HCCLM3 cells using a CD151 antibody, and associated proteins were identified by mass spectrometry. The interaction of CD151 and its molecular partners, and their roles in invasiveness and metastasis of HCC cells were assayed through disruption of the CD151 network. Finally, the clinical implication of CD151 complexes in HCC patients was also examined. In this study, we identified 58 proteins, characterized the tetraspanin CD151 web, and chose integrin β1 as a main partner to further investigate. When the CD151/integrin β1 complex in HCC cells was disrupted, migration, invasiveness, secretion of matrix metalloproteinase 9, and metastasis were markedly influenced. However, both CD151 and integrin β1 expression were untouched. HCC patients with high expression of CD151/integrin β1 complex had the poorest prognosis of the whole cohort of patients. Together, our data show that CD151 acts as an important player in the progression of HCC in an integrin β1-dependent manner.

  16. Non-Invasive Radiofrequency-Induced Targeted Hyperthermia for the Treatment of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Mustafa Raoof

    2011-01-01

    Full Text Available Targeted biological therapies for hepatocellular cancer have shown minimal improvements in median survival. Multiple pathways to oncogenesis leading to rapid development of resistance to such therapies is a concern. Non-invasive radiofrequency field-induced targeted hyperthermia using nanoparticles is a radical departure from conventional modalities. In this paper we underscore the need for innovative strategies for the treatment of hepatocellular cancer, describe the central paradigm of targeted hyperthermia using non-invasive electromagnetic energy, review the process of characterization and modification of nanoparticles for the task, and summarize data from cell-based and animal-based models of hepatocellular cancer treated with non-invasive RF energy. Finally, future strategies and challenges in bringing this modality from bench to clinic are discussed.

  17. Modeling invasive breast cancer: growth factors propel progression of HER2-positive premalignant lesions.

    Science.gov (United States)

    Pradeep, C-R; Zeisel, A; Köstler, W J; Lauriola, M; Jacob-Hirsch, J; Haibe-Kains, B; Amariglio, N; Ben-Chetrit, N; Emde, A; Solomonov, I; Neufeld, G; Piccart, M; Sagi, I; Sotiriou, C; Rechavi, G; Domany, E; Desmedt, C; Yarden, Y

    2012-08-01

    The HER2/neu oncogene encodes a receptor-like tyrosine kinase whose overexpression in breast cancer predicts poor prognosis and resistance to conventional therapies. However, the mechanisms underlying aggressiveness of HER2 (human epidermal growth factor receptor 2)-overexpressing tumors remain incompletely understood. Because it assists epidermal growth factor (EGF) and neuregulin receptors, we overexpressed HER2 in MCF10A mammary cells and applied growth factors. HER2-overexpressing cells grown in extracellular matrix formed filled spheroids, which protruded outgrowths upon growth factor stimulation. Our transcriptome analyses imply a two-hit model for invasive growth: HER2-induced proliferation and evasion from anoikis generate filled structures, which are morphologically and transcriptionally analogous to preinvasive patients' lesions. In the second hit, EGF escalates signaling and transcriptional responses leading to invasive growth. Consistent with clinical relevance, a gene expression signature based on the HER2/EGF-activated transcriptional program can predict poorer prognosis of a subgroup of HER2-overexpressing patients. In conclusion, the integration of a three-dimensional cellular model and clinical data attributes progression of HER2-overexpressing lesions to EGF-like growth factors acting in the context of the tumor's microenvironment.

  18. Occult Invasive Lobular Carcinoma of Breast Detected by Stomach Metastasis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    KIm, So Jung; Jung, Hae Kyoung; Ko, Kyung Hee; Yoon, Jung Hyun [Dept. of Radiology, Bundang CHA general Hospital, CHA University College of Medicine, Seongnam (Korea, Republic of)

    2012-02-15

    Gastric metastasis from primary breast cancer is a rare phenomenon that is more prevalent in the invasive lobular type of breast cancer. We describe a very rare case of occult invasive lobular cancer of the breast detected by the initial presentation of gastric metastasis in a patient without a history of breast cancer. A 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) which showed increased FDG uptake in the stomach, abdominal mesentery and the right breast, and played pivotal roles in the detection of occult primary breast cancer and a diagnosis of gastric metastasis as an ancillary method for obtaining histological results and immunohistochemical stains.

  19. Occult Invasive Lobular Carcinoma of Breast Detected by Stomach Metastasis: A Case Report

    International Nuclear Information System (INIS)

    Gastric metastasis from primary breast cancer is a rare phenomenon that is more prevalent in the invasive lobular type of breast cancer. We describe a very rare case of occult invasive lobular cancer of the breast detected by the initial presentation of gastric metastasis in a patient without a history of breast cancer. A 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) which showed increased FDG uptake in the stomach, abdominal mesentery and the right breast, and played pivotal roles in the detection of occult primary breast cancer and a diagnosis of gastric metastasis as an ancillary method for obtaining histological results and immunohistochemical stains.

  20. Correlation of primary tumor FDG uptake with clinicopathologic prognostic factors in invasive ductal carcinoma of the breast

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the correlation of primary tumor FDG uptake to clinicopathological prognostic factors in invasive ductal carcinoma of the breast. We retrospectively reviewed 136 of 215 female patients with pathologically proven invasive ductal breast cancer from January 2008 to December 2011 who underwent F-18 FDG PET/CT for initial staging and follow-up after curative treatment with analysis of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2). The maximum standardized uptake value (SUVmax) of the primary breast tumor was measured and compared with hormonal receptor and HER2 overexpression status. The high SUVmax of primary breast tumors is significantly correlated with the clinicopathological factors: tumor size, histologic grade, TNM stage, negativity of ER, negativity of PR, HER2 overexpression and triple negativity. The recurrent group with non-triple negative cancer had a higher SUVmax compared with the non-recurrent group, though no significant difference in FDG uptake was noted between the recurrence and non-recurrent groups in subjects with triple-negative cancer. Lymph node involvement was the independent risk factor for cancer recurrence in the multivariate analysis. In conclusion, high FDG uptake in primary breast tumors is significantly correlated with clinicopathological factors, such as tumor size, histologic grade, TNM stage, negativity of the hormonal receptor, HER2 overexpression and triple negativity. Therefore, FDG PET/CT is a helpful prognostic tool to direct the further management of patients with breast cancer

  1. PARD3 Inactivation in Lung Squamous Cell Carcinomas Impairs STAT3 and Promotes Malignant Invasion

    OpenAIRE

    Bonastre, Ester; Verdura, Sara; Zondervan, Ilse; Facchinetti, Federica; Lantuejoul, Sylvie; Chiara, Maria Dolores; Rodrigo, Juan Pablo; Carretero, Julian; Condom, Enric; Vidal, Agustin; Sidransky, David; Villanueva, Alberto; Roz, Luca; Brambilla, Elisabeth; Savola, Suvi

    2015-01-01

    Correct apicobasal polarization and intercellular adhesions are essential for the appropriate development of normal epithelia. Here, we investigated the contribution of the cell polarity regulator PARD3 to the development of lung squamous cell carcinomas (LSCC). Tumor-specific PARD3 alterations were found in 8% of LSCCs examined, placing PARD3 among the most common tumor suppressor genes in this malignancy. Most PAR3-mutant proteins exhibited a relative reduction in the ability to mediate for...

  2. Using neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy for nasopharyngeal carcinoma with intracranial invasion to protect critical normal tissue

    International Nuclear Information System (INIS)

    To investigate the feasibility of neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy (IMRT) for intracranial invasion nasopharyngeal carcinoma (NPC). From June 2007 to January 2012, 32 patients with intracranial invasion NPC treated with TPF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, 5-FU 2500 mg/m2 every 3 weeks for 3 cycles) neoadjuvant chemotherapy, and replanning IMRT with concurrent chemotherapy were retrospectively studied. The first IMRT plan for each patient was generated based on the original planning CT scan acquired before the start of treatment. Because of tumor shrinkage during radiotherapy, modified gross tumor volume of primary tumor (GTV-P) and high risk clinical target volume (CTV-H), and a new plan was generated and used to complete the course of IMRT. The DVHs of IMRT plan with or without replanning were compared. There weren’t statistically significant differences in the V95, D-mean, D-95, and D-99 to the modified PTVGTV-P and PTVCTV-H with and without replanning IMRT. Replanning reduced the doses to the brain stem, optic nerve, optic chiasm and temporal lobe. Objective responses were 100.0% 3 months after completion of radiotherapy. Acute toxicities were well tolerated, except for the relatively high incidence of neutropenia. The 2-year local control rates and distant-metastasis free survival were 88.2% (95% CI, 72.9% to 100.0%) and 89.6% (95% CI, 75.9% to 100.0%). Neoadjuvant chemotherapy and replanning IMRT according to tumor shrinkage during the treatment is essential to ensure safe doses to normal tissues, and produces encouraging outcome for intracranial invasion NPC

  3. Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

    Directory of Open Access Journals (Sweden)

    Kucuk Omer

    2007-01-01

    Full Text Available Abstract Background We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC model established in our laboratory. Methods The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. Results In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. Conclusion Our studies in both RCC and prostate tumor models demonstrate that the

  4. A minority of carcinoma cells producing acidic fibroblast growth factor induces a community effect for tumor progression.

    OpenAIRE

    Jouanneau, J; Moens, G; Bourgeois, Y; Poupon, M. F.; Thiery, J P

    1994-01-01

    It is generally accepted that primary tumors become heterogeneous as a consequence of tumor-cell genetic instability. Clonal dominance has been shown to occur in some experimental models allowing a subpopulation of cells to overgrow the primary heterogeneous tumor and to metastasize. Alternatively, interactions among coexisting tumor subpopulations may contribute to the emergence of a malignant invasive primary solid tumor. We asked the question whether emergence of carcinoma cells producing ...

  5. Matrix metalloproteinase-13 expression in the progression of colorectal adenoma to carcinoma : Matrix metalloproteinase-13 expression in the colorectal adenoma and carcinoma.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

    2014-06-01

    Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence. PMID:24563279

  6. Early growth responsive gene 3 in human breast carcinoma: a regulator of estrogen-meditated invasion and a potent prognostic factor.

    Science.gov (United States)

    Suzuki, Takashi; Inoue, Akio; Miki, Yasuhiro; Moriya, Takuya; Akahira, Jun-ichi; Ishida, Takanori; Hirakawa, Hisashi; Yamaguchi, Yuri; Hayashi, Shin-ichi; Sasano, Hironobu

    2007-06-01

    Early growth responsive gene 3 (EGR3) is a zinc-finger transcription factor and plays important roles in cellular growth and differentiation. We recently demonstrated estrogen-mediated induction of EGR3 in breast carcinoma cells. However, EGR3 has not yet been examined in breast carcinoma tissues and its significance remains unknown. Therefore, in this study, we examined biological functions of EGR3 in the breast carcinoma by immunohistochemistry, in vitro study, and nude mouse xenograft model. EGR3 immunoreactivity was detected in carcinoma cells in 99 (52%) out of 190 breast carcinoma tissues and was associated with the mRNA level. EGR3 immunoreactivity was positively associated with lymph node status, distant metastasis into other organs, estrogen receptor alpha, or EGR3 immunoreactivity in asynchronous recurrent lesions in the same patients, and was negatively correlated with tubule formation. EGR3 immunoreactivity was significantly associated with an increased risk of recurrence and adverse clinical outcome by both uni- and multivariate analyses. Egr3-expressing transformant cell lines derived from MCF-7 Tet-Off cells (Eg-10 and Eg-11) significantly enhanced the migration and invasion properties according to the treatment of doxycyclin, but did not significantly change the cell proliferation. Moreover, Eg-11 cells injected into athymic mice irregularly invaded into the adjacent peritumoral tissues, although Clt-7, which was stably transfected with empty vector as a control, demonstrated a well-circumscribed tumor. Eg-11 cells were significantly associated with invasive components and less tubule formation in the xenograft model. These results suggest that EGR3 plays an important role in estrogen-meditated invasion and is an independent prognostic factor in breast carcinoma. PMID:17639044

  7. Plasma miR-185 is decreased in patients with esophageal squamous cell carcinoma and might suppress tumor migration and invasion by targeting RAGE.

    Science.gov (United States)

    Jing, Rongrong; Chen, Wen; Wang, Huimin; Ju, Shaoqing; Cong, Hui; Sun, Baolan; Jin, Qin; Chu, Shaopeng; Xu, Lili; Cui, Ming

    2015-11-01

    The receptor for advanced-glycation end products (RAGE) is upregulated in various cancers and has been associated with tumor progression, but little is known about its expression and regulation by microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). Here, we describe miR-185, which represses RAGE expression, and investigate the biological role of miR-185 in ESCC. In this study, we found that the high level of RAGE expression in 29 pairs of paraffin-embedded ESCC tissues was correlated positively with the depth of invasion by immunohistochemistry, suggesting that RAGE was involved in ESCC. We used bioinformatics searches and luciferase reporter assays to investigate the prediction that RAGE was regulated directly by miR-185. Besides, overexpression of miR-185 in ESCC cells was accompanied by 27% (TE-11) and 49% (Eca-109) reduced RAGE expression. The effect was further confirmed in RAGE protein by immunofluorescence in both cell lines. The effects were reversed following cotransfection with miR-185 and high-level expression of the RAGE vector. Furthermore, the biological role of miR-185 in ESCC cell lines was investigated using assays of cell viability, Ki-67 staining, and cell migration and invasion, as well as in a xenograft model. We found that overexpression of miR-185 inhibited migration and invasion by ESCC cells in vitro and reduced their capacity to develop distal pulmonary metastases in vivo partly through the RAGE/heat shock protein 27 pathway. Interestingly, in clinical specimens, the level of plasma miR-185 expression was decreased significantly (P = 0.002) in patients with ESCC [0.500; 95% confidence interval (CI) 0.248-1.676] compared with healthy controls (2.410; 95% CI 0.612-5.671). The value of the area under the receiver-operating characteristic curve was 0.73 (95% CI 0.604-0.855). In conclusion, our findings shed novel light on the role of miR-185/RAGE in ESCC metastasis, and plasma miR-185 has potential as a novel diagnostic biomarker

  8. Stable SET knockdown in breast cell carcinoma inhibits cell migration and invasion

    International Nuclear Information System (INIS)

    Highlights: • We employed RNA interference to knockdown SET expression in breast cancer cells. • Knockdown of SET expression inhibits cell proliferation, migration and invasion. • Knockdown of SET expression increases the activity and expression of PP2A. • Knockdown of SET expression decreases the expression of MMP-9. - Abstract: Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer

  9. Stable SET knockdown in breast cell carcinoma inhibits cell migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jie [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Yang, Xi-fei [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Ren, Xiao-hu [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Meng, Xiao-jing [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Huang, Hai-yan [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zhao, Qiong-hui [Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen (China); Yuan, Jian-hui; Hong, Wen-xu; Xia, Bo; Huang, Xin-feng; Zhou, Li [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Liu, Jian-jun, E-mail: bio-research@hotmail.com [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zou, Fei, E-mail: zoufei616@163.com [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China)

    2014-10-10

    Highlights: • We employed RNA interference to knockdown SET expression in breast cancer cells. • Knockdown of SET expression inhibits cell proliferation, migration and invasion. • Knockdown of SET expression increases the activity and expression of PP2A. • Knockdown of SET expression decreases the expression of MMP-9. - Abstract: Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer.

  10. Overexpressed HDAC4 is associated with poor survival and promotes tumor progression in esophageal carcinoma

    Science.gov (United States)

    Mai, Shi-Juan; Wang, Meng-He; Zhang, Mei-Yin; Zheng, X.F. Steven; Wang, Hui-Yun

    2016-01-01

    Histone deacetylases (HDACs) mediate histone deacetylation, leading to transcriptional repression, which is involved in many diseases, including age-related tissue degeneration, heart failure and cancer. In this study, we were aimed to investigate the expression, clinical significance and biological function of HDAC4 in esophageal carcinoma (EC). We found that HDAC4 mRNA and protein are overexpressed in esophageal squamous cell carcinoma (ESCC) tissues and cell lines. HDAC4 overexpression is associated with higher tumor grade, advanced clinical stage and poor survival. Mechanistically, HDAC4 promotes proliferation and G1/S cell cycle progression in EC cells by inhibiting cyclin-dependent kinase (CDK) inhibitors p21 and p27 and up-regulating CDK2/4 and CDK-dependent Rb phosphorylation. HDAC4 also enhances ESCC cell migration. Furthermore, HDAC4 positively regulates epithelial-mesenchymal transition (EMT) by increasing the expression of Vimentin and decreasing the expression of E-Cadherin/α-Catenin. Together, our study shows that HDAC4 overexpression is important for the oncogenesis of EC, which may serve as a useful prognostic biomarker and therapeutic target for this malignancy. PMID:27295551

  11. Factors Associated with Post-Progression Survival in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

    Directory of Open Access Journals (Sweden)

    Taiga Otsuka

    2015-05-01

    Full Text Available Sorafenib exerts modest antitumor activity in patients with advanced hepatocellular carcinoma (HCC, and radiological progressive disease (rPD does not always correspond to so-called clinical progressive disease (cPD. We evaluated 101 patients who initiated sorafenib treatment for HCC and assessed post-progression survival (PPS using the Cox proportional hazards model. PPS was calculated from the date of the first rPD until the date of death or the last follow-up. Using Cox model analysis of the 76 patients who experienced first rPD, we identified the Child-Pugh class, Eastern Cooperative Oncology Group performance status, the best antitumor response during treatment (using Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1 and α-fetoprotein levels as independent factors affecting PPS. When these factors were used to define scores ranging from zero to five with a cutoff value of two, PPS of patients who received best supportive care (BSC after rPD was not statistically significantly different from that of patients who received post-rPD therapy with scores ≥2 (p = 0.220. In contrast, the PPS for the post-rPD therapy group was significantly longer compared with the BSC patients with scores <2 (p < 0.001. Patients who scored ≥2 at their first rPD were judged cPD and as candidates for BSC.

  12. Tumor progression locus 2 ablation suppressed hepatocellular carcinoma development by inhibiting hepatic inflammation and steatosis in mice

    Science.gov (United States)

    Background: Tumor progression locus 2 (TPL2), a serine threonine kinase, functions as a critical regulator of inflammatory pathways and mediates oncogenic events. The potential role of Tpl2 in nonalcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) development remains unkn...

  13. A20 inhibits human salivary adenoid cystic carcinoma cells invasion via blocking nuclear factor-κB activation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bin; GUAN Cheng-chao; CHEN Wan-tao; ZHANG Ping; YAN Ming; SHI Jiu-hui; QIN Chun-lin; YANG Qian

    2007-01-01

    Background A20, also known as tumor necrosis factor α induced protein 3 (TNFaip3), is a cytoplasmic zinc finger protein that inhibits nuclear factor kappa-B (NF-κB) activity and prevents tumor necrosis factor (TNF)-mediated programmed cell death. NF-κB is a transcription factor that regulates expression of genes involved in cell proliferation,cell survival and anti-apoptosis. Several studies have implicated that the NF-κB signal pathway is associated with angiogenesis and clinico-pathological process of adenoid cystic carcinoma (ACC) of the salivary glands.Methods The ability of overexpression of A20 to influence the biological behavior and invasion of ACC cells was examined. The cells were stably transfected with full-length A20 cDNA. Stable gene transfer was verified by realtime-polymerase chain reaction (PCR) and Western blot analysis. The change of cell biological behavior was examined by methyl thiazolyl tetrazolium (MTT) and NF-κB luciferase reporter assay and the invasion of the cells was examined by a Matrigel invasion chamber.Results pEGPFN3-A20 gene was stably transferred into ACC-2 cells and overexpressed. When cells were treated with TNFα, the NF-κB activity of ACC-2-A20 cells could be down-regulated about 46.32% in contrast to ACC-2-GFP cells (P<0.05). A20 potently inhibited growth of A20 transfectant ACC-2-A20 compared with control vector transfected groups and the ACC-2 empty control group (P<0.05). The ACC-2-A20 cells showed significantly reduced ability to invade through Matrigei-coated filters compared to ACC-2-GFP and ACC-2 cells. The inhibition rate was up to 71.05% (P<0.05).Conclusions A20 gene transfer is associated with decreased tumor invasion, in part via the down-regulation of NF-κB expression, providing evidence for a potential application of A20 in designing a treatment modality for salivary gland cancers such as ACC.

  14. Urothelial carcinoma involving the distal penis

    OpenAIRE

    Dason, Shawn; Sheikh, Adeel; Wang, Jing Gennie; Tauqir, Syeda; Davies, Timothy O.; Shayegan, Bobby

    2012-01-01

    Urothelial carcinoma (UC) rarely metastasizes to the penis and skin. We report the case of a 73-year-old man with UC metastases to the corpus spongiosum and dermis of the distal penis. We also review the clinicopathologic characteristics and management options for UC metastasizing to the penis. The patient presented with priapism and edema of the genital region. This follows a 5-year history of urothelial carcinoma in situ that progressed to invasive cancer despite intravesical immunotherapy....

  15. Progression after spontaneous regression in lung large cell neuroendocrine carcinoma: Report of a curative resection.

    Science.gov (United States)

    Tomizawa, Kenji; Suda, Kenichi; Takemoto, Toshiki; Iwasaki, Takuya; Sakaguchi, Masahiro; Kuwano, Hiroyuki; Mitsudomi, Tetsuya

    2015-09-01

    We present the first reported case of lung large cell neuroendocrine carcinoma (LCNEC) with spontaneous regression followed by progression. An 85-year-old woman presented with a 2.8-cm nodule in the right upper lung lobe on chest computed tomography. After four months, the tumor decreased to 1.8 cm and remained unchanged in size for the next three months, but it grew to 8.6 cm and invaded the mediastinal fat tissue after approximately one year. Ultrasound echo-guided percutaneous biopsy revealed the tumor to be LCNEC. The patient underwent a right upper lobectomy with lymph node dissection. She had a good postoperative course with no complications. Physicians and surgeons should be aware that radiographic regression of a pulmonary nodule does not necessarily exclude the possibility of lung cancer. PMID:26443884

  16. Low-grade Serous Carcinoma of the Ovary: Clinicopathologic Analysis of 52 Invasive Cases and Identification of a Possible Noninvasive Intermediate Lesion.

    Science.gov (United States)

    Ahn, Geunghwan; Folkins, Ann K; McKenney, Jesse K; Longacre, Teri A

    2016-09-01

    Low-grade serous carcinoma (LGSC) is an uncommon but distinct histologic subtype of ovarian carcinoma. Although the histologic features and natural history of LGSC have been described in the literature, there is no robust correlative study that has specifically addressed histologic features in correlation with clinical follow-up. To refine the criteria for invasion patterns of LGSC and determine additional clinically pertinent morphologic features of LGSC predisposing to a more aggressive clinical course, the clinicopathologic features of 52 LGSCs were evaluated and compared with those of a large series of serous borderline tumors (SBT), with and without invasive implants. To qualify for LGSC, the tumor needed to demonstrate destructive invasion, nuclear atypia that was mild to moderate at most (grade 1 or 2), and a mitotic index that did not exceed 12 mitoses per 10 high-power fields. On the basis of histologic evaluation, destructive invasion was classified into 7 primary architectural patterns: (1) micropapillary and/or complex papillary; (2) compact cell nests; (3) inverted macropapillae; (4) cribriform; (5) glandular and/or cystic; (6) solid sheets with slit-like spaces; and (7) single cells. Five-year overall survival and disease-free survival for LGSC were 82% (median, 72 mo) and 47% (median, 54 mo), respectively. All the patients with fatal outcome demonstrated tumors showing invasion with predominant patterns of cribriform glands, micropapillae and/or complex papillae, or compact cell nests. Notably, 2 of 9 patients with fatal outcome had only small foci of destructive invasion (2 and 3 mm, respectively) with compact cell nests and cribriform glands as the predominant patterns. There was no statistically significant association between pattern of invasion and disease-free survival. Classic stromal microinvasion, as defined by nondestructive stromal invasion low-grade serous carcinomatous cells were also identified in 8 SBTs, in either solid or compact

  17. Prognostic impact of extent of vascular invasion in low-grade encapsulated follicular cell–derived thyroid carcinomas: a clinicopathologic study of 276 cases☆

    Science.gov (United States)

    Xu, Bin; Wang, Laura; Tuttle, R. Michael; Ganly, Ian; Ghossein, Ronald

    2016-01-01

    Summary Continuous controversy surrounds the predictive value of the degree of vascular invasion (VI) in low-grade encapsulated follicular cell–derived thyroid carcinomas (LGEFCs). Some guidelines advocate conservative therapy in LGEFCs with focal VI. There is therefore a need to assess the survival rates of LGEFC patients with various degrees of VI to better stratify patients for subsequent therapy. Furthermore, the prognostic effect of VI within the different histotypes of LGEFCs is not well known. A total of 276 patients with LGEFCs were subjected to a meticulous histopathologic analysis. They were classified as encapsulated papillary thyroid carcinoma, encapsulated follicular carcinoma (EFC), and encapsulated Hurthle cell carcinoma (EHCC). Of the 276 patients, 24 had extensive VI (EVI) (≥4 foci) and 28 displayed focal (thyroid carcinoma. Median follow-up was 6 years. All 14 tumors with adverse behavior harbored distant metastases (DMs), of which 9 had DMs at presentation. All 3 patients without EVI who had aggressive carcinomas harbored DMs at presentation. EVI was an independent predictor of poor recurrence-free survival. Excluding cases with DMs at presentation, only patients with EVI had recurrence, and all relapsed cases were EHCC. EVI is an independent predictor of recurrence-free survival in LGEFCs. EHCC with EVI has a particularly high risk of recurrence. When DMs are not found at presentation, patients with focal VI are at a very low risk of recurrence even if not treated with radioactive iodine. PMID:26482605

  18. Type-specific human papillomavirus distribution in invasive cervical carcinomas in Paraguay. A study of 432 cases.

    Science.gov (United States)

    Kasamatsu, Elena; Cubilla, Antonio L; Alemany, Laia; Chaux, Alcides; Tous, Sara; Mendoza, Laura; Paez, Malvina; Klaustermeier, Jo Ellen; Quint, Wim; Lloveras, Belen; de Sanjose, Silvia; Muñoz, Nubia; Bosch, Francisco Xavier

    2012-10-01

    Cervical carcinoma is the most common malignant tumor among woman in Paraguay. Cytological screening programs have not been successful and a plan for human papillomavirus (HPV) based-screening program and/or vaccination is under evaluation. This study aimed to identify the contribution of HPV genotypes in invasive cervical cancer in Paraguay to provide essential background data to guide and assess the introduction and impact of new preventive strategies based on HPV. Four hundred thirty two histologically confirmed cases (1960-2004) were analyzed. HPV detection in paraffin blocks was performed at the Catalan Institute of Oncology using PCR with SPF-10 broad spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridization line probe analysis. The majority of cases were squamous cell carcinoma (92.8%). Mean patients age was 48 years old. HPV DNA was detected in 73.1% of the cases and single infections were predominant (97.8%). The most common HPV single types were 16, 18, 45, 33, 31, 52, 35, and 39. 73.1% of HPV positive cases had an HPV 16, 18 as single infection. HPV16 was frequent in SCC whereas HPV 18 and 45 were prevalent in glandular tumors. Significant decrease of HPV 16 with age groups (P-trend = 0.022) and increase in other HPV types (P-trend > 0.001) were observed. The potential impact of HPV 16 and 18 for a vaccination program was 73.1%. The study provide a profile of the HPV situation in the country, with robust clinical, pathological and virological data which would permit a better cervical cancer screening and vaccination programs.

  19. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder

    Science.gov (United States)

    Massari, Francesco; Bria, Emilio; Ciccarese, Chiara; Munari, Enrico; Modena, Alessandra; Zambonin, Valentina; Sperduti, Isabella; Artibani, Walter; Cheng, Liang; Martignoni, Guido; Tortora, Giampaolo; Brunelli, Matteo

    2015-01-01

    Background To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential. Methods In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0–3); c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive. Results beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively); 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02) and c-Myc 28 low vs 8 high (p-value 0.007). Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006). Conclusions c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies. PMID:26046361

  20. Prognostic Value of Beta-Tubulin-3 and c-Myc in Muscle Invasive Urothelial Carcinoma of the Bladder.

    Directory of Open Access Journals (Sweden)

    Francesco Massari

    Full Text Available To date, putative prognostic biomarkers have shown limited utility from the clinical perspective for bladder urothelial carcinoma. Herein, the expression of beta-tubulin-3 and c-Myc was evaluated to determine their prognostic potential.In formalin fixed-paraffin embedded blocks, immunohistochemical expression of c-Myc and beta-tubulin-3 was evaluated. H score ranging from 0 to 300 was obtained by multiplying the percentage of positive cells by intensity (0-3; c-Myc and beta-tubulin-3 expression was defined: 0: negative, 1: weakly positive, 2: strongly positive.beta-tubulin-3 and c-Myc immunoexpression was available for 46 cases. At the univariate analysis, node-involvement, beta-tubulin-3 and c-Myc overexpression discriminate shorter DFS (HR 2.19, p = 0.043; HR 3.10, p = 0.24 and HR 3.05, p = 0.011, respectively; 2-yrs DFS log-rank analysis according to low versus high level of immunoexpression were statistically significant; beta-tubulin-3, 53% low vs 12.7% high (p = value 0.02 and c-Myc 28 low vs 8 high (p-value 0.007. Patients displaying negative beta-tubulin-3/c-Myc had statistically significant better 2-yrs DFS than those with mixed expression or double positivity (54.5% versus 18.7% versus 0%, log-rank p = 0.006.c-Myc and beta-tubulin-3 show improvement for prognostic risk stratification in patients with muscle invasive bladder urothelial carcinoma. These molecular pathways may also be candidate to improve predictiveness to targeted therapies.

  1. The diagnostic contribution of computed tomography in intranasal carcinoma with retrobulbar, oral and brain invasion in a canine: case report

    International Nuclear Information System (INIS)

    Intranasal tumors are uncommon and in most cases are malignant, aggressive and with low to moderate potential for metastasis. Clinical signs are usually caused by progressive obstruction of the upper airways. The test cytopathological also is a diagnosis method, but the definitive diagnosis is made by histopathological. Computed tomography (CT) is recommended to treatment planning. A poodle was attended at the veterinary hospital with a clinical history of epistaxis and nasal and ocular secretions, seizures and severe dyspnoea. The animal underwent to radiographic examination of the chest and skull as well as helical computed tomography of the nasal cavity and brain before and after the administration of intravenous contrast. The CT findings revealed an expansive bilateral nasal cavity neoformation, with involvement of the retrobulbar space, right frontal sinus, brain and oral cavity, suggesting a neoplastic or an infectious process. The CT examination allowed the material collection, directly from the mass, to cytological examination, providing the diagnosis of carcinoma. CT also allowed the determination of the unfavorable prognosis of the patient and the treatment planning which not included the surgical excision of the neoformation. Although CT was not conclusive in the diagnosis of carcinoma, it was essential to accurately define the extent of the lesion, to guide the collection of material directly from the tumor and to determine the prognosis of the animal, proving to be an extremely useful tool in cases of tumors intranasal in dogs. (author)

  2. C2-O-sLeX glycoproteins are E-selectin ligands that regulate invasion of human colon and hepatic carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Catherine A St Hill

    Full Text Available Similar to mechanisms of recruitment of activated leukocytes to inflamed tissues, selectins mediate adhesion and extravasation of circulating cancer cells. Our objective was to determine whether sialyl Lewis X modified core 2 O-glycans (C2-O-sLe(X present on colon and hepatic carcinoma cells promote their adhesion and invasion. We examined membrane expression of C2-O-sLe(X, selectin binding, invasion of human colon and hepatic carcinoma cell lines, and mRNA levels of alpha-2,3 fucosyltransferase (FucT-III and core 2 beta-1,6 N-acetylglucosaminyltransferase (C2GnT1 genes, necessary for C2-O-sLe(X synthesis, by quantitative reverse-transcriptase (RT PCR. Synthesis of core 2 branched O-glycans decorated by sLe(X is dependent on C2GnT1 function and thus we determined enzyme activity of C2GnT1. The cell lines that expressed C2GnT1 and FucT-III mRNA by quantitative RT-PCR were highly positive for C2-O-sLe(X by flow cytometry, and colon carcinoma cells possessed highly active C2GnT1 enzyme. Cells bound avidly to E-selection but not to P- and L-selectin. Gene knock-down of C2GnT1 in colon and hepatic carcinoma cells using short hairpin RNAs (shRNA resulted in a 40-90% decrease in C2-O-sLe(X and a 30-50% decrease in E-selectin binding compared to control cells. Invasion of hepatic and colon carcinoma cells containing C2GnT1 shRNA was significantly reduced compared to control cells in Matrigel assays and C2GnT1 activity was down-regulated in the latter cells. The sLe(X epitope was predominantly distributed on core 2 O-glycans on colon and hepatic carcinoma cells. Our findings indicate that C2GnT1 gene expression and the resulting C2-O-sLe(X carbohydrates produced mediate the adhesive and invasive behaviors of human carcinomas which may influence their metastatic potential.

  3. Oncocytic-type intraductal papillary mucinous neoplasm (IPMN-derived invasive oncocytic pancreatic carcinoma with brain metastasis - a case report

    Directory of Open Access Journals (Sweden)

    Chiang Kun-Chun

    2012-07-01

    Full Text Available Abstract Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.

  4. Selective Inguinal Lymphadenectomy in the Treatment of Invasive Squamous Cell Carcinoma of the Vulva

    Directory of Open Access Journals (Sweden)

    Christopher P. DeSimone

    2011-01-01

    Full Text Available En bloc radical vulvectomy with bilateral inguinofemoral lymphadenectomy has now been replaced by radical wide excision and selective inguinal lymphadenectomy based on the stage and location of invasive vulvar cancer. Early stage lateral cancers can be effectively treated by radical wide excision and ipsilateral superficial inguinal lymphadenectomy. Lymph node mapping using perilesional injection of radiocolloid and blue dye may identify sentinel lymph nodes which can be removed, thereby avoiding the morbidity of full inguinal lymphadenectomy in selected patients with early stage disease.

  5. Genomic and gene expression signature of the pre-invasive testicular carcinoma in situ

    DEFF Research Database (Denmark)

    Almstrup, Kristian; Ottesen, Anne Marie; Sonne, Si Brask;

    2005-01-01

    in cultured undifferentiated embryonic stem cells after spontaneous amplification in similar regions. The gene expression profile of CIS cells has remarkable similarity to that of embryonic stem cells and supports our long-standing hypothesis of an early developmental origin of CIS and testicular germ cell......Testicular cancer is the most common malignancy among men in the reproductive age and the incidence is increasing, probably caused by environmental factors. Most testicular cancers are testicular germ cell tumours and all originate from a carcinoma in situ (CIS) pattern. In this review, we focus...... and increased transcriptional activation and/or deficiency in the epigenetic silencing of specific loci. Amplification of chromosome 12p, appears to be a good genomic marker of the transition from the pre-malignant to malignant CIS cell; this is consistent with recent findings of propagation advantages...

  6. Development and evaluation of a prediction model for underestimated invasive breast cancer in women with ductal carcinoma in situ at stereotactic large core needle biopsy.

    Directory of Open Access Journals (Sweden)

    Suzanne C E Diepstraten

    Full Text Available BACKGROUND: We aimed to develop a multivariable model for prediction of underestimated invasiveness in women with ductal carcinoma in situ at stereotactic large core needle biopsy, that can be used to select patients for sentinel node biopsy at primary surgery. METHODS: From the literature, we selected potential preoperative predictors of underestimated invasive breast cancer. Data of patients with nonpalpable breast lesions who were diagnosed with ductal carcinoma in situ at stereotactic large core needle biopsy, drawn from the prospective COBRA (Core Biopsy after RAdiological localization and COBRA2000 cohort studies, were used to fit the multivariable model and assess its overall performance, discrimination, and calibration. RESULTS: 348 women with large core needle biopsy-proven ductal carcinoma in situ were available for analysis. In 100 (28.7% patients invasive carcinoma was found at subsequent surgery. Nine predictors were included in the model. In the multivariable analysis, the predictors with the strongest association were lesion size (OR 1.12 per cm, 95% CI 0.98-1.28, number of cores retrieved at biopsy (OR per core 0.87, 95% CI 0.75-1.01, presence of lobular cancerization (OR 5.29, 95% CI 1.25-26.77, and microinvasion (OR 3.75, 95% CI 1.42-9.87. The overall performance of the multivariable model was poor with an explained variation of 9% (Nagelkerke's R(2, mediocre discrimination with area under the receiver operating characteristic curve of 0.66 (95% confidence interval 0.58-0.73, and fairly good calibration. CONCLUSION: The evaluation of our multivariable prediction model in a large, clinically representative study population proves that routine clinical and pathological variables are not suitable to select patients with large core needle biopsy-proven ductal carcinoma in situ for sentinel node biopsy during primary surgery.

  7. The prognostic value of sentinel lymph node micrometastases in patients with invasive breast carcinoma.

    Science.gov (United States)

    Cipolla, Calogero; Graceffa, Giuseppa; La Mendola, Roberta; Fricano, Salvatore; Fricano, Martina; Vieni, Salvatore

    2015-01-01

    Il significato prognostico delle micrometastasi nel linfonodo sentinella nelle pazienti affette da carcinoma della mammella è ancora ampiamente dibattuto. Anche se, in assenza di univoche linee guida, nella pratica clinica la linfadenectomia ascellare in queste pazienti non viene più eseguita di routine. Abbiamo condotto uno studio retrospettivo su 746 patienti affette da carcinoma invasivo della mammella con linfonodi ascellari negativi, sottoposte a chirurgia conservativa o a mastectomia totale con biopsia del linfonodo sentinella. Le pazienti in cui è stata diagnostica la presenza di micrometastasi del linfonodo sentinella sono state considerate in due diversi gruppi. In un primo gruppo, trattato con linfadenectomia ascellare totale è stata valutata l’incidenza di metastasi a carico dei rimanenti linfonodi ascellari. Un secondo gruppo non ha ricevuto alcun trattamento aggiuntivo dell’ascella e le pazienti sono state seguite con controlli periodici clinico strumentali. In entrambi i gruppi è stata valutata l’incidenza di eventuali recidive ascellari. All’esame istologico estemporaneo ed al successivo esame istologico definitivo del linfonodo sentinella, in 51 pazienti (6,83%) sono state evidenziate micrometastasi, in 8 pazienti (1,07%) erano presenti cellule tumorali isolate. Quindici di queste pazienti sono state sottoposte a linfadenectomia ascellare totale. Solo in 2 casi (13,33%) sono state ritrovate metastasi a carico dei rimanenti linfonodi ascellari. Quarantaquattro pazienti non hanno ricevuto alcun trattamento aggiuntivo dell’ascella. In queste pazienti nessuna recidiva ascellare è stata registrata durante un follow-up medio di 65,3±9,65 mesi (range 42-78 mesi). Sulla base dei risultati ottenuti in questo studio ed in linea con alcuni recenti trials randomizzati si ci sentiamo di concludere che la linfadenectomia ascellare può essere evitata nei casi con micrometastasi nel linfonodo sentinella. Una sua eventuale indicazione può essere

  8. Multifocal intraportal invasion of breast carcinoma diagnosed by laparoscopy-assisted liver biopsy

    Institute of Scientific and Technical Information of China (English)

    Tomoki Nakajima; Takeshi Mazaki; Akio Yanagisawa; Takeshi Okanoue; Satoru Sekoguchi; Taichirou Nishikawa; Hidetaka Takashima; Tadashi Watanabe; Masahito Minami; Yoshito Itoh; Naruhiko Mizuta; Hiroo Nakajima

    2005-01-01

    Hepar lobatum carcinomatosum (HLC) is defined as an acquired hepatic deformity consisting of an irregularly lobulated hepatic contour caused by intravascular infiltration of metastatic carcinoma. To date, only nine cases of HLC have been reported in the literature. We report a case of a 68-year-old woman showing hepatic metastasis of breast carcinoma in radiologically unidentified form. Initially, she received left partial mastectomy for breast cancer but solid hepatic metastases were identified in S2 and S6, 9 mo after surgery. Then, they responded to chemotherapy and radiologically disappeared. After radiological disappearance of the liver tumors, the patient's blood chemistry showed abnormal liver function. A CT scan demonstrated heterogeneous enhancement effect in the liver in the late phase,suggesting uneven hepatic blood supply. Hepatic deformity was not obvious. Laparoscopy revealed a slightly deformed liver surface with multiple indentations and shallow linear depressions. Furthermore, a wide scar was observed on the surface of S2 possibly at the site where the metastatic tumor existed before chemotherapy. Liver biopsy from the wide scar lesion showed intraportal tumor thrombi with desmoplastic change. Because of its similarity to the histology of the original breast cancer, we concluded that the hepatic functional abnormalities and slightly deformed liver surface were derived from the circulatory disturbance caused by microscopic tumor thrombi. Besides, since the wide scar was located at the site of the pre-existing tumor,it is probable that chemotherapy was an important cause of fibrous scarring as a result of tumor regression. These morphologic findings are compatible with those of HLC.Laparoscopy-assisted liver biopsy was useful to make definite diagnosis, even though the hepatic deformity was radiologically undetectable.

  9. Slit2-Robo1 signaling promotes the adhesion, invasion and migration of tongue carcinoma cells via upregulating matrix metalloproteinases 2 and 9, and downregulating E-cadherin

    Science.gov (United States)

    Zhao, Yuan; Zhou, Feng-Li; Li, Wei-Ping; Wang, Jing; Wang, Li-Jing

    2016-01-01

    Whether Slit homologue 2 (Slit2) inhibits or promotes tumor cell migration remains controversial, and the role of Slit2-Roundabout 1 (Robo1) signaling in oral cancer remains to be fully elucidated. The aim of the present study was to investigate the role of Slit2-Robo1 signaling in the adhesion, invasion and migration of tongue carcinoma cells, and the mechanism by which Slit2-Robo1 signaling inhibits or promotes tumor cell migration. Tca8113 tongue carcinoma cells were treated with the monoclonal anti-human Robo1 antibody, R5, to inhibit the Slit2-Robo1 signaling pathway, with immunoglobulin (Ig)G2b treatment as a negative control. The expression levels of Slit2 and Robo1 were determined using flow cytometry. The effects of R5 on the adhesion, invasion and migration of Tca8113 tongue carcinoma cells were investigated. Gelatin zymography was used to investigate the activity of matrix metalloproteinase 2 (MMP2) and MMP9. Western blot analysis was used to evaluate the expression levels of E-cadherin in Tca8113 cells treated with 10 µg/ml of either R5 or IgG2b. Slit2 and Robo1 proteins were found to be expressed in the Tca8113 cells. R5 significantly inhibited the adhesion, invasion and migration of Tca8113 cells in vitro. R5 also inhibited the activities of MMP2 and MMP9, and increased the expression of E-cadherin in the Tca8113 cells. These results suggested that Slit2-Robo1 signaling promoted the adhesion, invasion and migration of tongue carcinoma cells by upregulating the expression levels of MMP2 and MMP9 and, downregulating the expression of E-cadherin. PMID:27431199

  10. Immunohistochemical demonstration of EphA2 processing by MT1-MMP in invasive cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Tatsukawa, Ryoko; Koga, Kaori; Aoki, Mikiko; Koshikawa, Naohiko; Imafuku, Shinichi; Nakayama, Juichiro; Nabeshima, Kazuki

    2016-07-01

    Erythropoietin-producing hepatocellular receptor-2 (EphA2) overexpression is prevalent in many types of human cancers, and it has been reported that high EphA2 expression is correlated with malignancy. Recent studies revealed that processing of EphA2 by cleaving off the N-terminal portion by membrane-type 1 matrix metalloproteinase (MT1-MMP) promotes invasion via stimulation of Ras in cancer cells in vitro. The objectives of this study were to investigate the presence and role of EphA2 processing in cutaneous squamous cell carcinoma (SCC) tissues. EphA2 (C-terminal and N-terminal) and MT1-MMP expression patterns and levels were analyzed immunohistochemically in SCC (n = 70) and Bowen disease (BD; n = 20). Levels of MT1-MMP and EphA2 expression were evaluated using digital image analysis. Proximity between MT1-MMP and EphA2 in cancer cells and its effect on EphA2 processing were investigated using a combination of in situ proximity ligation assay (PLA) and Western blotting. Immunohistochemical analyses showed that levels of EphA2 N-terminal expression were significantly lower than those of EphA2 C-terminal expression in SCC, whereas levels of EphA2 C- and N-terminal expression were similar in BD. Western blotting showed processed EphA2 fragments in human SCC tissues. Expression levels of MT1-MMP, EphA2, and processed EphA2 fragments were higher in SCC than BD. Proximity between MT1-MMP and EphA2 in SCC was demonstrated by in situ PLA. Our results suggest possible involvement of MT1-MMP processing of EphA2 in invasiveness of cutaneous SCC. PMID:27056569

  11. Correlation of primary tumor FDG uptake with clinicopathologic prognostic factors in invasive ductal carcinoma of the breast

    Energy Technology Data Exchange (ETDEWEB)

    Jo, I; Kim, Sung Hoon; Kim, Hae Won; Kang, Sung Hee [Keimyung University, School of Medicine, Daegu (Korea, Republic of); Zeon, Seok Kil [Dept. of Nuclear Medicine, Bundang Jesaeng General Hospital, Sungnam (Korea, Republic of); Kim, Su Jin [Dept. of Anesthesiology and Pain Medicine, Dongguk University, School of Medicine, Gyeongju (Korea, Republic of)

    2015-03-15

    The purpose of this study was to investigate the correlation of primary tumor FDG uptake to clinicopathological prognostic factors in invasive ductal carcinoma of the breast. We retrospectively reviewed 136 of 215 female patients with pathologically proven invasive ductal breast cancer from January 2008 to December 2011 who underwent F-18 FDG PET/CT for initial staging and follow-up after curative treatment with analysis of estrogen receptor (ER), progesterone receptor (PR) and human epithelial growth factor receptor 2 (HER2). The maximum standardized uptake value (SUV{sub max}) of the primary breast tumor was measured and compared with hormonal receptor and HER2 overexpression status. The high SUV{sub max} of primary breast tumors is significantly correlated with the clinicopathological factors: tumor size, histologic grade, TNM stage, negativity of ER, negativity of PR, HER2 overexpression and triple negativity. The recurrent group with non-triple negative cancer had a higher SUV{sub max} compared with the non-recurrent group, though no significant difference in FDG uptake was noted between the recurrence and non-recurrent groups in subjects with triple-negative cancer. Lymph node involvement was the independent risk factor for cancer recurrence in the multivariate analysis. In conclusion, high FDG uptake in primary breast tumors is significantly correlated with clinicopathological factors, such as tumor size, histologic grade, TNM stage, negativity of the hormonal receptor, HER2 overexpression and triple negativity. Therefore, FDG PET/CT is a helpful prognostic tool to direct the further management of patients with breast cancer.

  12. Emprego dos marcadores de prognóstico no tratamento para o carcinoma invasor de colo Use of the prognosis markers in the treatment for the invasive cervical carcinoma

    Directory of Open Access Journals (Sweden)

    Agnaldo Lopes Silva Filho

    2009-09-01

    Full Text Available O carcinoma invasor do colo uterino representa um grande problema de Saúde Pública, especialmente nos países em desenvolvimento. O seu tratamento, baseado na histerectomia radical, radioterapia e/ou quimioterapia, apresenta uma morbidade considerável. Os marcadores prognósticos devem ser considerados no planejamento terapêutico, de forma a otimizar os resultados, diminuir as complicações e aumentar a sobrevida das pacientes. São considerados marcadores prognósticos o estadiamento, o tamanho tumoral, o tipo histológico, o grau de diferenciação, a invasão linfovascular, a profundidade da invasão estromal, a presença de metástases linfonodais e o acometimento de margens cirúrgicas. Esse estudo visou fazer uma revisão da literatura em relação à utilização desses marcadores no planejamento terapêutico das mulheres com carcinoma invasor do colo uterino. O tratamento baseado nesses marcadores pode apresentar melhores resultados, com menor taxa de complicações e melhora na sobrevida das pacientes.The uterine cervix invasive carcinoma represents a major public health problem, mainly in the developing countries. Its treatment, based on radical hysterectomy, radiotherapy and/or chemotherapy presents a considerable morbidity. Prognostic markers should be taken into consideration in the therapeutic planning, so that the results would be optimized, complications reduced, and patients' survival prolonged. Accepted prognostic markers are: stage, tumoral size, histological type, degree of differentiation, lymphovascular invasion, depth of the stromal invasion, presence of lymph nodal metastases, and surgical margins involvement. This study aims at making a literature review concerning the use of theses markers in the therapeutic planning of women with uterine cervix invasive carcinoma. The treatment based on these markers may present better results, with lower ratio of complications and an improvement in the patients' survival.

  13. The role of APE/Ref-1 signaling pathway in hepatocellular carcinoma progression.

    Science.gov (United States)

    Yang, Zhen; Yang, Sun; Misner, Bobbye J; Liu-Smith, Feng; Meyskens, Frank L

    2014-11-01

    Hepatocellular carcinoma (HCC) is responsible for a third of the estimated cancer-caused deaths worldwide. To deeply understand the mechanisms controlling HCC progression is of primary importance to develop new approaches for treatment. Apurinic/apyrimidinic endonuclease-1/redox effector factor 1 (APE/Ref-1) has been uncovered elevated in various types of cancer, including HCC. Additionally, HCC progression is always correlated with elevated copper (Cu). Our previous data demonstrated that Cu treatment initiated APE/Ref-1 expression and its downstream targets. Therefore, we hypothesized that APE/Ref-1 may be involved in HCC progression through mediating the effect of Cu to its signaling cascades. Following different treatments, human HCC cell line (Hep3B) and immortalized non-malignant hepatocyte cell line (THLE3) were analyzed to explore the role of APE/Ref-1 signaling pathway. Unstained human tissue microarrays (TMA) were subjected to IHC analysis to study the relationship between APE/Ref-1 expression and clinic features. APE/Ref-1 was upregulated in HCC cells consistent with the strong expression of APE/Ref-1 in HCC tissue microarray. Greater cytoplasmic accumulation of APE/Ref-1 was found in poorly differentiated and more aggressive tumors. Also we provide evidence to show that APE/Ref-1 signaling pathway stimulates cellular proliferation, enhances anti-apoptosis, and facilitates metastasis through experimental knockdown of APE/Ref-1 using siRNA in Hep3B cells or overexpressing APE/Ref-1 in THLE3 cells. These results define a novel role of APE/Ref-1 in HCC progression as being an important mediating and potentiating molecule, and also provide a basis for further investigations utilizing appropriate APE/Ref-1 inhibitors in combination with chemo-drugs for HCC treatment.

  14. Progress in the treatment of pulmonary metastases after liver transplantation for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhan-Wang; Xiang; Lin; Sun; Guo-Hong; Li; Rakesh; Maharjan; Jin-Hua; Huang; Chuan-Xing; Li

    2015-01-01

    Hepatocellular carcinoma(HCC) is the fifth most common cancer in the world, and is the third leading cause of cancer-related death. Liver transplantation(LT) has become a curative treatment for patients with HCC. However, recurrence and metastasis after LT are the main factors reducing long-term survival in patients, and the lung is the most common site of metastasis after LT for HCC, although metastasis to liver, para-aortic lymph nodes and renal periphery are observed. Thus, the treatment of pulmonary metastases after LT for HCC has become a hot research topic, the successful treatment of pulmonary metastases can significantly prolong the survival of LT patients. Although single conventional treatment(chemotherapy, surgery and external beam radiation therapy), immunosuppression, image-guided minimally invasive therapy(radiofrequency ablation, microwave ablation, cryoablation, and brachytherapy) and molecular targeted drugs have had a significant effect, patients do not have durable remission and the long-term survival rate is disappointing. Therefore, improving existing treatments and identifying a more effective combination therapy are important research issues in the prevention and treatment of pulmonary metastases after LT for HCC. The paper reviewed single conventional treatments, new treatments, and combination therapy, to provide a basis for the best treatment of these patients.

  15. Pathologic Complete Response of HER-2 Neu-Positive Invasive Ductal Carcinoma and Ductal Carcinoma In Situ following Neoadjuvant Chemotherapy plus Trastuzumab: A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Sommer R. Gunia

    2012-01-01

    Full Text Available Pathologic complete response (pCR after NC has been consistently associated with improved outcomes. Residual DCIS after NC does not portray worse prognosis compared to complete eradication of all disease but has clinical implications regarding surgical management. We report a case of pCR of DCIS associated with invasive carcinoma in an HER-2 + tumor after NC plus trastuzumab despite persistence of malignant-appearing microcalcifications mammographically. A 41-year-old Caucasian female presented with a 4×4 cm mass in the right breast and a 2.5 cm right axillary node. Mammogram showed a 2.5 cm mass and a 12 cm area of linear pleomorphic, suspicious calcifications in the upper part of the breast. Core biopsy revealed invasive ductal carcinoma and DCIS associated with calcifications (ER 85%, PR 6%, Her2neu 3+ by IHC. Axillary node FNA was positive for malignancy. The patient received doxorubicin/cyclophosphamide (AC → paclitaxel plus T with complete clinical and radiologic response but no significant change in the microcalcifications. Final pathology showed no residual invasive carcinoma or DCIS despite the presence of numerous ducts with microcalcifications. Documented eradication of DCIS has not been reported following NC when malignant-appearing calcifications persist and this observation may have important clinical implications regarding surgical management.

  16. Hepatoma-Derived Growth Factor: Its Possible Involvement in the Progression of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Hirayuki Enomoto

    2015-06-01

    Full Text Available The development of hepatocellular carcinoma (HCC is an important complication of viral infection induced by hepatitis virus C, and our major research theme is to identify a new growth factor related to the progression of HCC. HDGF (hepatoma-derived growth factor is a novel growth factor that belongs to a new gene family. HDGF was initially purified from the conditioned medium of a hepatoma cell line. HDGF promotes cellular proliferation as a DNA binding nuclear factor and a secreted protein acting via a receptor-mediated pathway. HDGF is a unique multi-functional protein that can function as a growth factor, angiogenic factor and anti-apoptotic factor and it participates in the development and progression of various malignant diseases. The expression level of HDGF may be an independent prognostic factor for predicting the disease-free and overall survival in patients with various malignancies, including HCC. Furthermore, the overexpression of HDGF promotes the proliferation of HCC cells, while a reduction in the HDGF expression inhibits the proliferation of HCC cells. This article provides an overview of the characteristics of HDGF and describes the potential role of HDGF as a growth-promoting factor for HCC.

  17. miR-125/Pokemon auto-circuit contributes to the progression of hepatocellular carcinoma.

    Science.gov (United States)

    Kong, Jing; Liu, Xiaoping; Li, Xiangqian; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

    2016-01-01

    Hepatocellular carcinoma (HCC) is a type of human malignant tumor occurring in hepatic tissues with high mortality. Patients benefit little from current therapeutic modalities, at least partially due to the lack of complete elucidation of molecular network regulating HCC. miR-125 and Pokemon are well-recognized tumor suppressor and oncogenes for HCC, respectively. However, the underlying mechanism by which the two genes exert their functions and the relationship between miR-125 and Pokemon is still unexplored yet. In this study, we found that there is an inverse association between miR-125 and Pokemon expression levels in HCC specimen and cell lines. Online database mining indicated that there are three putative mRNA recognition elements (MREs) of miR-125 within 3' untranslated region (3'UTR) of Pokemon. MREs of miR-125 confer the expression of luciferase with a miR-125-dependent fashion. The alteration in miR-125 abundance regulates the expression of Pokemon at both protein and mRNA levels. Overexpression of Pokemon is able to abrogate the inhibitory effect of miR-125 on HCC progression. Further study showed that Pokemon inhibits the expression of miR-125 by binding of recognition sites within its promoter. In conclusion, we found that there is an auto-regulatory circuit consisting of miR-125 and Pokemon, which promotes the progression of HCC and may be a promising therapeutic target in clinical HCC treatment. PMID:26227218

  18. Differential impact of telomere dysfunction on initiation and progression of hepatocellular carcinoma.

    Science.gov (United States)

    Farazi, Paraskevi A; Glickman, Jonathan; Jiang, Shan; Yu, Alice; Rudolph, Karl Lenhard; DePinho, Ronald A

    2003-08-15

    Telomere maintenance and telomerase reactivation are near universal features of human hepatocellular carcinoma (HCC), yet the shorter telomeres and highly abnormal cytogenetic profiles of HCC suggest that telomere erosion and dysfunction may be operative during the formative stages of tumorigenesis. Previous studies have established that the cancer-enhancing or suppressing impact of telomere dysfunction is highly dependent on several parameters including cell type, tumor stage, and p53 status. Here, to understand better the pathogenetic role of telomere dysfunction in the initiation and progression in human HCC, we have used three mechanistically distinct liver cancer-prone model systems (urokinase plasminogen activator transgenic mice, carbon tetrachloride exposure, and diethylnistrosamine treatment) in the context of successive generations of telomerase-deficient mice null for the telomerase RNA component, mTERC. Across all of the HCC model systems, telomere dysfunction suppressed both the incidence and growth of HCC lesions, a trend that mirrored the level of intratumoral proliferative arrest and apoptosis. On the histological level, telomere dysfunction was associated with a significant increase in the number of early stage neoplastic lesions and a reciprocal decline in the occurrence of high-grade malignancies. These genetic data in the mouse indicate that telomere dysfunction exerts an opposing role in the initiation versus progression of HCC and provide a framework for understanding the intimate link among chronic liver disease, chromosomal instability, and increased HCC in humans. PMID:12941829

  19. Matrix metalloproteinase 12 is induced by heterogeneous nuclear ribonucleoprotein K and promotes migration and invasion in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Overexpression of heterogeneous nuclear ribonucleoprotein K (hnRNP K), a DNA/RNA binding protein, is associated with metastasis in nasopharyngeal carcinoma (NPC). However, the mechanisms underlying hnRNP K-mediated metastasis is unclear. The aim of the present study was to determine the role of matrix metalloproteinase (MMP) in hnRNP K-mediated metastasis in NPC. We studied hnRNP K-regulated MMPs by analyzing the expression profiles of MMP family genes in NPC tissues and hnRNP K-knockdown NPC cells using Affymetrix microarray analysis and quantitative RT-PCR. The association of hnRNP K and MMP12 expression in 82 clinically proven NPC cases was determined by immunohistochemical analysis. The hnRNP K-mediated MMP12 regulation was determined by zymography and Western blot, as well as by promoter, DNA pull-down and chromatin immunoprecipitation (ChIP) assays. The functional role of MMP12 in cell migration and invasion was demonstrated by MMP12-knockdown and the treatment of MMP12-specific inhibitor, PF-356231. MMP12 was overexpressed in NPC tissues, and this high level of expression was significantly correlated with high-level expression of hnRNP K (P = 0.026). The levels of mRNA, protein and enzyme activity of MMP12 were reduced in hnRNP K-knockdown NPC cells. HnRNP K interacting with the region spanning −42 to −33 bp of the transcription start site triggered transcriptional activation of the MMP12 promoter. Furthermore, inhibiting MMP12 by MMP12 knockdown and MMP12-specific inhibitor, PF-356231, significantly reduced the migration and invasion of NPC cells. Overexpression of MMP12 was significantly correlated with hnRNP K in NPC tissues. HnRNP K can induce MMP12 expression and enzyme activity through activating MMP12 promoter, which promotes cell migration and invasion in NPC cells. In vitro experiments suggest that NPC metastasis with high MMP12 expression may be treated with PF-356231. HnRNP K and MMP12 may be potential therapeutic markers for NPC, but

  20. Stereotactic body radiation therapy for the treatment of early-stage minimally invasive adenocarcinoma or adenocarcnioma in situ (formerly bronchioloalveolar carcinoma: a patterns of failure analysis

    Directory of Open Access Journals (Sweden)

    Badiyan Shahed N

    2013-01-01

    Full Text Available Abstract Introduction Ongoing prospective trials exploring stereotactic body radiation therapy (SBRT for early stage non-small cell lung cancer (NSCLC often exclude minimally invasive adenocarcinoma or adenocarcnioma in situ, formerly bronchioloalveolar carcinoma (BAC, due to concerns for accurate target delineation on CT. We performed a patterns of failure analysis to compare outcomes between BAC and other NSCLC subtypes. Methods One hundred twenty patients with early stage NSCLC were treated with SBRT from 2004–2009. Pathologic confirmation of NSCLC was obtained in 97 patients. Radiotherapy was delivered according to RTOG guidelines. The log-rank test was used to compare outcomes between BAC and other NSCLC. Results Median follow-up was 29 months. The median SBRT dose was 5400 cGy. Thirteen patients had radiographically diagnosed BAC and five patients had biopsy confirmed BAC, of which two had both. The three-year local control was 100% for biopsy-proven or radiographically diagnosed BAC (n = 18 and 86% for all other NSCLC subtypes (n = 102 (p = 0.13. Likewise, no significant difference was detected between BAC and other NSCLC for 3-year regional failure (12% vs. 20%, p = 0.45, progression-free survival (57.6% vs. 53.5%, p = 0.84 or overall survival (35% vs. 47%, p = 0.66. There was a trend towards lower three-year rates of freedom from distant failure in patients with any diagnosis of BAC compared to those without (26% vs. 38%, p = 0.053. Conclusions Compared to other NSCLC subtypes, BAC appears to have similar patterns of failure and survival after treatment with SBRT, however there may be an increased risk of distant metastases with BAC. RTOG guideline-based target delineation provides encouraging local control rates for patients with BAC.

  1. Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Deep, Gagan [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States); Kumar, Rahul; Jain, Anil K. [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); Agarwal, Chapla [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States); Agarwal, Rajesh, E-mail: Rajesh.agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States)

    2014-10-15

    cleaved caspase 3), EMT (E-cadherin and β-catenin), and cell survival (survivin and Akt) related signaling molecules in PC3 cells. Furthermore, PC3-xenograft tissue analyses confirmed the inhibitory effect of silibinin on fibronectin and integrins expression. Together, these results showed that silibinin targets PCA cells’ interaction with fibronectin and inhibits their motility, invasiveness and survival; thus further supporting silibinin use in PCA intervention including its metastatic progression.

  2. Risk factors for invasive carcinoma of the uterine cervix in Latin America.

    Science.gov (United States)

    Herrero, R; Brinton, L A; Reeves, W C; Brenes, M M; Tenorio, F; de Britton, R C; Gaitán, E; Montalván, P; García, M; Rawls, W E

    1990-01-01

    A study of 759 cervical cancer patients, 1,430 controls, and 689 sex partners in four Latin American countries has made it possible to assess the influence of multiple factors upon the risk of invasive cervical cancer. The principal risk factors identified were the woman's age at first coitus, the number of her steady sex partners, her number of live births, the presence of DNA from human papillomavirus (HPV) types 16 or 18, a history of venereal disease, nonparticipation in early detection programs, and low socioeconomic status. There is good reason to believe that extensive detection programs directed mainly at high-risk groups in the Americas can reduce the high incidence of cervical cancer in this Region. PMID:2171706

  3. Assessment of depth of myometrial invasion by endometrial carcinoma: comparison of T2-weighted SE and contrast-enhanced dynamic GRE MR imaging

    International Nuclear Information System (INIS)

    A prospective study was undertaken to assess the value of both T2-weighted spin-echo (SE) and contrast-enhanced dynamic gradient-echo (GRE) sequences using MR imaging in differentiating the deep myometrial invasion from lower stages produced by endometrial carcinoma. For the correlation of MR findings with the histopathologic findings, patients who had no myometrial invasion (stage 1 a) and patients in whom tumors were confined to the superficial myometrium (stage 1 b) at pathologic examination were combined as lower stages. Twenty patients with endometrial carcinoma were studied using both techniques. The absence of any detectable tumor (stage 1 a) or the presence of a tumor confined to inner half of myometrium (stage 1 b) and extention of tumor to the outer half of myometrium (stage 1 c) were used as the diagnostic criteria. In pathologic examination of excised specimens, deep myometrial invasion was detected in 9 of 20 patients. The sensitivity, specificity, accuracy, positive predictive values (PPV) and negative predictive values (NPV) of T2-weighted SE in differentiating deep myometrial invasion from combined lower stages were 88, 91, 90, 88, and 91 %, respectively, whereas corresponding values for contrast-enhanced dynamic GRE sequences were 78, 100, 90, 100, and 85 %. Statistical difference between two sequences did not reach a significant level. We conclude that in cases of absence of visible junctional zone with SE sequence, contrast-enhanced dynamic GRE MR imaging may be helpful. (orig.)

  4. 水通道蛋白在光化性角化病、Bowen病和浸润性鳞状细胞癌中的表达及其意义%Expression and significance of aquaporin in actinic keratosis, Bowen’s disease and invasive squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    王小勇; 陶承军; 任金平; 袁丞达; 王敏磊; 应航宇

    2015-01-01

    Objective: To explore the expression and signiifcance of aquaporin (AQP) 1, 3, 9, 10 in lesions of actinic keratosis, Bowen’s disease and invasive squamous cell carcinoma.Methods: Immunohistochemistry was utilized to measure the expression of AQP 1, 3, 9, 10 in tissue samples from normal human skin, actinic kera-tosis, Bowen’s disease and invasive squamous cell carcinoma.Results: The expression of AQP 3, 9, 10 in tissue samples from actinic keratosis, Bowen’s disease and invasive squamous cell carcinoma all increased signiifcantly compared with the normal skin tissue. The high staining of AQP1 was observed in vascular inner membrance and endothelial cells of invasive squamous cell carcinoma. The expression of AOP9 and AQP10 in tissue samples from invasive squamous cell carcinoma increased significantly compared with actinic keratosis.Conclusion:The upregulated expression of AQP1, 3, 9, 10 may correlated with the carcinogenesis and progression of invasive squamous cell carcinoma.%目的:探讨水通道蛋白(AQP)1、3、9、10在光化性角化病(AK)、Bowen病(BD)和浸润性皮肤鳞状细胞癌(SCC)中的表达及其意义。方法:应用免疫组织化学方法检测AQP1、AQP3、AQP9、AQP10在人正常皮肤组织、AK、BD和浸润性SCC中的表达情况。结果:与正常皮肤组织比较,AQP3、AQP9和AQP10表达在AK、BD和浸润性SCC中均显著增高;AQP1在浸润性SCC的血管内膜和血管内皮细胞中强度染色;浸润性SCC中AQP9、AQP10的表达水平显著高于AK。结论:AQP1、AQP3、AQP9、AQP10的表达上调与浸润性SCC的发生、发展可能相关。

  5. Role of preoperative breast MRI in ductal carcinoma in situ for prediction of the presence and assessment of the extent of occult invasive component.

    Science.gov (United States)

    Nori, Jacopo; Meattini, Icro; Giannotti, Elisabetta; Abdulcadir, Dalmar; Mariscotti, Giovanna; Calabrese, Massimo; Angelino, Francesca; Chiesa, Fabio; Saieva, Calogero; Vanzi, Ermanno; Boeri, Cecilia; Bianchi, Simonetta; Sanchez, Luis; Orzalesi, Lorenzo; Casella, Donato; Susini, Tommaso; Livi, Lorenzo

    2014-01-01

    Ductal carcinoma in situ (DCIS) is a common neoplasm that may be associated with focal invasive breast cancer lesions. The aim of our study was to evaluate the role of preoperative magnetic resonance imaging (MRI) in determining occult invasive presence and disease extent in patients with preoperative diagnosis of pure DCIS. We analyzed 125 patients with postoperative pure DCIS (n = 91) and DCIS plus invasive component (n = 34). Diagnostic mammography (MRX) showed a size underestimation rate of 30.4% while MRI showed an overestimation rate of 28.6%. Comparing the mean absolute error between preoperative MRI and MRX evaluations and final disease extent, MRI showed an improved accuracy of 51.2%. In our analysis preoperative breast MRI showed a better accuracy in predicting postoperative pathologic extent of disease, adding strength to the growing evidences that preoperative MRI can lead to a more appropriate management of DCIS patients. PMID:24750509

  6. Comparative Gene Expression Analyses Identify Luminal and Basal Subtypes of Canine Invasive Urothelial Carcinoma That Mimic Patterns in Human Invasive Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Deepika Dhawan

    Full Text Available More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well.

  7. Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Zhi-Qiang Wang

    Full Text Available Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed in post-chemotherapy (CT primary cultures derived from serous epithelial ovarian cancer (EOC patients, when compared to primary cultures derived from matched primary (prior to CT tumors. However, we found no differences in the RUNX2 methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA methylation-based epigenetic mechanisms have no impact on RUNX2 expression in advanced (metastatic stage of the disease. Moreover, RUNX2 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. Knockdown of the RUNX2 expression in EOC cells led to a sharp decrease of cell proliferation and significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as various genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX2 gene in serous EOC progression and suggest that RUNX2 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX2 and other members of the RUNX gene family in ovarian tumorigenesis.

  8. Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells.

    Science.gov (United States)

    Wang, Zhi-Qiang; Keita, Mamadou; Bachvarova, Magdalena; Gobeil, Stephane; Morin, Chantale; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Trinh, Xuan Bich; Bachvarov, Dimcho

    2013-01-01

    Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed in post-chemotherapy (CT) primary cultures derived from serous epithelial ovarian cancer (EOC) patients, when compared to primary cultures derived from matched primary (prior to CT) tumors. However, we found no differences in the RUNX2 methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA methylation-based epigenetic mechanisms have no impact on RUNX2 expression in advanced (metastatic) stage of the disease. Moreover, RUNX2 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. Knockdown of the RUNX2 expression in EOC cells led to a sharp decrease of cell proliferation and significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as various genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX2 gene in serous EOC progression and suggest that RUNX2 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX2 and other members of the RUNX gene family in ovarian tumorigenesis.

  9. The role of breast MR imaging in pre-operative determination of invasive disease for ductal carcinoma in situ diagnosed by needle biopsy

    International Nuclear Information System (INIS)

    To evaluate whether magnetic resonance (MR) imaging features can predict the presence of occult invasion in cases of biopsy-proven pure ductal carcinoma in situ (DCIS). We retrospectively reviewed 92 biopsy-proven pure DCIS in 92 women who underwent MR imaging. The following MR imaging findings were compared between confirmed DCIS and invasive breast cancer (IBC): lesion size, type, morphological and kinetic assessments by ACR BI-RADS MRI, and findings of fat-suppressed T2-weighted (FS-T2W) imaging. Sixty-eight of 92 (74%) were non-mass-like enhancements (NMLE) and 24 were mass lesions on MR imaging. Twenty-one of 68 (31%) NMLE and 13 of 24 (54%) mass lesions were confirmed as IBC. In NMLE lesions, large lesions (P = 0.007) and higher signal intensities (SI) on FS-T2W images (P = 0.032) were significantly associated with IBC. Lesion size remained a significant independent predictor of invasion in multivariate analysis (P = 0.032), and combined with FS-T2W SIs showed slightly higher observer performances (area under the curve, AUC, 0.71) than lesion size alone (AUC 0.68). There were no useful findings that enabled the differentiation of mass-type lesions. Breast MR imaging is potentially useful to predict the presence of occult invasion in biopsy-proven DCIS with NMLE. MR mammography permits more precise lesion assessment including ductal carcinoma in situ A correct diagnosis of occult invasion before treatment is important for clinicians This study showed the potential of MR mammography to diagnose occult invasion Treatment and/or aggressive biopsy can be given with greater confidence MR mammography can lead to more appropriate management of patients. (orig.)

  10. The role of breast MR imaging in pre-operative determination of invasive disease for ductal carcinoma in situ diagnosed by needle biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Goto, Mariko; Yuen, Sachiko; Akazawa, Kentaro; Nishida, Kaori; Yamada, Kei [Kyoto Prefectural University of Medicine, Departments of Radiology, Graduate School of Medical Science, Kyoto (Japan); Konishi, Eiichi [Kyoto Prefectural University of Medicine, Departments of Pathology, Graduate School of Medical Science, Kyoto (Japan); Kajihara, Mariko [Kyoto Breast Center Sawai Memorial Clinic, Departments of Radiology, Kyoto (Japan); Shinkura, Nobuhiko [Kyoto Breast Center Sawai Memorial Clinic, Departments of Surgery, Kyoto (Japan)

    2012-06-15

    To evaluate whether magnetic resonance (MR) imaging features can predict the presence of occult invasion in cases of biopsy-proven pure ductal carcinoma in situ (DCIS). We retrospectively reviewed 92 biopsy-proven pure DCIS in 92 women who underwent MR imaging. The following MR imaging findings were compared between confirmed DCIS and invasive breast cancer (IBC): lesion size, type, morphological and kinetic assessments by ACR BI-RADS MRI, and findings of fat-suppressed T2-weighted (FS-T2W) imaging. Sixty-eight of 92 (74%) were non-mass-like enhancements (NMLE) and 24 were mass lesions on MR imaging. Twenty-one of 68 (31%) NMLE and 13 of 24 (54%) mass lesions were confirmed as IBC. In NMLE lesions, large lesions (P = 0.007) and higher signal intensities (SI) on FS-T2W images (P = 0.032) were significantly associated with IBC. Lesion size remained a significant independent predictor of invasion in multivariate analysis (P = 0.032), and combined with FS-T2W SIs showed slightly higher observer performances (area under the curve, AUC, 0.71) than lesion size alone (AUC 0.68). There were no useful findings that enabled the differentiation of mass-type lesions. Breast MR imaging is potentially useful to predict the presence of occult invasion in biopsy-proven DCIS with NMLE. MR mammography permits more precise lesion assessment including ductal carcinoma in situ A correct diagnosis of occult invasion before treatment is important for clinicians This study showed the potential of MR mammography to diagnose occult invasion Treatment and/or aggressive biopsy can be given with greater confidence MR mammography can lead to more appropriate management of patients. (orig.)

  11. Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma

    NARCIS (Netherlands)

    van de Nieuwenhof, Hedwig P.; Bulten, Johan; Hollema, Harrie; Dommerholt, Rianne G.; Massuger, Leon F. A. G.; van der Zee, Ate G. J.; de Hullu, Joanne A.; van Kempen, Leon C. L. T.

    2011-01-01

    Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a dif

  12. BRCA-mutated Invasive Breast Carcinomas: Immunohistochemical Analysis of Insulin-like Growth Factor II mRNA-binding Protein (IMP3), Cytokeratin 8/18, and Cytokeratin 14.

    Science.gov (United States)

    Mohanty, Sambit K; Lai, Jin-Ping; Gordon, Ora K; Pradhan, Dinesh; Bose, Shikha; Dadmanesh, Farnaz

    2015-01-01

    To evaluate the expression of insulin-like growth factor II mRNA-binding protein (IMP3), CK8/18, and CK14 in BRCA mutated and sporadic invasive breast carcinoma. Immunohistochemistry for IMP3, CK8/18, and CK14 was performed on 39 cases of invasive breast carcinomas with BRCA mutation (24 BRCA1, 14 BRCA2, and 1 dual BRCA1/BRCA2) and 54 cases of sporadic invasive breast carcinomas. The relationship between the IMP3, CK8/18, and CK14 and the tumor grade and molecular phenotypes were analyzed. IMP3, CK8/18, and CK14 positivity were present in 20 (51%), 22 (56%), and 14 (36%) of 39 BRCA-mutated breast carcinomas, and 11 (20%), 53 (98%), and 24 (44%) of 54 sporadic breast carcinomas respectively. The rates of IMP3 expression and absence of CK8/18 (44% versus 2%) in BRCA-mutated breast carcinomas was significantly higher than the sporadic breast carcinomas (p = 0.002 and p carcinomas in the immunoprofile for IMP3, CK8/18, and CK14. No significant correlation was identified between the expression of IMP3 and CK8/18 and the tumor grade in both BRCA-mutated and sporadic breast carcinomas (p > 0.05). In cases with luminal A and B phenotypes, the rates of expression of IMP3 and loss of CK8/18 were significantly higher in BRCA-mutated as compared to sporadic breast carcinoma (p carcinomas (54% versus 0%, p = 0.001), while no difference was observed for IMP3 expression (p = 0.435). Regardless of mutation type, histologic grade, or molecular phenotype, the absence of CK8/18 expression and presence of IMP3 expression are seen at much higher rate in BRCA mutated breast carcinomas.

  13. Hydronephrotic urine in the obstructed kidney promotes urothelial carcinoma cell proliferation, migration, invasion through the activation of mTORC2-AKT and ERK signaling pathways.

    Directory of Open Access Journals (Sweden)

    Chi-Hao Chang

    Full Text Available Obstructive nephropathy is the most common presentation of urothelial carcinoma. The role of the urine in the obstructed kidney namely "hydronephrotic urine" in urothelial carcinoma has not been extensively explored. This study aims to evaluate whether hydronephrotic urine in the obstructed kidney could promote urothelial carcinoma. The hydronephrotic urine was collected from the obstructed kidneys of Sprague-Dawley rats induced by different periods of unilateral ureteral obstruction (UUO. By the inhibition of LY294002 and PD184352, we confirm that hydronephrotic urine promotes urothelial carcinoma cell (T24 and immortalized normal urothelial cells (E6 proliferation, migration and invasion in a dose-dependent manner through the activation of the mTORC2-AKT and ERK signaling pathways. Hydronephrotic urine also increases the expression of cyclin-D2, cyclin-B and CDK2. It also decreases the expression of p27 and p21 in both urothelial carcinoma cells and normal urothelial cells. By the protein array study, we demonstrate that many growth factors which promote tumor cell survival and metastasis are over-expressed in a time-dependent manner in the hydronephrotic urine, including beta-FGF, IFN-γ, PDGF-BB, PIGF, TGF-β, VEGF-A, VEGF-D and EGF. These results suggest that hydronephrotic urine promotes normal and malignant urothelial cells proliferation, migration and invasion, through the activation of the mTORC2-AKT and ERK signaling pathways. Further investigation using live animal models of tumor growth may be needed to clarify aspects of these statements.

  14. Patients with nipple-areola Paget's disease and underlying invasive breast carcinoma have very poor survival: a matched cohort study.

    Directory of Open Access Journals (Sweden)

    Hong Ling

    Full Text Available Paget's disease (PD of the breast is a rare disease. The survival rate of PD was reported to depend on the characteristics of the underlying carcinoma. This study aimed to investigate the characteristics and survival rate of PD patients with underlying invasive breast carcinoma (IBC. Fifty-two patients were diagnosed with PD and an associated IBC from 2001 to 2005 in Fudan University Shanghai Cancer Center. Twenty-four (46.2% had no clinical manifestation of PD and were diagnosed unexpectedly by a histologic examination. The 52 patients were all recruited in this study as the PD group. They tended to have greater chances of lymph node involvement (53.8% vs. 35.7%, lower hormone receptor expression (34.6% vs. 69.7%, higher human epidermal growth factor receptor 2 (HER2 expression (76.9% vs. 21.3%, and worse survival (5-year relapse-free survival (RFS 52.2% vs. 86.7%, P<0.01; breast cancer-specific overall survival (OS 62.1% vs. 91.8%, P<0.01 when compared with patients diagnosed with IBC. A matched study was then performed to investigate whether the poor survival of patients in the PD group was due to the unfavorable prognosis of the underlying IBC. One hundred and fifty-six (3∶1 ratio of controls to PD patients patients diagnosed with IBC only were recruited into the matched group. The match was conducted according to four variables: dimension of IBC, lymph node status, hormone receptor status and HER2 status. The 5-year RFS (52.2% vs. 81.4%, P<0.01 and OS (62.1% vs. 85.9%, P<0.01 were both lower for patients in the PD group than those in the matched group. Patients with PD and underlying IBC had poor survival. Their survival was worse than that of patients with IBC of similar stage and characteristics. For patients with no clinical PD manifestation who were histologically diagnosed as PD, survival might be worse compared to patients with clinically diagnosed PD.

  15. Diagnostic accuracy of cone-beam CT in the assessment of mandibular invasion of lower gingival carcinoma: Comparison with conventional panoramic radiography

    International Nuclear Information System (INIS)

    Purpose: To evaluate the diagnostic accuracy of cone-beam CT in assessing mandibular invasion by lower gingival carcinoma and compare it with that of panoramic radiography. Patients and methods: Fifty patients with squamous cell carcinoma of the lower gingiva who were examined by both panoramic radiography and cone-beam CT before surgery were included in this study. Five radiologists used a 6-point rating scale to independently evaluate cone-beam CT and panoramic images for the presence or absence of alveolar bone and mandibular canal involvement by tumor. Using the histopathogical findings as the gold standard, we calculated and compared the area under the receiver operating characteristic curve (Az value) and the sensitivity and specificity of the two imaging modalities. Results: In evaluations of both alveolar bone and mandibular canal involvement, the mean Az value for cone-beam CT (0.918 and 0.977, respectively) was significantly higher than that for panoramic radiography (0.793 and 0.872, respectively). The mean sensitivity for cone-beam CT (89% and 99%, respectively) was significantly higher than that for panoramic radiography (73% and 56%, respectively). There was no significant difference in the mean specificity. While cone-beam CT could provide high-resolution three-dimensional images, the image quality around the alveolar crest was often hampered by severe dental artifacts and image noise, resulting in difficulties in detecting subtle alveolar invasion. Conclusion: Cone-beam CT was significantly superior to panoramic radiography in evaluating mandibular invasion by lower gingival carcinoma. Its diagnostic value in detecting subtle alveolar invasion, however, may be limited by severe dental artifacts and image noise.

  16. Diagnostic accuracy of cone-beam CT in the assessment of mandibular invasion of lower gingival carcinoma: Comparison with conventional panoramic radiography

    Energy Technology Data Exchange (ETDEWEB)

    Momin, Mohammad A. [Oral and Maxillofacial Radiology, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan)], E-mail: momin.orad@tmd.ac.jp; Okochi, Kiyoshi [Oral and Maxillofacial Radiology, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan)], E-mail: kiyoshi.orad@tmd.ac.jp; Watanabe, Hiroshi [Oral and Maxillofacial Radiology, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan)], E-mail: hiro.orad@tmd.ac.jp; Imaizumi, Akiko [Oral and Maxillofacial Radiology, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan)], E-mail: ima.orad@tmd.ac.jp; Omura, Ken [Oral Surgery, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan)], E-mail: omura.osur@tmd.ac.jp; Amagasa, Teruo [Maxillofacial Surgery, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan)], E-mail: t-amagasa.mfs@tmd.ac.jp; Okada, Norihiko [Diagnostic Oral Pathology, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan)], E-mail: nokd.opth@tmd.ac.jp; Ohbayashi, Naoto [Oral and Maxillofacial Radiology, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan)], E-mail: nao.orad@tmd.ac.jp; Kurabayashi, Tohru [Oral and Maxillofacial Radiology, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8549 (Japan)], E-mail: kura.orad@tmd.ac.jp

    2009-10-15

    Purpose: To evaluate the diagnostic accuracy of cone-beam CT in assessing mandibular invasion by lower gingival carcinoma and compare it with that of panoramic radiography. Patients and methods: Fifty patients with squamous cell carcinoma of the lower gingiva who were examined by both panoramic radiography and cone-beam CT before surgery were included in this study. Five radiologists used a 6-point rating scale to independently evaluate cone-beam CT and panoramic images for the presence or absence of alveolar bone and mandibular canal involvement by tumor. Using the histopathogical findings as the gold standard, we calculated and compared the area under the receiver operating characteristic curve (Az value) and the sensitivity and specificity of the two imaging modalities. Results: In evaluations of both alveolar bone and mandibular canal involvement, the mean Az value for cone-beam CT (0.918 and 0.977, respectively) was significantly higher than that for panoramic radiography (0.793 and 0.872, respectively). The mean sensitivity for cone-beam CT (89% and 99%, respectively) was significantly higher than that for panoramic radiography (73% and 56%, respectively). There was no significant difference in the mean specificity. While cone-beam CT could provide high-resolution three-dimensional images, the image quality around the alveolar crest was often hampered by severe dental artifacts and image noise, resulting in difficulties in detecting subtle alveolar invasion. Conclusion: Cone-beam CT was significantly superior to panoramic radiography in evaluating mandibular invasion by lower gingival carcinoma. Its diagnostic value in detecting subtle alveolar invasion, however, may be limited by severe dental artifacts and image noise.

  17. Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling.

    Science.gov (United States)

    Deep, Gagan; Kumar, Rahul; Jain, Anil K; Agarwal, Chapla; Agarwal, Rajesh

    2014-10-01

    results showed that silibinin targets PCA cells' interaction with fibronectin and inhibits their motility, invasiveness and survival; thus further supporting silibinin use in PCA intervention including its metastatic progression. PMID:25285031

  18. Mast Cells in Adjacent Normal Colon Mucosa rather than Those in Invasive Margin are Related to Progression of Colon Cancer

    Institute of Scientific and Technical Information of China (English)

    Qing Xia; Xiao-shi Zhang; Ying-bo Chen; Ya Ding; Xiao-jun Wu; Rui-qing Peng; Qiang Zhou; Jing Zeng; Jing-hui Hou; Xing Zhang; Yi-xin Zeng

    2011-01-01

    Objective:Mast cells (MC) reside in the mucosa of the digestive tract as the first line against bacteria and toxins.Clinical evidence has implied that the infiltration of mast cells in colorectal cancers is related to malignant phenotypes and a poor prognosis.This study compared the role of mast cells in adjacent normal colon mucosa and in the invasive margin during the progression of colon cancer.Methods:Specimens were obtained from 39 patients with colon adenomas and 155 patients with colon cancers treated at the Sun Yat-sen University Cancer Center between January 1999 and July 2004.The density of mast cells was scored by an immunohistochemical assay.The pattern of mast cell distribution and its relationship with dinicopathologic parameters and 5-year survival were analyzed.Results:The majority of mast cells were located in the adjacent normal colon mucosa,followed by the invasive margin and least in the cancer stroma.Mast cell count in adjacent normal colon mucosa (MCCadjacent) was associated with pathologic classification,distant metastases and hepatic metastases,although it was not a prognostic factor.In contrast,mast cell count in the invasive margin (MCCinvasive) was associated with neither the clinicopathlogic parameters nor overall survival.Conclusion:Mast cells in the adjacent normal colon mucosa were related to the progression of colon cancer,suggesting that mast cells might modulate tumor progression via a long-distance mechanism.

  19. Tumor-associated macrophages are involved in tumor progression in papillary renal cell carcinoma.

    Science.gov (United States)

    Behnes, Carl Ludwig; Bremmer, Felix; Hemmerlein, Bernhard; Strauss, Arne; Ströbel, Philipp; Radzun, Heinz-Joachim

    2014-02-01

    Tumor-associated macrophages (TAMs) play a key role in cancer development. Especially, the immunosuppressive M2 phenotype is associated with increased tumor growth, invasiveness and metastasis. The differentiation of macrophages to the alternative phenotype M2 is mediated, inter alia, by macrophage colony-stimulating factor (M-CSF). Papillary renal cell carcinoma (RCC) represents a rare tumor type which, based upon histological criteria, can be subdivided into two subtypes (I and II), of which type II is associated with poor prognosis. In both subtypes, typically, a dense infiltrate of macrophages is found. In the present study, the expression of CD68, CD163, M-CSF, Ki-67, and CD31 was examined in 30 type I and 30 type II papillary RCCs (n = 60). Both types of papillary RCCs contained an equally dense infiltrate of CD68-positive macrophages. Nearly all macrophages in papillary RCC type II expressed CD163, a characteristic for M2 macrophages. In type I papillary RCC, less than 30 % of macrophages expressed CD163. Furthermore, tumor cells in type II papillary RCC expressed significantly more M-CSF and showed increased (Ki-67 expression defined) proliferative activity in comparison with type I papillary RCC. In addition, the (CD31 defined) capillary density was higher in type II than in type I papillary RCC. A dense infiltrate of M2 phenotype TAM and high M-CSF expression in tumor cells are key features of type II papillary RCC. These findings might explain why the prognosis of papillary RCC type II is worse than that of type I. PMID:24327306

  20. RSK activation of translation factor eIF4B drives abnormal increases of laminin γ2 and MYC protein during neoplastic progression to squamous cell carcinoma.

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    Martin Degen

    Full Text Available Overexpression of the basement membrane protein Laminin γ2 (Lamγ2 is a feature of many epidermal and oral dysplasias and all invasive squamous cell carcinomas (SCCs. This abnormality has potential value as an immunohistochemical biomarker of premalignancy but its mechanism has remained unknown. We recently reported that Lamγ2 overexpression in culture is the result of deregulated translation controls and depends on the MAPK-RSK signaling cascade. Here we identify eIF4B as the RSK downstream effector responsible for elevated Lamγ2 as well as MYC protein in neoplastic epithelial cells. Premalignant dysplastic keratinocytes, SCC cells, and keratinocytes expressing the E6 oncoprotein of human papillomavirus (HPV type 16 displayed MAPK-RSK and mTOR-S6K1 activation and overexpressed Lamγ2 and MYC in culture. Immunohistochemical staining of oral dysplasias and SCCs for distinct, RSK- and S6K1-specific S6 phosphorylation events revealed that their respective upstream pathways become hyperactive at the same time during neoplastic progression. However, pharmacologic kinase inhibitor studies in culture revealed that Lamγ2 and MYC overexpression depends on MAPK-RSK activity, independent of PI3K-mTOR-S6K1. eIF4B knockdown reduced Lamγ2 and MYC protein expression, consistent with the known requirement for eIF4B to translate mRNAs with long, complex 5' untranslated regions (5'-UTRs. Accordingly, expression of a luciferase reporter construct preceded by the Lamγ2 5'-UTR proved to be RSK-dependent and mTOR-independent. These results demonstrate that RSK activation of eIF4B is causally linked to elevated Lamγ2 and MYC protein levels during neoplastic progression to invasive SCC. These findings have potential clinical significance for identifying premalignant lesions and for developing targeted drugs to treat SCC.

  1. Radix Tetrastigma hemsleyani flavone inhibits proliferation, migration, and invasion of human lung carcinoma A549 cells

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    Zhong LR

    2016-02-01

    Full Text Available Liangrui Zhong,1 Junxian Zheng,2 Qianqian Sun,3 Kemin Wei,2 Yijuan Hu2 1Department of Oncology, Tongde Hospital of Zhejiang Province, Affiliated to Zhejiang Chinese Medical University, 2Department of Chinese Medicine, Zhejiang Academy of Traditional Chinese Medicine, 3Department of Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China Abstract: Radix Tetrastigma hemsleyani flavone (RTHF is widely used as a traditional herb and has detoxification and anti-inflammatory effects. In this study, we investigated the potential effects of RTHF on the growth and metastasis of human lung adenocarcinoma A549 cells and evaluated its mechanisms. A549 cells were treated with RTHF at various concentrations for different periods. In vitro Cell Counting Kit-8 assay and colony formation methods showed that RTHF had dose- and time-dependent antiproliferation effects on A549 cells. A cell adhesion assay showed that RTHF decreased A549 cell adhesion in a dose-dependent manner. Cell invasion and migration were investigated using the Transwell assay and observed using an inverted microscope; the results showed that cell metastasis was significantly lower in the treatment group than that in the control group (P<0.01. Expression of metastasis-related matrix metalloproteinases (MMPs and tissue inhibitors of metalloproteinases (TIMPs was detected by real-time polymerase chain reaction and Western blotting. The results showed that the expression of MMP-2, MMP-9, and TIMP-1 decreased, while that of TIMP-2 increased significantly in the RTHF group when compared with the results of the control group. These results show that RTHF exhibits antigrowth and antimetastasis activity in lung cancer A549 cells by decreasing the expression of MMP-2/-9 and TIMP-1 and increasing that of TIMP-2. Keywords: flavone, radix Tetrastigma hemsleyani, metastasis, lung cancer

  2. Analysis of the risk factors for early death due to disease recurrence or progression within 1 year after hepatectomy in patients with hepatocellular carcinoma

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    Kamiyama Toshiya

    2012-06-01

    Full Text Available Abstract Background Liver resection for hepatocellular carcinoma (HCC has the highest local controllability among all local treatments and results in a good survival rate. However, the recurrence rates of HCC continue to remain high even after curative hepatectomy Moreover, it has been reported that some patients with HCC have an early death due to recurrence. We analyzed the preoperative risk factors for early cancer death. Methods Between 1997 and 2009, 521 consecutive patients who underwent hepatectomy for HCC at our center were assigned to group ED (death due to HCC recurrence or progression within 1 year after hepatectomy and group NED (alive over 1 year after hepatectomy. Risk factors for early cancer death were analyzed. Results Group ED included 48 patients, and group NED included 473 patients. The cause of death included cancer progression (150; 78.1%, operation-related (1; 0.5%, hepatic failure (15; 7.8%, and other (26; 13.5%. Between the ED and NED groups, there were significant differences in albumin levels, Child-Pugh classifications, anatomical resections, curability, tumor numbers, tumor sizes, macroscopic vascular invasion (portal vein and hepatic vein, alpha-fetoprotein (AFP levels, AFP-L3 levels, protein induced by vitamin K absence or antagonism factor II (PIVKA-II levels, differentiation, microscopic portal vein invasion, microscopic hepatic vein invasion, and distant metastasis by univariate analysis. Multivariate analysis identified specific risk factors, such as AFP level > 1,000 ng/ml, tumor number ≥ 4, tumor size ≥ 5 cm, poor differentiation, and portal vein invasion. With respect to the preoperative risk factors such as AFP level, tumor number, and tumor size, 3 (1.1% of 280 patients with no risk factors, 12 (7.8% of 153 patients with 1 risk factor, 24 (32.9% of 73 patients with 2 factors, and 9 (60.0% of 15 patients with 3 risk factors died within 1 year of hepatectomy (p  Conclusions Hepatectomy

  3. MicroRNA-122 triggers mesenchymal-epithelial transition and suppresses hepatocellular carcinoma cell motility and invasion by targeting RhoA.

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    Sheng-Chun Wang

    Full Text Available The loss of microRNA-122 (miR-122 expression is strongly associated with increased invasion and metastasis, and poor prognosis of hepatocellular carcinoma (HCC, however, the underlying mechanisms remain poorly understood. In the present study, we observed that miR-122 over-expression in HCC cell lines Sk-hep-1 and Bel-7402 triggered the mesenchymal-epithelial transition (MET, as demonstrated by epithelial-like morphological changes, up-regulated epithelial proteins (E-cadherin, ZO-1, α-catenin, occludin, BVES, and MST4, and down-regulated mesenchymal proteins (vimentin and fibronectin. The over-expression of miRNA-122 also caused cytoskeleton disruption, RhoA/Rock pathway inactivation, enhanced cell adhesion, and suppression of migration and invasion of Sk-hep-1 and Bel-7402 cells, whereas, these effects could be reversed through miR-122 inhibition. Additional studies demonstrated that the inhibition of wild-type RhoA function induced MET and inhibited cell migration and invasion, while RhoA over-expression reversed miR-122-induced MET and inhibition of migration and invasion of HCC cells, suggesting that miR-122 induced MET and suppressed the migration and invasion of HCC cells by targeting RhoA. Moreover, our results demonstrated that HNF4α up-regulated its target gene miR-122 that subsequently induced MET and inhibited cell migration and invasion, whereas miR-122 inhibition reversed these HNF4α-induced phenotypes. These results revealed functional and mechanistic links among the tumor suppressors HNF4α, miR-122, and RhoA in EMT and invasive and metastatic phenotypes of HCC. Taken together, our study provides the first evidence that the HNF4α/miR-122/RhoA axis negatively regulates EMT and the migration and invasion of HCC cells.

  4. Inhibition of Oesophageal Squamous Cell Carcinoma Progression by in vivo Targeting of Hyaluronan Synthesis

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    Savani Rashmin C

    2011-03-01

    Full Text Available Abstract Background Oesophageal cancer is a highly aggressive tumour entity with at present poor prognosis. Therefore, novel treatment options are urgently needed. Hyaluronan (HA is a polysaccharide present in the matrix of human oesophageal squamous cell carcinoma (ESCC. Importantly, in vitro ESCC cells critically depend on HA synthesis to maintain the proliferative phenotype. The aim of the present study is (1 to study HA-synthase (HAS expression and regulation in human ESCC, and (2 to translate the in vitro results into a mouse xenograft model of human ESCC to study the effects of systemic versus tumour targeted HAS inhibition on proliferation and distribution of tumour-bound and stromal hyaluronan. Methods mRNA expression was investigated in human ESCC biopsies by semiquantitative real-time RT PCR. Furthermore, human ESCC were xenografted into NMRI nu/nu mice. The effects on tumour progression and morphology of 4-methylumbelliferone (4-MU, an inhibitor of HA-synthesis, and of lentiviral knock down of HA-synthase 3 (HAS3, the main HAS isoform in the human ESCC tissues and the human ESCC cell line used in this study, were determined. Tumour progression was monitored by calliper measurements and by flat-panel detector volume computed tomography (fpVCT. HA content, cellular composition and proliferation (Ki67 were determined histologically. Results mRNA of HAS isoform 3 (HAS3 was upregulated in human ESCC biopsies and HAS3 mRNA was positively correlated to expression of the epidermal growth factor (EGF receptor. EGF was also proven to be a strong inductor of HAS3 mRNA expression in vitro. During the course of seven weeks, 4-MU inhibited progression of xenograft tumours. Interestingly, remodelling of the tumour into a more differentiated phenotype and inhibition of cell proliferation were observed. Lentiviral knockdown of HAS3 in human ESCC cells prior to xenografting mimicked all effects of 4-MU treatment suggesting that hyaluronan produced by

  5. miRNA-7/21/107 contribute to HBx-induced hepatocellular carcinoma progression through suppression of maspin

    OpenAIRE

    Chen, Wen-Shu; Yen, Chia-Jui; Chen, Yun-Ju; Chen, Jhen-Yu; Wang, Li-Yun; Chiu, Shu-Jun; Shih, Wen-Ling; Ho, Chien-Yi; Wei, Tzu-Tang; Pan, Hsiao-Lin; Chien, Pei-Hsuan; Hung, Mien-Chie; Chen, Ching-Chow; Huang, Wei-Chien

    2015-01-01

    Maspin suppresses tumor progression by promoting cell adhesion and apoptosis and by inhibiting cell motility. However, its role in tumorigenesis of hepatocellular carcinoma (HCC) remains unclear. The gene regulation of maspin and its relationship with HCC patient prognosis were investigated in this study. Maspin expression was specifically reduced in HBV-associated patients and correlated with their poor prognosis. Maspin downregulation in HCC cells was induced by HBx to promote their motilit...

  6. Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway.

    Science.gov (United States)

    Ma, Lijie; Dong, Pingping; Liu, Longzi; Gao, Qiang; Duan, Meng; Zhang, Si; Chen, She; Xue, Ruyi; Wang, Xiaoying

    2016-04-29

    Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. PMID:27003260

  7. EVALUATION OF STEROID HORMONES AND THEIR RECEPTORS IN DEVELOPMENT AND PROGRESSION OF RENAL CELL CARCINOMA

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    Nigel Bennett

    2014-06-01

    Full Text Available Steroid hormones and their receptors have important roles in normal kidney biology, and alterations in their expression and function help explain the differences in development of kidney diseases, such as nephrotic syndrome and chronic kidney disease. The distinct gender difference in incidence of renal cell carcinoma (RCC, with males having almost twice the incidence as females globally, also suggests a role for sex hormones or their receptors in RCC development and progression. There was a peak in interest in evaluating the roles of androgen and estrogen receptors in RCC pathogenesis in the late 20th century, with some positive outcomes for RCC therapy that targeted estrogen receptors, especially for metastatic disease. Since that time, however, there have been few studies that look at use of steroid hormone modulators for RCC, especially in the light of new therapies such as the tyrosine kinase inhibitors and new immune therapies, which are having some success for treatment of metastatic RCC. This review summarises past and current literature and attempts to stimulate renewed interest in research into the steroid hormones and their receptors, which might be used to effect, for example, in combination with the other newer targeted therapies for RCC.

  8. Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma.

    Science.gov (United States)

    Wu, Yi-Ju; Jan, Yee-Jee; Ko, Bor-Sheng; Liang, Shu-Man; Liou, Jun-Yang

    2015-01-01

    There are seven mammalian isoforms of the 14-3-3 protein, which regulate multiple cellular functions via interactions with phosphorylated partners. Increased expression of 14-3-3 proteins contributes to tumor progression of various malignancies. Several isoforms of 14-3-3 are overexpressed and associate with higher metastatic risks and poorer survival rates of hepatocellular carcinoma (HCC). 14-3-3β and 14-3-3ζ regulate HCC cell proliferation, tumor growth and chemosensitivity via modulating mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and p38 signal pathways. Moreover, 14-3-3ε suppresses E-cadherin and induces focal adhesion kinase (FAK) expression, thereby enhancing epithelial-mesenchymal transition (EMT) and HCC cell migration. 14-3-3ζ forms complexes with αB-crystallin, which induces EMT and is the cause of sorafenib resistance in HCC. Finally, a recent study has indicated that 14-3-3σ induces heat shock protein 70 (HSP70) expression, which increases HCC cell migration. These results suggest that selective 14-3-3 isoforms contribute to cell proliferation, EMT and cell migration of HCC by regulating distinct targets and signal pathways. Targeting 14-3-3 proteins together with specific downstream effectors therefore has potential to be therapeutic and prognostic factors of HCC. In this article, we will overview 14-3-3's regulation of its downstream factors and contributions to HCC EMT, cell migration and proliferation. PMID:26083935

  9. Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yi-Ju [Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan (China); Jan, Yee-Jee [Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Ko, Bor-Sheng [Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan (China); Liang, Shu-Man; Liou, Jun-Yang, E-mail: jliou@nhri.org.tw [Institute of Cellular and System Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan 350, Taiwan (China)

    2015-06-15

    There are seven mammalian isoforms of the 14-3-3 protein, which regulate multiple cellular functions via interactions with phosphorylated partners. Increased expression of 14-3-3 proteins contributes to tumor progression of various malignancies. Several isoforms of 14-3-3 are overexpressed and associate with higher metastatic risks and poorer survival rates of hepatocellular carcinoma (HCC). 14-3-3β and 14-3-3ζ regulate HCC cell proliferation, tumor growth and chemosensitivity via modulating mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) and p38 signal pathways. Moreover, 14-3-3ε suppresses E-cadherin and induces focal adhesion kinase (FAK) expression, thereby enhancing epithelial-mesenchymal transition (EMT) and HCC cell migration. 14-3-3ζ forms complexes with αB-crystallin, which induces EMT and is the cause of sorafenib resistance in HCC. Finally, a recent study has indicated that 14-3-3σ induces heat shock protein 70 (HSP70) expression, which increases HCC cell migration. These results suggest that selective 14-3-3 isoforms contribute to cell proliferation, EMT and cell migration of HCC by regulating distinct targets and signal pathways. Targeting 14-3-3 proteins together with specific downstream effectors therefore has potential to be therapeutic and prognostic factors of HCC. In this article, we will overview 14-3-3’s regulation of its downstream factors and contributions to HCC EMT, cell migration and proliferation.

  10. Involvement of 14-3-3 Proteins in Regulating Tumor Progression of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Yi-Ju Wu

    2015-06-01

    Full Text Available There are seven mammalian isoforms of the 14-3-3 protein, which regulate multiple cellular functions via interactions with phosphorylated partners. Increased expression of 14-3-3 proteins contributes to tumor progression of various malignancies. Several isoforms of 14-3-3 are overexpressed and associate with higher metastatic risks and poorer survival rates of hepatocellular carcinoma (HCC. 14-3-3β and 14-3-3ζ regulate HCC cell proliferation, tumor growth and chemosensitivity via modulating mitogen-activated protein kinase (MAPK, c-Jun N-terminal kinase (JNK and p38 signal pathways. Moreover, 14-3-3ε suppresses E-cadherin and induces focal adhesion kinase (FAK expression, thereby enhancing epithelial-mesenchymal transition (EMT and HCC cell migration. 14-3-3ζ forms complexes with αB-crystallin, which induces EMT and is the cause of sorafenib resistance in HCC. Finally, a recent study has indicated that 14-3-3σ induces heat shock protein 70 (HSP70 expression, which increases HCC cell migration. These results suggest that selective 14-3-3 isoforms contribute to cell proliferation, EMT and cell migration of HCC by regulating distinct targets and signal pathways. Targeting 14-3-3 proteins together with specific downstream effectors therefore has potential to be therapeutic and prognostic factors of HCC. In this article, we will overview 14-3-3's regulation of its downstream factors and contributions to HCC EMT, cell migration and proliferation.

  11. HMGA2 overexpression plays a critical role in the progression of esophageal squamous carcinoma

    Science.gov (United States)

    Palumbo, Antonio; Meireles Da Costa, Nathalia; Esposito, Francesco; De Martino, Marco; D'Angelo, Daniela; de Sousa, Vanessa Paiva Leite; Martins, Ivanir; Nasciutti, Luiz Eurico; Fusco, Alfredo; Pinto, Luis Felipe Ribeiro

    2016-01-01

    Esophageal Squamous Cell Carcinoma (ESCC) is the most common esophageal tumor worldwide. However, there is still a lack of deeper knowledge about biological alterations involved in ESCC development. High Mobility Group A (HMGA) protein family has been related with poor outcome and malignant cell transformation in several tumor types. In this way, the aim of this study was to analyze the expression of HMGA1 and HMGA2 expression in ESCC and their role in crucial cellular features. We evaluated HMGA1 and HMGA2 mRNA expression in 52 paired ESCC and normal surrounding tissue samples by qRT-PCR. Here, we show that HMGA2, but not HMGA1, is overexpressed in ESCC samples. This result was further confirmed by the immunohistochemical analysis. Indeed, accordingly to mRNA expression data, HMGA2, but not HMGA1, was overexpressed in approximately 90% of ESCC samples, while it was barely expressed in the respective control. Conversely, HMGA1, but not HMGA2, was overexpressed in esophageal adenocarcinoma samples. Interestingly, HMGA2 abrogation attenuated the malignant phenotype of two ESCC cell lines, suggesting that HMGA2 overexpression is involved in ESCC progression. PMID:27027341

  12. NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway

    Science.gov (United States)

    Ai, Runna; Sun, Yulin; Guo, Zhimin; Wei, Wei; Zhou, Lanping; Liu, Fang; Hendricks, Denver T.; Xu, Yang; Zhao, Xiaohang

    2016-01-01

    ABSTRACT N-myc down-regulated gene 1 (NDRG1) has been shown to regulate tumor growth and metastasis in various malignant tumors and also to be dysregulated in esophageal squamous cell carcinoma (ESCC). Here, we show that NDRG1 overexpression (91.9%, 79/86) in ESCC tumor tissues is associated with poor overall survival of esophageal cancer patients. When placed in stable transfectants of the KYSE 30 ESCC cell line generated by lentiviral transduction with the ectopic overexpression of NDRG1, the expression of transducin-like enhancer of Split 2 (TLE2) was decreased sharply, however β−catenin was increased. Mechanistically, NDRG1 physically associates with TLE2 and β−catenin to affect the Wnt pathway. RNA interference and TLE2 overexpression studies demonstrate that NDRG1 fails to active Wnt pathway compared with isogenic wild-type controls. Strikingly, NDRG1 overexpression induces the epithelial mesenchymal transition (EMT) through activating the Wnt signaling pathway in ESCC cells, decreased the expression of E-cadherin and enhanced the expression of Snail. Our study elucidates a mechanism of NDRG1-regulated Wnt pathway activation and EMT via affecting TLE2 and  β-catenin expression in esophageal cancer cells. This indicates a pro-oncogenic role for NDRG1 in esophageal cancer cells whereby it modulates tumor progression. PMID:27414086

  13. Usefulness of Levocarnitine and/or Branched-Chain Amino Acids during Invasive Treatment for Hepatocellular Carcinoma.

    Science.gov (United States)

    Iwasa, Motoh; Sugimoto, Ryosuke; Ishihara, Tomoaki; Sekoguchi-Fujikawa, Noriko; Yoshikawa, Kyoko; Mifuji-Moroka, Rumi; Tanaka, Hideaki; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Takei, Yoshiyuki

    2015-01-01

    Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatments for hepatocellular carcinoma (HCC). However, the extent of treatment depends on hepatic functional reserve. L-Carnitine is a vitamin-like substance and several reports have described the usefulness of L-carnitine supplementation in cases of cirrhosis, with confirmed effectiveness against refractory hepatic encephalopathy. On the other hand, we have previously reported that in patients who underwent TACE or RFA, administration of branched-chain amino acids (BCAAs) pre-intervention significantly reduced inflammatory reactions. We first determined serum levels of total, free, and acyl-carnitine before and at 7 d after performing TACE in 10 HCC patients. We administered levocarnitine (L-carnitine chloride, a biologically active form of carnitine) at 900 mg/d to 69 consecutive HCC patients hospitalized to undergo TACE and/or RFA, and compared changes in blood test values with those in 119 consecutive patients not administered this drug. Sixty-seven patients had a history of using BCAAs at the time of admission. We found that after 7 d of TACE, serum levels of total and acyl-carnitine are significantly decreased. On comparing the four groups, the carnitine+BCAA, carnitine-alone, and BCAA-alone groups showed significantly higher values for changes in NH3 when compared with the non-dosed group. The decrease in albumin (Alb) was significantly suppressed in the carnitine+BCAA and BCAA-alone groups. We also conducted the same examinations in a subset of patients classified as Child-Pugh class A, and noted the same trends. Administration of levocarnitine and/or BCAAs during invasive treatments reduced blood NH3 concentrations and suppressed decreases in Alb. PMID:26875483

  14. Inhibition of AQP1 Hampers Osteosarcoma and Hepatocellular Carcinoma Progression Mediated by Bone Marrow-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Pelagalli, Alessandra; Nardelli, Anna; Fontanella, Raffaela; Zannetti, Antonella

    2016-01-01

    The complex cross-talk between tumor cells and their surrounding stromal environment plays a key role in the pathogenesis of cancer. Among several cell types that constitute the tumor stroma, bone marrow-derived mesenchymal stem cells (BM-MSCs) selectively migrate toward the tumor microenvironment and contribute to the active formation of tumor-associated stroma. Therefore, here we elucidate the involvement of BM-MSCs to promote osteosarcoma (OS) and hepatocellular carcinoma (HCC) cells migration and invasion and deepening the role of specific pathways. We analyzed the function of aquaporin 1 (AQP1), a water channel known to promote metastasis and neoangiogenes. AQP1 protein levels were analyzed in OS (U2OS) and HCC (SNU-398) cells exposed to conditioned medium from BM-MSCs. Tumor cell migration and invasion in response to BM-MSC conditioned medium were evaluated through a wound healing assay and Boyden chamber, respectively. The results showed that the AQP1 level was increased in both tumor cell lines after treatment with BM-MSC conditioned medium. Moreover, BM-MSCs-mediated tumor cell migration and invasion were hampered after treatment with AQP1 inhibitor. These data suggest that the recruitment of human BM-MSCs into the tumor microenvironment might cause OS and HCC cell migration and invasion through involvement of AQP1. PMID:27409610

  15. The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis

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    Flores-Estrada Diana

    2007-02-01

    Full Text Available Abstract Background Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. Methods We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. Results For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. Conclusion The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach

  16. The Role of Embryologic Fusion Planes in the Invasiveness and Recurrence of Basal Cell Carcinoma: A Classic Mix-Up of Causation and Correlation

    Science.gov (United States)

    Armstrong, Linus T. D.; Guppy, Michelle P. B.

    2015-01-01

    Abstract Background: The facial embryologic fusion planes as regions of mesenchymal and ectodermal fusion of the primordial facial processes during embryological development have been suggested to influence the spread, invasiveness, pathogenesis, and recurrence of cutaneous carcinoma. This study sought to establish whether basal cell carcinoma (BCC) originating in embryologic fusion planes has a greater propensity for earlier depth of invasion, leading to an increased rate of lesion recurrence. Methods: Facial BCCs excised in a single surgeon practice over 2 years were allocated into 2 anatomic domains according to their correlation with embryologic fusion planes. Lesion depth of invasion, surface area, and margins of excision were analyzed in conjunction with recurrence data over the following 70–80 months. Results: Of the 331 lesions examined, 70 were located in embryologic fusion planes. No difference was found in the mean surface area and depth of invasion for lesions located in the 2 domains (P > 0.05). Ten lesion recurrences were identified, none of which were located in embryologic fusion planes. Recurrent lesions were excised with a significantly greater percentage of close and incomplete excision margins (P < 0.05). Conclusions: BCC arising in embryologic fusion planes are not more invasive or at greater risk of recurrence. Excision margins seem to have the greatest influence on lesion recurrence. Because of the paucity of superfluous tissue and the cosmetic and functionally sensitive nature of these areas of embryologic fusion, specialist treatment of these lesions is recommended to ensure that adequacy of excision is not neglected at the cost of ease of closure and cosmesis. PMID:26894007

  17. Invasion rather than nuclear features correlates with outcome in encapsulated follicular tumors: further evidence for the reclassification of the encapsulated papillary thyroid carcinoma follicular variant.

    Science.gov (United States)

    Ganly, Ian; Wang, Laura; Tuttle, R Michael; Katabi, Nora; Ceballos, Gustavo A; Harach, H Ruben; Ghossein, Ronald

    2015-05-01

    The prognosis of the encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) and its relationship to encapsulated follicular carcinoma (EFC) and follicular adenoma (FA) is subject to controversy. All EFVPTCs, EFCs, and FAs identified at a single institution between 1981 and 2003 were analyzed microscopically. A cohort of FAs from a different hospital was also examined. EFVPTCs were subdivided into noninvasive EFVPTC (NIEFVPTC) and invasive EFVPTC (IEFVPTC) displaying capsular/vascular invasion. There were 83 EFVPTCs (57 noninvasive, 26 invasive), 14 EFCs, and 52 FAs. Similar to FA, over a median follow-up of 9.5 years, none of the NIEFVPTCs manifested lymph node metastasis (LNM) or recurred. Furthermore, with a median follow-up of 10.5 years, none of 39 NIEFVPTCs without radioactive iodine therapy recurred. Four (15%) of 26 IEFVPTCs and none of 14 EFCs harbored distant metastasis (P = .29). There was no difference in LNM rate and degree of vascular or capsular invasion between IEFVPTC and EFC (P > .1). All 4 IEFVPTCs with adverse behavior presented with distant metastasis and no LNM. Sixteen percent of IEFVPTCs had poor outcome, whereas there was none in the NIEFVPTCs (P = .007). In conclusion, NIEFVPTC seems to behave similarly to FA, whereas IEFVPTC can metastasize and spread like EFC. Thus, invasion rather than nuclear features drives outcome in encapsulated follicular tumors. Non-IEFVPTC could be treated in a conservative manner sparing patients unnecessary total thyroidectomy and radioactive iodine therapy. The position of the EFVPTC in the classification of thyroid neoplasia should be reconsidered. PMID:25721865

  18. High nuclear grade, frequent mitotic activity, cyclin D1 and p53 overexpression are associated with stromal invasion in mammary intracystic papillary carcinoma.

    Science.gov (United States)

    Zhang, Cunxian; Zhang, Peng; Hao, Jie; Quddus, M Ruhul; Steinhoff, Margaret M; Sung, C James

    2005-01-01

    Stromal invasion is identified with difficulty in routine hematoxylin-eosin-stained sections of core needle biopsy specimens from mammary intracystic papillary carcinomas. The goal of this study was to determine if nuclear grade, mitotic activity, and immunohistochemical stains for p53 and cyclin D1 would assist in differentiating intracystic papillary carcinomas without stromal invasion (ICPC) from tumors with stromal invasion (ICPC-INVA). Eight cases of ICPC and 12 cases of ICPC-INVA were reviewed. Hematoxylin-eosin slides were examined to determine the histologic features. Immunohistochemistry was performed using monoclonal antibodies to human p53 and cyclin D1. Fisher's exact test was used to compare the nuclear grade, mitotic activity, and immunoreactivity between ICPC and ICPC-INVA. High nuclear grade was more often associated with ICPC-INVA than with ICPC, although the difference was not statistically significant (p = 0.069). Frequent mitotic activity was associated with ICPC-INVA more than with ICPC (p = 0.0198). All cases of ICPC were negative for either p53 or cyclin D1, whereas 7 of 12 cases (58.3%) of ICPC-INVA were positive for either cyclin D1 alone (3 cases), p53 alone (3 cases), or both cyclin D1 and p53 (1 case) (p = 0.0147). Identical nuclear grade, mitotic activity, and immunostaining patterns were seen in the intracystic and the invasive components, and in the core biopsy and the excision of the same tumor. When any one of the positive indicators (high nuclear grade, frequent mitotic activity, or positive immunostains for cyclin D1 and/or p53) was present, the positive predictive value for stromal invasion was 91.7%. When none of the positive indicators was present, the negative predictive value was 87.5%.

  19. Invasion rather than nuclear features correlates with outcome in encapsulated follicular tumors: further evidence for the reclassification of the encapsulated papillary thyroid carcinoma follicular variant☆

    Science.gov (United States)

    Ganly, Ian; Wang, Laura; Tuttle, R. Michael; Katabi, Nora; Ceballos, Gustavo A.; Harach, H. Ruben; Ghossein, Ronald

    2016-01-01

    Summary The prognosis of the encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) and its relationship to encapsulated follicular carcinoma (EFC) and follicular adenoma (FA) is subject to controversy. All EFVPTCs, EFCs, and FAs identified at a single institution between 1981 and 2003 were analyzed microscopically. A cohort of FAs from a different hospital was also examined. EFVPTCs were subdivided into noninvasive EFVPTC (NIEFVPTC) and invasive EFVPTC (IEFVPTC) displaying capsular/vascular invasion. There were 83 EFVPTCs (57 noninvasive, 26 invasive), 14 EFCs, and 52 FAs. Similar to FA, over a median follow-up of 9.5 years, none of the NIEFVPTCs manifested lymph node metastasis (LNM) or recurred. Furthermore, with a median follow-up of 10.5 years, none of 39 NIEFVPTCs without radioactive iodine therapy recurred. Four (15%) of 26 IEFVPTCs and none of 14 EFCs harbored distant metastasis (P = .29). There was no difference in LNM rate and degree of vascular or capsular invasion between IEFVPTC and EFC (P > .1). All 4 IEFVPTCs with adverse behavior presented with distant metastasis and no LNM. Sixteen percent of IEFVPTCs had poor outcome, whereas there was none in the NIEFVPTCs (P = .007). In conclusion, NIEFVPTC seems to behave similarly to FA, whereas IEFVPTC can metastasize and spread like EFC. Thus, invasion rather than nuclear features drives outcome in encapsulated follicular tumors. Non-IEFVPTC could be treated in a conservative manner sparing patients unnecessary total thyroidectomy and radioactive iodine therapy. The position of the EFVPTC in the classification of thyroid neoplasia should be reconsidered. PMID:25721865

  20. Aberrant Wnt-1/beta-catenin signaling and WIF-1 deficiency are important events which promote tumor cell invasion and metastasis in salivary gland adenoid cystic carcinoma.

    Science.gov (United States)

    Wang, Ruinan; Geng, Ning; Zhou, Yuqiao; Zhang, Dunfang; Li, Longjiang; Li, Jing; Ji, Ning; Zhou, Min; Chen, Yu; Chen, Qianming

    2015-01-01

    This study investigates whether Wnt components play a role in carcinogenesis, or the invasion and metastasis of salivary glands, also referred to as adenoid cystic carcinoma (sAdCC). Several sAdCC cell lines with low invasive potential (ACC-2), high metastatic potential (ACC-M), and higher invasive potential (T-ACC-M) were examined to determine whether Wnt components correlate with tumors' invasive and metastatic behavior. Immunohistochemistry was performed in a sAdCC tissue array. ACC-M expressed higher levels of Wnt-1, beta-catenin and lower WIF-1 compared to ACC-2 (PWIF-1 compared to ACC-2 and ACC-M. Immuno-histochemistry showed up-regulation of Wnt-1 and down-regulation of WIF-1 in sAdCC compared with normal salivary glands. Beta-catenin was found in the cytoplasm and nuclei of sAdCC. Dislocation of E-cadherin in sAdCC was observed. These results suggest that sAdCC exhibits diverse expressions of Wnt components. It has an important relationship with the invasive phenotype of these cells. PMID:26405993

  1. A Comparison of the Progression and Recurrence Risk Index in Non-Muscle-Invasive Bladder Tumors Detected by Narrow-Band Imaging Versus White Light Cystoscopy, Based on the EORTC Scoring System

    Directory of Open Access Journals (Sweden)

    Shadpour

    2016-01-01

    Full Text Available Background Transitional cell carcinoma of the bladder, the second most common urologic malignancy, is amenable to early diagnosis. This study presents the potential prognostic benefit for a less invasive modification to the standard endoscopic approach. Objectives To evaluate the risk index for the progression and recurrence of additional tumors detected with narrow-band imaging (NBI cystoscopy compared to standard white light imaging (WLI cystoscopy in non-muscle-invasive bladder cancer (NMIBC, based on the European organization for research and treatment of cancer (EORTC scoring system. Patients and Methods Patients with NMIBC, who were scheduled for resection between May 2012 and May 2013, were studied and mapped under NBI and WLI cystoscopy by independent surgeons prior to resection. Detection rates and tumor characteristics, including EORTC progression and the recurrence risk index, were compared. Results Fifty patients, aged 63.86 ± 10.05 years, were enrolled. The overall detection rate was 98.9% for NBI vs. 89.4% for WLI (P = 0.001, and the false-positive rates were 9.6% and 5.8%, respectively (P = 0.051. Ten tumors were detected by NBI alone, including four grade I tumors, four grade III tumors, and two carcinomas in situ. The tumor progression index was not significantly reduced with NBI compared to WLI (P > 0.05; however, the recurrence index was significantly lower in the NBI group (P < 0.05. Conclusions NBI cystoscopy improved the detection rate. Although false positives were more common with NBI, this was not statistically significant. NBI found additional aggressive tumors, which underscores the impact of detection in EORTC recurrence risk scoring.

  2. The RUNX1 transcription factor is expressed in serous epithelial ovarian carcinoma and contributes to cell proliferation, migration and invasion

    Science.gov (United States)

    Keita, Mamadou; Bachvarova, Magdalena; Morin, Chantale; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Trinh, Xuan Bich; Bachvarov, Dimcho

    2013-01-01

    Previously, we have identified the RUNX1 gene as hypomethylated and overexpressed in post-chemotherapy (CT) primary cultures derived from epithelial ovarian cancer (EOC) patients, when compared with primary cultures derived from matched primary (prior to CT) tumors. Here we show that RUNX1 displays a trend of hypomethylation, although not significant, in omental metastases compared with primary EOC tumors. Surprisingly, RUNX1 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. The RUNX1 expression levels were almost identical in primary tumors and omental metastases, suggesting that RUNX1 hypomethylation might have a limited impact on its overexpression in advanced (metastatic) stage of the disease. Knockdown of the RUNX1 expression in EOC cells led to sharp decrease of cell proliferation and induced G1 cell cycle arrest. Moreover, RUNX1 suppression significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as numerous genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX1 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX1 gene in EOC progression and suggest that RUNX1 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX1 and other members of the RUNX gene family in ovarian tumorigenesis. PMID:23442798

  3. Simultaneous inactivation of Par-4 and PTEN in vivo leads to synergistic NF-κB activation and invasive prostate carcinoma

    Science.gov (United States)

    Fernandez-Marcos, Pablo J.; Abu-Baker, Shadi; Joshi, Jayashree; Galvez, Anita; Castilla, Elias A.; Cañamero, Marta; Collado, Manuel; Saez, Carmen; Moreno-Bueno, Gema; Palacios, Jose; Leitges, Michael; Serrano, Manuel; Moscat, Jorge; Diaz-Meco, Maria T.

    2009-01-01

    Prostate cancer is one of the most common neoplasias in men. The tumor suppressor Par-4 is an important negative regulator of the canonical NF-κB pathway and is highly expressed in prostate. Here we show that Par-4 expression is lost in a high percentage of human prostate carcinomas, and this occurs in association with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss. Par-4 null mice, similar to PTEN-heterozygous mice, only develop benign prostate lesions, but, importantly, concomitant Par-4 ablation and PTEN-heterozygosity lead to invasive prostate carcinoma in mice. This strong tumorigenic cooperation is anticipated in the preneoplastic prostate epithelium by an additive increase in Akt activation and a synergistic stimulation of NF-κB. These results establish the cooperation between Par-4 and PTEN as relevant for the development of prostate cancer and implicate the NF-κB pathway as a critical event in prostate tumorigenesis. PMID:19470463

  4. Minimally Invasive Early Operative Treatment of Progressive Foot and Ankle Deformity Associated With Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Boffeli, Troy J; Tabatt, Jessica A

    2015-01-01

    Charcot-Marie-Tooth disease is a neuromuscular disorder that commonly results in a predictable pattern of progressive bilateral lower extremity weakness, numbness, contracture, and deformity, including drop foot, loss of ankle eversion strength, dislocated hammertoes, and severe cavus foot deformity. Late stage reconstructive surgery will be often necessary if the deformity becomes unbraceable or when neuropathic ulcers have developed. Reconstructive surgery for Charcot-Marie-Tooth deformity is generally extensive and sometimes staged. Traditional reconstructive surgery involves a combination of procedures, including tendon lengthening or transfer, osteotomy, and arthrodesis. The described technique highlights our early surgical approach, which involves limited intervention before the deformity becomes rigid, severe, or disabling. We present 2 cases to contrast our early minimally invasive technique with traditional late stage reconstruction. Charcot-Marie-Tooth disease affects different muscles at various stages of disease progression. As 1 muscle becomes weak, the antagonist will overpower it and cause progressive deformity. The focus of the early minimally invasive approach is to decrease the forces that cause progressive deformity yet maintain function, where possible. Our goal has been to maintain a functional and braceable foot and ankle, with the hope of avoiding or limiting the extent of future major reconstructive surgery. The presented cases highlight the patient selection criteria, the ideal timing of early surgical intervention, the procedure selection criteria, and operative pearls. The early minimally invasive approach includes plantar fasciotomy, Achilles tendon lengthening, transfer of the peroneus longus to the fifth metatarsal, Hibbs and Jones tendon transfer, and hammertoe repair of digits 1 to 5.

  5. Genomic amplification of the human telomerase gene (hTERC associated with human papillomavirus is related to the progression of uterine cervical dysplasia to invasive cancer

    Directory of Open Access Journals (Sweden)

    Liu Hongqian

    2012-10-01

    Full Text Available Abstract Background Human papillomavirus (HPV infection plays an etiological role in the development of cervical dysplasia and cancer. Amplification of human telomerase gene (hTERC and over expression of telomerase were found to be associated with cervical tumorigenesis. This study was performed to analyze genomic amplification of hTERC gene, telomerase activity in association with HPV infection in different stages of cervical intraepithelial neoplasia (CIN and cervical cancer. We were studying the role of hTERC in the progression of uterine cervical dysplasia to invasive cancer, and proposed an adjunct method for cervical cancer screening. Methods Exfoliated cervical cells were collected from 114 patients with non neoplastic lesion (NNL, n=27, cervical intraepithelial neoplasia (CIN1, n=26, CIN2, n=16, CIN3, n=24 and cervical carcinoma (CA, n=21, and analyzed for amplification of hTERC with two-color fluorescence in situ hybridization (FISH probe and HPV-DNA with Hybrid Capture 2. From these patients, 53 were taken biopsy to analyze telomerase activity by telomeric repeat amplification protocol (TRAP and expression of human telomerase reverse transcriptase (hTERT, with immunohistochemistry (IHC. All biopsies were clinically confirmed by phathologists. Results Amplification of hTERC was significantly associated with the histologic diagnoses (p Conclusions hTERC ampliffication can be detected with FISH technique on exfoliated cervical cells. Amplification of hTERC and HPV infection are associated with more progressive CIN3 and CA. The testing of hTERC amplification might be a supplementary to cytology screening and HPV test, especially high-risk patients. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1857134686755648.

  6. Research progress of molecular marker in metastasis of nasopharyngeal carcinoma%鼻咽癌转移相关分子标志物的研究进展

    Institute of Scientific and Technical Information of China (English)

    詹德超; 余忠华

    2015-01-01

    Nasopharyngeal carcinoma is a malignant neoplasm which arises from the mucosal epithelium cells of the nasopharynx,it is also one of the common malignant tumors in southern China. Most nasopharyngeal carcinomas are poorly differentiated carcinomas. Nasopharyngeal carcinomas are high degree of malignancy,which prone to distant metastasis.The invasion and metastasis of neoplasm are associated with the perverted movement of cells,which is a dy-namic process of biologic behavior interactions among adhesion,degradation and angiogenesis in cancer cells. Howev-er,the molecular mechanisms underlying NPC invasion and metastasis have not fully elucidated. With the development of Modem molecular biology,more and more new molecular markers in NPC,such as biomarkers have been gotten to know the related molecules expression and molecular regulation, which play important roles in screening tumor mark-ers with more high sensitivity and specificity,achieving early diagnosis ,predicting treatment prognoses and providing new therapeutic strategies to make it more pertinent in anti-tumor therapy. This study is aimed to review the research progress of molecular marker in metastasis of nasopharyngeal carcinoma.%鼻咽癌是一种来源于鼻黏膜上皮细胞的恶性肿瘤,是我国南方常见的恶性肿瘤之一。鼻咽癌大多数为低分化癌,恶性程度较高,易发生远处转移。国内外研究表明,肿瘤的侵袭和转移与细胞的异常运动有关,是肿瘤细胞的粘附、降解、运动以及血管生成等多种生物学行为互相作用的动态过程。但是NPC浸润转移的分子机制至今尚未完全阐明。随着现代分子生物学的发展,越来越多鼻咽癌转移的相关分子标志物逐渐被发现。深入了解这些分子标志物的表达及调控,筛选出对鼻咽癌具有较高敏感性、特异性并可进行早期诊断及评估预后的标记物,寻找出药物新靶点进行针对性更强的抗肿瘤治疗具有

  7. Role of Brg1 in progression of esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Shahram Torkamandi

    2014-11-01

    Full Text Available Objective(s: Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes such as SWI/SNF. Brg1 also known as SMARCA4 is a catalytic subunit of SWI/SNF, which is necessary for MMPs expression. Matrix metalloproteinases (MMPs are known as important player enzymes during tumor progression and metastasis. Aberrant epigenetic modification of chromatin should be precisely clarified to reveal probable unknown pathways in ESCC progression. Probable role of Brg1 in ESCC tumorigenesis and metastasis was studied through the assessment of Brg1 mRNA expression in KYSE30, and further evaluation about the biology of Brg1 was performed through the Brg1 silencing. Materials and Methods: Level of Brg1 mRNA expression in KYSE30 was compared to normal tissues using the real time polymerase chain reaction (PCR. Moreover, KYSE30 cells were transfected with Brg1-siRNA to silence the Brg1. Results: Our results showed for the first time that Brg1 mRNA expression was increased in KYSE30 cell line (ESCC cell line compared with normal esophageal tissue of ESCC patients. Rate of transfection in KYSE30 was also between 40 to 50%, using the pSilencer-Brg1shRNA (1:1 ratio. Conclusion: Our data indicated that chromatin remodeling machinery is a novel aspect in tumor biology of ESCC, and overexpression of Brg1 as an important member of SWI/SNF might be involved in the migration and invasion of ESCC tumoral cells.

  8. The Inhibitory Effects of an Antisense u-PAR Vector on Invasion of Highly Invasive Human Prostate Carcinoma PC-3M Cell Subclones

    Institute of Scientific and Technical Information of China (English)

    廖国宁; 李清芬; 冯友梅; 邓耀祖; 李卓娅; 龚非力; 马丁

    2003-01-01

    Summary: To observe the inhibitory effects of an antisense u-PAR vector on invasion of highly inva-sive PC-3M cell subclones, the effects of the antisense u-PAR on activity of MMP-9 in those highlyinvasive cell subclones were detected by a quantitative RT-PCR and zymography. The monolayer in-vasion assay and colony formation assay in soft agar were used. And tumorigenesis rate and invasionsby the cell subclones with or without the antisense u-PAR were observed in nude mice. It was foundthat in vitro growth of highly invasive PC-3M cell subclones transfected with the antisense u-PARwas declined, and the ability of anchorage-independent growth of those cell subclones was found de-creased sharply, with the inhibiting rate becoming 79 % and 60 %, respectively. Although the anti-sense u-PAR didn't change MMP-9 gene transcription, they could inhibit the activation of MMP-9 ofhighly invasive PC-3M cell subclones. Moreover, the tumorigenesis rate of the cell subclones with theantisense u-PAR decreased and the growth of a neoplasm also slowed down. Thet tests showed thedifference between experimental and control groups was statistically significant (P<0. 01). The anti-sense u-PAR vector could not only inhibit the invasion ability of highly invasive PC-3M cell subclonesin vitro but also restrain the growth of those cell subclones in vivo.

  9. Renal Sinus Fat Invasion and Tumoral Thrombosis of the Inferior Vena Cava-Renal Vein: Only Confined to Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Turker Acar

    2014-01-01

    Full Text Available Epithelioid angiomyolipoma (E-AML, accounting for 8% of renal angiomyolipoma, is usually associated with tuberous sclerosis (TS and demonstrates aggressive behavior. E-AML is macroscopically seen as a large infiltrative necrotic tumor with occasional extension into renal vein and/or inferior vena cava. However, without history of TS, renal sinus and venous invasion E-AML would be a challenging diagnosis, which may lead radiologists to misinterpret it as a renal cell carcinoma (RCC. In this case presentation, we aimed to report cross-sectional imaging findings of two cases diagnosed as E-AML and pathological correlation of these aforementioned masses mimicking RCC.

  10. Comparative analysis of metastasis variants derived from human prostate carcinoma cells: roles in intravasation of VEGF-mediated angiogenesis and uPA-mediated invasion

    DEFF Research Database (Denmark)

    Conn, Erin M; Bøtkjær, Kenneth Alrø; Kupriyanova, Tatyana A;

    2009-01-01

    To analyze the process of tumor cell intravasation, we used the human tumor-chick embryo spontaneous metastasis model to select in vivo high (PC-hi/diss) and low (PC-lo/diss) disseminating variants from the human PC-3 prostate carcinoma cell line. These variants dramatically differed...... of vascular endothelial growth factor (VEGF), since treating developing tumors with a function-blocking anti-VEGF antibody simultaneously inhibited both processes without affecting primary tumor growth. PC-hi/diss cells were also more migratory and invasive, suggestive of heightened ability to escape from...

  11. In situ quantification of genomic instability in breast cancer progression

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz de Solorzano, Carlos; Chin, Koei; Gray, Joe W.; Lockett, Stephen J.

    2003-05-15

    Genomic instability is a hallmark of breast and other solid cancers. Presumably caused by critical telomere reduction, GI is responsible for providing the genetic diversity required in the multi-step progression of the disease. We have used multicolor fluorescence in situ hybridization and 3D image analysis to quantify genomic instability cell-by-cell in thick, intact tissue sections of normal breast epithelium, preneoplastic lesions (usual ductal hyperplasia), ductal carcinona is situ or invasive carcinoma of the breast. Our in situ-cell by cell-analysis of genomic instability shows an important increase of genomic instability in the transition from hyperplasia to in situ carcinoma, followed by a reduction of instability in invasive carcinoma. This pattern suggests that the transition from hyperplasia to in situ carcinoma corresponds to telomere crisis and invasive carcinoma is a consequence of telomerase reactivation afertelomere crisis.

  12. Imbalance between expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in invasiveness and metastasis of human gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sheng Zhang; Li Li; Jian-Yin Lin; Hua Lin

    2003-01-01

    AIM: The expressive balance between matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a critical role in maintaining the degradation and synthesis of extracellular matrix. Loss of such balance is associated with invasion and metastasis of tumors. This study aimed to determine the expression of MMP-9 and TIMP-1 in gastric carcinoma, and the association of the expressive imbalance between MMP9 and TIMP-1 with the invasion and metastasis and prognosis of gastric carcinoma.METHODS: We used immunohistochemistry to determine the expressions of MMP-9, TTMP-1 and proliferating cell nuclear antigen Ki-67 in the gastric specimens taken from 256 patients with primary gastric carcinoma. The patients were followed-up for up to 96 months.RESULTS: No association between the expression of MMP9 and TIMP-1 and patients' sex and age, tumor size and location of gastric carcinoma was observed. The incidence of the positive expression of MMP-9 in cases with tumors invasion to muscularis propria and visceral peritoneum (70.13% and 69.09%, respectively) was significantly higher than that in cases with tumor invasion only to lamina propria or submucosa (42.50 %, P=0.0162). The positive correlation between MMP-9 expression and the depth of tumor invasion was observed (Pearson correlation coefficient=0.2129,P=0.016). Along with the increase of the metastatic station of lymph nodes, the incidence of the MMP-9 expression was increased by degrees; a positive correlation between them was observed (Pearson correlation coefficient=0.2910,P=0.0001). There was also a significant correlation between MMP-9 expression and the TNM stage in gastric carcinoma (Pearson correlation coefficient=0.3027, P<0.0001). The incidence of MMP-9 expression in stage Ⅱ and Ⅲ/Ⅳ (75.00%and 76.15%, respectively) was significantly higher than those in stage Ⅰ (46.15 %, P<0.0001). A negative correlation between TIMP-1 immunoreactivity and the depth of invasion

  13. Differential expression proteomics of human colorectal cancer based on a syngeneic cellular model for the progression of adenoma to carcinoma.

    Science.gov (United States)

    Roth, Udo; Razawi, Hanieh; Hommer, Julia; Engelmann, Katja; Schwientek, Tilo; Müller, Stefan; Baldus, Stephan E; Patsos, Georgios; Corfield, Anthony P; Paraskeva, Christos; Hanisch, Franz-Georg

    2010-01-01

    This is the first differential expression proteomics study on a human syngeneic cellular in vitro progression model of the colorectal adenoma-to-carcinoma sequence, the anchorage-dependent non-tumorigenic adenoma derived cell line AA/C1 and the derived anchorage-independent and tumorigenic carcinoma cell line AA/C1/SB10C. The study is based on quantitative 2-DE and is complemented by Western blot validation. Excluding redundancies due to proteolysis and post-translational modified isoforms of over 2000 protein spots, 13 proteins were revealed as regulated with statistical variance being within the 95th confidence level and were identified by peptide mass fingerprinting in MALDI MS. Progression-associated proteins belong to the functional complexes of anaerobic glycolysis/gluconeogenesis, steroid biosynthesis, prostaglandin biosynthesis, the regulation and maintenance of the cytoskeleton, protein biosynthesis and degradation, the regulation of apoptosis or other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in colorectal carcinoma. Among upregulated proteins we identified 3-HMG-CoA synthase, protein phosphatase 1, prostaglandin E synthase 2, villin 1, annexin A1, triosephosphate isomerase, phosphoserine aminotransferase 1, fumarylacetoacetate hydrolase and pyrroline-5-carboxylate reductase 1 (PYCR1), while glucose-regulated protein 78, cathepsin D, lamin A/C and quinolate phosphoribosyltransferase were downregulated.

  14. A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Su Jin [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); New Drug Development Center, Osong Medical Innovation Foundation, Cheongwon, Chungbuk (Korea, Republic of); Chang, Suhwan [Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Lee, Yangsoon; Kim, Na Young; Hwang, Yeonsil; Min, Hye Jin; Yoo, Kyung-Sook; Park, Eun Hye; Kim, Seokho [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Chung, Young-Hwa [BK21-plus, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan (Korea, Republic of); Park, Young Woo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Koh, Sang Seok, E-mail: sskoh@dau.ac.kr [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Department of Biological Sciences, Dong-A University, Busan (Korea, Republic of)

    2014-11-07

    Highlights: • PMAb83, a human monoclonal antibody against PAUF, impaired tumor progression in vivo. • PMAb83 attenuated aggressiveness of tumor cells and suppressed angiogenesis. • PMAb83 in combination with gemcitabine conferred improved survival of mouse model. - Abstract: Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/β-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of β-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31{sup +} vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models.

  15. Neurovascular Invasion and Histological Grade Serve as the Risk Factors of Cervical Lymph Node Metastases in Early Tongue Squamous Cell Carcinoma.

    Science.gov (United States)

    Wu, Kailiu; Yang, Xi; Li, Liwen; Ruan, Min; Liu, Wei; Lu, Wei; Zhang, Chenping; Li, Siyi

    2016-07-01

    The objectives of this study were to analyze the regional characteristics of the cervical lymph node metastasis and to investigate the factors associated with the risk of lymph node involvement. One hundred seventy-one patients suffering from early primary squamous cell carcinoma (SCC) of the tongue (cT1-2N0) were enrolled. Gender, age, growth site, T stage, histological grade, and neurovascular invasion were statistically analyzed by K-M survival analysis and Cox multivariate analysis to evaluate the relationship between the factors and the neck lymph node metastasis. Of the 171 cases divided into the neck dissection group and observation group, 40 ended up with lymph node metastasis, of which 17 were metastasized to level I, 27 to level II, 10 to level III, 2 to level IV, and 1 to level V. Histological grade and neurovascular invasion were significantly associated with lymph node involvement in univariate and multivariate analyses. Age distribution was found to be significantly associated with the lymph node metastasis in multivariate analysis. The metastasis of early tongue SCC has a certain regularity at different sites. Age was not a critical risk factor for cervical lymph node metastasis after surgery. Tumor size was suspected to exert a negative effect on metastasis by influencing tumor invasion. Histological grade and neurovascular invasion were significantly associated with the risk of cervical lymph node metastasis of early tongue SCC. PMID:25911199

  16. Relationship between miRNA-338-3p expression and progression and prognosis of human colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sun Kai; Su Guiyuan; Deng Haijun; Dong Jingqing; Lei Shangtong; Li Guoxin

    2014-01-01

    Background miR-338-3p is a recently discovered miRNA and is involved in cell differentiation.However,few data are yet available on the aberrant expression of miR-338-3p in human colorectal carcinoma (CRC).This work aimed to investigate the relationship between miR-338-3p expression pattern and clinicopathological features of human CRC and the possible regulative mechanisms.Methods The 40 CRC,adjacent nontumorous tissues and 2 human CRC-derived cell lines (SW-480 and SW-620) were collected,respectively,and the total RNA and protein were isolated routinely.The miR-338-3p expression pattern was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Northern blotting.Smoothened (SMO,possible target of miR-338-3p) mRNA and corresponding protein expression pattern were detected by semiquantitative RT-PCR and Western blotting.miR-338-3p expression patterns were compared between nontumor mucosa and CRC samples,graded by progression-related factors.Disease outcome was calculated by Kaplan-Meier survival analysis to determine whether miR-338-3p was related to disease-free survival (DFS) and overall survival (OS) of patients.Moreover,SMO 3'-UTR fragment was PCR amplified from genome DNA of human colon and inserted into a luciferase reporter plasmid.The luciferase reporter plasmid construct was then transfected into CRC cells together with pre-miR-338-3p or anti-miR-338-3p and the luciferase activity in the transfected cells was detected.Results The expression of miR-338-3p was significantly downregulated in CRCs than those in the adjacent nontumorous tissues,and the value was negatively related to advanced TNM stage and local invasion (P <0.01).Furthermore,miR338-3p value was decreased markedly in SW-620 cell line relative to SW-480 (P <0.01).Low expression of miR-338-3p was associated with unfavorable outcome in DFS but not in OS independent of clinical covariates.Moreover,RT-PCR and Western blotting analysis demonstrated that there was no

  17. Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Li Xin

    2010-04-01

    Full Text Available Abstract Background The aim of the present study was to analyze the expression of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1 in nasopharyngeal carcinoma (NPC and its correlation with clinicopathologic features, including patients' survival time. Methods Using real-time PCR, we detected the expression of EIF4G1 in normal nasopharyngeal tissues, immortalized nasopharyngeal epithelial cell lines NP69, NPC tissues and cell lines. EIF4G1 protein expression in NPC tissues was examined using immunohistochemistry. Survival analysis was performed using Kaplan-Meier method. The effect of EIF4G1 on cell invasion and tumorigenesis were investigated. Results The expression levels of EIF4G1 mRNA were significantly greater in NPC tissues and cell lines than those in the normal nasopharyngeal tissues and NP69 cells (P EIF4G1 protein was higher in NPC tissues than that in the nasopharyngeal tissues (P EIF4G1 protein in tumors were positively correlated with tumor T classification (P = 0.039, lymph node involvement (N classification, P = 0.008, and the clinical stages (P = 0.003 of NPC patients. Patients with higher EIF4G1 expression had shorter overall survival time (P = 0.019. Multivariate analysis showed that EIF4G1 expression was an independent prognostic indicator for the overall survival of NPC patients. Using shRNA to knock down the expression of EIF4G1 not only markedly inhibited cell cycle progression, proliferation, migration, invasion, and colony formation, but also dramatically suppressed in vivo xenograft tumor growth. Conclusion Our data suggest that EIF4G1 can serve as a biomarker for the prognosis of NPC patients.

  18. Evaluation of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography in gastric carcinoma. Relation to histological subtypes, depth of tumor invasion, and glucose transporter-1 expression

    International Nuclear Information System (INIS)

    Variable uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) has been noticed in positron emission tomography (PET) studies of gastric carcinoma patients, with low uptake occurring especially in some particular histological subtypes and early carcinomas. But this phenomenon has not been adequately explained. The aim of the present study is to clarify FDG uptake in gastric carcinomas especially focusing on histological subtypes, the depth of tumor invasion, and glucose transporter-1 (GLUT-1) expression which is considered to be one of the major factors for higher FDG uptake in human malignant tumors. FDG-PET was performed on 35 preoperative patients with gastric carcinoma. Forty macroscopically distinguishable lesions on a surgical specimen were histologically classified into two subtypes: Cohesive type (papillary adenocarcinoma, tubular adenocarcinoma, and solid type poorly differentiated adenocarcinoma) or Non-cohesive type (signet-ring cell carcinoma and non-solid type poorly differentiated carcinoma). GLUT-1 expression was immunohistochemically determined. Histological parameters (GLUT-1 expression, histological subtypes, the depth of invasion, lymphatic permeation, venous invasion and tumor size) were evaluated, and factors for FDG uptake (detectability and the degree) and GLUT-1 overexpression were determined by multiple regression analysis. Nineteen of 40 gastric carcinomas showed detectable FDG uptake (48%), multiple regression analysis revealed that both the depth of invasion and histological subtypes are independent factors that influence the detectable FDG uptake in gastric carcinoma (R2=0.66). GLUT-1 expression was seen from an early cancer stage and the cohesive type was an independent factor influencing the overexpression of GLUT-1 (R2=0.66). GLUT-1 expression was the most influential factor for the degree of FDG uptake in gastric carcinoma (R2=0.68). This study provided important information on the clinical application of FDG-PET in gastric carcinoma that

  19. Inonotus obliquus-derived polysaccharide inhibits the migration and invasion of human non-small cell lung carcinoma cells via suppression of MMP-2 and MMP-9.

    Science.gov (United States)

    Lee, Ki Rim; Lee, Jong Seok; Song, Jeong Eun; Ha, Suk Jin; Hong, Eock Kee

    2014-12-01

    Polysaccharides isolated from the fruiting body of Inonotus obliquus (PFIO) are known to possess various pharmacological properties including antitumor activity. However, the anti-metastatic effect and its underlying mechanistic signaling pathway involved these polysaccharides in human non-small cell lung carcinoma remain unknown. The present study therefore aimed to determine the anti-metastatic potential and signaling pathways of PFIO in the highly metastatic A549 cells. We found that PFIO suppressed the migration and invasive ability of A549 cells while decreasing the expression levels and activity of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, PFIO decreased the phosphorylation levels of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) as well as the expression level of COX-2, and inhibited the nuclear translocation of nuclear factor κB (NF-κB) in A549 cells. These results suggested that PFIO could suppress the invasion and migration of human lung carcinoma by reducing the expression levels and activity of MMP-2 and MMP-9 via suppression of MAPKs, PI3K/AKT, and NF-κB signaling pathways. PMID:25270791

  20. Inonotus obliquus-derived polysaccharide inhibits the migration and invasion of human non-small cell lung carcinoma cells via suppression of MMP-2 and MMP-9.

    Science.gov (United States)

    Lee, Ki Rim; Lee, Jong Seok; Song, Jeong Eun; Ha, Suk Jin; Hong, Eock Kee

    2014-12-01

    Polysaccharides isolated from the fruiting body of Inonotus obliquus (PFIO) are known to possess various pharmacological properties including antitumor activity. However, the anti-metastatic effect and its underlying mechanistic signaling pathway involved these polysaccharides in human non-small cell lung carcinoma remain unknown. The present study therefore aimed to determine the anti-metastatic potential and signaling pathways of PFIO in the highly metastatic A549 cells. We found that PFIO suppressed the migration and invasive ability of A549 cells while decreasing the expression levels and activity of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, PFIO decreased the phosphorylation levels of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) as well as the expression level of COX-2, and inhibited the nuclear translocation of nuclear factor κB (NF-κB) in A549 cells. These results suggested that PFIO could suppress the invasion and migration of human lung carcinoma by reducing the expression levels and activity of MMP-2 and MMP-9 via suppression of MAPKs, PI3K/AKT, and NF-κB signaling pathways.

  1. Papillomavirus, p53 alteration, and primary carcinoma of the vulva.

    Science.gov (United States)

    Pilotti, S; D'Amato, L; Della Torre, G; Donghi, R; Longoni, A; Giarola, M; Sampietro, G; De Palo, G; Pierotti, M A; Rilke, F

    1995-12-01

    Twenty-nine samples from 28 cases of vulvar squamous cell carcinoma, of which 13 fulfilled the criteria of the bowenoid subtype (mean age 45 years, range 31-68) and 16 of the usual subtype of invasive squamous cell carcinoma (ISCC) (mean age 67.5 years, range 34-83) were investigated for human papillomavirus (HPV) DNA, TP53 alterations, and mdm2 and bcl-2 gene product deregulation. Microscopically all the bowenoid subtype cases (group I) showed a high-grade intraepithelial (VIN 3, carcinoma in situ) lesion associated with early invasive carcinoma in six cases and overt invasive carcinoma in one. By contrast, no evidence of early carcinoma was present in the ISCCs (group II). By in situ hybridization and/or Southern blot hybridization or polymerase chain reaction (PCR), HPV DNA was detected in all cases of group I and in four of 16 cases (25%) of group II, two only by Southern blot after PCR. By single-strand conformation polymorphism and immunocytochemistry only wild-type TP53 and absence of detectable p53 product, respectively, were found in all cases of group I, i.e., in high-risk HPV-positive carcinomas, whereas mutations and/or p53 overexpression accounted for 75% in group II, i.e., in mainly HPV-negative carcinomas. The TP53 gene mutations observed in invasive carcinomas were significantly related to node-positive cases (p = 0.04). Taken together and in agreement with in vitro data, these results support the view that an alteration of TP53, gained either by interaction with viral oncoproteins or by somatic mutations, is a crucial event in the pathogenesis of vulvar carcinomas, but that TP53 mutations are mainly associated with disease progression. Finally, a preliminary immunocytochemical analysis seems to speak against the possible involvement of both MDM2 and BCL-2 gene products in the development of vulvar carcinoma.

  2. Identification of HRAS as cancer-promoting gene in gastric carcinoma cell aggressiveness

    Science.gov (United States)

    Wu, Xiao Yu; Liu, Wen Tao; Wu, Zhen Feng; Chen, Che; Liu, Jia Yun; Wu, Guan Nan; Yao, Xue Quan; Liu, Fu Kun; Li, Gang

    2016-01-01

    Gastric carcinoma is one of the most lethal malignancies of cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that HRAS is markedly up-regulated in gastric carcinoma. Prognostic analysis indicated that HRAS expression might be a prognostic indicator for the survival of patients with gastric carcinoma. Ectopic expression of HRAS in gastric carcinoma cells accelerated proliferation, migration, invasion, angiogenesis, and clone formation ability of gastric carcinoma cells in vitro. Furthermore, HRAS over-expressing significantly promoted the tumorigenicity of gastric carcinoma cells in vivo whereas silencing endogenous HRAS caused opposite outcomes. Moreover, we demonstrated that HRAS enhanced gastric carcinoma aggressiveness by activating VEGFA/PI3K/AKT pathway and Raf-1 signaling. Together, our results provide new evidence that HRAS overexpression promotes the progression of gastric carcinoma and might represent a novel therapeutic target for its treatment. PMID:27725900

  3. One stage resection of spontaneous rupture of hepatocellular carcinoma in the triangular ligament with diaphragm invasion: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Park Kwang-Kuk

    2012-09-01

    Full Text Available Abstract A spontaneous rupture of hepatocellular carcinoma (HCC can lead to extensive hemorrhage and is a rare but life-threatening event. A 58-year-old male patient with no history of trauma presented at our institution with severe epigastric pain and abdominal distension for 6 h. His blood pressure was a 60/40 mmHg, and pulse rate was 132/min. Abdominal contrast enhanced computed tomography (CT imaging revealed a ruptured mass under the left diaphragm and fluid collection in the upper abdomen, flanks and pelvic cavity. Exploratory laparotomy confirmed the presence of an active bleeding tumor in the triangular ligament invading into the diaphragm. The tumor was resected with an appropriate diaphragm margin. The resected tumor was 5 cm in diameter and pathologically identified as hepatocellular carcinoma with a negative surgical margin. This case report shows that ruptured hepatocellular carcinoma should be considered in the differential diagnosis of non-traumatic hemoperitoneum. And it is necessary to set a surgical plan for unpredictable HCC rupture with direct diaphragm invasion.

  4. Comparison of outcomes of bone scan, clinical judgement and other imaging modalities in the pre-operative assessment of mandibular invasion by squamous cell carcinoma of oral cavity

    International Nuclear Information System (INIS)

    The squamous cell carcinoma of the oral cavity frequently involved mandible, necessitating surgical excision. To maximally preserve the mandible an accurate preoperative assessment is critical. In order to determine the relative accuracy of various investigative modalities, we compared clinical judgement, orthopantomography, computed tomography and bone scanning against decalcified mandibular histopathology as 'gold standard.' Thirty-three patients (18 males and 15 females, aged between 19 and 66 years with an average age of 53) with a previously untreated primary squamous cell carcinoma of the oral cavity underwent surgery at our Institute. In nineteen patients marginal, in 8 segmental and in 6 hemimandibulectomy was performed, based on clinical judgements. All patients had undergone pre-operative evaluation with orthopantomography, computed tomography and Tc-99m MDP bone scanning. Post-surgical histopathology revealed that 10 patients (30%) had positive evidence of mandibular involvement. Compared to histopathology the accuracy of clinical judgement, OPG, CT scan and bone scan were 64%, 73%, 88% and 88%, respectively. The sensitivity and specificity of clinical judgement, orthopantomography, computed tomography and bone scan were 90 and 52%, 40 and 87%, 70 and 96% and 100 and 83% respectively. There was no false negative bone scan. The study concluded that judicious use of clinical judgement and bone scanning can guide the surgeon in making decisions regarding mandibular excision in majority of cases of squamous cell carcinoma of the oral cavity. Negative bone scan virtually rules out mandibular invasion of the disease and more conservative surgery can be planned in these cases.(author)

  5. Structural alterations of transforming growth factor-beta receptor genes in human cervical carcinoma

    NARCIS (Netherlands)

    Chen, TP; De Vries, EGE; Hollema, H; Yegen, HA; Vellucci, VF; Strickler, HD; Hildesheim, A; Reiss, M

    1999-01-01

    The development and progression of invasive uterine cervical carcinomas appear to be associated with the progressive loss of sensitivity to transforming growth factor-beta (TGF beta)-mediated cell cycle arrest. In order to identify possible molecular mechanisms responsible for TGF beta resistance, w

  6. Prevalence of androgen receptors in invasive breast carcinoma and its relation with estrogen receptor, progesterone receptor and Her2/neu expression

    International Nuclear Information System (INIS)

    Background and aims: Although Breast carcinoma had many targeted bio markers for its treatment, however, it is a heterogeneous disease with different outcomes and need new markers especially for the triple negative group when estrogen receptor, progesterone receptors and Her2/ neu are negative. Androgen receptor is a new target with unclear role. The aim of this study was to examine the prevalence of androgen receptors in invasive breast cancer and tries to elucidate its relation to some well recognized clinico pathological and immunohistochemical markers. Materials and methods: One hundred and fifty cases of invasive breast carcinoma were evaluated for type, grade and stage and studied immunohistochemically for estrogen receptor, progesterone receptor, Her2/neu and androgen expression. Androgen receptor expression was correlated with histopathological factors and the three studied markers separately then the studied cases were classified into three groups according to estrogen, progesterone receptor and Her2/neu expression and correlated with androgen receptor expression. Results: Androgen receptor was expressed in 71% of breast cancer cases. Its expression is associated significantly with both the stage and the grade. Also it was significantly associated with estrogen receptor and Her2/neu expression. It was expressed in a significant number of triple negative breast carcinoma, in Her2/neu positive cases and in estrogen negative cases which indicate that androgen receptor could be a new target for the treatment of these groups. Conclusions: Although the impact of androgen receptor on breast cancer outcomes had not been clearly established, this result may provide evidence that androgen receptor is a good prognostic and predictive marker.

  7. A Study on the Mechanism of Low-Expressed Cancer Stem Cell Marker Lgr5 in Inhibition of the Proliferation and Invasion of Colorectal Carcinoma.

    Science.gov (United States)

    Jia, Houjun; Xiang, Lin; Wang, Ziwei; Zhou, Qipeng

    2015-11-01

    The present study intends to explore the influence of Lgr5 as a marker of tumor stem cells after siRNA interference on the proliferation and invasion of colorectal carcinoma (CRC) and its mechanism. The tissue samples were taken for biopsy from 32 cases of patients and 32 cases of normal subjects by colonoscopy. Real-time quantitative PCR was used to detect the differential expression of Lgr5. After siRNA interference of Lgr5 in CRC cell line CT-26 cells, RT-PCR method was used to detect the mRNA expression level of Lgr5 after interference of CT-26 cells. CCK8 method was used to observe the influence of Lgr5 interference on the proliferation, colony formation, and invasion of CT-26 cells. RT-PCR and Western blot were used to detect the E-cadherin mRNA and protein levels in CT-26 cells. Lgr5 expression level in CRC tissue was significantly higher than that in the corresponding para-carcinoma tissue and the control group, and the differences were statistically significant (P < 0.05). Lgr5 mRNA expression level in tissue with lymph node metastasis was significantly higher than that in the tissue without lymph node metastasis, and the difference was statistically significant (P < 0.05). Compared with the control group, CT-26 cell proliferation, colony formation, and migration capability after Lgr5 siRNA transfection were all significantly reduced, and the differences were statistically significant (P < 0.05). CT-26 cells after Lgr5 interference were found with significantly reduced E-cadherin mRNA and protein levels. Lgr5 facilitates the cell proliferation, colony formation, and migration of colorectal carcinoma, which may be closely related to the expression level of E-cadherin. PMID:27352328

  8. Comparing the expression of myoepithelial cell markers CD10 and smooth muscle actin with the estrogen receptor status in the invasive carcinoma breast: An immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Gaurav Arora

    2013-01-01

    Full Text Available Background: Breast cancer is the most frequent cancer in females throughout the world. Around 20% of breast carcinomas are estrogen receptor alpha (ER-negative. Thus, theoretically this negativity could be either the result of down-regulation of ER expression in the tumor cells, or the result of the tumor being derived from cells which normally lack that expression. Normal basal, including myoepithelial cells of the breast is ER-negative. CD10 and smooth muscle actin (SMA are used as markers for the demonstration of these basal cells. Aims: To compare the expression of positive staining for CD10 and SMA in ER-negative and ER-positive invasive breast carcinomas. Materials and Methods: The study was performed on 40 paraffin-embedded tissues of already diagnosed cases of invasive breast carcinomas with known ER status, i.e., thirty ER-negative and ten ER-positive cases. Expression of CD10 and SMA was demonstrated using avidin-biotin-peroxidase complex (ABC technique. Tumor was considered to be positive for both markers only when more than 10% of tumor cells were stained positive. Results: Overall, CD10 tumor cell staining was seen in eight, 23.3% (7/30 ER-negative cases and in 10% (1/10 ER-positive cases. Also the staining intensity was considered to be strong. SMA tumor cell staining was seen in only 6.7% (2/30 ER-negative cases and the staining intensity was considered to be moderate. Percentages of positively stained tumor cells varied between 13% to 72% and 23% to 45% for CD10 and SMA, respectively. Conclusion: CD10 is a better marker when compared to SMA, as it is expressed in more number of cases and gives strong positivity in tumor cells. Higher expression of CD10 and SMA is correlated with higher tumor grade and ER negativity.

  9. Nm23H1 mediates tumor invasion in esophageal squamous cell carcinoma by regulation of CLDN1 through the AKT signaling

    Science.gov (United States)

    Kuo, K-T; Chen, C-L; Chou, T-Y; Yeh, C-T; Lee, W-H; Wang, L-S

    2016-01-01

    Esophageal cancer is a lethal malignancy worldwide. Previously, low expression of metastasis suppressor Nm23H1 and tight junction (TJ) protein claudin-1 (CLDN1) have been known to correlate with poor prognosis in esophageal squamous cell carcinoma (ESCC). However, the molecular interaction between them has not been clarified. In the present study, we first examined the expression of Nm23H1 and CLDN1 in 74 surgical ESCC samples by immunohistochemistry (IHC) to verify their clinicopathologic significance. The biologic effects of Nm23H1 gene silencing or overexpression in ESCC cell lines were then studied by migration and invasion studies, and its regulation on CLDN1 expression was also investigated by western blot analysis. Moreover, the expression of Nm23H1 and CLDN1 at the same invasion front of ESCC tumors was verified by immunofluorescence. The results showed a significantly positive correlation between the expression of Nm23H1 and CLDN1 (γ=0.296, P=0.011) in surgical specimens, especially for the 34 tumors with lymph-node metastasis (γ=0.455, P=0.007). In ESCC cell lines, silencing of Nm23H1 expression markedly enhanced cell invasiveness, accompanied by increased Akt phosphorylation and decreased CLDN1 expression. Conversely, Nm23H1-expressed transfectants exhibited reduced invasiveness, decreased Akt phosphorylation and correspondingly increased CLDN1 expression. Regain of CLDN1 expression in ESCC cells significantly suppressed invasiveness, but did not influence the Akt phosphorylation. Moreover, treating Nm23H1-depleted cells with the AKT inhibitor MK2206 recovered CLDN1 expression, and diminished the invasiveness of ESCC cells. Finally, decreased expressions of both CLDN1 and E-cadherin were observed at the invasive front of the Nm23H1-negative tumors. Overall, our current study documented that reduced Nm23H1 expression activates the AKT signaling pathway, results in diminished CLDN1 expression and potentiates invasiveness of ESCC cells. Enhancement of Nm

  10. 胰腺癌神经浸润及临床研究新进展%Research progress of neural invasion of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    王保勋; 张群华

    2011-01-01

    The high occurrence of neural invasion in pancreatic carcinoma, which can be as much as 90%-l00%,leads to the poor survival rate in patients. The classical pathology includes invasion of both the extrapancreatic and intrapancreatic neurons. Metastasis into the extrapancreatic plexus promotes invasion into the intrapancreatic neurons and therefore results in pain. An increased in the diagnosis of new-onset diabetes mellitus, on the other hand, correlates with an increase in pancreatic cancer. This implies that hyperglycemia may promote neural invasion of pancreatic carcinoma. Novel auxiliary therapy of pancreatic carcinoma with neural invasion includes controlling of blood sugar and optogenetics, a new genetic technology which can further be utilized for surveillance.%胰腺癌的特点是神经浸润非常高发(可高达90%~100%),这与其生存率不高有关.肿瘤细胞胰内、胰外神经浸润是胰腺癌神经变化的典型表现.胰外神经丛浸润增加可以促进胰内神经浸润的发生,从而造成疼痛.胰腺癌诊断率的显著增加与新发糖尿病的诊断有关,高血糖也有促进胰腺癌神经浸润的可能.控制高血糖和光基因技术可作为胰腺癌神经浸润的辅助治疗,并且可以利用光基凶技术对胰腺癌的神经浸润进行监测.

  11. An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression

    Directory of Open Access Journals (Sweden)

    Jungsun Kim

    2013-06-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC carries a dismal prognosis and lacks a human cell model of early disease progression. When human PDAC cells are injected into immunodeficient mice, they generate advanced-stage cancer. We hypothesized that if human PDAC cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem cell (iPSC lines were not of the expected cancer genotype, one PDAC line, 10–22 cells, when injected into immunodeficient mice, generated pancreatic intraepithelial neoplasia (PanIN precursors to PDAC that progressed to the invasive stage. The PanIN-like cells secrete or release proteins from many genes that are known to be expressed in human pancreatic cancer progression and that predicted an HNF4α network in intermediate-stage lesions. Thus, rare events allow iPSC technology to provide a live human cell model of early pancreatic cancer and insights into disease progression.

  12. An atypical cause of rapidly progressing breast lump with abscess formation: Pure squamous cell carcinoma of the breast.

    Science.gov (United States)

    Cilekar, Murat; Erkasap, Serdar; Oner, Ulku; Akici, Murat; Ciftci, Evrim; Dizen, Hayrettin; Turel, Serkan; Kavak, Ozgu I; Yilmaz, Sezgin

    2015-01-01

    Squamous cell carcinoma (SCC) is a rare type of breast malignancy and little is known about long-term outcome. In the present report, the clinical features, histopathologic findings and postoperative course of a patient with squamous cell carcinoma are described. We have treated a 47-years-old woman who admitted for right breast mass without any discharge, bleeding and pain. The tumor was, 3 × 2 × 1.5 cm in size with central abscess formation. The result of surgical biopsy revealed large cell keratinizing type of SCC. The metastatic work-up studies ruled out any other probable sources of primary tumor. The patient was performed modified radical mastectomy and axillary dissection and received two cycles of chemotherapy. Squamous cell carcinoma of the breast (SCCB) is a rare entity and should be considered in patients with rapidly progressing breast mass. It should also be considered in breast lesions with abscess formation. The initial therapeutic approach should be surgical excision after histopathological diagnosis.

  13. Progress in Modeling Biological Invasion%生物入侵模型研究进展

    Institute of Scientific and Technical Information of China (English)

    王勤龙; 李百炼

    2011-01-01

    Biological invasion is now one of the six hot research topics in modern ecology.Modeling the invasion processes,the diffusions and the spreading mechanisms of invasive species including diseases is important not only for theoretical puposes,but also for practical purposes,such as in ecological risk assessments,and optimal control and management of those invasive species.In this paper the widely adopted models of biological invasion are systematically reviewed such as diffusion-reaction equations,integral-difference models,space-discrete models,and stochastic models.The fundamental issues of modeling biological invasions are discussed,and the characteristics and analytic conditions of various models are analyzed with typical exampies and recent research results.Various modeling techniques are compared,and some commonly used methods in solving biological invasion models are outlined,including numerical computing and simulating,exact solutions,methods for functional differential equation and qualitative analysis of differential equations Some key and unsolved problems in building mathematical models of biological invasion,and future research directions are also Hiscussed.%生物入侵的机制与控制已经成为生态学关注的重点和研究的热点问题.建立数学模型是解释生物入侵机制的主要手段,对外来生物包括疾病的入侵扩散过程进行模型分析不仅具有重要的理论意义,还有助于风险评估,特别对入侵进行早期预测、控制、科学管理与防治.然而,目前有关生物入侵的数理模型方法还远不能满足实际的需要,本文系统地介绍和分析了生物入侵模型的研究现状.首先分析了对于生物入侵过程建模所要考虑的基本问题;然后讨论了几类典型的入侵数学模型,分析了各自的特点及条件,同时给出了有代表性的实例和最近的研究成果;其次比较列出了入侵模型分析的各类方法:最后探讨了生物入侵建模与求

  14. Distribution of HPV Genotype in Invasive Cervical Carcinoma and Cervical Intraepithelial Neoplasia in Zhejiang Province, Southeast China: Establishing the Baseline for Surveillance

    Directory of Open Access Journals (Sweden)

    Xiao-Xian Xu

    2015-09-01

    Full Text Available Human papillomavirus (HPV are firmly established as the principal causative agent for cervical carcinoma. Current vaccines may provide some protection for women from cervical carcinoma linked to HPV genotype 16 and 18. This may be the best vaccine for Western women, but the geographical variation in HPV distributions may not make it the most appropriate vaccine for China or Asia. This study provided an observational, retrospective, hospital-based cross-sectional study on the distribution of HPV genotypes among 5410 women with invasive cervical cancer (ICC or cervical intraepithelial neoplasia (CIN. Overall, the positive rates of the four HPV types included in current prophylactic vaccines were counted, the two high-risk types (HPV-16 and -18 covered by current vaccines represented 66.9% of women with squamous cancer, 55.0% with adenocarcinoma, 64.9% with adenosquamous carcinoma and 77.4% of other type ICC, as well as 59.5% of CIN III, 45.0% of CIN II and 38.1% of CIN I cases. As expected, two low-risk types (HPV-6 and -11 included in the quadrivalent vaccine did not show good coverage data. Particularly worth mentioning is the fact that the addition of HPV-52 and -58 to the vaccine cocktail would increase cancer protection in our population, potentially preventing up to beyond 16% of squamous/adenosquamous carcinoma and other type of cervical cancers, and 7.75% of adenocarcinomas. It might also potentially reduce the rate of CIN III by a further 28.6% and CIN II and I by a third. This study established the baseline for surveillance in Zhejiang Province, and provides data for further vaccine designs: a quadrivalent HPV vaccine covering HPV-16/-58/-18/-52, would be more welcome in our region in the forthcoming year compared to the currently available vaccine.

  15. Inhibitory Effects of Isorhamnetin on the Invasion of Human Breast Carcinoma Cells by Downregulating the Expression and Activity of Matrix Metalloproteinase-2/9.

    Science.gov (United States)

    Li, Chenglin; Yang, Dan; Zhao, Yuanwei; Qiu, Yu; Cao, Xin; Yu, Yanyan; Guo, Hao; Gu, Xiaoke; Yin, Xiaoxing

    2015-01-01

    Matrix metalloproteinases (MMPs) play an active role in facilitating the invasion of cancer cells with excessive extracellular matrix (ECM) degradation. In the present study, we investigated the antiinvasive effects of isorhamnetin, a naturally occurring flavonoid, on MDA-MB-231 human breast carcinoma cells. The results indicated that isorhamnetin significantly inhibited the adhesion, migration, and invasion of the cells in vitro. Moreover, isorhamnetin suppressed the activity and expression of MMP-2 and MMP-9, which were determined by gelatin zymography, real-time PCR, and Western blot analysis, respectively. Besides, isorhamnetin had little effect on the secretion of urokinase plasminogen activator. Further elucidation of the mechanism revealed that isorhamnetin exerted an inhibitory effect on the phosphorylation of p38 and STAT3, although it had no effect on ERK1/2 and JNK. Taken together, these data demonstrated that isorhamnetin could significantly inhibit the invasion of MDA-MB-231 cells by downregulating the expression and activity of MMP-2 and MMP-9, which was potentially associated with the suppression of p38 MAPK and STAT3. Therefore, the findings provide new evidence for the anti-cancer activity of isorhamnetin. PMID:26359917

  16. Identification and Validation of Protein Biomarkers of Response to Neoadjuvant Platinum Chemotherapy in Muscle Invasive Urothelial Carcinoma.

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    Alexander S Baras

    Full Text Available The 5-year cancer specific survival (CSS for patients with muscle invasive urothelial carcinoma of the bladder (MIBC treated with cystectomy alone is approximately 50%. Platinum based neoadjuvant chemotherapy (NAC plus cystectomy results in a marginal 5-10% increase in 5-year CSS in MIBC. Interestingly, responders to NAC (

  17. Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

    International Nuclear Information System (INIS)

    Activation of nuclear factor erythroid 2-related factor (Nrf2), which belongs to the basic leucine zipper transcription factor family, is a strategy for cancer chemopreventive phytochemicals. It is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1 and peroxiredoxin 1, by activating the antioxidant response element (ARE). We hypothesized that (1) the citrus coumarin auraptene may suppress premalignant mammary lesions via activation of Nrf2/ARE, and (2) that Nrf2 knocko