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Sample records for low-grade invasive carcinoma

  1. Low grade papillary transitional cell carcinoma pelvic recurrence masquerading as high grade invasive carcinoma, ten years after radical cystectomy

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    Mortazavi Amir

    2008-09-01

    Full Text Available Abstract Background Tumor recurrence following radical cystectomy for a low-grade superficial transitional cell carcinoma (TCC is exceedingly uncommon and has not been reported previously. Case presentation We describe a case of a young male presenting with anorexia, weight loss and a large, painful locally destructive pelvic recurrence, ten years after radical cystoprostatectomy. The pathology was consistent with a low-grade urothelial carcinoma. After an unsuccessful treatment with cisplatin-based chemotherapy, the patient underwent a curative intent hemipelvectomy with complete excision of tumor and is disease free at one year follow-up. Conclusion A literature review related to this unusual presentation is reported and a surgical solutions over chemotherapy and radiotherapy is proposed.

  2. Low-grade salivary duct carcinoma or low-grade intraductal carcinoma? Review of the literature.

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    Kuo, Ying-Ju; Weinreb, Ilan; Perez-Ordonez, Bayardo

    2013-07-01

    Low-grade salivary duct carcinoma (LG-SDC) is a rare neoplasm characterized by predominant intraductal growth, luminal ductal phenotype, bland microscopic features, and favorable clinical behavior with an appearance reminiscent of florid to atypical ductal hyperplasia to low grade intraductal breast carcinoma. LG-SDC is composed of multiple cysts, cribriform architecture with "Roman Bridges", "pseudocribriform" proliferations with floppy fenestrations or irregular slits, micropapillae with epithelial tufts, fibrovascular cores, and solid areas. Most of the tumor cells are small to medium sized with pale eosinophilic cytoplasm, and round to oval nuclei, which may contain finely dispersed or dark condensed chromatin. Foci of intermediate to high grade atypia, and invasive carcinoma or micro-invasion have been reported in up to 23 % of cases. The neoplastic cells have a ductal phenotype with coexpression of keratins and S100 protein and are surrounded by a layer of myoepithelial cells in non-invasive cases. The main differential diagnosis of LG-SDC includes cystadenoma, cystadenocarcinoma, sclerosing polycystic adenosis, salivary duct carcinoma in situ/high-grade intraductal carcinoma, and papillary-cystic variant of acinic cell carcinoma. There is no published data supporting the continuous classification of LG-SDC as a variant of cystadenocarcinoma. Given that most LG-SDC are non-invasive neoplasms; the terms "cribriform cystadenocarcinoma" and LG-SDC should be replaced by "low-grade intraductal carcinoma" (LG-IDC) of salivary gland or "low-grade intraductal carcinoma with areas of invasive carcinoma" in those cases with evidence of invasive carcinoma.

  3. Non-invasive, low-grade papillary urothelial carcinoma in the urachus

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    Pedersen, Gyrithe Lynghøj; Dahl, Claus; Azawi, Nessn Htum

    2013-01-01

    urothelial carcinoma, and through a systematic literature search, we identified 12 additional cases of urachal urothelial carcinoma reported in English literature in the past 20 years. The cases were compared according to the Sheldon Staging System and the Mayo Staging System presented by Ashley et al...

  4. Association of a renal papillary carcinoma with a low grade tumour of the collecting ducts

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    Daniel, L; Zattara-Cannoni, H; Lechevallier, E; Pellissier, J

    2001-01-01

    This case report describes a 75 year old man who had a renal papillary carcinoma associated with a low grade tumour of the collecting ducts. These tumours showed different immunohistochemical patterns for epithelial membrane antigen, cytokeratin 19, and Ulex europaeus lectin expression. In addition, cytogenetic findings were 47, XY, +7 and 45, XY, -8, add(12)(q–ter) for the papillary renal carcinoma and the low grade tumour of the collecting ducts, respectively. This is the first report where these two types of tumour are associated and cytogenetically distinguished. Key Words: renal cell carcinomalow grade tumour of the collecting ducts PMID:11477121

  5. Multiphoton imaging of low grade, high grade intraepithelial neoplasia and intramucosal invasive cancer of esophagus

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    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2017-04-01

    Esophageal squamous cell carcinoma (ESCC) is devastating because of its aggressive lymphatic spread and clinical course. It is believed to occur through low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal invasive cancer (IMC) before transforming to submucosal cancer. In particular, these early lesions (LGIN, HGIN and IMC), which involve no lymph node nor distant metastasis, can be cured by endoscopic treatment. Therefore, early identification of these lesions is important so as to offer a curative endoscopic resection, thus slowing down the development of ESCC. In this work, spectral information and morphological features of the normal esophageal mucosa are first studied. Then, the morphological changes of LGIN, HGIN and IMC are described. Lastly, quantitative parameters are also extracted by calculating the nuclear-to-cytoplasmic ratio of epithelial cells and the pixel density of collagen in the lamina propria. These results show that multiphoton microscopy (MPM) has the ability to identify normal esophageal mucosa, LGIN, HGIN and IMC. With the development of multiphoton endoscope systems for in vivo imaging, combined with a laser ablation system, MPM has the potential to provide immediate pathologic diagnosis and curative treatment of ESCC before the transformation to submucosal cancer in the future.

  6. Low grade urothelial carcinoma mimicking basal cell hyperplasia and transitional metaplasia in needle prostate biopsy

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    Julian Arista-Nasr

    2016-04-01

    Full Text Available ABSTRACT Purpose The vast majority of urothelial carcinomas infiltrating the bladder are consistent with high-grade tumors that can be easily recognized as malignant in needle prostatic biopsies. In contrast, the histological changes of low-grade urothelial carcinomas in this kind of biopsy have not been studied. Materials and Methods We describe the clinicopathologic features of two patients with low-grade bladder carcinomas infiltrating the prostate. They reported dysuria and hematuria. Both had a slight elevation of the prostate specific antigen and induration of the prostatic lobes. Needle biopsies were performed. At endoscopy bladder tumors were found in both cases. Results Both biopsies showed nests of basophilic cells and cells with perinuclear clearing and slight atypia infiltrating acini and small prostatic ducts. The stroma exhibited extensive desmoplasia and chronic inflammation. The original diagnosis was basal cell hyperplasia and transitional metaplasia. The bladder tumors also showed low-grade urothelial carcinoma. In one case, the neoplasm infiltrated the lamina propria, and in another, the muscle layer. In both, a transurethral resection was performed for obstructive urinary symptoms. The neoplasms were positive for high molecular weight keratin (34BetaE12 and thrombomodulin. No metastases were found in either of the patients, and one of them has survived for five years. Conclusions The diagnosis of low-grade urothelial carcinoma in prostate needle biopsies is difficult and may simulate benign prostate lesions including basal cell hyperplasia and urothelial metaplasia. It is crucial to recognize low-grade urothelial carcinoma in needle biopsies because only an early diagnosis and aggressive treatment can improve the prognosis for these patients.

  7. Long-term Behavior of Serous Borderline Tumors Subdivided Into Atypical Proliferative Tumors and Noninvasive Low-grade Carcinomas

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    Vang, Russell; Hannibal, Charlotte G; Junge, Jette

    2017-01-01

    Ovarian serous borderline tumors (SBTs) have been the subject of considerable controversy, particularly with regard to terminology and behavior. It has been proposed that they constitute a heterogenous group of tumors composed, for the most part, of typical SBTs that are benign and designated...... "atypical proliferative serous tumor (APST)" and a small subset of SBTs with micropapillary architecture that have a poor outcome and are designated "noninvasive low-grade serous carcinoma (niLGSC)". It also has been argued that the difference in behavior between the 2 groups is not due to the subtype...... of the primary tumor but rather the presence of extraovarian disease, specifically invasive implants. According to the terminology of the 2014 WHO Classification, typical SBTs are equivalent to APSTs and SBTs displaying micropapillary architecture are synonymous with niLGSC. In addition, "invasive implants" were...

  8. KRAS/BRAF Analysis in Ovarian Low-Grade Serous Carcinoma Having Synchronous All Pathological Precursor Regions

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    Kohei Nakamura

    2016-04-01

    Full Text Available Ovarian low-grade serous carcinoma is thought to begin as a serous cystadenoma or adenofibroma that progresses in a slow stepwise fashion. Among the low-grade serous carcinomas, there is a high frequency of activating mutations in the KRAS or BRAF genes; however, it remains unclear as to how these mutations contribute to tumor progression. This is the first report to track the histopathological progression of serous adenofibroma to low-grade serous carcinoma. Each stage was individually analyzed by pathological and molecular genetic methods to determine what differences occur between the distinct stages of progression.

  9. Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family

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    Geyer, Felipe C; Berman, Samuel H.; Marchiò, Caterina; Burke, Kathleen A; Guerini-Rocco, Elena; Piscuoglio, Salvatore; Ng, Charlotte K Y; Pareja, Fresia; Wen, Hannah Y; Hodi, Zoltan; Schnitt, Stuart J; Rakha, Emad A; Ellis, Ian O; Norton, Larry; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative breast cancers. Here we report on a comparison of previously published data on eight carcinoma-associated microglandular adenosis and eight acinic cell carcinomas subjected to targeted massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer and/or DNA repair-related. Somatic mutations, insertions/deletions and copy number alterations were detected using state-of-the-art bioinformatic algorithms. All cases were of triple-negative phenotype. A median of 4.5 (1–13) and 4.0 (1–7) non-synonymous somatic mutations per carcinoma-associated microglandular adenosis and acinic cell carcinoma were identified, respectively. TP53 was the sole highly recurrently mutated gene (75% in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53 mutations were consistently coupled with loss of heterozygosity of the wild-type allele. Additional somatic mutations shared by both groups included those in BRCA1, PIK3CA and INPP4B. Recurrent (n=2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those affecting PTEN and MED12, or ERBB4, respectively. No significant differences in the repertoire of somatic mutations were detected between microglandular adenosis and acinic cell carcinomas, and between this group of lesions and 77 triple-negative carcinomas from The Cancer Genome Atlas. Microglandular adenosis and acinic cell carcinomas, however, were genetically distinct from estrogen receptor-positive and/or HER2-positive breast cancers from The Cancer Genome Atlas. Our findings support the contention that microglandular adenosis and acinic cell carcinoma are part of the same spectrum of lesions

  10. Squamous cell carcinoma - invasive (image)

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    This irregular red nodule is an invasive squamous cell carcinoma (a form of skin cancer). Initial appearance, shown here, may be very similar to a noncancerous growth called a keratoacanthoma. Squamous cell cancers ...

  11. Mast cells and eosinophils in invasive breast carcinoma

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    Amini, Rose-Marie; Aaltonen, Kirsimari; Nevanlinna, Heli; Carvalho, Ricardo; Salonen, Laura; Heikkilä, Päivi; Blomqvist, Carl

    2007-01-01

    Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas. Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome. Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours. A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers

  12. Cytopathologic differential diagnosis of low-grade urothelial carcinoma and reactive urothelial proliferation in bladder washings: a logistic regression analysis.

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    Cakir, Ebru; Kucuk, Ulku; Pala, Emel Ebru; Sezer, Ozlem; Ekin, Rahmi Gokhan; Cakmak, Ozgur

    2017-05-01

    Conventional cytomorphologic assessment is the first step to establish an accurate diagnosis in urinary cytology. In cytologic preparations, the separation of low-grade urothelial carcinoma (LGUC) from reactive urothelial proliferation (RUP) can be exceedingly difficult. The bladder washing cytologies of 32 LGUC and 29 RUP were reviewed. The cytologic slides were examined for the presence or absence of the 28 cytologic features. The cytologic criteria showing statistical significance in LGUC were increased numbers of monotonous single (non-umbrella) cells, three-dimensional cellular papillary clusters without fibrovascular cores, irregular bordered clusters, atypical single cells, irregular nuclear overlap, cytoplasmic homogeneity, increased N/C ratio, pleomorphism, nuclear border irregularity, nuclear eccentricity, elongated nuclei, and hyperchromasia (p ˂ 0.05), and the cytologic criteria showing statistical significance in RUP were inflammatory background, mixture of small and large urothelial cells, loose monolayer aggregates, and vacuolated cytoplasm (p ˂ 0.05). When these variables were subjected to a stepwise logistic regression analysis, four features were selected to distinguish LGUC from RUP: increased numbers of monotonous single (non-umbrella) cells, increased nuclear cytoplasmic ratio, hyperchromasia, and presence of small and large urothelial cells (p = 0.0001). By this logistic model of the 32 cases with proven LGUC, the stepwise logistic regression analysis correctly predicted 31 (96.9%) patients with this diagnosis, and of the 29 patients with RUP, the logistic model correctly predicted 26 (89.7%) patients as having this disease. There are several cytologic features to separate LGUC from RUP. Stepwise logistic regression analysis is a valuable tool for determining the most useful cytologic criteria to distinguish these entities. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  13. Verrucoid Variant of Invasive Squamous Cell Carcinoma in Oral Submucous Fibrosis: A Clinicopathological Challenge.

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    Ramani, Priya; Krithika, C; Ananthalakshmi, R; Singaram, Mamta; Jagdish, Praveena; Janardhanan, Sunitha; Jeevakarunyam, Sathiyajeeva

    2016-11-04

    Verrucous carcinoma (VC) is an exophytic, low-grade, well-differentiated variant of squamous cell carcinoma. It is described as a lesion appearing in the sixth or seventh decade of life that has minimal aggressive potential and, in long-standing cases, has been shown to transform into squamous cell carcinoma. Oral submucous fibrosis (OSMF) is a potentially malignant disorder, and about one-third of the affected population develop oral squamous cell carcinoma. The histopathological diagnosis of verrucous carcinoma is challenging, and the interpretation of early squamous cell carcinoma requires immense experience. Here we present a rare case of a 24-year-old male with OSMF transforming to verrucous carcinoma with invasive squamous cell carcinoma. Even though the case had a straightforward clinical diagnosis, the serial sectioning done for pathological diagnosis disclosed the squamous cell carcinoma.

  14. Invasive ductal carcinoma vs. invasive lobular carcinoma; mammographic findings

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    Lee, Eun Chun; Do, Young Soo; Oh, Hoon Il; Han, Yoon Hee; Kim, Ki Soo; Chin, Soo Yil [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1996-01-01

    The purpose of this study is to evaluate mammographic findings of invasive ductal carcinoma (IDC) and invasive lobular carcinoma(ILC) and to find differential points between the two. 239 patients, who underwent mammography prior to surgery and were proved to have IDC(patients) or ILC(15 patients) pathologically, were analized retrospectively. On mammogram, presence of mass and microcalcification were analized. When there was a mass on mammogram, lesion opacity was classified into high, equal, or low opacity and border of the mass was classified into spiculated, poorly marginated, and well-marginated. When there was no definite mass, mammographic findings were classifie into asymmetric opacity and no mass. Masses were observed in 168 patients(75%) of IDC and 12 patients(80%) of ILC. Border of the masses were spiculated(n=50, 22.3%), poorly marginated(n=112, 50%), or well-marginated(n=6, 2.7%) in patients with IDC. Spiculated and poorly marginated borders were observed in 8 patients(53.3%) and 4 patients(26.7%) respectively, in patients with ILC. Microcalcifications were seen in 88 patients(17.3%) of IDC and patients(33.3%) of ILC. Although equal or low opacities were observed more frequently in ILC and microcalcifications were noted more frequently in IDC, it was difficult to differentiate the two diseases based on mammographic findings.

  15. Invasive ductal carcinoma vs. invasive lobular carcinoma; mammographic findings

    International Nuclear Information System (INIS)

    Lee, Eun Chun; Do, Young Soo; Oh, Hoon Il; Han, Yoon Hee; Kim, Ki Soo; Chin, Soo Yil

    1996-01-01

    The purpose of this study is to evaluate mammographic findings of invasive ductal carcinoma (IDC) and invasive lobular carcinoma(ILC) and to find differential points between the two. 239 patients, who underwent mammography prior to surgery and were proved to have IDC(patients) or ILC(15 patients) pathologically, were analized retrospectively. On mammogram, presence of mass and microcalcification were analized. When there was a mass on mammogram, lesion opacity was classified into high, equal, or low opacity and border of the mass was classified into spiculated, poorly marginated, and well-marginated. When there was no definite mass, mammographic findings were classifie into asymmetric opacity and no mass. Masses were observed in 168 patients(75%) of IDC and 12 patients(80%) of ILC. Border of the masses were spiculated(n=50, 22.3%), poorly marginated(n=112, 50%), or well-marginated(n=6, 2.7%) in patients with IDC. Spiculated and poorly marginated borders were observed in 8 patients(53.3%) and 4 patients(26.7%) respectively, in patients with ILC. Microcalcifications were seen in 88 patients(17.3%) of IDC and patients(33.3%) of ILC. Although equal or low opacities were observed more frequently in ILC and microcalcifications were noted more frequently in IDC, it was difficult to differentiate the two diseases based on mammographic findings

  16. Office-Based Transurethral Devascularisation of Low Grade Non-Invasive Urothelial Cancer Using Diode Laser. A Feasibility Study

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    Hermann, Gregers G.; Mogensen, Karin; Lindvold, Lars René

    2015-01-01

    ‐based setting, without the need for sedation and pain control and where the patient can leave immediately after treatment. An in vitro model was developed to examine the dose/response relationship between laser power, treatment time, and distance between laser fibre and target, using a 980 nm diode laser....... The width of tissue destruction was 2–3 mm independent of laser illumination time. The in vivo laser treatments devascularised the tumour, which was later shed from the mucosa and passed out with the urine in the days following treatment. Pain score was 0 on a visual log scale (0–10). The tumour had...... completely disappeared two weeks after treatment. This diode laser technique may provide almost pain‐free office‐based treatment of low grade urothelial cancer using flexible cystoscopes in conscious patients. A prospective randomised study will be scheduled to compare the technique with standard TUR...

  17. Comparison of Utility of Histogram Apparent Diffusion Coefficient and R2* for Differentiation of Low-Grade From High-Grade Clear Cell Renal Cell Carcinoma.

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    Zhang, Yu-Dong; Wu, Chen-Jiang; Wang, Qing; Zhang, Jing; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin

    2015-08-01

    The purpose of this study was to compare histogram analysis of apparent diffusion coefficient (ADC) and R2* for differentiating low-grade from high-grade clear cell renal cell carcinoma (RCC). Forty-six patients with pathologically confirmed clear cell RCC underwent preoperative BOLD and DWI MRI of the kidneys. ADCs based on the entire tumor volume were calculated with b value combinations of 0 and 800 s/mm(2). ROI-based R2* was calculated with eight TE combinations of 6.7-22.8 milliseconds. Histogram analysis of tumor ADCs and R2* values was performed to obtain mean; median; width; and fifth, 10th, 90th, and 95th percentiles and histogram inhomogeneity, kurtosis, and skewness for all lesions. Thirty-three low-grade and 13 high-grade clear cell RCCs were found at pathologic examination. The TNM classification and tumor volume of clear cell RCC significantly correlated with histogram ADC and R2* (ρ = -0.317 to 0.506; p histogram ADC and R2* indexes, 10th percentile ADC had the highest accuracy (91.3%) in discriminating low- from high-grade clear cell RCC. R2* in discriminating hemorrhage was achieved with a threshold of 68.95 Hz. At this threshold, high-grade clear cell RCC had a significantly higher prevalence of intratumor hemorrhage (high-grade, 76.9%; low-grade, 45.4%; p Histogram analysis of ADC and R2* allows differentiation of low- from high-grade clear cell RCC with high accuracy.

  18. Synchronous lobular carcinoma in situ and invasive lobular cancer: marker or precursor for invasive lobular carcinoma.

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    Wallace, A S; Xiang, D; Hockman, L; Arya, M; Jeffress, J; Wang, Z; Dale, P S

    2014-10-01

    Lobular carcinoma in situ (LCIS) is a known risk factor for invasive breast carcinoma, but there is increasing data indicating a possible precursor relationship. This study investigates the incidence of lobular carcinoma in situ that occurs with invasive lobular carcinoma (ILC). Women diagnosed with ILC or LCIS from 2000 to 2010 were retrospectively identified and reviewed after institutional review board approval. This group was divided into two cohorts: ILC alone, and LCIS and ILC (ILC/LCIS). Patient demographics, disease characteristics, and treatment modalities were captured. p invasive ductal carcinoma at ∼40%. The association of pre-invasive and invasive lobular lesions should be further studied in a large scale prospective study to assess for a precursor relationship. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Spontaneous slip reduction of low-grade isthmic spondylolisthesis following circumferential release via bilateral minimally invasive transforaminal lumbar interbody fusion: technical note and short-term outcome.

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    Pan, Jie; Li, Lijun; Qian, Lie; Zhou, Wei; Tan, Jun; Zou, Le; Yang, Mingjie

    2011-02-15

    STUDY DESIGN.: Retrospective clinical data analysis. OBJECTIVE.: To investigate and verify our philosophy of spontaneous slip reduction following circumferential release via bilateral minimally invasive transforaminal lumbar interbody fusion (Mini-TLIF) for treatment of low-grade symptomatic isthmic spondylolisthesis. SUMMARY OF BACKGROUND DATA.: Symptomatic isthmic spondylolisthesis usually requires surgical intervention, and the most currently controversial focus is on method and degree of reduction; and Mini-TLIF is an attractive surgical procedure for isthmic spondylolisthesis. METHODS.: Between February 2004 and June 2008, 21 patients with low-grade isthmic spondylolisthesis underwent Mini-TLIF in our institute. Total resection of the scar around the pars interarticularis liberated the nerve roots, achieving posterior release as well. The disc was thoroughly resected, and the disc space was gradually distracted and thoroughly released with sequential disc shavers until rupture of anulus conjunct with anterior longitudinal ligament, accomplishing anterior release, so as to insert Cages. Because of circumferential release, the slipped vertebrae would tend to obtain spontaneous reduction, and with pedicle screw fixation, additional reduction would be achieved without any application of posterior translation force. Radiographs, Visual Analogue Scale, and Oswestry Disability Index were documented. All the cases were followed up for 10 to 26 months. RESULTS.: Slip percentage was reduced from 24.2% ± 6.9% to 10.5% ± 4.0%, and foraminal area percentage increased from 89.1% ± 3.0% to 93.6% ± 2.1%. Visual Analogue Scale and Oswestry Disability Index decreased from 7.8 ± 1.5 to 2.1 ± 1.1 and from 53.3 ± 16.2 to 17.0 ± 7.8, respectively. No neurologic complications were encountered. There were no signs of instrumentation failure. The fusion rate approached 100%. CONCLUSION.: Slip reduction is based on circumferential release. The procedure can be well performed

  20. Invasive cervical carcinoma (Stages IB-IIB)

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    Sironi, S.; Zanello, A.; Rodighiero, M.G.; Vanzulli, A.; Del Maschio, A.; Taccagni, G.L.; Belloni, C.

    1991-01-01

    In the patients with invasive cervical carcinoma, the accurate assessment of parametrial invasion greatly affects the therapeutic choice between surgery and radiation therapy. As a matter of fact, surgery is usually performed only in the patients with carcinoma confined to the cervix, whereas those with parametrial involvement, or more advanced stages, are treated with radiation therapy. This prospective study was aimed at investigating the comparative adequecy of CT and MR imaging in assessing parametrial status in the patients with invasive cervical cancer. Twenty-one consecutive patients, with histologic diagnosis of cervical carcinoma, were investigated. All of them were clinically considered as having invasive cervical cancer (FIGO stage IB-IIB) and subsequently underwent surgery. In all cases, detailed histology of the parametrium was obtained. Pathological data were compared with CT and MR findings in all cases. As for assessing parametrial involvement by cancer, CT had 62% accuracy, 63% sensitivity, and 60% specificity, versus MR imaging 81% accuracy, 69% sensitivity, and 80% specificify. Therefore, MR imaging appears to be superior to CT in assessing the parametrial status of patients with invasive cervical carcinoma; the method yields valuable information for treatment planning

  1. Sonomammographic characteristics of invasive lobular carcinoma

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    El-Damshety O

    2012-07-01

    Full Text Available Osama R Kombar,1,3 Dalia M Fahmy,1 Mary V Brown,3 Omar Farouk,2 Osama El-Damshety21Diagnostic Radiology Department, 2Surgical Oncology Department, Oncology Center, Mansoura University, Mansoura, Egypt; 3Diagnostic Radiology Department, Al-Amiri Hospital, Safat, KuwaitObjective: The objective of our study was to identify characteristic features of invasive lobular carcinoma on mammography and ultrasound examinationsMaterials and methods: This is a retrospective multicenter study of women with biopsy-proven invasive lobular carcinoma. All patients had undergone diagnostic sonomammography. The imaging findings were identified by experienced breast imagers. Final surgical pathology results were used as the reference standard.Results: Thirty-two women ranging in age from 42 to 63 years old (mean age, 53 years, All had biopsy-proven invasive lobular carcinomas. Common features on mammogram included dense mass followed by architectural distortion; three cases showed breast asymmetry and one case was reported as normal. On ultrasound, common features included solid mass with spiculated margins, posterior shadowing, and perpendicular to the skin.Conclusion: Although no specific features could be linked to invasive lobular carcinoma, care should be directed to subtle signs such as architectural distortion and breast asymmetry in order not to miss any lesions. The combination of mammographic and sonographic helps to decrease the relatively high false negative diagnosis of this type of breast cancer.Keywords: mammography, ultrasound, cancer, breast

  2. Histological outcomes in conventional cervical cytology for invasive carcinoma: not always cancer.

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    Peixoto Pereira, Flávia Regina; Soares, Leila Cristina; de Oliveira, Marco Aurélio Pinho

    2017-11-01

    The value of cytology for the detection of invasive cancer remains unknown. We performed a retrospective cohort study with 884 patients diagnosed of premalignant lesions and invasive carcinoma in cytology. 382 (43.2%) of them had cytological results of high-grade squamous intraepithelial lesions (HSIL), 244 (27.6%) showed low-grade squamous intraepithelial lesions (LSIL), 120 (13.6%) patients had atypical squamous cells of undetermined significance (ASC-US), 67 (7.6%) patients with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 38 (4.3%) had invasive carcinoma and 33 (3.7%) patients presented with atypical glandular cells (ACG). From 38 patients with cytological results of invasive carcinoma, 24 had confirmatory histological results (63.2%). The other 14 had 4 benign lesions and 10 HSIL. The predictive positive value (PPV) was 63.2%. Cytology results of carcinoma do not confer a definitive diagnosis of invasive lesion, but it is strongly an indication of, at least, a precancerous lesion.

  3. Unusual Metastatic Patterns of Invasive Lobular Carcinoma of the Breast

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    Sobinsky, Justin D.; Willson, Thomas D.; Podbielski, Francis J.; Connolly, Mark M.

    2013-01-01

    Invasive lobular carcinoma of the breast has similar patterns of metastatic disease when compared to invasive ductal carcinoma; however, lobular carcinoma metastasizes to unusual sites more frequently. We present a 65-year-old female with a history of invasive lobular breast carcinoma (T3N3M0) treated with modified radical mastectomy and aromatase-inhibitor therapy who underwent a surveillance PET scan, which showed possible sigmoid cancer. Colonoscopy with biopsy revealed a 3?cm sigmoid aden...

  4. Human papillomavirus (HPV) type distribution in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Venezuelan women.

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    Correnti, Maria; Medina, Francisco; Cavazza, María Eugenia; Rennola, Antonieta; Avila, Maira; Fernándes, Andreína

    2011-06-01

    Cervical cancer is an important cause of mortality among women in developing countries, especially in the Latin America and Caribbean (LAC) region. Infection with high-risk (HR) human papillomavirus (HPV) has been identified as the primary cause of cervical cancer. The aim of this study was to determine the frequency of HR-HPV genotypes in low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical carcinoma (CC) among Venezuelan women. Subjects with histopathological diagnosis of LSIL, HSIL, and CC (LSIL=200; HSIL=100; CC=150) were enrolled in the study after obtaining informed consent. Biopsy samples of these subjects were analyzed to determine the lesion type. HPV detection and typing was done using polymerase chain reaction (PCR) and reverse hybridization. HPV type specific prevalence was determined in subjects with single and multiple infections. HPV DNA was detected in 68%, 95%, and 98.7% of LSIL, HSIL, and CC cases, respectively. HR-HPV and low-risk oncogenic HPV (LR-HPV) was observed in 66.9%/11.8% of LSIL cases, 87.3%/3.2% of HSIL cases, and 91.2%/0.7% of CC cases. HPV types -16/-18 (65%) were the most common high-risk HPV types observed, followed by types -52, -33, -45, and -31. Cervical cancer burden in Venezuelan women is substantial. HPV types -16/-18 were the most common types prevalent among Venezuelan women followed by types -52, -33, -45, and -31 (prevalence, ~90.1%). The results of this study provide baseline information on the HPV type distribution, which may facilitate the development of a cervical cancer prevention and control program in Venezuela. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Sonomammographic characteristics of invasive lobular carcinoma

    OpenAIRE

    Fahmy, Dalia Monir; Kombar,; Farouk,Omar; El-damshety,; Brown,

    2012-01-01

    Osama R Kombar,1,3 Dalia M Fahmy,1 Mary V Brown,3 Omar Farouk,2 Osama El-Damshety21Diagnostic Radiology Department, 2Surgical Oncology Department, Oncology Center, Mansoura University, Mansoura, Egypt; 3Diagnostic Radiology Department, Al-Amiri Hospital, Safat, KuwaitObjective: The objective of our study was to identify characteristic features of invasive lobular carcinoma on mammography and ultrasound examinationsMaterials and methods: This is a retrospective multicenter study of women with ...

  6. Gastric Metastasis of Triple Negative Invasive Lobular Carcinoma.

    Science.gov (United States)

    Geredeli, Caglayan; Dogru, Osman; Omeroglu, Ethem; Yilmaz, Farise; Cicekci, Faruk

    2015-05-05

    Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis of an invasive lobular carcinoma. In this report, we present a case of gastric metastasis from triple-negative invasive lobular breast cancer. It is important to make an accurate diagnosis by distinguishing gastric metastasis from breast cancer in order to select the best initial treatment for systemic diseases of breast cancer. Considering our case, healthcare professionals should take into account that cases with invasive lobular breast cancer may experience unusual metastases.

  7. Gastric metastasis of triple negative invasive lobular carcinoma

    OpenAIRE

    Caglayan Geredeli; Osman Dogru; Ethem Omeroglu; Farise Yilmaz; Faruk Cicekci

    2015-01-01

    Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis o...

  8. CT differentiation of invasive thymoma and thymic carcinoma

    International Nuclear Information System (INIS)

    Lee, Eun Jung; Jung, Gyoo Sik; Kim, Seong Min; Huh, Jin Do; Joh, Young Duk; Shin, Mi Jung; Kim, Jung Sik; Suh, Soo Jhi

    1998-01-01

    In order to determine the differential points between them, we analyzed the CT findings of invasive thymoma and thymic carcinoma. We retrospectively reviewed the CT scans of 14 patients with invasive thymoma and 15 with thymic carcinoma, confirmed by surgery(n=3D19) or percutaneous needle aspiration(n=3D10) between 1988 and 1996. CT findings were evaluated in each group for intrathoracic spread(posterior, direct posterior, and anterolateral), obliteration of the fat plane between the mass and vascular structures, vessel encasement, invasion of adjacent mediastinal structures, pleural implants, mediastinal nodes and distant metastasis. Direct posterior spread was more common in thymic carcinoma than invasive thymoma;it was seen in one case (7%) of invasive thymoma and 12(80%) of thymic carcinoma(p=3D0.00). Posterior spread was seen in six cases (43%) of in vasive thymoma and nine (60%) of thymic carcinoma. Anterolateral spread was seen only in two cases (13%) of thymic carcinoma. Obliteration of the fat plane was seen in nine cases (64%) of invasive thymoma and 14 (93%) of thymic carcinoma, while vessel encasement was seen in two cases (14%) of invasive thymoma and 13(87%) of thymic carcinoma(p=3D0.00). Invasion of adjacent structures was seen in two cases (14%) of invasive thymoma and eight (53%) of thymic carcinoma. Pleural implants were more common in invasive thymoma than thymic carcinoma, being seen in six cases (43%) of the former and one (7%) of the latter(p=3D0.04). Mediastinal lymphadenopathy was seen in three cases (21%) of invasive thymoma and ten (67%) of thymic carcinoma. Distant metastases were observed only in six cases (40%) of thymic carcinoma(p=3D0.02). Although differentiation between invasive thymoma and thymic carcinoma is difficult on the basis of CT findings, there are certain differential points. Thymic carcinomas showed a higher rate of direct posterior intrathoracic spread, vessel encasement, mediastinal nodes and distant metastases than

  9. Primary invasive squamous carcinoma of the vagina

    International Nuclear Information System (INIS)

    Pride, G.L.; Schultz, A.E.; Chuprevich, T.W.; Buchler, D.A.

    1979-01-01

    Forty-three cases of primary vaginal squamous cell cancer were treated at the University of Wisconsin Hospital between 1956 and 1971. These cases comprised of 1.2% of patients admitted to the University Hospital with female genital tract cancer. Evidence is presented to support a modification of the currently accepted FIGO staging system for vaginal carcinoma (Stage II disease). Radiation therapy using both external beam and brachyradium equivalents or interstitial implantation of suitable isotopes was an effective method for the treatment of patients having early and locally advanced invasive vaginal cancer. The 5-year absolute survival rate for the entire series was 37.2%. Absolute survival rate by modified FIGO clinical staging was 66% for Stages I and IIA, 31% for Stage IIB, 25% for Stage III, and 0% for Stage IV

  10. Expression of Lipid Metabolism-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma.

    Science.gov (United States)

    Cha, Yoon Jin; Kim, Hye Min; Koo, Ja Seung

    2017-01-23

    We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast. A total of 584 breast cancers (108 ILC and 476 IDC) were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL), perilipin A, fatty acid binding protein (FABP)4, carnitine palmitoyltransferase (CPT)-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN). HSL, perilipin A, and FABP4 expression (all p invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC ( p cancers, HSL and FABP4 were more highly expressed in ILC ( p < 0.001). Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity ( p = 0.004) and acyl-CoA oxidase 1 positivity ( p = 0.032) and of shorter overall survival with acyl-CoA oxidase 1 positivity ( p = 0.027). In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression.

  11. Expression of Lipid Metabolism-Related Proteins Differs between Invasive Lobular Carcinoma and Invasive Ductal Carcinoma

    Directory of Open Access Journals (Sweden)

    Yoon Jin Cha

    2017-01-01

    Full Text Available We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC and invasive ductal carcinoma (IDC of the breast. A total of 584 breast cancers (108 ILC and 476 IDC were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL, perilipin A, fatty acid binding protein (FABP4, carnitine palmitoyltransferase (CPT-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN. HSL, perilipin A, and FABP4 expression (all p < 0.001 differed significantly: HSL and FABP4 were more frequently present in ILC, whereas perilipin A was more frequently detected in IDC. Among all invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC (p < 0.001 and perilipin A in luminal A-type IDC (p = 0.007. Among luminal B-type cancers, HSL and FABP4 were more highly expressed in ILC (p < 0.001. Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity (p = 0.004 and acyl-CoA oxidase 1 positivity (p = 0.032 and of shorter overall survival with acyl-CoA oxidase 1 positivity (p = 0.027. In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression.

  12. Invasive ductal carcinoma with lobular features: a comparison study to invasive ductal and invasive lobular carcinomas of the breast.

    Science.gov (United States)

    Arps, David P; Healy, Patrick; Zhao, Lili; Kleer, Celina G; Pang, Judy C

    2013-04-01

    Invasive ductal carcinoma with lobular features (IDC-L) is not recognized as a distinct subtype of breast cancer, and its clinicopathologic features and outcomes are unknown. In this retrospective study, we focused on characterization of clinicopathologic features and outcomes of IDC-L and compared them to invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). 183 cases of IDC-L from 1996 to 2011 were compared with 1,499 cases of IDC and 375 cases of ILC. Available slides of IDC-L (n = 150) were reviewed to quantify the lobular component (≤ 20, 21-50, 51-80, >80 %), defined as small cells individually dispersed, arranged in linear cords, or in loose aggregates without the formation of tubules or cohesive nests. E-cadherin immunostain was performed to confirm ductal origin. Compared to IDC, IDC-L was more likely to have lower histologic grade (p lobular component in IDC-L had no impact on the size, nodal status, stage, or outcome. Our data suggest that although IDC-L may be a variant of IDC, with >90 % of cases being E-cadherin positive, the clinical and biological characteristics are more similar to that of ILC.

  13. Minimally Invasive Follicular Thyroid Carcinoma in Pediatric Age

    International Nuclear Information System (INIS)

    Romero, Alfredo; Diaz, Julio; Messa Oscar; Chinchilla, Sandra; Gomez, Constanza; Restrepo, Ligia

    2009-01-01

    Thyroid carcinomas are rare during childhood and adolescence. They have increased recently probably due to a higher frequency radiation over the head, neck and mediastinum. The papillary carcinoma is the most common and true follicular carcinoma is far less common. Follicular thyroid carcinoma is associated with endemic goiter, genetic disorders, and increased TSH levels. Its morphological characteristics are peculiar and have been recently redefined, thus helping the diagnosis. A minimally invasive follicular thyroid carcinoma in 13 years old girl is described, presenting a hypocaptant thyroid nodule in the left lobe lower pole. The fine needle aspiration biopsy revealed a follicular cell lesion suspicious of malignancy. Thyroid lobectomy was performed reporting minimally invasive follicular carcinoma.

  14. Invasive lobular carcinoma with extracellular mucin as a distinct variant of lobular carcinoma: a case report

    OpenAIRE

    Haltas, Hacer; Bayrak, Reyhan; Yenidunya, Sibel; Kosehan, Dilek; Sen, Meral; Akin, Kayihan

    2012-01-01

    Abstract The differences between invasive lobular and ductal carcinomas affect the diagnostic and therapeutic management for patients with breast cancer. In most cases, this can be accomplished because of distinct histomorphologic features. However, occasionally, this task may become quite difficult, in particular when dealing with the variants of infiltrating lobular carcinoma. Lobular carcinoma has been considered a variant of mucin-secreting carcinoma with only intracytoplasmic mucin. The ...

  15. Pathologic Pattern of Invasive Bladder Carcinoma: Impact of ...

    African Journals Online (AJOL)

    Objective: To describe the pathologic pattern of invasive bladder carcinoma in cystectomy specimens in relation to bilharziasis. Patients and Methods: Between April 2002 and October 2006, 148 consecutive patients with invasive bladder cancer were subjected to radical cystectomy and orthotopic sigmoid bladder ...

  16. Reproducibility of measurement of myometrial invasion in endometrial carcinoma

    NARCIS (Netherlands)

    Putten, L.J.M. van der; Vijver, K. van der; Bartosch, C.; Davidson, B.; Gatius, S.; Matias-Guiu, X.; McCluggage, W.G.; Toledo, G.; Wurff, A.A. van der; Pijnenborg, J.M.A.; Massuger, L.F.A.G.; Bulten, J.

    2017-01-01

    Myometrial invasion (MI) as a percentage (%MI), categorized into <50 or >/=50 %, is an important predictor of prognosis in endometrial carcinoma. Recent studies suggest that tumor-free distance (TFD) to serosa and the absolute depth of invasion (DOI) might be stronger predictors of prognosis.

  17. Risk factors for the development of invasive cancer in unresected ductal carcinoma in situ.

    Science.gov (United States)

    Maxwell, Anthony J; Clements, Karen; Hilton, Bridget; Dodwell, David J; Evans, Andrew; Kearins, Olive; Pinder, Sarah E; Thomas, Jeremy; Wallis, Matthew G; Thompson, Alastair M

    2018-04-01

    The natural history of ductal carcinoma in situ (DCIS) remains uncertain. The risk factors for the development of invasive cancer in unresected DCIS are unclear. Women diagnosed with DCIS on needle biopsy after 1997 who did not undergo surgical resection for ≥1 year after diagnosis were identified by breast centres and the cancer registry and outcomes were reviewed. Eighty-nine women with DCIS diagnosed 1998-2010 were identified. The median age at diagnosis was 75 (range 44-94) years with median follow-up (diagnosis to death, invasive disease or last review) of 59 (12-180) months. Twenty-nine women (33%) developed invasive breast cancer after a median interval of 45 (12-144) months. 14/29 (48%) with high grade, 10/31 (32%) with intermediate grade and 3/17 (18%) with low grade DCIS developed invasive cancer after median intervals of 38, 60 and 51 months. The cumulative incidence of invasion was significantly higher in high grade DCIS than other grades (p = .0016, log-rank test). Invasion was more frequent in lesions with calcification as the predominant feature (23/50 v. 5/25; p = .042) and in younger women (p = .0002). Endocrine therapy was associated with a lower rate of invasive breast cancer (p = .048). High cytonuclear grade, mammographic microcalcification, young age and lack of endocrine therapy were risk factors for DCIS progression to invasive cancer. Surgical excision of high grade DCIS remains the treatment of choice. Given the uncertain long-term natural history of non-high grade DCIS, the option of active surveillance of women with this condition should be offered within a clinical trial. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  18. 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.

  19. Invasive ductal carcinoma within fibroadenoma: a case report

    Science.gov (United States)

    2009-01-01

    Introduction Fibroadenoma is the most common benign tumor of the female breast with the highest incidence before age 30. Fibroadenoma may be associated with fibrocystic changes, proliferative epithelial changes, and extremely rarely, with non-invasive and invasive cancer. Case presentation We present a rare case of a 39 years old female with invasive ductal carcinoma arising within fibroadenoma. Conclusion There is a low percentage of fibroadenomas harboring carcinoma; however, all breast lumps should be seriously managed; extirpation and histological examination is recommended. PMID:19946485

  20. Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma.

    Science.gov (United States)

    Adachi, Yayoi; Ishiguro, Junko; Kotani, Haruru; Hisada, Tomoka; Ichikawa, Mari; Gondo, Naomi; Yoshimura, Akiyo; Kondo, Naoto; Hattori, Masaya; Sawaki, Masataka; Fujita, Takashi; Kikumori, Toyone; Yatabe, Yasushi; Kodera, Yasuhiro; Iwata, Hiroji

    2016-03-25

    The pathological and clinical features of invasive lobular carcinoma (ILC) differ from those of invasive ductal carcinoma (IDC). Several studies have indicated that patients with ILC have a better prognosis than those with ductal carcinoma. However, no previous study has considered the molecular subtypes and histological subtypes of ILC. We compared prognosis between IDC and classical, luminal type ILC and developed prognostic factors for early breast cancer patients with classical luminal ILC. Four thousand one hundred ten breast cancer patients were treated at the Aichi Cancer Center Hospital from 2003 to 2012. We identified 1,661 cases with luminal IDC and 105 cases with luminal classical ILC. We examined baseline characteristics, clinical outcomes, and prognostic factors of luminal ILC. The prognosis of luminal ILC was significantly worse than that of luminal IDC. The rates of 5-year disease free survival (DFS) were 91.9% and 88.4% for patients with luminal IDC and luminal ILC, respectively (P = 0.008). The rates of 5-year overall survival (OS) were 97.6% and 93.1% for patients with luminal IDC and luminal ILC respectively (P = 0.030). Although we analyzed prognosis according to stratification by tumor size, luminal ILC tended to have worse DFS than luminal IDC in the large tumor group. In addition, although our analysis was performed according to matching lymph node status, luminal ILC had a significantly worse DFS and OS than luminal IDC in node-positive patients. Survival curves showed that the prognosis for ILC became worse than IDC over time. Multivariate analysis showed that ILC was an important factor related to higher risk of recurrence of luminal type breast cancer, even when tumor size, lymph node status and histological grade were considered. Luminal ILC had worse outcomes than luminal IDC. Consequently, different treatment approaches should be used for luminal ILC than for luminal IDC.

  1. Feasibility of the Less Is More Approach in Treating Low-Risk Ductal Carcinoma In Situ Diagnosed on Core Needle Biopsy: Ten-Year Review of Ductal Carcinoma In Situ Upgraded to Invasion at Surgery.

    Science.gov (United States)

    Podoll, Mirna B; Reisenbichler, Emily S; Roland, Lania; Bruner, Andrew; Mizuguchi, Sarah; Sanders, Mary Ann G

    2018-03-27

    - Ductal carcinoma in situ (DCIS) represents 20% of screen-detected breast cancers. The likelihood that certain types of DCIS are slow growing and may never progress to invasion suggests that our current standards of treating DCIS could result in overtreatment. The LORIS (LOw RISk DCIS) and LORD (LOw Risk DCIS) trials address these concerns by randomizing patients with low-risk DCIS to either active surveillance or conventional treatment. - To determine the upgrade rate of DCIS diagnosed on core needle biopsy to invasive carcinoma at surgery and to evaluate the safety of managing low-risk DCIS with surveillance alone, by characterizing the pathologic and clinical features of upgraded cases and applying criteria of the LORD and LORIS trials to these cases. - A 10-year retrospective analysis of DCIS on core needle biopsy with subsequent surgery. - We identified 1271 cases of DCIS on core needle biopsy: 200 (16%) low grade, 649 (51%) intermediate grade, and 422 (33%) high grade. Of the 1271 cases, we found an 8% upgrade rate to invasive carcinoma (n = 105). Nineteen of the 105 upgraded cases (18%) had positive lymph nodes. Low-grade DCIS was least likely to upgrade to invasion, comprising 10% (10 of 105) of upgraded cases. Three of the 105 upgraded cases (3%) met criteria for the LORD trial, and all were low-grade DCIS on core needle biopsy with favorable biology on follow-up. - There is a clear risk of upgrade to invasion on follow-up excision; however, applying strict criteria of the LORD trial effectively decreases the likelihood of a missed invasive component or missed aggressive pathologic features.

  2. Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma

    International Nuclear Information System (INIS)

    Adachi, Yayoi; Ishiguro, Junko; Kotani, Haruru; Hisada, Tomoka; Ichikawa, Mari; Gondo, Naomi; Yoshimura, Akiyo; Kondo, Naoto; Hattori, Masaya; Sawaki, Masataka; Fujita, Takashi; Kikumori, Toyone; Yatabe, Yasushi; Kodera, Yasuhiro; Iwata, Hiroji

    2016-01-01

    The pathological and clinical features of invasive lobular carcinoma (ILC) differ from those of invasive ductal carcinoma (IDC). Several studies have indicated that patients with ILC have a better prognosis than those with ductal carcinoma. However, no previous study has considered the molecular subtypes and histological subtypes of ILC. We compared prognosis between IDC and classical, luminal type ILC and developed prognostic factors for early breast cancer patients with classical luminal ILC. Four thousand one hundred ten breast cancer patients were treated at the Aichi Cancer Center Hospital from 2003 to 2012. We identified 1,661 cases with luminal IDC and 105 cases with luminal classical ILC. We examined baseline characteristics, clinical outcomes, and prognostic factors of luminal ILC. The prognosis of luminal ILC was significantly worse than that of luminal IDC. The rates of 5-year disease free survival (DFS) were 91.9 % and 88.4 % for patients with luminal IDC and luminal ILC, respectively (P = 0.008). The rates of 5-year overall survival (OS) were 97.6 % and 93.1 % for patients with luminal IDC and luminal ILC respectively (P = 0.030). Although we analyzed prognosis according to stratification by tumor size, luminal ILC tended to have worse DFS than luminal IDC in the large tumor group. In addition, although our analysis was performed according to matching lymph node status, luminal ILC had a significantly worse DFS and OS than luminal IDC in node-positive patients. Survival curves showed that the prognosis for ILC became worse than IDC over time. Multivariate analysis showed that ILC was an important factor related to higher risk of recurrence of luminal type breast cancer, even when tumor size, lymph node status and histological grade were considered. Luminal ILC had worse outcomes than luminal IDC. Consequently, different treatment approaches should be used for luminal ILC than for luminal IDC. The online version of this article (doi:10.1186/s12885

  3. Invasive lobular carcinoma with extracellular mucin as a distinct variant of lobular carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Haltas Hacer

    2012-08-01

    Full Text Available Abstract The differences between invasive lobular and ductal carcinomas affect the diagnostic and therapeutic management for patients with breast cancer. In most cases, this can be accomplished because of distinct histomorphologic features. However, occasionally, this task may become quite difficult, in particular when dealing with the variants of infiltrating lobular carcinoma. Lobular carcinoma has been considered a variant of mucin-secreting carcinoma with only intracytoplasmic mucin. The presence of extracellular mucin is a feature of ductal carcinoma. Herein is presented a case of lobular carcinoma with extracellular and intracellular mucin in a 43-year-old female patient, and confirmed by immunohistochemistry. Up to the present, infiltrating lobular carcinoma displaying extracellular mucin has not been described in the literature except two case. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1839906067716744

  4. Re-excision rates of invasive ductal carcinoma with lobular features compared with invasive ductal carcinomas and invasive lobular carcinomas of the breast.

    Science.gov (United States)

    Arps, David P; Jorns, Julie M; Zhao, Lili; Bensenhaver, Jessica; Kleer, Celina G; Pang, Judy C

    2014-12-01

    Invasive ductal carcinoma (IDC) with lobular features (IDC-L) is not recognized as a subtype of breast cancer. We previously showed that IDC-L may be a variant of IDC with clinicopathological characteristics more similar to invasive lobular carcinoma (ILC). We sought to determine the re-excision rates of IDC-L compared with ILC and IDC, and the feasibility of diagnosing IDC-L on core biopsies. Surgical procedure, multiple tumor foci, tumor size, and residual invasive carcinoma on re-excision were recorded for IDC-L (n = 178), IDC (n = 636), and ILC (n = 251). Re-excision rates were calculated by excluding mastectomy as first procedure cases and including only re-excisions for invasive carcinoma. Slides of correlating core biopsies for IDC-L cases initially diagnosed as IDC were re-reviewed. For T2 tumors (2.1-5.0 cm), re-excision rates for IDC-L (76 %) and ILC (88 %) were higher than that for IDC (42 %) (p = 0.003). Multiple tumor foci were more common in IDC-L (31 %) and ILC (26 %) than IDC (7 %) (p < 0.0001), which was a significant factor in higher re-excision rates when compared with a single tumor focus (p < 0.001). Ninety-two of 149 patients (62 %) with IDC-L were diagnosed on core biopsies. Of the 44 patients initially diagnosed as IDC, 30 were re-reviewed, of which 24 (80 %) were re-classified as IDC-L. Similar to ILC, re-excision rates for IDC-L are higher than IDC for larger tumors. Patients may need to be counseled about the higher likelihood of additional procedures to achieve negative margins. This underscores the importance of distinguishing IDC-L from IDC on core biopsies.

  5. High-dose-rate intracavitary brachytherapy (HDR-IC) in treatment of cervical carcinoma: 5-year results and implication of increased low-grade rectal complication on initiation of an HDR-IC fractionation scheme

    International Nuclear Information System (INIS)

    Wang Chongjong; Wan Leung, Stephen; Chen Huichun; Sun Limin; Fang Fumin; Changchien Chanchao; Huang Engyen; Wu Jiaming; Chen Chuhnchih

    1997-01-01

    Purpose: To report the treatment results and rectal/bladder complications of cervical carcinoma radically treated with high-dose-rate intracavitary brachytherapy (HDR-IC). The current policy of using three-fraction scheme was examined. Methods and Materials: Between November 1987 and August 1990, 173 patients with cervical carcinoma were treated with curative-intent radiation therapy. Whole pelvic irradiation was administered with 10-MV X ray. Dose to the central cervix was 40-44 Gy in 20-22 fractions, following by pelvic wall boost 6-14 Gy in three to seven fractions with central shielding. 60 Co sources were used for HDR-IC, and 7.2 Gy was given to Point A for three applications, 1-2 weeks apart. Duration of follow-up was 5-7.8 years. Results: Twenty-eight patients (16%) developed central-regional recurrences. Overall 5-year actuarial pelvic control rate was 83%. By stage, 5-year actuarial pelvic control rates were 94%, 87%, and 72% for Stages IB + IIA, IIB + IIIA, and IIIB + IVA, respectively. Thirty-one patients (18%) developed distant metastasis. Overall 5-year actuarial survival rate was 58%. By stage, 5-year actuarial survival rates were 79%, 59%, and 41% for Stages IB + IIA, IIB + IIIA, and IIIB + IVA, respectively. Sixty-six (38%) and 19 patients (11%) developed rectal and bladder complications, respectively. For rectal complication, the overall actuarial rate was 38% at 5 years. By grade, 5-year actuarial rectal complication rates were 24%, 15%, 4%, and 3% for Grades 1-4, respectively. Overall prevalence of rectal complications was 37% and 14% at 2 and 5 years, respectively. Prevalence of low-grade rectal complication (Grades 1 and 2) was dominant at 2 years (30%), but declined to 8% at 5 years. Prevalence of high-grade, severe rectal complication (Grades 3 and 4) remained steady at 2 and 5 years (7% and 6%, respectively). Five-year actuarial bladder complication was 9%. Five-year prevalence of bladder complication was 2%. Conclusion: Using a three

  6. Risk Factors Associated with Invasive Cervical Carcinoma among ...

    African Journals Online (AJOL)

    BACKGROUND: Cervical cancer is a more serious public health problem than other cancers in women in Sub-Saharan Africa in general and in Ethiopia in particular. Thus, this study assessed risk factors related to invasive cervical carcinomas in southwestern Ethiopia. METHODS: Unmatched case control study was ...

  7. Invasive ductal carcinoma within fibroadenoma and lung metastases

    Science.gov (United States)

    Abu-Rahmeh, Zuhair; Nseir, William; Naroditzky, Inna

    2012-01-01

    Fibroadenomas are one of the most common benign tumors of the breast. Malignant transformation from fibroadenoma to cancer is rare. We present a case of an invasive ductal carcinoma within an otherwise benign fibroadenoma with lung metastasis in a 69-year-old woman. PMID:22259257

  8. Phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma.

    Science.gov (United States)

    Nagle, R. B.; Brawer, M. K.; Kittelson, J.; Clark, V.

    1991-01-01

    Thirty-one snap-frozen human prostate specimens containing examples of benign hyperplasia, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma were analyzed using a panel of 24 antibodies and one lectin. Twenty-seven additional routinely processed radical prostatectomy specimens were studied using selected probes known to work on formalin-fixed paraffin-embedded material. Three probes, anticytokeratin KA4, anti-vimentin V9, and the lectin from Ulex europaeus (UEA-1), demonstrated phenotypic similarities between PIN and invasive carcinoma. Whereas the luminal cells of normal or hyperplastic prostatic epithelium are minimally reactive with KA4 (4%) or UEA-1 (0%) and strongly reactive with anti-vimentin (91%), both the PIN and invasive carcinoma are reactive with KA4 (89% and 93%, respectively) and UEA-1 (96% and 93%, respectively) and minimally reactive with anti-vimentin (15% and 0%, respectively). The increased KA4 staining was shown to be in part due to detection of cytokeratin 19, by using cytokeratin-19-specific antibodies, 4.62 and LP2K. The reasons for the increased expression of this cytokeratin and the decreased expression of vimentin are unclear but seem to indicate a phenotypic relationship between the PIN lesions and invasive carcinoma. Images Figure 4 Figure 1 Figure 2 Figure 3 PMID:1987760

  9. Tumor-associated macrophages: Oblivious confederates in invasive mammary carcinoma

    Directory of Open Access Journals (Sweden)

    Imtiaz Ahmed

    2017-01-01

    Full Text Available Background: The infiltrating margins of carcinomas are associated with presence of inflammatory cell infiltrate which are an integral part of the tumor microenvironment. Amongst the inflammatory cells, Tumor Associated Macrophages (TAMs play a key role in the tumorigenesis. This study elucidates the density of TAMs in invasive mammary carcinomas and attempts to establish aa association with the following pathological variables: tumor size, histological grade, nodal status, hormonal expression status and Her2Neu overexpression. Materials and Methods: 90 diagnosed archival cases of invasive mammary carcinomas at a tertiary care centre were included. Density of TAMs was assessed by using CD68 which is a pan-macrophage marker by immunohistochemistry on the archival tissue blocks. The density TAMs (CD68 positive cells was dichotomised into high (>50 CD68 positive cells/ HPF and low (<5050 CD68 positive cells/ HPF and compared with the above mentioned pathological variables using appropriate statistical tests. Results: The density of TAMs was significantly higher around the infiltrating edge of the carcinoma in comparison to the adjoining normal terminal duct lobular units. The density of TAMs was more in the infiltrating edge of the tumor than within the tumor nodule/nests. A higher TAM density showed a significant association in tumors having large tumor size, higher histological grade, nodal metastasis, absence of ER and PR expression and Her2Neu overexpression (p value <0.05. Conclusion: TAMs play an important role in tumor progression in invasive mammary carcinomas. This is as a result of the multiple roles enacted by TAMs in the various stages of tumor development starting from tumor growth, invasion, angiogenesis and metastases. Targeted therapy against TAMs has great potential in the being important components of future treatment strategies against breast carcinomas.

  10. 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.

  11. Regulation of In Situ to Invasive Breast CarcinomaTransition

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

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    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.

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

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    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

  14. Large mammary hamartoma with focal invasive ductal carcinoma

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    Pervatikar Suneet

    2009-04-01

    Full Text Available Mammary hamartomas are uncommon benign lesions rarely associated with malignancy. We report a case of a 25-year-old female patient presenting with a lump in the left breast. Fine needle aspiration cytology showed features of invasive ductal carcinoma along with normal benign glands that were mistaken for normal breast tissue. However, the mastectomy specimen revealed the malignant mass within a larger hamartomatous mass. Mammary hamartomas are benign lesions but, on exceedingly rare occasions, they may be involved by incidental, coexisting carcinoma, as illustrated in this case report.

  15. 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.

  16. Urothelial Carcinoma of the Urinary Bladder in Young Adults — Clinical Experience at Taipei Veterans General Hospital

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    Yu-Ching Wen

    2005-06-01

    Conclusion: Urothelial carcinoma of the urinary bladder in young adults is usually associated with low grade and low stage. Invasive bladder cancer had no worse a survival rate than superficial bladder cancer.

  17. Differentiated thyroid carcinomas: prediction of tumor invasion with MR imaging

    International Nuclear Information System (INIS)

    Takashima, S.; Takayama, F.; Wang, Q.; Kawakami, S.; Saito, A.; Sone, S.; Kobayashi, S.

    2000-01-01

    Purpose: To assess diagnostic accuracy for tumor invasion of surrounding organs by measurement of tumor circumferences on MR images in patients with differentiated thyroid carcinomas. Material and Methods: Surgical and MR imaging findings in 50 patients with differentiated thyroid carcinoma (43 primary, 7 recurrent lesions) were retrospectively reviewed. The degrees of circumference of tumor encroachment to the organs were measured, and the measurements and morphologic diagnosis of tumor invasion made by a head and neck radiologist were compared with surgical and pathologic findings using receiver operating characteristic curves. Results: Diagnosis of tumor invasion by the radiologist was superior to the measurements of the carotid artery and cartilage, while the reverse was true for the trachea and esophagus. However, no statistical differences were noted between them for each structure. Optimal thresholds for tumor invasion were 90 deg or more for the cartilage (94% accuracy) and esophagus (86% accuracy), 135 deg or more for the trachea (86% accuracy), and 225 deg or more for the carotid artery (90% accuracy). Conclusion: Tumor invasion was more accurately diagnosed by measurement of tumor circumferences of each organ on MR images

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

    Science.gov (United States)

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

    2016-05-05

    Breast cancer in men is uncommon, accounting for cancers. Even though lobular structures are quite infrequent in the male breast, rare cases of invasive lobular breast carcinoma have been described, representing 1-2% of all breast cancers in men. Risk factors include undescended testes, congenital inguinal hernia, orchiectomy, orchitis, testicular injury, infertility and Klinefelter's syndrome, previous thoracic radiotherapy, alterations of the oestrogen-testosterone 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. 2016 BMJ Publishing Group Ltd.

  19. Expression of cancer-associated fibroblast-related proteins differs between invasive lobular carcinoma and invasive ductal carcinoma.

    Science.gov (United States)

    Park, Cheol Keun; Jung, Woo Hee; Koo, Ja Seung

    2016-08-01

    Cancer-associated fibroblasts (CAFs) are classified into various functional subtypes such as fibroblast activation protein-α (FAP-α), fibroblast specific protein-1 (FSP-1), platelet-derived growth factor receptor-α (PDGFR-α), and PDGFR-β. In this study, we compared the expression of CAF-related proteins in invasive lobular carcinoma (ILC) with those in invasive carcinoma of no special type (NST) and assessed the implications of the differences observed. Using tissue microarrays of 104 ILC and 524 invasive carcinoma (NST) cases, immunohistochemistry for CAF-related proteins [podoplanin, prolyl 4-hydroxylase, FAP-α, FSP-1/S100A4, PDGFR-α, PDGFR-β, and chondroitin sulfate proteoglycan (NG2)] was conducted. In invasive carcinoma (NST), tumor cells expressed a high level of PDGFR-α, whereas ILC tumor cells expressed high levels of podoplanin, prolyl 4-hydroxylase, FAP-α, and FSP-1/S100A4. In stromal cells of invasive carcinoma (NST), high expression levels of prolyl 4-hydroxylase, PDGFR-α, and NG2 were observed, whereas ILC stromal cells expressed high levels of FAP-α, FSP-1/S100A4, and PDGFR-β. In ILC, tumoral FSP-1/S100A4 positivity was associated with higher Ki-67 labeling index (p = 0.010) and non-luminal A type cancer (p = 0.014). Stromal PDGFR-α positivity was associated with lymph node metastasis (p = 0.011). On survival analysis of entire cases, tumoral FSP-1/S100A4 positivity (p = 0.002), stromal podoplanin positivity (p = 0.041), and stromal FSP-1/S100A4 negativity (p = 0.041) were associated with shorter disease-free survival; only tumoral FSP-1/S100A4 positivity (p = 0.044) was associated with shorter overall survival. In ILC, the expression of FAP-α and FSP-1/S100A4 was higher in both tumor and stromal cells than that observed in invasive carcinoma (NST). These results indicate that CAFs are a potential target in ILC treatment.

  20. Grp78 promotes the invasion of hepatocellular carcinoma

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    Li Hongdan

    2010-01-01

    Full Text Available Abstract Background Glucose regulated protein 78 (Grp78 is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism. Methods The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining. Results Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased

  1. Grp78 promotes the invasion of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Su, Rongjian; Li, Zhen; Li, Hongdan; Song, Huijuan; Bao, Cuifen; Wei, Jia; Cheng, Liufang

    2010-01-01

    Glucose regulated protein 78 (Grp78) is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism. The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+)-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining. Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased RhoA-GTP level, and Grp78 siRNA knockdown rescued Rho

  2. [Second operation more frequent following breast-conserving treatment for invasive lobular than for invasive non-lobular carcinoma

    NARCIS (Netherlands)

    Zeeuw, S. de; Wildenberg, F.; Strobbe, L.; Wobbes, T.

    2009-01-01

    OBJECTIVE: To establish the frequency of re-excision or mastectomy in women who had breast-conserving treatment for invasive lobular mammary carcinoma. DESIGN: Retrospective. METHOD: Data on the number of patients with invasive carcinoma from 1998-2006 were obtained from the national pathology

  3. Comparative proteomic analysis of ductal and lobular invasive breast carcinoma.

    Science.gov (United States)

    Oliveira, N C S; Gomig, T H B; Milioli, H H; Cordeiro, F; Costa, G G; Urban, C A; Lima, R S; Cavalli, I J; Ribeiro, E M S F

    2016-04-04

    Breast cancer is the second most common cancer worldwide and the first among women. Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological subtypes, and the clinical and molecular differences between them justify the search for new markers to distinguish them. As proteomic analysis allows for a powerful and analytical approach to identify potential biomarkers, we performed a comparative analysis of IDC and ILC samples by using two-dimensional electrophoresis and mass spectrometry. Twenty-three spots were identified corresponding to 10 proteins differentially expressed between the two subtypes. ACTB, ACTG, TPM3, TBA1A, TBA1B, VIME, TPIS, PDIA3, PDIA6, and VTDB were upregulated in ductal carcinoma compared to in lobular carcinoma samples. Overall, these 10 proteins have a key role in oncogenesis. Their specific functions and relevance in cancer initiation and progression are further discussed in this study. The identified peptides represent promising biomarkers for the differentiation of ductal and lobular breast cancer subtypes, and for future interventions based on tailored therapy.

  4. Prognostic factors in invasive bladder carcinoma treated by combined modality protocol (organ-sparing approach)

    International Nuclear Information System (INIS)

    Matos, Tadeja; Cufer, Tanja; Cervek, Jozica; Borstnar, Simona; Kragelj, Borut; Zumer-Pregelj, Mirjana

    2000-01-01

    from conservative treatment approach include those with good performance status, absence of hydronephrosis, and histologic low grade transitional cell carcinoma

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

    Directory of Open Access Journals (Sweden)

    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

  6. Collecting Duct Carcinoma of the Kidney Mimicking Invasive Transitional Cell Carcinoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Joo Nam; Lim, Hyung Guhn; Lim, Sung Chul [Chosun University College of Medicine, Gwangju (Korea, Republic of)

    2007-06-15

    Approximately 100 cases of collecting duct carcinoma have been reported in the medical literature. We herein report on a case of collecting duct carcinoma of the kidney in a 75-year-old patient. The abdominal sonography depicted a relatively poorly defined 7x6 cm sized, isoechoic mass lesion, as compared to the normal parenchyma, at the left kidney lower pole and the affected kidney showed preservation of the reniform shape. CT revealed a heterogeneous poorly defined low-attenuation mass that was mainly located in the medulla with involvement of the cortex and the lower half of the renal pelvis. Retrograde ureter opyelography showed a filling defect at the lower renal pelvis and severe narrowing of the left proximal ureter. We initially thought this lesion was invasive transitional cell carcinoma. Subsequent surgery confirmed a collecting duct carcinoma

  7. Conservative treatment for invasive lobular carcinoma of the breast

    International Nuclear Information System (INIS)

    Dilhuydy, Jean-Marie; Salem, Naji; Durand, Michel; Prie, Loiec; Stoeckle, Eberhard; Benyoucef, Ahmed; Dilhuydy, Marie-Helene

    1997-01-01

    Purpose/Objective: To evaluate the place of conservative treatment in invasive lobular carcinoma. Materials and Methods: From 01/01/85 to 31/12/92, 109 patients with clinically and mammographically unifocal invasive lobular carcinoma of the breast (T<35 mm) underwent tumorectomy, axillary dissection and radiation therapy; they received an adjuvant treatment in case of nodal involvement (n = 31) or lack of estrogen and progesterone receptors (n = 16). The entire breast received 50 Gy with a systematic boost of 10 Gy. Results: With a median follow-up of 86 months, we observed 11 isolated local recurrences (T0 = (3(19)), T1 = (6(41)), T2 = (2(49))), 7 local recurrences associated with metastases (T1 = (3(41)), T2 = (4(49))) and 7 cases of metastatic diseases (T1 = (4(41)), T2 = (3(49))). Among the 11 patients with isolated local recurrence, 7 are alive with no evidence of disease after salvage mastectomy. Nine contro-lateral breast cancers occurred, 2 synchronous and 7 metachronous. The 5-year actuarial local relapse free survival, metastase free survival and overall survival are respectively 87.3%, 89.5% and 92.5%, whatever histological subtypes. These results are comparable to those obtained in 1393 cases of infiltrating ductal carcinoma similarly treated during the same period in our institute, except for local relapse (87.3% vs 91%, p = 0.008). Conclusion: Conservative treatment for invasive lobular carcinoma of the breast (T<35 mm) is appropriate in the absence of clinical or mammographic multifocality

  8. Hepatocellular carcinoma: computed tomography assessment after invasive treatment

    International Nuclear Information System (INIS)

    Kozima, Shigeru; Larranaga, Nebil; Wulfson, Gabriela; Eisele, Guillermo; Ridruejo, Ezequiel; Mando, Oscar; Perazzo, Florencia

    2008-01-01

    Objective: To show the computed tomography (CT) usefulness after treatment with transcatheter arterial quimioembolization and radiofrequency ablation of hepatocellular carcinoma. Material and methods: In a period between march 2006 to april 2008 a total of 90 patient presenting 148 nodular lesions with diagnosis of hepatocellular carcinoma were controlled with triphasic CT. All the lesions were treated with minimally invasive procedure. For the treatment, the patients were classified in two groups following Milan criteria. The first group, constituted by 75 patients with 109 nodules, was treated with quimioembolization. The second group, of 15 patients with 25 nodules, was treated with radiofrequency ablation. In our population, a subgroup of 10 patients was treated with both methods. Results: Of 90 patients after CT control on a month, 3 months and for each 3 months during 2 years, on 63 cases (70%) was observed homogeneous accumulation of iodized oil, partial defect without enhancement or absence of enhancement on treated lesions. In these patients a new treatment after initial one was not performed. The remaining 27 patients (30%) underwent new treatment because we founded partial defect or absence of iodized oil with enhancement or peripheral enhancement on arterial phase in treated lesions. In this last group, 16 treated patients (17.7%) had new nodular enhancement on the remaining hepatic parenquimal. Conclusion: The CT unenhanced and the arterial phase on a month and for each 3 months, allow monitoring the effectiveness, residual disease and/or relapse of hepatocellular carcinoma after minimally invasive treatment. (authors) [es

  9. Combined detection of Twist1, Snail1 and squamous cell carcinoma antigen for the prognostic evaluation of invasion and metastasis in cervical squamous cell carcinoma.

    Science.gov (United States)

    Yang, Huilun; Hu, Haiyang; Gou, Yanling; Hu, Yuhong; Li, Hui; Zhao, Hongwei; Wang, Beidi; Li, Peiling; Zhang, Zongfeng

    2018-04-01

    Cervical cancer is one of the most common malignant tumours of the female reproductive system, ranking second only to breast cancer in morbidity worldwide. Essential features of the progression of cervical cancer are invasion and metastasis, which are closely related to disease prognosis and mortality rate. At the present time there is no effective method to evaluate cancer invasion and metastasis before surgery. Here we report our study on molecular changes in biopsy tissue for the prognostic evaluation of cancer invasion and metastasis. Expression of the epithelial-mesenchymal transition-inducing transcription factors Twist1 and Snail1 was detected by immunohistochemistry in 32 normal, 36 low-grade squamous intraepithelial neoplasia (LSIL), 54 high-grade squamous intraepithelial neoplasia (HSIL) and 320 cervical squamous cell carcinoma (CSCC) samples. The correlation between the expression of Twist1, Snail1 and squamous cell carcinoma antigen (SCCA) in CSCC tissues and clinical pathology results was evaluated. A transwell migration and invasion assay was used to explore the roles of Twist1 and Snail1 in the invasion of cancer cells. Lymph node metastasis and lymphovascular space invasion (LVSI) rates for the following groups were analysed: SCCA(+) group, Twist1(+) group, Snail1(+) group, Twist1(+)Snail1(+)group, Twist1(+)SCCA(+)group, Snail1(+)SCCA(+)group and Twist1(+)Snail1(+)SCCA(+) group. The expression of Twist1 and Snail1 was significantly upregulated in HSIL and CSCC (p  0.05). The expression of SCCA was associated with LVSI, lymph node metastasis, FIGO stage and histological grade (p  0.05). Twist1 was an independent factor contributing to the invasion ability of cervical cancer cells. In addition, the positive rate of lymph node metastasis and LVSI was higher in the Twist1(+)Snail1(+)SCCA(+) group than in the SCCA(+) group, Twist1(+) group and Snail1(+) group, respectively (p < 0.05). Combined detection of Twist1 and Snail1 in SCCA-positive biopsy

  10. Mucinous subtype of invasive ductal carcinoma arising within a fibroadenoma.

    Science.gov (United States)

    Monsefi, Nahid; Nikpour, Hossein; Safavi, Moienadin; Lashkarizadeh, Mohammad Reza; Dabiri, Shahriar

    2013-06-01

    Fibroadenoma is a common benign tumor observed during the second and third decades of life. Malignancy transformation in the epithelial component of a fibroadenoma is rare and can occur 20 years after its diagnosis. Mammographic findings in this phenomenon include indistinct margins and microcalcifications. Here we present a 58-year-old woman with a mobile, lateral upper quadrant mass that was rather firm when palpated. The mammography showed a lobulated mass without calcification suggestive of a benign process, most probably fibroadenoma. However the excisional biopsy contained both an intracanalicular fibroadenoma and invasive ductal carcinoma with mucinous components.

  11. Outcome of invasive lobular carcinoma of breast in Malaysia

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    Kamudin Nur Allaiyna Ferdaus

    2017-12-01

    Full Text Available Background: Breast cancer is the commonest cancer and 2nd most common cause of cancer death among women worldwide. Histologically breast cancer can be divided into Invasive Lobular Carcinoma (ILC, Invasive Ductal Carcinoma (IDC and others. ILC has its own unique patient’s demographic, histological appearance, imaging characteristics and clinical outcome. Previous published study has shown that ILC has better overall survival compared to IDC. Sadly, despite being so common, there is still lack of study comparing ILC and IDC in Malaysia setting. Methods: 5225 of patients diagnosed with ILC and IDC were managed in University Malaya Medical Center within 1993 to 2013 has been included in this study. Chi square test were performed to determine the demographic and clinical factors associated with ILC and IDC. Kaplen-Meier method was used to obtain overall survival of these patients. Through a Cox regression analysis, mortality in patients diagnosed with ILC and IDC were identified, by adjusting the possible confounding factors. Results: ILC is more common in elderly compared to younger patients. There is no association between ethnicity and types of invasive carcinoma. Patients with ILC were more likely to have lymph nodes involvement (p = 0.001, estrogen receptor positive (p = 0.001, absent of lymphovascular invasion (p = 0.028, mastectomy (p = 0.022 and hormonal therapy (p = 0.002 compared to IDC and it is statistically significant. Nevertheless, survival was not significantly different between ILC and IDC; 5-year OS; 77.4% (95% CI 77.34 to 77.46 and 71.3% (95% CI 71.29 to 71.30, respectively; the 10 year OS; 52.2% (95% CI 52.13 to 52.27 and 49.7% (95% CI 49.68 to 49.72, respectively. The adjusted hazard ratio comparing ILC and IDC using Cox regression was 1.21 (0.85 to 1.72 showing there is no significant difference between patients presented with ILC and IDC in terms of survival. Conclusion: Based on Malaysian data gathered from University

  12. Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review

    International Nuclear Information System (INIS)

    Mayer, R.; Stuecklschweiger, G.F.; Prettenhofer, U.; Stranzl, H.; Hackl, A.; Beham-Schmid, C.; Groell, R.; Smolle-Juettner, F.M.; Renner, H.; Quehenberger, F.

    1999-01-01

    All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) of biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. Results: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77,4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p=0.04). Considering local control, radiation dose was a significant prognostic factor (p=0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5 year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p=0.007) and DFS (p=0.0007). Conclusion: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival. (orig.) [de

  13. Transcatheter arterial chemoembolization of hepatocellular carcinoma with portal vein invasion

    International Nuclear Information System (INIS)

    Lee, Young Rahn; Lee, Ki Yeol; Cho, Seong Beom; Cha, In Ho; Chung, Kyoo Byung

    1993-01-01

    Transcatheter arterial chemoembolization(TACE) is an imperative method for the management of inoperable hepatocellular carcinoma(HCC). It is well known that primary HCC frequently invades the portal venous system and forms a tumor thrombus obstructing the portal blood flow which makes unfavorable prognosis of patient. We retrospectively reviewed 58 patients who reviewed TACE(minimum 3 times) of HCC invading into portal venous system. Group 1(n=29) which showed peripheral portal vein invasion had better clinical and laboratory response. Group 2(n=17) which showed first order portal branch invasion had similar response to Group 3(n=12), which had main portal invasion. Group 1 showed no difference in survival time between TAC and TACE, but, in Group 2 and 3, embolization with chemotherapy made longer survival than chemotherapy only. Clinical level of AFP was meaningful in Group 1 and 2 as decreasing value. Our results provides that careful selection of TAE and case by case Coil/Gelfoam embolization can improve the mean survival and clinical response when HCC evidently invades portal venous system

  14. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    Wu Xiaofeng; Fan Jia; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-01-01

    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

  15. Role of cytologic grading in prognostication of invasive breast carcinoma

    Directory of Open Access Journals (Sweden)

    Khan Nazoora

    2009-01-01

    noninvasive, cytologic grading is comparable to histologic grading and might provide relevant information on the aggressiveness of invasive ductal carcinoma of breast and could be a useful parameter to take into consideration when selecting mode of therapy and to predict tumor behavior.

  16. Locally Advanced Basal Cell Carcinoma with Intraocular Invasion

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2018-01-01

    Full Text Available We present a 103 - year - old patient, with duration of complaints of about ten years. The initial complaint had been presented as a small nodule, located on the eyebrow, which subsequently ulcerated and encompassed larger regions of the upper and lower eyelids. For the past three years, the patient also had complaints of a worsening of his vision, without seeking for medical help. Within the dermatological examination, an intraocular and periocular localised tumour was established, characterised by a raised peripheral edge and central ulceration. More careful examination revealed that the bulb was fully consumed. The patient refused further diagnosis and treatment. Advanced basal cell carcinomas with intraocular invasion are rare in general. If the patient refuses surgery, radiotherapy and systemic therapy with modern medications such as Vismodegib or Sonidegib are available as treatment options.

  17. Unusual uterine metastasis of invasive ductal carcinoma: A case report

    Directory of Open Access Journals (Sweden)

    Tayfur Çift

    2016-09-01

    Full Text Available Metastatic carcinoma of the uterus usually originates from other genital sites. Extragenital metastases such as breast are rare. A woman aged 34 years with a history of breast cancer was referred to the gynecology outpatient clinic for routine follow-up. Diagnostic tests and gynecologic examination revealed a uterine mass, which was removed with laparotomy. The pathologic investigation revealed metastasis of invasive lobular breast cancer. Chemotherapy was given and the patient has been under follow-up for 3 years with normal imaging on comput-erized tomographic examination and positron-emission tomography-computerized tomographic. It should be kept in mind that patients with breast cancer who have received tamoxifen may develop primary endometrial cancers, and may also demonstrate uterine metastases. With successful treatment these patients can obtain dis-ease-free survival.

  18. A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis.

    Science.gov (United States)

    Philippar, Ulrike; Roussos, Evanthia T; Oser, Matthew; Yamaguchi, Hideki; Kim, Hyung-Do; Giampieri, Silvia; Wang, Yarong; Goswami, Sumanta; Wyckoff, Jeffrey B; Lauffenburger, Douglas A; Sahai, Erik; Condeelis, John S; Gertler, Frank B

    2008-12-01

    The spread of cancer during metastatic disease requires that tumor cells subvert normal regulatory networks governing cell motility to invade surrounding tissues and migrate toward blood and lymphatic vessels. Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) proteins regulate cell motility by controlling the geometry of assembling actin networks. Mena, an Ena/VASP protein, is upregulated in the invasive subpopulation of breast cancer cells. In addition, Mena is alternately spliced to produce an invasion isoform, Mena(INV). Here we show that Mena and Mena(INV) promote carcinoma cell motility and invasiveness in vivo and in vitro, and increase lung metastasis. Mena and Mena(INV) potentiate epidermal growth factor (EGF)-induced membrane protrusion and increase the matrix degradation activity of tumor cells. Interestingly, Mena(INV) is significantly more effective than Mena in driving metastases and sensitizing cells to EGF-dependent invasion and protrusion. Upregulation of Mena(INV) could therefore enable tumor cells to invade in response to otherwise benign EGF stimulus levels.

  19. Extrauterine Low-Grade Endometrial Stromal Sarcoma

    Directory of Open Access Journals (Sweden)

    Yu-Ju Chen

    2005-12-01

    Conclusions: Low-grade endometrial stromal sarcoma typically has an indolent clinical course and favorable prognosis. Surgical resection is the primary therapeutic approach, and adjuvant therapy with radiotherapy, chemotherapy, or progesterone therapy should be considered for the management of residual or recurrent low-grade endometrial stromal sarcomas.

  20. Invasive lobular carcinoma of the breast: A special histological type compared with invasive ductal carcinoma

    Science.gov (United States)

    Chen, Zheling; Yang, Jiao; Li, Shuting; Lv, Meng; Shen, Yanwei; Wang, Biyuan; Li, Pan; Yi, Min; Zhao, Xiao’ai; Zhang, Lingxiao; Wang, Le

    2017-01-01

    The clinical outcomes and therapeutic strategies for infiltrating ductal carcinoma (IDC) and infiltrating lobular carcinoma (ILC) are not uniform. The primary objectives of this study were to identify the differences in the clinical characteristics and prognoses between ILC and IDC, and identify the high-risk population based on the hormone receptor status and metastasis sites. The Surveillance, Epidemiology, and End Results Program database was searched and patients diagnosed with ILC or IDC from 1990 to 2013 were identified. In total,796,335 patients were analyzed, including 85,048 withILC (10.7%) and 711,287 withIDC (89.3%). The ILC group was correlatedwith older age, larger tumor size, later stage, lower grade, metastasis disease(M1) disease, and greater counts ofpositive lymph nodesandestrogen-receptor-positive (ER)/progesterone receptor-positive (PR) positive nodes. The overall survival showed an early advantage for ILC but a worse outcome after 5 years. Regarding the disease-specific survival, the IDC cohort had advantages over the ILC group, both during the early years and long-term. In hormone status and metastasis site subgroup analyses, the ER+/PR+ subgroup had the best survival, while the ER+/PR- subgroup had the worst outcome, especially the ILC cohort. ILC and IDC had different metastasis patterns. The proportion of bone metastasis was higher in the ILC group (91.52%) than that in the IDC (76.04%), and the ILC group was more likely to have multiple metastasis sites. Survival analyses showed patients with ILC had a higher risk of liver metastasis (disease-specific survival[DSS]; P = 0.046), but had a better overall survival than the bone metastasis group (P<0.0001). We concluded that the long-term prognosis for ILC was poorer than that for IDC, and the ER+/PR- subgroup had the worst outcome. Therefore, the metastasis pattern and prognosis must be seriously evaluated, and a combination of endocrine therapy and chemotherapy should be considered. PMID

  1. Aggressive venous invasion in the area of carcinoma correlates with liver metastasis as an index of metastasis for invasive ductal carcinoma of the pancreas.

    Science.gov (United States)

    Hamada, Yoshihiro; Nakayama, Yoshifuku

    Invasive ductal carcinoma of the pancreas (IDCP) predominantly causes death through liver metastasis (LM) and peritoneal dissemination with local recurrence. However, whether its venous invasion is from the enlarged carcinoma accompanied by tumor growth, or from a distinct carcinoma group, for which venous invasion is facilitated by proximity to the origin, is unclear. We analyzed the correlation between LM and venous invasion in patients with small IDCP tumors. Of 388 patients who were diagnosed with IDCP, 20 (5.2%) had tumors with diameters IDPC. Patients in whom ≥60% of veins were invaded by IDCP should be prepared for LM. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  2. Invasive lobular carcinoma co-existing with benign phylloides tumor

    Directory of Open Access Journals (Sweden)

    S Shrestha

    2014-04-01

    Full Text Available Phylloides tumor constitutes less than 1% of all breast tumors and 2 - 3% of fibroepithelial breast tumors. Several histological parameters should be evaluated, including stromal cellularity, atypia, mitoses, stromal overgrowth, infiltrative borders, and presence or absence of necrosis. Here we report a case of a 60 years- old female who presented with left breast lump. Fine needle aspiration cytology was done which suggested epithelial hyperplasia with fibrocystic changes. Biopsy was performed which showed predominance of stromal hypercellularity with proliferation of spindle cells (no atypia, mitosis and stromal overgrowth were noticed. However, a focus showed proliferation of discohesive tumor cells arranged singly and in single file. A diagnosis of benign phylloides tumor with foci of invasive lobular carcinoma was made. The diagnosis was confirmed with IHC which showed intense 80%positivity for estrogen and progesterone receptor and spindle cells showing positivity for bcl-2. In situ lobular carcinoma component was not observed. DOI: http://dx.doi.org/10.3126/jpn.v4i7.10321   Journal of Pathology of Nepal (2014 Vol. 4, 597-599

  3. Incidental serous tubal intraepithelial carcinoma and early invasive serous carcinoma in the nonprophylactic setting: analysis of a case series.

    Science.gov (United States)

    Morrison, Jane C; Blanco, Luis Z; Vang, Russell; Ronnett, Brigitte M

    2015-04-01

    A precursor for invasive ovarian/pelvic high-grade serous carcinoma, termed serous tubal intraepithelial carcinoma (STIC), has been identified and characterized through careful analysis of the fallopian tubes in both prophylactic salpingo-oophorectomy specimens obtained from women with either a family history of breast and/or ovarian cancer or germline mutations of BRCA1 and BRCA2 and in cases of pelvic high-grade serous carcinoma. Data on incidental STICs and clinically occult microscopic invasive high-grade serous carcinomas are limited. We analyzed the clinicopathologic features of 22 cases, including 15 pure STICs and 7 STICs associated with microscopic invasive high-grade serous carcinomas, identified incidentally in fallopian tubes removed for nonprophylactic indications. Patient age ranged from 39 to 79 years (mean: 62.7; median: 61), with only 1 patient under the age of 50. No patients were known to carry BRCA1 or BRCA2 mutations. Of the 12 pure STICs for which the location in the fallopian tube could be established, 9 were in the fimbriated portion, 1 was at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. Of the 7 STICs with associated invasive high-grade serous carcinoma, 3 were located in the fimbriated portion, 2 were at the junction of the fimbria and infundibulum, and 2 were in the nonfimbriated tube. The invasive components were in the fallopian tube in 6 cases, 4 in subepithelial stroma of tubal mucosa, and 2 as an intramucosal (exophytic) luminal lesion without invasion of underlying subepithelial stroma (size range: 1 to 4 mm). The remaining case had a microscopic focus of high-grade serous carcinoma within the ipsilateral ovary (1.3 mm cortical focus) identified only on deeper sections, without an associated invasive component in the fallopian tube. The preferential finding of atypical epithelium with the cytologic features of high-grade serous carcinoma, namely STIC, in the fallopian tubes rather than the

  4. Metastatic nonpalpable invasive lobular breast carcinoma presenting as rectal stenosis: a case report.

    Science.gov (United States)

    Osaku, Tadatoshi; Ogata, Hideaki; Magoshi, Shunsuke; Kubota, Yorichika; Saito, Fumi; Kanazawa, Shinsaku; Kaneko, Hironori

    2015-04-24

    Invasive lobular carcinomas have an increased propensity for distant metastases, particularly to the peritoneum, ovaries, and uterus. In contrast, distant metastases of nonpalpable lobular carcinomas are extremely rare, and the causes of underlying symptoms of primary carcinomas remain unclear. We report a case of an asymptomatic invasive lobular carcinoma with a primary mammary lesion in a patient with rectal stenosis. A 69-year-old Japanese woman presented to our hospital for treatment of constipation. Although rectal stenosis was confirmed, thorough testing of her lower digestive tract did not identify its cause. Thus, an exploratory laparotomy and tissue biopsy was performed, and the presence of an invasive lobular carcinoma was confirmed. Subsequent breast examinations showed that the invasive lobular carcinoma that led to the rectal stenosis was a metastatic lesion from a primary lesion of the breast duct. As the present breast lobular carcinoma was asymptomatic and nonpalpable, we did not initially consider metastatic breast cancer as a cause of her symptoms, and the final diagnosis was delayed. Peritoneal metastasis from nonpalpable invasive lobular carcinomas is very rare. However, breast cancer metastasis should be considered when carcinomatous peritonitis is present in a patient with an unknown primary cancer.

  5. Review of Topical Treatment of Upper Tract Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Kenneth G. Nepple

    2009-01-01

    Full Text Available A select group of patients with upper tract urothelial carcinoma may be appropriate candidates for minimally invasive management. Organ-preserving endoscopic procedures may be appropriate for patients with an inability to tolerate major surgery, solitary kidney, bilateral disease, poor renal function, small tumor burden, low-grade disease, or carcinoma in situ. We review the published literature on the use of topical treatment for upper tract urothelial carcinoma and provide our approach to treatment in the office setting.

  6. Differentiation of widely invasive and minimally invasive follicular thyroid carcinoma with sonography

    International Nuclear Information System (INIS)

    Shin, Jung Hee; Han, Boo-Kyung; Ko, Eun Young; Oh, Young Lyun; Kim, Jung Han

    2010-01-01

    Purpose: We evaluated the sonographic findings that can help differentiate widely invasive follicular thyroid carcinomas (WIFTC) from minimally invasive follicular thyroid carcinomas (MIFTC). Methods: We retrospectively compared the sonographic and clinical findings of 24 patients (M:F = 5:19) with 24 MIFTCs and 12 patients (M:F = 1:11) with 13 WIFTCs that were confirmed pathologically and available in sonography at our institution between 1995 and 2007. Results: WIFTC was more common in elderly patients than MIFTC (p < 0.0001). WIFTC was seen with a larger size than MIFTC (p = 0.0092). The best cut-off values for age and size were 49 years and 5.6 cm, respectively. On sonography, all tumors were seen as a well-defined oval or round mass. Heterogeneous mulberry-like echotexture was more common for WIFTC than for MIFTC (77% vs. 25%) (p = 0.0046). The presence of calcifications was more frequent in WIFTC than in MIFTC (54% vs. 8%) (p = 0.0041). Ring calcifications (86%) were the most common type for WIFTC. WIFTC was commonly hypoechoic (70%) and rarely cystic change (8%), but without statistical differences. When WIFTCs represented tumors with two or more findings with a statistical difference, the specificity was 96%. Conclusion: WIFTC is distinguishable from MIFTC by sonography for patients with an age ≥49 years, a tumor ≥5.6 cm, a heterogeneous mulberry-like echotexure, or the presence of calcifications. The sonographic impression of a WIFTC can support a preoperative or intraoperative diagnosis of a difficult case as determined by FNA or with a frozen section.

  7. Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Marmor, Schelomo; Hui, Jane Yuet Ching; Huang, Jing Li; Kizy, Scott; Beckwith, Heather; Blaes, Anne H; Rueth, Natasha M; Tuttle, Todd M

    2017-08-15

    Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have distinct clinical, pathologic, and genomic characteristics. The objective of the current study was to compare the relative impact of adjuvant chemotherapy on the survival of patients with ILC versus those with IDC. Women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 1 (HER2) -negative, stage I/II IDC and ILC who received endocrine therapy were identified from the 2000 to 2014 California Cancer Registry. Patient, tumor, and treatment characteristics were collected. Ten-year overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional-hazards modeling. In total, 32,997 women with IDC and 4638 with ILC were identified. The receipt of chemotherapy significantly decreased during the study for both subtypes. For patients with IDC, the 10-year OS rate was 95% among those who received endocrine therapy alone versus 93% (P chemotherapy. For patients with ILC, the 10-year OS rate was 94% among those who received endocrine therapy alone versus 92% (P chemotherapy. After adjusting for patient and treatment factors, adjuvant chemotherapy was significantly associated with a decreased 10-year hazard of death for patients with IDC (hazard ratio, 0.83; 95% confidence interval, 0.74-0.92). In contrast, adjuvant chemotherapy was not independently associated with the adjusted 10-year hazard of death for patients with ILC (hazard ratio, 1.14; 95% confidence interval, 0.90-1.46). Adjuvant chemotherapy was not associated with improved OS for patients with ER-positive, HER2-negative, stage I/II ILC. Avoidance of ineffective chemotherapy will markedly reduce the adverse effects and economic burden of breast cancer treatment for a large proportion of patients with breast cancer. Cancer 2017;123:3015-21. © 2017 American Cancer Society. © 2017 American Cancer Society.

  8. Definitive Radiotherapy for Skin and Adenoid Cystic Carcinoma with Perineural Invasion

    OpenAIRE

    Mendenhall, William M.; Dagan, Roi; Bryant, Curtis M.; Amdur, Robert J.

    2016-01-01

    Adenoid cystic carcinomas (ACC) and, to a lesser extent, cutaneous squamous cell carcinomas and basal cell carcinomas may exhibit perineural invasion (PNI). A subset of patients have tumors with extensive PNI tracking to the skull base that are incompletely resectable and are treated with definitive radiotherapy (RT). RT may be administered with intensity-modulated RT or proton RT. Patients with ACC may also be considered for neutron RT, although the number of available neutron facilities is ...

  9. Recurrent invasive lobular carcinoma presenting as a ruptured breast implant

    International Nuclear Information System (INIS)

    Botros, Maikel; Chang, Kenneth; Miller, Robert; Krishnan, Sunil; Iott, Matthew

    2011-01-01

    For years, the treatment for invasive lobular carcinoma (ILC) has been mastectomy secondary to the lack of studies investigating the efficacy of breast conservation therapy on patients afflicted with ILC and due to the lack of long-term follow up investigating locoregional recurrence in this patient population. In this article we report the clinical course of a patient diagnosed with ILC. We describe the case of a 50-year-old woman with stage IIB (T2N1M0) ER/PR positive right breast ILC who underwent a right modified radical mastectomy, postoperative chemotherapy, a prophylactic left simple mastectomy with bilateral breast reconstruction and tamoxifen. Approximately 12 years later, she presented with a deflated breast implant and recurrent breast cancer with metastatic spread. She received palliative radiotherapy then palliative chemotherapy. Unfortunately, she succumbed to the cancer less than a year after being diagnosed with metastatic disease. This may be the first case report of a ruptured breast implant presenting at the same time as the diagnosis of recurrent breast cancer

  10. [Triexponential diffusion analysis in invasive ductal carcinoma and fibroadenoma].

    Science.gov (United States)

    Nakagawa, Masayuki; Miyati, Tosiaki; Hayashi, Tatsuya; Kanao, Syotaro; Taniguchi, Masahiro; Higashimura, Kyoji; Toi, Masakazu; Togashi, Kaori

    2014-03-01

    To simultaneously obtain information on diffusion and perfusion in breast lesions by diffusion-weighted magnetic resonance imaging (DWI), we analyzed three diffusion components using a triexponential function. Eighteen subjects [10 with invasive ductal carcinoma (IDC), 8 with fibroadenoma] were evaluated using DWI with multiple b-values. We derived perfusion-related diffusion, fast free diffusion, and slow restricted diffusion coefficients (Dp, Df, Ds) calculated from the triexponential function using the DWI data. Moreover, the triexponential analysis was compared with biexponential and monoexponential analyses. Each diffusion coefficient with a triexponential function was correlated to a relative enhancement ratio (RER) using dynamic contrast-enhanced MRI. In triexponential analysis, Dp and Ds in IDC were significantly higher than those for fibroadenoma. There was no correlation between each diffusion coefficient from the triexponential analysis in any of the groups (Dp, Df, and Ds), but biexponential analysis revealed a positive correlation between each diffusion coefficient in breast lesions. Strong correlations were found between Dp and RERs. Triexponential analysis thus makes it possible to obtain, in noninvasive fashion, more detailed diffusion and perfusion information in breast lesions.

  11. Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review

    Energy Technology Data Exchange (ETDEWEB)

    Mayer, R.; Stuecklschweiger, G.F.; Prettenhofer, U.; Stranzl, H.; Hackl, A. [Univ. Graz (Austria). Dept. of Radiotherapy; Beham-Schmid, C. [Univ. Graz (Austria). Dept. of Pathology; Groell, R. [Univ. Graz (Austria). Dept. of Radiology; Smolle-Juettner, F.M.; Renner, H. [Univ. Graz (Austria). Dept. of Thoracic and Hyperbaric Surgery; Quehenberger, F. [Univ. Graz (Austria). Dept. of Medical Informatics, Statistics and Documentation

    1999-06-01

    All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) of biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. Results: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77,4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p=0.04). Considering local control, radiation dose was a significant prognostic factor (p=0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5 year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p=0.007) and DFS (p=0.0007). Conclusion: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival. (orig.) [Deutsch] Alle 33 Patienten wurden nach kompletter Resektion (n=16), Teilresektion (n=9) oder Biopsie (n=8) mit einer mittleren Dosis von 50 Gy (30 bis 60 Gy) bestrahlt. Die Stadieneinteilung nach Masaoka ergab jeweils zwoelf Patienten in Stadium II und III sowie neun Patienten im Stadium IV. Ergebnisse: Patienten mit einem invasivem Thymom Masaoka-Stadium II bis IV (mediane Nachsorgezeit 54,4 Monate) hatten ein Fuenf-Jahres-Gesamtueberleben, krankheitsspezifisches und

  12. Assessment of lymphovascular invasion in gastric carcinoma; do they always indicate lymph node metastasis?

    Directory of Open Access Journals (Sweden)

    Kricha Pande

    2018-04-01

    Full Text Available Background: Stomach cancer is one of the leading causes of cancer death. The grading and staging of this cancer plays an important prognostic role. Lymphovascular invasion predicts poor outcome in gastric cancer. Among the others, lymphovascular invasion provides useful information for the clinical management of patients with gastric cancer. Nevertheless, data about lymphovascular invasion in early-stage and in lymph node-positive gastric cancer are lacking. Hence, significance of lymphovascular invasion to metastatic lymph nodes impacting nodal status in gastric cancer has been studied in this study.Materials and methods: This is a retrospective analysis of twenty nine (29 histologically confirmed gastric carcinoma cases received in the department of Pathology at NMCTH dating from October 2014 to September 2016.Results:  There was male preponderance to gastric carcinoma with male to female ratio of 2.2:1. The age varied from 31- 84 years. There were 17 cases (59% of intestinal type and 11 cases (38% of diffuse type of gastric carcinoma and 1 case (3% of adeno-neuroendocrine carcinoma. Microscopic evaluation for depth of invasion showed tumor invasion till the subserosal connective tissue layer (69% suggesting pT3 stage.  lymphovascular invasion was identified in 21 cases (72%. There was statistically significant correlation (p value 0.01 between   lymphovascular invasion and nodal status (N0 status. Conclusion: Presence of lymphovascular invasion is considered as poor prognostic marker in case of gastric adenocarcinoma. Pathologist have been reporting their presence or absence in each gastrectomy reports related to gastric carcinoma.This study has established a significant relation between presence of lymphovascular invasion and nodal staging of gastric carcinoma.

  13. Immunohistochemical Expression of Tissue Inhibitor of Metalloproteinase-1 (Timp-1 in Invasive Breast Carcinoma

    Directory of Open Access Journals (Sweden)

    Suada Kuskunović

    2009-05-01

    Full Text Available Tissue inhibitor of metalloproteinase-1 (TIMP-1 is a natural inhibitor of matrix metalloproteinas-es (MMPs. Aim of this study was to assess the immunohistochemical expression of TIMP-1 in invasive breast carcinomas, and to examine its association with classical clinico-pathological parameters, oestrogen receptor, progesterone receptor and Her-2/neu protein expression. Immuno-histochemistry was used to determine the expression of TIMP-1 on 38 paraffin-embedded breast tissue specimens - 18 with invasive ductal carcinoma, 10 with invasive lobular carcinoma, and 10 specimens from patients with fibrocystic breast disease. TIMP-1 protein was immunodetected in the carcinoma cells, fibroblasts and inflammatory cells of the stroma in 92,9%, 65,8%, and 65,8% of cases, respectively. TIMP-1 protein expression in carcinoma cells showed positive correlation with TIMP-1 protein expression in peritumoural fibroblasts (p=0,010. Positive peritumoural fibroblast TIMP-1 expression was associated with histological tumour type with higher frequency in ductal carcinomas (p=0,023. Negative association was found between TIMP-1 protein expression in carcinoma cells and HER-2/neu nuclear staining (p=0,005. TIMP-1 may be particularly useful as a predictive marker in breast carcinoma when evaluated along with HER-2/neu protein being a promising indicator of favourable prognosis in breast carcinoma.

  14. 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.)

  15. A case of invasive papillary breast carcinoma: Fierce façade with favorable prognosis

    Directory of Open Access Journals (Sweden)

    D Vani

    2015-01-01

    Full Text Available Invasive papillary carcinoma of the breast is a rare, distinct variant comprising approximately less than 1-2% of all newly diagnosed cases of breast carcinoma and is usually found in postmenopausal women with a more favorable prognosis. We report an unusual case in a 45-year-old perimenopausal female who came with a complaint of lump in right breast for duration of 1 year. A simple mastectomy was undertaken for histopathological study and immunohistochemistry (IHC which showed characteristic features of an invasive papillary breast carcinoma. We present this case in view of its rarity and to highlight this clinicopathological subtype for its good prognosis and to avoid overtreatment.

  16. MicroRNA and protein profiles in invasive versus non-invasive oral tongue squamous cell carcinoma cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Korvala, Johanna, E-mail: johanna.korvala@oulu.fi [Cancer and Translational Medicine Research Unit, University of Oulu, The Medical Research Center Oulu, Oulu University Hospital, Aapistie 5A, 90014 Oulu (Finland); Jee, Kowan [Department of Pathology, University of Turku, Turku University Hospital, Turku (Finland); Department of Pathology, Haartman Institute, University of Helsinki, Helsinki (Finland); Porkola, Emmi [Cancer and Translational Medicine Research Unit, University of Oulu, The Medical Research Center Oulu, Oulu University Hospital, Aapistie 5A, 90014 Oulu (Finland); Almangush, Alhadi [Department of Pathology, Haartman Institute, University of Helsinki, Helsinki (Finland); Mosakhani, Neda [Department of Pathology, HUSLAB, Helsinki (Finland); Bitu, Carolina [Cancer and Translational Medicine Research Unit, University of Oulu, The Medical Research Center Oulu, Oulu University Hospital, Aapistie 5A, 90014 Oulu (Finland); Cervigne, Nilva K. [Department of Oral Diagnosis, School of Dentistry, University of Campinas (UNICAMP), Av. Limeira, 901 – Bairro Areião, CEP: 13414-903 Piracicaba, São Paulo (Brazil); Department of Clinical and Pathology, Faculty of Medicine of Jundiai - FMJ, Jundiai, SP (Brazil); Zandonadi, Flávia S.; Meirelles, Gabriela V.; Leme, Adriana Franco Paes [Laboratório Nacional de Biociências, LNBio, CNPEM, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas/SP, P.O.Box 6192, CEP 13083-970 Campinas, São Paulo (Brazil); Coletta, Ricardo D. [Department of Oral Diagnosis, School of Dentistry, University of Campinas (UNICAMP), Av. Limeira, 901 – Bairro Areião, CEP: 13414-903 Piracicaba, São Paulo (Brazil); and others

    2017-01-01

    Complex molecular pathways regulate cancer invasion. This study overviewed proteins and microRNAs (miRNAs) involved in oral tongue squamous cell carcinoma (OTSCC) invasion. The human highly aggressive OTSCC cell line HSC-3 was examined in a 3D organotypic human leiomyoma model. Non-invasive and invasive cells were laser-captured and protein expression was analyzed using mass spectrometry-based proteomics and miRNA expression by microarray. In functional studies the 3D invasion assay was replicated after silencing candidate miRNAs, miR-498 and miR-940, in invasive OTSCC cell lines (HSC-3 and SCC-15). Cell migration, proliferation and viability were also studied in the silenced cells. In HSC-3 cells, 67 proteins and 53 miRNAs showed significant fold-changes between non-invasive vs. invasive cells. Pathway enrichment analyses allocated “Focal adhesion” and “ECM-receptor interaction” as most important for invasion. Significantly, in HSC-3 cells, miR-498 silencing decreased the invasion area and miR-940 silencing reduced invasion area and depth. Viability, proliferation and migration weren’t significantly affected. In SCC-15 cells, down-regulation of miR-498 significantly reduced invasion and migration. This study shows HSC-3 specific miRNA and protein expression in invasion, and suggests that miR-498 and miR-940 affect invasion in vitro, the process being more influenced by mir-940 silencing in aggressive HSC-3 cells than in the less invasive SCC-15.

  17. An unusual case of intracystic papillary carcinoma of breast with invasive component

    Directory of Open Access Journals (Sweden)

    Suryawanshi Kishor H, Nikumbh Dhiraj B, Damle Rajshri P, Dravid NV, Tayde Yogesh

    2014-07-01

    Full Text Available Papillary carcinoma of the breast is a rare malignant tumor, constituting 1-2 % of breast neoplasms mostly affecting elderly postmenopausal women. Intracystic (Encysted papillary carcinoma (IPC is a rare distinct entity with slow growth rate and overall favourable prognosis regardless of whether it is in situ alone or associated with invasive component. Treatment modalities vary from conservative surgery to radical surgery with or without adjuvant therapy depending upon the associated component (DCIS or invasive of the tumor. Herein, we report a case of 55-year-old female presented with a painless lump in the right breast. FNAC yielded haemorrhagic fluid with scanty cellularity of atypical ductal epithelial cells. Patient underwent wide local excision. The final histopathological diagnosis revealed intracystic papillary carcinoma associated with invasive ductal carcinoma, NOS type.

  18. Chest wall invasion by bronchogenic carcinoma. Evaluation with Cine-MRI

    International Nuclear Information System (INIS)

    Nawano, Shigeru; Murakami, Kohji; Ohnuma, Hiroshi; Iwata, Ryoko; Hayashi, Takayuki; Moriyama, Noriyuki; Nishiwaki, Yutaka; Nagai, Kanji

    1996-01-01

    With the view of examining possible chest wall invasion of bronchogenic carcinoma, Cine-MRI was performed on 22 such cases. These cases were suspected of having above chest wall invasion by CT and their histopathological findings were obtained in surgery. The judgment of the chest wall invasion by Cine-CT was made such that non-moving up and down of the tumor with respiration involves its invasion, moving of the tumor without any up-and-down movement suspects its invasion and moving up and down of the tumor with respiration involves no invasion. The chest wall invasion was observed in 5 of 7 cases of invasion judged by Cine-MRI. For 2 false-positive cases, the histopathological findings presumed that tumor cells disappeared from the chest wall invaded region as the result of preoperative chemotherapy. The above invasion was observed in 1 of 4 cases suspected of possible invasion. Correct diagnosis was formed of 11 cases judged invasion-free by Cine-MRI. The above results suggested Cine-MRI to be useful for diagnosis of chest wall invasion of bronchogenic carcinoma. (author)

  19. 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....... Using unbiased stereology, the three-dimensional mean nuclear size, v v(nuc), was estimated in routine histological sections, along with morphometric point-counting based estimates of the mean nuclear profile area, aH(nuc), and estimates of the nuclear density index, NI, the mitotic index, MI......) 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...

  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....... Using unbiased stereology, the three-dimensional mean nuclear size, v v(nuc), was estimated in routine histological sections, along with morphometric point-counting based estimates of the mean nuclear profile area, aH(nuc), and estimates of the nuclear density index, NI, the mitotic index, MI...... 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 lesions...

  1. Invasive Pleomorphic Lobular Carcinoma of the Breast: Pathologic, Clinical, and Therapeutic Considerations.

    Science.gov (United States)

    Al-Baimani, Khalid; Bazzarelli, Amy; Clemons, Mark; Robertson, Susan J; Addison, Christina; Arnaout, Angel

    2015-12-01

    Pleomorphic lobular carcinoma is an uncommon form of breast cancer and a subtype of invasive lobular carcinoma. It has unique histopathologic features that translate to a more aggressive phenotype with an associated poor prognosis. Unlike classical invasive lobular carcinoma, it can lose estrogen and progesterone receptor expression and demonstrate HER-2/neu amplification. It remains to be determined, however, whether the pleomorphic histology independently predicts a worse outcome or whether other known associated negative prognostic factors such as larger tumor size, increased metastatic disease, and associated worse molecular subtypes commonly present in pleomorphic carcinoma account for the poor prognosis. Here we present an updated review of the unique pathologic and clinical features of pleomorphic lobular carcinoma needed to guide management for women with this subtype of cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Processing of low-grade uranium ores

    International Nuclear Information System (INIS)

    Michel, P.

    1975-01-01

    Four types of low grade ores are studied. Low grade ores which must be extracted because they are enclosed in a normal grade deposit. Heap leaching is the processing method which is largely used. It allows to obtain solutions or preconcentrates which may be delivered at the nearest plant. Normal grade ores contained in a low amplitude deposit which can be processed using leaching as far as the operation does not need any large expensive equipment. Medium grade ores in medium amplitude deposits to which a simplified conventional process can be applied using fast heap leaching. Low grade ores in large deposits. The processing possibilities leading to use in place leaching are explained. The operating conditions of the method are studied (leaching agent, preparation of the ore deposit to obtain a good tightness with regard to the hydrological system and to have a good contact between ore and reagent) [fr

  3. Processing of low grade uranium ores

    International Nuclear Information System (INIS)

    Michel, P.

    1978-10-01

    Four types of low-grade ores are studied: (1) Low-grade ores that must be extracted because they are enclosed in a normal-grade deposit. Heap leaching is the processing method which is largely used. (2) Normal-grade ores contained in low-amplitude deposits. They can be processed using in-place leaching as far as the operation does not need any large and expensive equipment. (3) Medium-grade ores in medium-amplitude deposits. A simplified conventional process can be applied using fast heap leaching. (4) Low-grade ores in large deposits. The report explains processing possibilities leading in most cases to the use of in-place leaching. The operating conditions of this method are laid out, especially the selection of the leaching agents and the preparation of the ore deposit

  4. Tumor microenvironment in invasive lobular carcinoma: possible therapeutic targets.

    Science.gov (United States)

    Nakagawa, Saki; Miki, Yasuhiro; Miyashita, Minoru; Hata, Shuko; Takahashi, Yayoi; Rai, Yoshiaki; Sagara, Yasuaki; Ohi, Yasuyo; Hirakawa, Hisashi; Tamaki, Kentaro; Ishida, Takanori; Watanabe, Mika; Suzuki, Takashi; Ohuchi, Noriaki; Sasano, Hironobu

    2016-01-01

    Invasive ductal and lobular carcinomas (IDC and ILC) are the two most common histological types of breast cancer, and have been considered to develop from terminal duct lobular unit but their molecular, pathological, and clinical features are markedly different between them. These differences could be due to different mechanisms of carcinogenesis and tumor microenvironment, especially cancer-associated fibroblasts (CAFs) but little has been explored in this aspect. Therefore, in this study, we evaluated the status of angiogenesis, maturation of intratumoral microvessels, and proliferation of CAFs using immunohistochemistry and PCR array analysis to explore the differences of tumor microenvironment between ILC and IDC. We studied grade- and age-matched, luminal-like ILC and IDC. We immunolocalized CD34 and αSMA for an evaluation of CAFs and CD31, Vasohibin-1, a specific marker of proliferative endothelial cells and nestin, a marker of pericytes for studying the status of proliferation and maturation of intratumoral microvessel. We also performed PCR array analysis to evaluate angiogenic factors in tumor stromal components. The number of CAFs, microvessel density, and vasohibin-1/CD31 positive ratio were all significantly higher in ILC than IDC but nestin immunoreactivity in intratumoral microvessel was significantly lower in ILC. These results did indicate that proliferation of CAFs and endothelial cells was more pronounced in ILC than IDC but newly formed microvessels were less mature than those in IDC. PCR array analysis also revealed that IGF-1 expression was higher in ILC than IDC. This is the first study to demonstrate the differences of tumor microenvironment including CAFs and proliferation and maturation of intratumoral vessels between ILC and IDC.

  5. Fibrocartilaginous mesenchymoma with low-grade malignancy

    International Nuclear Information System (INIS)

    Dahlin, D.C.; Bertoni, F.; Beabout, J.W.; Campanacci, M.

    1984-01-01

    In a review of cases of fibrous cartilaginous dysplasia of bone, five of fibrocartilaginous lesions were found to be different in clinical behavior and radiographic and morphologic features from the others. We have named these previously undescribed tumors ''fibrocartilaginous mesenchymomas with low-grade malignancy in the fibrous elements.'' (orig.)

  6. Better utilization of low-grade woods

    Science.gov (United States)

    Peter Koch

    1957-01-01

    The objective of this paper is threefold: to outline briefly some of the avenues of approach so far employed in utilizing low-grade wood, to comment on the economic aspects of the problem, and finally, to speculate about what developments the future might bring to the field of utilization.

  7. Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report.

    Science.gov (United States)

    Toyoshima, Masafumi; Iwahashi, Hideki; Shima, Takashi; Hayasaka, Atsushi; Kudo, Takako; Makino, Hiromitsu; Igeta, Saori; Matsuura, Rui; Ishigaki, Nobuko; Akagi, Kozo; Sakurada, Junko; Suzuki, Hiroyoshi; Yoshinaga, Kosuke

    2015-02-14

    Solitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma. A 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause. Seven years prior to her presentation, she was diagnosed with breast cancer and underwent a partial resection of her right breast for stage IIA invasive lobular carcinoma. She underwent adjuvant chemotherapy, radiotherapy, and five years of anastrozole hormonal therapy. She presented with a growing uterine mass. Her tumor marker levels were markedly increased over the course of her follow-up, but a systemic examination revealed only a solitary uterine tumor. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A histopathological examination, including detailed immunohistochemistry, confirmed metastatic invasive lobular carcinoma, infiltrating both her uterine myometrium and fibroid tissue. We report a very rare metastatic pattern of invasive lobular carcinoma and demonstrate that gross cystic disease fluid protein-15 and mammaglobin are useful in the diagnosis of metastatic breast cancer.

  8. Which features of advanced head and neck basal cell carcinoma are associated with perineural invasion?

    Directory of Open Access Journals (Sweden)

    André Bandiera de Oliveira Santos

    Full Text Available Abstract Introduction Perineural invasion is a unique route for tumor dissemination. In basal cell carcinomas, the incidence is low, but increases in advanced cases. Its importance is recognized but not fully understood. Objective To compare head and neck basal cell carcinomas with and without perineural invasion. Methods A retrospective medical chart review of multidisciplinary surgeries for basal cell carcinomas that required a head and neck surgery specialist in a tertiary referral center was performed. Clinical-demographics and histopathological features were analyzed. Results Of 354 cases, perineural invasion was present in 23.1%. Larger tumors and morpheaform subtype were statistically related to perineural invasion. Nodular and superficial subtypes were less frequent in positive cases. No significant difference was found in gender, age, ulceration, location, and mixed histology. Conclusion In this series of selected patients with basal cell carcinomas submitted to major resections, perineural invasion was clearly related to morpheaform subtype and to larger tumors. Other classically associated features, such as location in high-risk mask zone of the face, male gender and mixed histology, were not so strongly linked to perineural invasion.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Pancreatic metastasis from invasive pleomorphic lobular carcinoma of the breast: a rare case report.

    Science.gov (United States)

    Sun, Xiangjie; Zuo, Ke; Huang, Dan; Yu, Baohua; Cheng, Yufan; Yang, Wentao

    2017-07-11

    Invasive pleomorphic lobular carcinoma (PLC) is an aggressive subtype of invasive lobular carcinoma of the breast, which has its own histopathological and biological features. The metastatic patterns for PLC are distinct from those of invasive ductal carcinoma. In addition, pancreatic metastasis from PLC is extremely rare. We report a rare case of a 48-year-old woman presenting with clinical gastrointestinal symptoms and pancreatic metastasis of PLC. The pancreatic tumor was composed of pleomorphic tumor cells arranged in the form of solid sheets and nests and as single files, with frequent mitotic figures, nucleolar prominence, high nuclear to cytoplasmic ratio and loss of cohesion. The malignant cells were positive for p120 (cytoplasmic) and GATA3 and negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, E-cadherin, gross cystic disease fluid protein 15 and mammaglobin, which indicated a lobular carcinoma phenotype of the breast. To the best of our knowledge, this is one of the few reported cases in the literature of pancreatic metastasis of invasive lobular carcinoma of the breast, of which the definitive diagnosis was obtained only after surgery. Rare metastasis sites should be considered, particularly, when a patient has a medical history of PLC.

  11. A low-grade extraskeletal osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Kyoji; Ito, Hiroki; Miyakoshi, Naohisa; Itoi, Eiji [Department of Orthopedic Surgery, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan); Sageshima, Masato [Department of Clinical Pathology, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543 (Japan); Nishida, Jun [Department of Orthopedic Surgery, Iwate Medical School, 19-1 Uchimaru, Morioka 020-8505 (Japan)

    2003-03-01

    The case of a 35-year-old woman with low-grade extraskeletal osteosarcoma of the left leg is presented. Radiographs showed peripheral ossification of the lesion, suggesting myositis ossificans. Most of the tumor was composed of cartilage, and the cellularity and cell atypia of the proliferating chondrocytes were mild to moderate. In the periphery, bone formation with a relatively clear margin and proliferation of spindle cells with minimal nuclear atypia were observed. The average percentage of cells positive for MIB-1 was 9.0%. A diagnosis of low-grade extraskeletal osteosarcoma was made on the basis of these histologic findings. The clinical course 47 months after a wide excision was uneventful. (orig.)

  12. Cognition Effects of Low-Grade Hypoxia

    Science.gov (United States)

    2016-07-01

    human short-term memory . Br J Anaesth. 1971; 43(6):548–552. 3. Crow TJ, Kelman GR. Psychological effects of mild acute hypoxia. Br J Anaesth. 1973; 45...Journal Article 3. DATES COVERED (From – To) Jan 2003 – Sep 2005 4. TITLE AND SUBTITLE Cognition Effects of Low-Grade Hypoxia 5a. CONTRACT NUMBER... cognitive function are reported in this paper. The study compared cognitive function during short exposures at four different altitudes. Ninety-one

  13. Clinicopathologic study of serous tubal intraepithelial carcinoma with invasive carcinoma: is serous tubal intraepithelial carcinoma a reliable feature for determining the organ of origin?

    Science.gov (United States)

    Gao, Faye F; Bhargava, Rohit; Yang, Huaitao; Li, Zaibo; Zhao, Chengquan

    2013-08-01

    In the past several decades, the concept of serous ovarian carcinoma has been revised repeatedly. However, the exact pathogenesis remains controversial. The most popular current concept is origin from the epithelium of the fimbriated ends of the fallopian tubes. The objective of our study was to evaluate the characteristic clinical and morphologic features of serous tubal intraepithelial carcinoma (STIC) and associated invasive carcinomas. One hundred sixteen consecutive cases of STIC seen from 2007 to 2011 were included in this study. High-grade serous carcinoma (HGSC) with or without a mixed component was identified in 107 cases (92.2%), non-HGSC in 5 cases, and STICs without invasive carcinoma in 4 cases. Using conventional criteria, HGSCs were classified as fallopian tube in origin in 65 cases (60.7%), as ovarian in 30 (28.0%), as peritoneal in 9 (8.4%), and as endometrial in 3 (2.8%). Among the 107 cases with HGSCs, most STICs (86; 80%) were present unilaterally, whereas invasive tumors more commonly involved the ovaries bilaterally (79%; 84 cases). These findings support the hypothesis that STIC acts as a precursor lesion for most fallopian tube, ovarian, and peritoneal HGSCs, but not for endometrial HGSC. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Uranium production from low grade Swedish shale

    International Nuclear Information System (INIS)

    Carlsson, O.

    1977-01-01

    In view of the present nuclear programmes a steep increase in uranium demand is foreseen which will pose serious problems for the uranium industry. The annual additions to uranium ore reserves must almost triple within the next 15 years in order to support the required production rates. Although there are good prospects for the discovery of further conventional deposits of uranium there is a growing interest in low grade uranium deposits. Large quantities of uranium exist in black shales, phosphates, granites, sea water and other unconventional sources. There are however factors which limit the utilization of these low grade materials. These factors include the extraction costs, the environmental constrains on mining and milling of huge amounts of ore, the development of technologies for the beneficiation of uranium and, in the case of very low grade materials, the energy balance. The availability of by-product uranium is limited by the production rate of the main product. The limitations differ very much according to types of ores, mining and milling methods and the surroundings. As an illustration a description is given of the Swedish Ranstad uranium shale project, its potential, constraints and technical solutions

  15. Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling

    Science.gov (United States)

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most common form of liver cancer (~80%), and it is one of the few cancer types with rising incidence in the United States. This highly invasive cancer is very difficult to detect until its later stages, resulting in limited treatment options and low survival rates. There is a dearth of knowledge regarding the mechanisms associated with the effects of biomechanical forces such as interstitial fluid flow (IFF) on hepatocellular carcinoma invasion. We hypothesized that interstitial fluid flow enhanced hepatocellular carcinoma cell invasion through chemokine-mediated autologous chemotaxis. Utilizing a 3D in vitro invasion assay, we demonstrated that interstitial fluid flow promoted invasion of hepatocellular carcinoma derived cell lines. Furthermore, we showed that autologous chemotaxis influences this interstitial fluid flow-induced invasion of hepatocellular carcinoma derived cell lines via the C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12) signaling axis. We also demonstrated that mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling affects interstitial fluid flow-induced invasion; however, this pathway was separate from CXCR4/CXCL12 signaling. This study demonstrates, for the first time, the potential role of interstitial fluid flow in hepatocellular carcinoma invasion. Uncovering the mechanisms that control hepatocellular carcinoma invasion will aid in enhancing current liver cancer therapies and provide better treatment options for patients. PMID:26560447

  16. NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

    Science.gov (United States)

    Sasahira, Tomonori; Kurihara, Miyako; Nishiguchi, Yukiko; Fujiwara, Rina; Kirita, Tadaaki; Kuniyasu, Hiroki

    2016-08-01

    Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.

  17. Dual energy spectral CT imaging for the evaluation of small hepatocellular carcinoma microvascular invasion.

    Science.gov (United States)

    Yang, Chuang-Bo; Zhang, Shuang; Jia, Yong-Jun; Yu, Yong; Duan, Hai-Feng; Zhang, Xi-Rong; Ma, Guang-Ming; Ren, Chenglong; Yu, Nan

    2017-10-01

    To study the clinical value of dual-energy spectral CT in the quantitative assessment of microvascular invasion of small hepatocellular carcinoma. This study was approved by our ethics committee. 50 patients with small hepatocellular carcinoma who underwent contrast enhanced spectral CT in arterial phase (AP) and portal venous phase (VP) were enrolled. Tumour CT value and iodine concentration (IC) were measured from spectral CT images. The slope of spectral curve, normalized iodine concentration (NIC, to abdominal aorta) and ratio of IC difference between AP and VP (RIC AP-VP : [RIC AP-VP =(IC AP -IC VP )/IC AP ]) were calculated. Tumours were identified as either with or without microvascular invasion based on pathological results. Measurements were statistically compared using independent samples t test. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of tumours microvascular invasion assessment. The 70keV images were used to simulate the results of conventional CT scans for comparison. 56 small hepatocellular carcinomas were detected with 37 lesions (Group A) with microvascular invasion and 19 (Group B) without. There were significant differences in IC, NIC and slope in AP and RIC AP-VP between Group A (2.48±0.70mg/ml, 0.23±0.05, 3.39±1.01 and 0.28±0.16) and Group B (1.65±0.47mg/ml, 0.15±0.05, 2.22±0.64 and 0.03±0.24) (all phepatocellular carcinoma with and without microvascular invasion. Quantitative iodine concentration measurement in spectral CT may be used to provide a new method to improve the evaluation for small hepatocellular carcinoma microvascular invasion. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. An Unusual Clinical Presentation of Gastrointestinal Metastasis From Invasive Lobular Carcinoma of Breast

    Directory of Open Access Journals (Sweden)

    Bathmapriya Balakrishnan MD

    2016-03-01

    Full Text Available Introduction. We present an unusual case of metastatic lobular breast carcinoma. Typical areas of metastasis include bone, gynecological organs, peritoneum, retroperitoneum, and gastrointestinal (GI tract, in order of frequency. With regard to GI metastasis, extrahepatic represents a rare site. Case. Two years after being diagnosed with invasive lobular breast carcinoma, a 61-year-old female complained of 3 months of nonspecific abdominal pain and diarrhea. A colonoscopy revealed 5 tubular adenomatous polyps in the ascending and transverse colon. Contrast computed tomography (CT of the abdomen and pelvis was done 7 months after the colonoscopy to further evaluate persistent diarrhea. The CT results were consistent with infectious or inflammatory enterocolitis. Despite conservative management, symptoms failed to improve and a repeat diagnostic colonoscopy was obtained. Random colonic biopsies revealed metastatic high-grade adenocarcinoma of the colon. Discussion. Metastatic lobular breast carcinoma to the GI tract can distort initial interpretation of endoscopic evaluation with lesions mimicking inflammation. The interval between discovery of GI metastasis and diagnosis of lobular breast cancer can vary widely from synchronous to 30 years; however, progression is most often much sooner. Nonspecific symptoms and subtle appearance of metastatic lesions may confound the diagnosis. A high index of suspicion is needed for possible metastatic spread to the GI tract in patients with a history of invasive lobular breast carcinoma. Perhaps, patients with nonspecific GI symptoms should have an endoscopic examination with multiple random biopsies as invasive lobular carcinoma typically mimics macroscopic changes consistent with colitis.

  19. Status of Her2 over expression in muscle invasive urothelial bladder carcinoma: Report of 21 cases

    Directory of Open Access Journals (Sweden)

    Nesrine Mejri

    2014-01-01

    Four patients died from disease, one of them had Her2 3+ score. Conclusion: Her2 overexpression can be observed in muscle invasive urothelial bladder carcinoma in an important number of patients. Evaluation criteria must be standardized, especially with heterogeneous cases. Metastases tests can also readdress the expression of Her2, which gives the patient a supplementary therapeutic tool.

  20. Cytologic follow-up of patients with invasive cervical carcinoma treated by radiotherapy

    International Nuclear Information System (INIS)

    Muram, D.; Curry, R.H.; Drouin, P.

    1982-01-01

    In an 11-year study done at the Ottawa Civic Hospital, cytologic assessment of 323 patients treated by radiotherapy for invasive cervical carcinoma was reviewed. The value and limitations of gynecologic cytology in the follow-up of these patients are discussed

  1. Reflectance confocal microscopy: non-invasive distinction between actinic keratosis and squamous cell carcinoma

    NARCIS (Netherlands)

    Peppelman, M.; Nguyen, K.P.; Hoogedoorn, L.; Erp, P.E.J. van; Gerritsen, M.J.P.

    2015-01-01

    BACKGROUND: Early recognition of squamous cell carcinoma (SCC) is difficult. Non-invasive reflectance confocal microscopic (RCM) imaging of the skin is a promising diagnostic technique. Although several RCM features for SCC and AK have been described, it is not determined whether RCM has the ability

  2. Bilateral Invasive Lobular Breast Carcinoma in a Young Woman: Case Report

    International Nuclear Information System (INIS)

    Abella Calle, Jose; Valenzuela Gallego, Marcela

    2012-01-01

    The histopathological and clinical features of invasive lobular carcinoma (ILCs) are responsible for its varying imaging appearance; therefore, an adequate correlation between the different imaging modalities available aids in determining tumor extension and in identifying the number of lesions. This article presents the case of a young woman diagnosed with multiple and bilateral ILC with metastatic disease.

  3. MRI versus CT for detecting cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinoma

    NARCIS (Netherlands)

    Wegner, Inge; Hooft, Lotty; Reitsma, Johannes B.; Pameijer, Frank A.; de Bree, Remco; Stegeman, Inge

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To determine and compare the diagnostic accuracy of preoperative conventional MRI and conventional CT for detecting cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinoma, who

  4. 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...... 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......(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P

  5. MR imaging of invasive carcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Lien, H.H.

    1999-01-01

    MR imaging is noninvasive and provides direct multiplanar images with good contrast between different soft tissues. It has a potential in distinguishing normal from abnormal tissue and is a valuable technique in examination of the female pelvis. This report reviews the present role of MR imaging in the initial work-up of patients with carcinoma of the uterine cervix. (orig./AJ)

  6. Low grade gastric MALT lymphoma: Radiographic findings

    International Nuclear Information System (INIS)

    Brown, J.A.; Carson, B.W.; Gascoyne, R.D.; Cooperberg, P.L.; Connors, J.M.; Mason, A.C.

    2000-01-01

    AIMS: Gastric MALT (mucosa-associated lymphoid tissue) lymphoma is now recognized as a distinct entity within extranodal non-Hodgkin's lymphoma. The purpose of this study was to describe the radiographic findings in low grade gastric MALT lymphoma. MATERIALS AND METHODS: We retrospectively reviewed the radiographic findings in 22 cases of low-grade gastric MALT lymphoma. The study group consisted of 15 men and seven women (median age 68 years, range 41-91 years). Lesions were designated as infiltrative or polypoid by consensus of two radiologists. Polypoid lesions were categorized by number and size. Anatomical site within the stomach and presence of transpyloric or oesophagogastric extension was determined for each case. The presence of abdominal lymphadenopathy was categorized as regional or distant. The presence of Helicobacter pylori was determined from endoscopic and surgical biopsies. RESULTS: Computed tomography (CT) revealed abnormalities of the stomach in 19 cases of the 21 in which it was performed. There were 14 infiltrative lesions and five polypoid lesions. Of the 14 infiltrative lesions, the mean gastric wall thickness was 2.2 cm (range 0.8-6.0 cm). There were three single and two multiple polypoid lesions (mean size 2.2 cm, range 1.5-2.7 cm). Transpyloric extension was observed in two cases and oesophagogastric extension in one. Abdominal lymphadenopathy was observed in 10 of 21 patients. Helicobacter pylori was found in 19 of 22 cases (86%). CONCLUSION: Low grade B cell gastric MALT lymphomas present with an infiltrative form on CT in about three-quarters of cases and a polypoid pattern in the remainder. Abdominal lymphadenopathy is seen in approximately one-half of cases. There is a high association with Helicobacter pylori. Brown, J.A. 2000. Clinical Radiology 55, 384-389

  7. 3D-CRT, Proton, or Brachytherapy APBI in Treating Patients With Invasive and Non-invasive Breast Cancer

    Science.gov (United States)

    2017-12-29

    Ductal Breast Carcinoma In Situ; Estrogen Receptor Positive; Grade 1 Invasive Breast Carcinoma; Grade 2 Invasive Breast Carcinoma; Grade 3 Invasive Breast Carcinoma; Invasive Ductal and Lobular Carcinoma In Situ; Mucinous Breast Carcinoma; Tubular Breast Carcinoma

  8. EMMPRIN contributes to the in vitro invasion of human salivary adenoid cystic carcinoma cells

    Science.gov (United States)

    YANG, XINJIE; ZHANG, PU; MA, QIN; KONG, LIANG; LI, YUAN; LIU, BAOLIN; LEI, DELIN

    2012-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that is involved in tumor invasion by stimulating matrix metalloproteinase (MMP) expression. Our previous immunohistochemical study found that the expression of EMMPRIN in salivary adenoid cystic carcinoma (SACC) was positively correlated with tumor perineural and perivascular invasion. The present study was designed to further investigate the role of EMMPRIN in the invasion of SACC. Western blot results showed that EMMPRIN was upregulated in the highly metastatic SACC cell line SACC-LM, compared to SACC-83, a SACC cell line with low metastatic ability. Blocking of EMMPRIN by its antibody significantly decreased the adhesion, secretion of MMP-2 and MMP-9, and invasion activity of SACC-LM cells in vitro (PEMMPRIN may play an important role in the invasion of SACC by stimulating the expression of MMP-2 and MMP-9 in tumor and stromal cells. PMID:22200897

  9. Current treatment of low grade astrocytoma

    DEFF Research Database (Denmark)

    Pedersen, Christina Louise; Romner, Bertil

    2013-01-01

    Through a comprehensive review of the current literature, the present article investigates several aspects of low grade astrocytomas (LGA), including prognostic factors, treatment strategies and follow-up regimes. LGA are in general relatively slow-growing primary brain tumours, but they have a v...... effective in discriminating between tumour progression and radiation necrosis. The research into biomarkers is currently limited with regards to their applications in LGA diagnostics, and therefore further studies including larger patient populations are needed.......Through a comprehensive review of the current literature, the present article investigates several aspects of low grade astrocytomas (LGA), including prognostic factors, treatment strategies and follow-up regimes. LGA are in general relatively slow-growing primary brain tumours, but they have...... as the course of disease. The current literature seems to support the idea that treatment with radical tumour resection, where possible, yields better long term outcome for patients with LGA. However, adjuvant therapy is often necessary. Administering early postoperative radiotherapy to patients with partially...

  10. EVALUATION OF LYMPHATIC SPREAD, VISCERAL METASTASIS AND TUMORAL LOCAL INVASION IN ESOPHAGEAL CARCINOMAS.

    Science.gov (United States)

    Tustumi, Francisco; Kimura, Cintia Mayumi Sakurai; Takeda, Flavio Roberto; Sallum, Rubens Antônio Aissar; Ribeiro-Junior, Ulysses; Cecconello, Ivan

    2016-01-01

    Knowing esophageal tumors behavior in relationship to lymph node involvement, distant metastases and local tumor invasion is of paramount importance for the best esophageal tumors management. To describe lymph node involvement, distant metastases, and local tumor invasion in esophageal carcinoma, according to tumor topography and histology. A total of 444 patients with esophageal squamous cell carcinoma and 105 adenocarcinoma were retrospectively analyzed. They were divided into four groups: adenocarcinoma and squamous cell carcinoma in the three esophageal segments: cervical, middle, and distal. They were compared based on their CT scans at the time of the diagnosis. Nodal metastasis showed great relationship with of primary tumor site. Lymph nodes of hepatogastric, perigastric and peripancreatic ligaments were mainly affected in distal tumors. Periaortic, interaortocaval and portocaval nodes were more commonly found in distal squamous carcinoma; subcarinal, paratracheal and subaortic nodes in middle; neck chains were more affected in cervical squamous carcinoma. Adenocarcinoma had a higher frequency of peritoneal involvement (11.8%) and liver (24.5%) than squamous cell carcinoma. Considering the local tumor invasion, the more cranial neoplasia, more common squamous invasion of airways, reaching 64.7% in the incidence of cervical tumors. Middle esophageal tumors invade more often aorta (27.6%) and distal esophageal tumors, the pericardium and the right atrium (10.4%). Esophageal adenocarcinoma and squamous cell carcinoma in different topographies present peculiarities in lymph node involvement, distant metastasis and local tumor invasion. These differences must be taken into account in esophageal cancer patients' care. Conhecer o comportamento das neoplasias esofágicas em relação à disseminação linfonodal, distribuição de metástases e invasão local do tumor, pode auxiliar o manejo dos pacientes. Descrever o envolvimento linfonodal, disseminação metast

  11. 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.

  12. [Some morphometric parameters of nucleoli and nuclei in invasive ductal breast carcinomas in women].

    Science.gov (United States)

    Karpinska-Kaczmarczyk, Katarzyna

    2009-01-01

    The purpose of this study was to correlate seven morphometric parameters of nucleoli and nuclei of invasive ductal cancer cells with some clinico-pathological factors such as age, tumor size, axillary lymph node status, MIB-1 proliferation index, and estrogen receptor expression in tumor cells. Methyl green-pyronin Y (MG-PY) was used for simultaneous staining of nuclei and nucleoli in histological sections of 150 invasive ductal breast carcinomas. Next, morphometric parameters of nucleoli and nuclei of tumor cells were measured with computerized image analysis. Nuclear area and number of nucleoli in breast tumor cells were greater in younger axillary node-negative patients. The number of nucleoli and nucleolar shape polymorphism were reduced in tumors measuring 20 mm or less or with lower histological grade. Nuclear area, nucleolar number, and nucleolar polymorphism in carcinomas with low proliferation index and estrogen receptor expression were smaller than in carcinomas with high proliferation index and no estrogen receptor expression. Nucleolar area in primary tumors without axillary node involvement was greater than in tumors with more than three axillary nodes positive. MG-PY selectively and simultaneously stains nucleoli and nuclei of tumor cells enabling standardized and reproducible examination of these structures with computerized image analysis. Univariate statistical analysis disclosed that some morphometric parameters of nucleoli and nuclei of tumor cells correlated with several established clinico-pathological prognostic factors. Therefore, the prognostic significance of these parameters should be studied in a larger group of patients with invasive ductal breast carcinomas.

  13. Association of Ulex europaeus agglutinin I binding with invasion in endometrial carcinoma.

    Science.gov (United States)

    Ambros, R A; Kurman, R J

    1993-10-01

    Ulex europaeus agglutinin I (UEA-I), a lectin which specifically binds L-fucose, has been shown to extensively bind endometrial carcinoma cells but not benign endometrial glands. Patterns of UEA-I binding were examined in five cases of uteri containing proliferative endometrium, five cases of endometrial hyperplasia, and 54 cases of endometrioid (typical) carcinoma of the endometrium and correlated with the histologic features of the tumor and its behavior. Whereas proliferative endometrium showed luminal staining only, diffuse cytoplasmic staining was frequently seen in hyperplasia and carcinoma. Carcinomas with a high percentage of tumor cells staining with UEA-I tended to be high-grade with a greater tendency to deep myometrial and vascular invasion than tumors with little or no staining. By univariate survival analysis, the extent of UEA-I binding was found to correlate with patient survival. By multivariate analysis, however, survival correlated most closely with the presence of deep myometrial and vascular invasion, and UEA-I binding was not found to be an independent prognostic indicator. This study suggests that increased fucosylation of proteins in endometrioid cancer cells may play a role in myometrial and vascular invasion.

  14. Clinico-pathological features and prognosis of invasive micropapillary carcinoma compared to invasive ductal carcinoma: a population-based study from China.

    Directory of Open Access Journals (Sweden)

    Wen-Biao Shi

    Full Text Available Invasive micropapillary carcinoma (IMPC of the breast is a rare subtype of breast cancer that is associated with a high incidence of regional lymph node metastases and a poor clinical outcome. However, the clinico-pathological features and prognostic factors of IMPC are not well understood.A total of 188 IMPC cases and 1,289 invasive ductal carcinoma (IDC cases were included. The clinical features, breast cancer-specific survival (BCSS and recurrence/metastasis-free survival (RFS of the patients were compared between these two groups.The IMPC patients exhibited more features of aggressive carcinoma than the IDC patients, including larger tumor size, higher tumor stage, a greater proportion of nodal involvement and an increased incidence of lymphovascular invasion. Patients with IMPC had lower 5-year BCSS and RFS rates (75.9% and 67.1%, respectively than patients with IDC (89.5% and 84.5%, respectively. Compared to IDC patients, the patients with IMPC had a significantly higher percentage of stage III breast cancer (51.3% versus 21.7%. In a stage-matched Kaplan-Meier analysis, the patients with stage III IMPC had lower 5-year BCSS and RFS rates than patients with stage III IDC (BCSS, P = 0.004; RFS, P = 0.034. A multivariate analysis revealed that TNM stage was an independent prognostic factor for patients with IMPC. The proportion of cancers with a luminal-like subtype was significantly higher in IMPC than in IDC (P<0.001. However, after matching by molecular subtype, the patients with IMPC had significantly worse clinical outcomes than patients with IDC.In Chinese women, IMPCs displayed more aggressive behaviors than IDCs, resulting in poorer clinical outcomes for patients with IMPC, regardless of a favorable molecular subtype. Our findings illustrate that the poorer survival of patients with IMPC might be due to an increased incidence and aggressiveness of tumors in TNM stage III.

  15. Leptomeningeal carcinomatosis from perineural invasion of a lip squamous cell carcinoma

    International Nuclear Information System (INIS)

    Sullivan, L.M.; Smee, R.

    2006-01-01

    Perineural invasion resulting in leptomeningeal carcinomatosis is a rare, but well-recognized phenomenon in head and neck carcinomas. We report the rare case of a patient with a squamous cell carcinoma of the lip resulting in leptomeningeal carcinomatosis and review the relevant published work. A 51-year-old man presented with progressive facial paraesthesia after treatment for a recurrent squamous cell carcinoma of the lower lip. Cavernous sinus involvement was confirmed on MRI and he received stereotactic radiotherapy. He subsequently developed progressive lower limb neurological signs. An MRI showed multiple enhancing leptomeningeal nodules in the cervical and lumbar spine consistent with leptomeningeal carcinomatosis. Whole spine radiotherapy and dexametha-sone resulted in short-term stabilization of symptoms only and he rapidly succumbed to progressive neurological disease. To our knowledge, this is the first published report of a squamous cell carcinoma of the lip resulting in leptomeningeal disease of the cauda equina. It illustrates the potential aggressive natural history of squamous cell carcinomas with perineural invasion Copyright (2006) Blackwell Publishing Asia Pty Ltd

  16. Microbial leaching of low grade copper ores

    International Nuclear Information System (INIS)

    Rauf, A.; Ashfaq, M.

    1991-01-01

    Biotechnology is regarded as one of the most promising and revolutionary solution to various problems which are generally faced in the extraction of metals from their ores such as high energy, capital costs and environmental pollution. The paper deals with the study of low grade copper ores for their beneficiation and extraction of copper. The ores used were chalcopyrite and oxidized copper ores. Microorganisms play a vital role in the solubilization of valuable contents from ores such as copper and other metals. Studies have been conducted on the indigenous copper ores by using thiobacillus ferro oxidans and thiobacillus thio oxidans. For comparison purpose some experiments have also been conducted by chemical leaching. The results of bacterial leaching are encouraging. (author)

  17. The Reproducibility of Nuclear Morphometric Measurements in Invasive Breast Carcinoma

    Directory of Open Access Journals (Sweden)

    Pauliina Kronqvist

    1997-01-01

    Full Text Available The intraobserver and interobserver reproducibility of computerized nuclear morphometry was determined in repeated measurements of 212 samples of invasive breast cancer. The influence of biological variation and the selection of the measurement area was also tested. Morphometrically determined mean nuclear profile area (Pearson’s r 0.89, grading efficiency (GE 0.95 and standard deviation (SD of nuclear profile area (Pearson’s r 0.84, GE 0.89 showed high reproducibility. In this respect, nuclear morphometry equals with other established methods of quantitative pathology and exceeds the results of subjective grading of nuclear atypia in invasive breast cancer. A training period of eight days was sufficient to produce clear improvement in consistency of nuclear morphometry results. By estimating the sources of variation it could be shown that the variation associated with the measurement procedure itself is small. Instead, sample associated variation is responsible for the majority of variation in the measurements (82.9% in mean nuclear profile area and 65.9% in SD of nuclear profile area. This study points out that when standardized methods are applied computerized morphometry is a reproducible and reliable method of assessing nuclear atypia in invasive breast cancer. For further improvement special emphasize should be put on sampling rules of selecting the microscope fields and measurement areas.

  18. Carcinoma of the cervix. Value of dynamic magnetic resonance imaging in assessing early stromal invasion

    International Nuclear Information System (INIS)

    Kojima, Yumi; Aoki, Yoichi; Kase, Hiroaki; Kodama, Shoji; Tanaka, Kenichi

    1998-01-01

    The purpose of this study was to assess the accuracy of contrast-enhanced magnetic resonance imaging (dynamic MR imaging) in the evaluation of preinvasive and early invasive cancer of the cervix. Twenty-nine women with untreated squamous cell carcinoma of the cervix with either no stromal invasion or early stromal invasion underwent pretreatment MR imaging and dynamic MR imaging within 4 weeks of surgical evaluation. The images were evaluated for tumor detection and compared with results of histologic examination of the surgical specimens. The lesions in 17 cases with histologically proven stromal invasion of 4 mm or greater were detected with dynamic MR imaging, whereas lesions in only 8 of these cases were detected with T2 imaging. In 9 cases with stromal invasion between 4.0 mm and 5.0 mm, lesions were represented as early phase focal enhancement on dynamic MR images, but not detected on T2-weighted images. In the 12 cases with less than 4 mm stromal invasion, no lesions were visualized on either T2-weighted images or dynamic MR images, except in 1 case of glandular involvement without stromal invasion that appeared as enhancement on early-phase dynamic MR imaging. Dynamic MR imaging detected more lesions of early stromal invasion in pretreatment imaging for cervical cancer than nonenhanced MR imaging. (author)

  19. Thyroid cartilage invasion in laryngeal and hypopharyngeal squamous cell carcinoma treated with total laryngectomy.

    Science.gov (United States)

    Koopmann, Mario; Weiss, Daniel; Steiger, Matthias; Elges, Sandra; Rudack, Claudia; Stenner, Markus

    2016-11-01

    The objective of this study is to analyze the accuracy of computed tomography in detecting malignant thyroid cartilage invasion. In a retrospective chart review, 120 patients with carcinoma of the larynx and hypopharynx underwent computed tomography before total laryngectomy. These data were compared with the histological specimens. Multidetector computed tomography (MDCT) scan had a positive predictive value (PPV) of 76 % and a negative predictive value (NPV) of 69 %. The specificity of MDCT was 89 % and sensitivity was 46 %. Comparison between radiologic suspected cartilage invasion and histologic results showed a significant correlation (p < 0.02). We found no significant impact of cartilage invasion concerning survival rates (5-year overall survival p = 0.683; 5-year disease-free survival p = 0.711). Preoperative CT scan is an important instrument in detecting neoplastic cartilage invasion.

  20. Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Li Fan

    2010-04-01

    Full Text Available Abstract Background In spite of recent advances in diagnostic and therapeutic measures, the prognosis of hepatocellular carcinoma (HCC patients remains poor. Therefore, it is crucial to understand what factors are involved in promoting development of HCC. Evidence is accumulating that members of the chemokine receptor family are viewed as promising therapeutic targets in the fight against cancer. More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of HCC cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in hepatocellular carcinoma tissues and cell lines and to evaluate the role of CXCR7 in tumor growth, angiogenesis and invasion of HCC cells. Methods We constructed CXCR7 expressing shRNA, and CXCR7shRNA was subsequently stably transfected into human HCC cells. We evaluated the effect of CXCR7 inhibition on cell invasion, adhesion, VEGF secretion, tube formation and tumor growth. Immunohistochemistry was done to assess the expression of CXCR7 in human hepatocellular carcinoma tissues and CD31 in tumor of mice. We also evaluated the effect of VEGF stimulation on expression of CXCR7. Results CXCR7 was overexpressed in hepatocellular carcinoma tissues. We showed that high invasive potential HCC cell lines express high levels of CXCR7. In vitro, CXCL12 was found to induce invasion, adhesion, tube formation, and VEGF secretion in SMMC-7721 cells. These biological effects were inhibited by silencing of CXCR7 in SMMC-7721 cells. In addition, we also found that VEGF stimulation can up-regulate CXCR7 expression in SMMC-7721 cells and HUVECs. More importantly, enhanced expression of CXCR7 by VEGF was founctional. In vivo, tumor growth and angiogenesis were suppressed by knockdown of CXCR7 in SMMC-7721 cells. However, silencing of CXCR7 did not affect metastasis of tumor in vivo

  1. 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.

  2. Invasive cervical carcinoma (stage IB-IIB): assessment with MR imaging

    International Nuclear Information System (INIS)

    Sironi, S.; Del Maschio, A.; Belloni, C.; Taccagni, L.

    1990-01-01

    In patients with cervical carcinoma the selection of the optimal therapy depends on the precise preoperative assessment of the extent of disease. Currently, decisions regarding the management of these patients are made on the basis of clinical (FIGO) staging that has 50% mean error rate. To investigate the value of MR imaging in staging patients with invasive cervical cancer, we performed 25 MR examinations on 23 patients with histologic diagnosis of cervical cancer. All patients were clinically considered as having stage IB or IIB disease and underwent radical hysterectomy, providing specimens for pathologic correlation. The overall accuracy of MR imaging in staging cervical carcinoma (stage IB-IIB) was 78.1%. MR imaging seems to be the most reliable preoperative modality for staging invasive cervical cancer

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

    International Nuclear Information System (INIS)

    Brearley, M.J.; Hayes, A.M.; Murphy, S.

    1999-01-01

    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

  4. 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.

  5. Abdominal Wall Metastasis from an Invasive Lobular Carcinoma of the Breast: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hana; Son, Eun Ju; Youk, Ji Hyun; Chung, Jin [Dept. of Radiology, Gangnam Severance Hospital, Yensei University College of Medicine, Seoul (Korea, Republic of); Noh, Song Mi; Jung, Woo Hee [Dept. of Diagnostic Pathology, Gangnam Severance Hospital, Yensei University College of Medicine, Seoul (Korea, Republic of)

    2011-06-15

    Breast cancer is one of the most common malignancies in women. Breast cancer frequently metastasizes to the bones, lungs, and liver. However, the recurrence of distant soft-tissue metastasis except to the chest wall is extremely rare. Here, we describe our experience with a patient in whom invasive lobular carcinoma of the breast with metastasis to the abdominal wall presented as subcutaneous nodules without local recurrence.

  6. Abdominal Wall Metastasis from an Invasive Lobular Carcinoma of the Breast: A Case Report

    International Nuclear Information System (INIS)

    Kim, Hana; Son, Eun Ju; Youk, Ji Hyun; Chung, Jin; Noh, Song Mi; Jung, Woo Hee

    2011-01-01

    Breast cancer is one of the most common malignancies in women. Breast cancer frequently metastasizes to the bones, lungs, and liver. However, the recurrence of distant soft-tissue metastasis except to the chest wall is extremely rare. Here, we describe our experience with a patient in whom invasive lobular carcinoma of the breast with metastasis to the abdominal wall presented as subcutaneous nodules without local recurrence.

  7. Comparison of SPECT and CT in detecting skull base invasion in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Zhang Li; Wang Jinchuan; Pu Nuo; Song Wenzhong; Chen Mingxi

    2002-01-01

    Objective: To investigate the detecting ability of single photon emission computed tomography (SPECT) and CT in skull base invasion in nasopharyngeal carcinoma. Methods: Sixty-three patients with nasopharyngeal carcinoma were examined by whole body and skull base SPECT and CT of nasopharynx and skull base before radiotherapy. The results were double-blind compared and evaluated. Results: The overall positive rates of skull base invasion detected by SPECT and CT were 63.5% and 25.4%. In patients with headache, cranial nerve palsy and both, they were 87.9%, 93.3%, 92.3% and 42.4%, 46.7%, 46.2%. In patients with T 1 + T 2 and T 3 + T 4 lesions, they were 37.5%, 90.3% and 0.0%, 51.6%. In patients with N 0 + N 1 and N 2 + N 3 lesions, they were 63.9%, 63.0% and 19.4%, 33.3%. The positive rates of SPECT were higher than those of CT (McNemar Test, P < 0.05). The conformation rate between SPECT and CT was 61.9% and the dissimilitude rate was 38.1%. Binary Logistic regression analysis showed that headache and T stages were risk factors of positive SPECT rate (ORheadache = 3.864, ORTstage= 6.422) while Tstage and Nstage were the risk factors for positive CT rate (ORTstage = 48.932, ORNstage = 2.860). Conclusions: The detection sensitivity of SPECT in skull base invasion in nasopharyngeal carcinoma is superior to that of CT. But its specificity is inferior to that of CT. The detecting results in SPECT are better related to symptoms, signs and stage. Combining headache and cranial nerve palsy with T and N stage, the authors may much improve the results of SPECT and CT in the detection of skull base invasion in nasopharyngeal carcinoma. Further study is warranted

  8. Malignant Solitary Fibrous Tumor Metastatic to Widely Invasive Hurthle Cell Thyroid Carcinoma: A Distinct Tumor-to-Tumor Metastasis.

    Science.gov (United States)

    Kolson Kokohaare, Eva; Riva, Francesco M G; Bernstein, Jonathan M; Miah, Aisha B; Thway, Khin

    2018-04-01

    We illustrate a case of synchronous malignant solitary fibrous tumor of the thoracic cavity, and widely invasive thyroid Hurthle cell carcinoma. The Hurthle cell carcinoma was found to harbor distinct areas of malignant solitary fibrous tumor. This is a unique case of tumor-to-tumor metastasis that, to the best of our knowledge, has not been previously reported.

  9. Factors Associated with Delayed Reporting of Invasive Carcinoma Cervix in a Rural Tertiary Care Center.

    Science.gov (United States)

    Radha, K R; Reena, R P

    2016-10-01

    The delay in detection of premalignant and malignant lesions can have an adverse impact on the outcome of carcinoma cervix. In spite of relatively good healthcare facilities, women in Kerala continue to report in advanced stages of cervical malignancy. To analyze factors associated with delayed reporting and to evaluate awareness about screening and vaccination programs for prevention of carcinoma cervix. A cross-sectional study design was used to evaluate the subjects diagnosed to have carcinoma cervix in the outpatient Department of Obstetrics and Gynecology, Government Medical College, Thrissur, Kerala for a period of two years. One-hundred and fifteen women diagnosed to have invasive carcinoma during the study were evaluated. Data analysis was done and expressed as means and percentages. One-hundred and fifteen women participated in the study. Only 26 (21.7 %) of the subjects were diagnosed in a relatively early stage, i.e., up to stage 2a. Most of them were from families living below poverty line (63.9 %) and were either widowed or divorced (57.3 %). Illiteracy was common (48.9 %) among them, and many (71.3 %) worked as manual laborers. None of the subjects was aware about the availability of screening and vaccination programs for prevention of carcinoma cervix. There is a wide gap between the awareness of availability of healthcare and its proper utilization by the poor. Scaling up of public awareness of preventive programs and the availability of healthcare facilities are essential to enable the timely utilization of such services to facilitate early detection of invasive carcinoma cervix.

  10. Invasive Ductal Carcinoma of Breast : Correlation between Sonographic Posterior Acoustic Patterns with Histopathology

    International Nuclear Information System (INIS)

    Cho, Hyun Cheol; Lee, Yong Woo; Hwang, Mi Soo; Cho, Kil Ho; Chang, Jae Chun; Kim, Dong Sug; Bae, Young Kyung

    1996-01-01

    To evaluate the frequency of posterior sonic attenuation and enhancement in invasive ductal carcinoma of breast on ultrasound, and to compare with histo-pathologic findings. Sonographic findings of 26 histologically proven invasive ductal carcinomas were retrospectively reviewed in point of posterior echo pattern regardless other ultrasonic features. They were classified in two groups according to posterior echo pattern such as enhancement or shadowing, and compared with various internal histologic characteristics such as amount of connective tissue, degree of elastosis, necrosis, gross circumscription,harboring inflammation, histologic differentiation, nuclear pleomorphism, and mitotic index. The acoustic shadowing was seen in 34.6%, whereas posterior sonic enhancement was seen in 65.4% of cases. The acoustic shadowing group had more connective tissue, elastosis, and poor demarcated margin than the sonic enhancement group(p < 0.05). But no significant differences were seen in other histopathologic findings representing malignancy between two groups. A close relationship between posterior echo pattern and amount of connective tissue or elastosis is found in invasive ductal carcinoma of breast. The acoustic shadowing known as a characteristic ultrasonographic finding of malignant breast mass does not represent the degree of malignancy

  11. Protease-activated receptor 2 modulates proliferation and invasion of oral squamous cell carcinoma cells.

    Science.gov (United States)

    Al-Eryani, Kamal; Cheng, Jun; Abé, Tatsuya; Maruyama, Satoshi; Yamazaki, Manabu; Babkair, Hamzah; Essa, Ahmed; Saku, Takashi

    2015-07-01

    Based on our previous finding that protease-activated receptor 2 (PAR-2) regulates hemophagocytosis of oral squamous cell carcinoma (SCC) cells, which induces their heme oxygenase 1-dependent keratinization, we have formulated a hypothesis that PAR-2 functions in wider activities of SCC cells. To confirm this hypothesis, we investigated immunohistochemical profiles of PAR-2 in oral SCC tissues and its functional roles in cell proliferation and invasion in SCC cells in culture. The PAR-2 expression modes were determined in 48 surgical tissue specimens of oral SCC. Using oral SCC-derived cell systems, we determined both gene and protein expression levels of PAR-2. SCC cell proliferation and invasive properties were also examined in conditions in which PAR-2 was activated by the synthetic peptide SLIGRL. PAR-2 was immunolocalized in oral SCC and carcinoma in situ cells, especially in those on the periphery of carcinoma cell foci (100% of cases), but not in normal oral epithelia. Its expression at both gene and protein levels was confirmed in 3 oral SCC cell lines including ZK-1. Activation of PAR-2 induced ZK-1 cell proliferation in a dose-dependent manner. PAR-2-activated ZK-1 cells invaded faster than nonactivated ones. The expression of PAR-2 is specific to oral malignancies, and PAR-2 regulates the growth and invasion of oral SCC cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Imaging and the clinical-pathologic features of invasive micropapillary carcinoma of the breast

    International Nuclear Information System (INIS)

    Kim, Dae Sik; Cho, Nariya; Ko, En Sook; Kim, Do Youn; Yang, Sang Kyu; Kim, Seung Ja; Moon, Woo Kyung

    2007-01-01

    The purpose of this study was to describe the mammographic and sonographic appearances and the clinical-pathologic features of invasive micropapillary carcinoma. Between December 1999 and March 2005, among the 3,109 patients who underwent operation for breast cancer, 25 patients proved to have invasive micropaillary carcinoma. Among the 25 patients, we included 22 patients (mean age: 48, range: 26-77 years) who had undergone preoperative mammography and ultrasound. The mammographic and sonographic findings of the lesions were analyzed retrospectively. The pathologic findings were analyzed via the clinical records and pathology reports. Patients manifested with a palpable mass (77%, 17/22), bloody nipple discharge (14%, 3/22) or incidental lesion on the screening mammography (9%, 2/22). On mammography, a mass with an irregular (86%, 12/14) shape and an indistinct (43%, 6/14) or spiculated (43%, 6/14) margin was the most common findings on mammography. On sonography, a hypoechoic (91%, 20/22) mass with irregular shape (73%, 16/22) and an indistinct (32%, 7/22) or microlobulated (32%, 7/22) margin was the most common findings. Pathologically, axillary lymph node metastasis was present in 73% (16/22) of the patients. Invasive micropapillary carcinoma appeared an irregular shaped mass with an indistinct margin mass or microcalcifications on mammography and/or sonography. The tumors were frequently associated with axillary lymph node metastasis

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

    International Nuclear Information System (INIS)

    Kim, Cherry; Choi, Hyuck Jae; Cho, Kyoung-Sik

    2014-01-01

    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

  14. Predictive factors and prognosis for recurrent laryngeal nerve invasion in papillary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Chen W

    2017-09-01

    Full Text Available Wenjie Chen,1 Jianyong Lei,1 Jiaying You,2 Yali Lei,3 Zhihui Li,1 Rixiang Gong,1 Huairong Tang,3 Jingqiang Zhu1 1Thyroid and Parathyroid Surgery Center, 2West China School of Clinical Medicine, 3Health and Management Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China Background: Recurrent laryngeal nerve (RLN invasion in papillary thyroid carcinoma (PTC is one of the main predictors of poor prognosis. The present study investigated the risk factors for RLN invasion in PTC patients.Methods: A total of 3,236 patients who received thyroidectomy due to PTC in Thyroid and Parathyroid Surgery Center of West China Hospital of Sichuan University were reviewed. Demographics and clinical factors, imaging examination (ultrasonography characteristics, surgical details, postoperative pathological details, recurrence, and postoperative complications were recorded. Univariate and multivariate analyses were used to study the risk factors of RLN invasion, Kaplan–Meier method was performed to compare the outcomes of tumor recurrence.Results: Patients with RLN invasion had a higher recurrence rate than those in the control group (p<0.001. Multivariate analyses showed that age greater than 45 years (p<0.001, a largest tumor size bigger than 10 mm (p<0.001, clinical lymph node metastasis (cN1 (p<0.001, posterior focus (p<0.001, extrathyroidal extension (p<0.001, esophageal extension (p<0.001, tracheal extension (p<0.001, and preoperative vocal cord paralysis (p<0.001 were independent predictors for RLN invasion.Conclusion: PTC patients with RLN invasion have a negative prognosis and a higher recurrence rate. Meticulous operation and careful follow-up of patients with the above factors is recommended. Keywords: papillary thyroid carcinoma, recurrent laryngeal nerve invasion, predictive factors, lymph node metastases, Hashimoto’s thyroiditis

  15. Correlation of thyroid papillary carcinoma CEUS characteristics with cancer cell proliferation and invasion

    Directory of Open Access Journals (Sweden)

    Jing Wan

    2017-04-01

    Full Text Available Objective: To study the correlation of thyroid papillary carcinoma CEUS characteristics with cancer cell proliferation and invasion. Methods: A total of 128 patients with thyroid papillary carcinoma who received surgical treatment in the hospital between May 2013 and May 2016 were collected, CEUS was used to make clear the peak intensity (PI and area under the curve (AUC of tumor tissue and surrounding normal tissue, and the median of PI and AUC was referred to further divide the patients into high PI group and low PI group as well as high AUC group and low AUC group, 64 cases in each group. Fluorescent quantitative PCR was used to determine proliferation and invasion gene mRNA expression in tumor tissues. Results: PI and AUC levels in tumor tissue were lower than those in surrounding normal tissue; proliferation genes EZH2, Livin, hTERT, HMGA1 and Wip1 mRNA expression of low PI group were higher than those of high PI group, and invasion gene Ki-67 mRNA expression was higher than that of high PI group while P53 and MRP-1 mRNA expression were lower than those of high PI group; proliferation genes EZH2, Livin, hTERT, HMGA1 and Wip1 mRNA expression of low AUC group were higher than those of high AUC group, and invasion gene Ki-67 mRNA expression was higher than that of high AUC group while P53 and MRP-1 mRNA expression were lower than those of high AUC group. Conclusion: Thyroid papillary carcinoma CEUS parameters PI and AUC levels can quantifiably reflect the cancer cell proliferation and invasion activity.

  16. [Knockdown of NEDD9 inhibits the proliferation, invasion and migration of esophageal carcinoma EC109 cells].

    Science.gov (United States)

    Zhang, Wen; Li, Shaojun; Zhao, Yunlong; Guo, Nannan; Li, Yingjie

    2016-12-01

    Objective To observe the expression of the neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) in esophageal cancer, to investigate the impact of decreased expression of NEDD9 on invasion and migration, and to explicit the function of NEDD9 in EC109 human esophageal cancer cell line. Methods Immunohistochemical staining was used to detect the expression of NEDD9 in human esophageal cancer tissues and paracancerous normal tissues. RNA interfering (RNAi) was used to knockdown NEDD9 in EC109 cells. The interference efficiency was detected by reverse transcription PCR (RT-PCR) and Western blot analysis. Cell proliferation was determined by MTT assay and the invasion and migration abilities of EC109 cells were monitored by Transwell TM assay. The protein levels of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 were tested by Western blotting. Results The positive expression rate of NEDD9 in esophageal carcinoma tissues was significantly higher compared with that in the paracancerous tissues. After NEDD9 expression was successfully downregulated in EC109 cells by siRNA, the proliferation, invasion and migration rates in transfection group were significantly lower than those in control group; meanwhile, the expression of Bcl-2 was reduced and Bax expression was enhanced. Conclusion The protein expression level of NEDD9 is higher in esophageal carcinoma tissues than that in adjacent normal tissues. Knockdown of NEDD9 expression can restrain the proliferation, invasion and migration of EC109 cells.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Pokemon promotes the invasiveness of hepatocellular carcinoma by enhancing MEF2D transcription.

    Science.gov (United States)

    Kong, Jing; Liu, Xiaoping; Li, Xiangqian; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

    2016-05-01

    Pokemon, a master oncogene crucial for the tumorigenicity and progression of a variety of cancers, has been demonstrated to enhance the proliferation and survival of hepatocellular carcinoma (HCC). However, the contribution of Pokemon to the invasiveness of HCC has not yet been studied. In this study, we employed HCC cells to investigate the role of Pokemon in the invasion of HCC with multidisciplinary approaches. Pokemon overexpression was found to be closely associated with invasion and intrahepatic metastasis of HCC in clinical specimens. Suppression of Pokemon attenuated the invasion of HCC cells by in vitro transwell and wound-healing assays. Myocyte enhancer factor 2D (MEF2D), an oncogene that can promote the invasiveness of HCC, was found to be underexpressed during Pokemon silencing in HCC cells. Restoration of MEF2D abolished the effect of Pokemon downregulation on the migration of HCC cells. Further experiments verified that Pokemon binds two putative recognition sites located within the upstream region of the MEF2D promoter and enhances its transcription. The association between Pokemon and MEF2D was further confirmed in HCC specimens. Animal experiments further confirmed that Pokemon downregulation attenuated the metastasis of HCC cells in mice. Collectively, Pokemon was found to enhance the migration and invasion of HCC by increasing MEF2D expression. Thus, targeting Pokemon and MEF2D may be an effective strategy to suppress the metastasis of HCC.

  19. Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Robert Lesurf

    2016-07-01

    Full Text Available Breast cancer consists of at least five main molecular “intrinsic” subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.

  20. Pancreatic invasion of gastric carcinoma in emaciated patients: The value of combined analysis with CT and upper gastrointestinal series

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Mun; Kim, Hyun; Kim, Choon Yul; Bahk, Yong Whee [Catholic University Medical College, Seoul (Korea, Republic of)

    1992-03-15

    The obliteration of a fat plane between the gastric carcinoma and the pancreas is a major criterion on CT scan for pancreatic invasion of gastric carcinoma. However, this sign is not always a reliable indicator of invasion, as the patients with gastric carcinoma are often emaciated, producing a false positive CT findings. The purpose of our study is to improve the diagnostic accuracy of pancreatic invasion of gastric carcinoma in cases which the fat plane between the gastric carcinoma and the pancreas is obliterated in conventional CT scan. The authors performed lateral decubitus as well as supine CT scans and upper gastrointestinal series(UGIS) in 49 pathologically proven cases in which the fat plane was obliterated between the gastric carcinoma and the pancreas on conventional supine CT scan. Pancreatic invasion was suggested when the fat plane was obliterated persistently in the lateral decubitus view as well as the spine CT images and the involved gastric wall and adjacent pancreas maintained constant approximation despite postural change(CT+), and when the gastric tumor moved downward on the erect view of the UGIS no more than 1.5 times the height of the first lumbar vertebral body(UGIS+). Among 49 cases in which the fat plane between the gastric carcinoma and the pancreas was obliterated on supine CT scan, pancreatic invasion was confirmed pathologically in 11 cases(22.4%). Eight of 11 cases proven as pancreatic invasion were correctly diagnosed as pancreatic invasion by this combined analysis(CT+/UGIS+, 72.7%). Twenty seven of 38 cases proven as no pancreatic invasion were correctly diagnosed as no pancreatic invasion(CT-/UGIS-, 71.1%). Twelve cases showed CT+/UGIS- or CT-/UGIS+, so it was inconclusive whether there was invasion or not. The overall diagnostic accuracy was 71.4%. In conclusion, combined analysis with supine and lateral decubitus CT and UGIS is useful for improving diagnostic accuracy for pancreatic invasion by gastric carcinoma in patients of

  1. Pancreatic invasion of gastric carcinoma in emaciated patients: The value of combined analysis with CT and upper gastrointestinal series

    International Nuclear Information System (INIS)

    Lee, Jae Mun; Kim, Hyun; Kim, Choon Yul; Bahk, Yong Whee

    1992-01-01

    The obliteration of a fat plane between the gastric carcinoma and the pancreas is a major criterion on CT scan for pancreatic invasion of gastric carcinoma. However, this sign is not always a reliable indicator of invasion, as the patients with gastric carcinoma are often emaciated, producing a false positive CT findings. The purpose of our study is to improve the diagnostic accuracy of pancreatic invasion of gastric carcinoma in cases which the fat plane between the gastric carcinoma and the pancreas is obliterated in conventional CT scan. The authors performed lateral decubitus as well as supine CT scans and upper gastrointestinal series(UGIS) in 49 pathologically proven cases in which the fat plane was obliterated between the gastric carcinoma and the pancreas on conventional supine CT scan. Pancreatic invasion was suggested when the fat plane was obliterated persistently in the lateral decubitus view as well as the spine CT images and the involved gastric wall and adjacent pancreas maintained constant approximation despite postural change(CT+), and when the gastric tumor moved downward on the erect view of the UGIS no more than 1.5 times the height of the first lumbar vertebral body(UGIS+). Among 49 cases in which the fat plane between the gastric carcinoma and the pancreas was obliterated on supine CT scan, pancreatic invasion was confirmed pathologically in 11 cases(22.4%). Eight of 11 cases proven as pancreatic invasion were correctly diagnosed as pancreatic invasion by this combined analysis(CT+/UGIS+, 72.7%). Twenty seven of 38 cases proven as no pancreatic invasion were correctly diagnosed as no pancreatic invasion(CT-/UGIS-, 71.1%). Twelve cases showed CT+/UGIS- or CT-/UGIS+, so it was inconclusive whether there was invasion or not. The overall diagnostic accuracy was 71.4%. In conclusion, combined analysis with supine and lateral decubitus CT and UGIS is useful for improving diagnostic accuracy for pancreatic invasion by gastric carcinoma in patients of

  2. Concomitant endometrial and gallbladder metastasis in advanced multiple metastatic invasive lobular carcinoma of the breast: A rare case report.

    Science.gov (United States)

    Bezpalko, Kseniya; Mohamed, Mohamed A; Mercer, Leo; McCann, Michael; Elghawy, Karim; Wilson, Kenneth

    2015-01-01

    At time of presentation, fewer than 10% of patients have metastatic breast cancer. The most common sites of metastasis in order of frequency are bone, lung, pleura, soft tissue, and liver. Breast cancer metastasis to the uterus or gallbladder is rare and has infrequently been reported in the English literature. A 47 year old female with a recent history of thrombocytopenia presented with abnormal vaginal bleeding. Pelvic ultrasound revealed multiple uterine fibroids and endometrial curettings revealed cells consistent with lobular carcinoma of the breast. Breast examination revealed edema and induration of the lower half of the right breast. Biopsy of the right breast revealed invasive lobular carcinoma. Bone marrow aspiration obtained at a previous outpatient visit revealed extensive involvement by metastatic breast carcinoma. Shortly after discharge, the patient presented with acute cholecystitis and underwent cholecystectomy. Microscopic examination of the gallbladder revealed metastatic infiltrating lobular carcinoma. The final diagnosis was invasive lobular carcinoma of the right breast with metastasis to the bone marrow, endometrium, gallbladder, regional lymph nodes, and peritoneum. The growth pattern of invasive lobular carcinoma of the breast is unique and poses a challenge in diagnosing the cancer at an early stage. Unlike other types of breast cancer, it tends to metastasize more to the peritoneum, ovary, and gastrointestinal tract. Metastasis to the endometrium or gallbladder is rare. Metastatic spread should be considered in the differential diagnosis of patients with invasive lobular breast carcinoma presenting with abnormal vaginal bleeding or acute cholecystitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Correlation of Slug gene expression with lymph node metastasis and invasion molecule expression in oral squamous cell carcinoma tissue

    Directory of Open Access Journals (Sweden)

    Shan-Ming Lu

    2017-10-01

    Full Text Available Objective: To study the correlation of Slug gene expression with lymph node metastasis and invasion molecule expression in oral squamous cell carcinoma tissue. Methods: Oral squamous cell carcinoma tissue surgical removed in Affiliated Stomatological Hospital of Nanjing Medical University between March 2015 and April 2017 was selected and divided into the oral squamous cell carcinoma tissue with neck lymph node metastasis and the oral squamous cell carcinoma tissues without lymph node metastasis according to the condition of lymph node metastasis. The expression of Slug, epithelial-mesenchymal transition molecules and invasion molecules in the oral squamous cell carcinoma tissue were detected. Results: Slug, N-cadherin, Vimentin, CD147, OPN, GRP78, SDF-1 and CXCR4 protein expression in oral squamous cell carcinoma tissue with neck lymph node metastasis were significantly higher than those in oral squamous cell carcinoma tissue without lymph node metastasis while E-cadherin, P120ctn and ZO-1 protein expression were significantly lower than those in oral squamous cell carcinoma tissue without lymph node metastasis; N-cadherin, Vimentin, CD147, OPN, GRP78, SDF-1 and CXCR4 protein expression in oral squamous cell carcinoma tissue with high Slug expression were significantly higher than those in oral squamous cell carcinoma tissue with low Slug expression while E-cadherin, P120ctn and ZO-1 protein expression were significantly lower than those in oral squamous cell carcinoma tissue with low Slug expression. Conclusion: The highly expressed Slug in oral squamous cell carcinoma tissue can promote the epithelial-mesenchymal transition and invasion of the cells to participate in the lymph node metastasis of tumor cells.

  4. Invasive lobular carcinoma of the male breast – a systematic review with an illustrative case study

    Science.gov (United States)

    Senger, Jenna-Lynn; Adams, Scott J; Kanthan, Rani

    2017-01-01

    Male breast cancer is rare, comprising only 1% of all mammary cancers; invasive ductal carcinoma is by far the commonest subtype in both men and women. Though lobular breast cancer is the second most common subtype seen in women, such cancers are extremely uncommon in men, and this is likely related to the lack of lobular development in the male breast. Thus, due to the rarity of this subtype among breast cancers, compounded by the overall rarity of breast cancer in men, current understanding of the pathogenesis of this disease and its management is largely derived from case series and extrapolation of information from the larger cohort of female patients. This paper provides a systematic review on invasive lobular carcinoma of the male breast in the context of an illustrative case study. A comprehensive analysis of the National Cancer Institute’s Surveillance, Epidemiology, and End Results Data 1973–2013 leading to an exploration of the pathogenesis, epidemiology, clinical presentation, diagnosis, tumor characteristics, and management of lobular breast carcinoma in men is also discussed. Lobular subtype of breast cancer remains an enigmatic elusive disease that needs additional research to unravel its overall pathogenesis and molecular profile to provide insight for improved therapeutic management options. PMID:28553141

  5. Invasive lobular carcinoma of the male breast - a systematic review with an illustrative case study.

    Science.gov (United States)

    Senger, Jenna-Lynn; Adams, Scott J; Kanthan, Rani

    2017-01-01

    Male breast cancer is rare, comprising only 1% of all mammary cancers; invasive ductal carcinoma is by far the commonest subtype in both men and women. Though lobular breast cancer is the second most common subtype seen in women, such cancers are extremely uncommon in men, and this is likely related to the lack of lobular development in the male breast. Thus, due to the rarity of this subtype among breast cancers, compounded by the overall rarity of breast cancer in men, current understanding of the pathogenesis of this disease and its management is largely derived from case series and extrapolation of information from the larger cohort of female patients. This paper provides a systematic review on invasive lobular carcinoma of the male breast in the context of an illustrative case study. A comprehensive analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results Data 1973-2013 leading to an exploration of the pathogenesis, epidemiology, clinical presentation, diagnosis, tumor characteristics, and management of lobular breast carcinoma in men is also discussed. Lobular subtype of breast cancer remains an enigmatic elusive disease that needs additional research to unravel its overall pathogenesis and molecular profile to provide insight for improved therapeutic management options.

  6. Chemo-elastic modeling of invasive carcinoma development accompanied by oncogenic epithelial-mesenchymal transition

    Science.gov (United States)

    Bratsun, D. A.; Krasnyakov, I. V.; Pismen, L.

    2017-09-01

    We present a further development of a multiscale chemo-mechanical model of carcinoma growth in the epithelium tissue proposed earlier. The epithelium is represented by an elastic 2D array of polygonal cells, each with its own gene regulation dynamics. The model allows the simulation of evolution of multiple cells interacting via the chemical signaling or mechanically induced strain. The algorithm takes into account the division and intercalation of cells. The latter is most important since, first of all, carcinoma cells lose cell-cell adhesion and polarity via the oncogenic variant of the epithelial-mesenchymal transition (EMT) at which cells gain migratory and invasive properties. This process is mediated by E-cadherin repression and requires the differentiation of tumor cells with respect to the edge of the tumor that means that front cells should be most mobile. Taking into account this suggestion, we present the results of simulations demonstrating different patterns of carcinoma invasion. The comparison of our results with recent experimental observations is given and discussed.

  7. Comparative Long-term Study of a Large Series of Patients with Invasive Ductal Carcinoma and Invasive Lobular Carcinoma. Loco-Regional Recurrence, Metastasis, and Survival.

    Science.gov (United States)

    García-Fernández, Antonio; Lain, Josep María; Chabrera, Carol; García Font, Marc; Fraile, Manel; Barco, Israel; Torras, Merçe; Reñe, Asumpta; González, Sonia; González, Clarissa; Piqueras, Mercedes; Veloso, Enrique; Cirera, Lluís; Pessarrodona, Antoni; Giménez, Nuria

    2015-01-01

    Our aim was to compare histologic and immunohistochemical features, surgical treatment and clinical course, including disease recurrence, distant metastases, and mortality between patients with invasive ductal carcinoma (IDC) or invasive lobular carcinoma (ILC). We included 1,745 patients operated for 1,789 breast tumors, with 1,639 IDC (1,600 patients) and 145 patients with ILC and 150 breast tumors. The median follow-up was 76 months. ILC was significantly more likely to be associated with a favorable phenotype. Prevalence of contralateral breast cancer was slightly higher for ILC patients than for IDC patients (4.0% versus 3.2%; p = n.s). ILC was more likely multifocal, estrogen receptor positive, Human Epidermal Growth Factor Receptor-2 (HER2) negative, and with lower proliferative index compared to IDC. Considering conservative surgery, ILC patients required more frequently re-excision and/or mastectomy. Prevalence of stage IIB and III stages were significantly more frequent in ILC patients than in IDC patients (37.4% versus 25.3%, p = 0.006). Positive nodes were significantly more frequent in the ILC patients (44.6% versus 37.0%, p = 0.04). After adjustment for tumor size and nodal status, frequencies of recurrence/metastasis, disease-free and specific survival were similar among patients with IDC and patients with ILC. In conclusion, women with ILC do not have worse clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics rather than on lobular versus ductal histology. © 2015 Wiley Periodicals, Inc.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    International Nuclear Information System (INIS)

    Yoon, Hai-Jeon; Kim, Yemi; Kim, Bom Sahn

    2015-01-01

    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 18 F-FDG PET, diffusion-weighted imaging (DWI), or breast-specific gamma imaging (BSGI). We measured SUV 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 min ) and ADC difference (ADC 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 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 min (p = 0.016) and higher ADC 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 18 F-FDG PET was the most important predictor of invasive components of DCIS. (orig.)

  10. miR-367 promotes proliferation and invasion of hepatocellular carcinoma cells by negatively regulating PTEN

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Xiangrui, E-mail: mengxiangruibb2008@163.com [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Fan, Qingxia [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)

    2016-01-29

    MicroRNAs play important roles in the carcinogenesis of many types of cancers by inhibiting gene expression at posttranscriptional level. However, the roles of microRNAs in hepatocellular carcinoma, are still unclear. Here, we identified that miR-367 promotes hepatocellular carcinoma (HCC) cell proliferation by negatively regulates its target gene PTEN. The expression of miR-367 and PTEN are significantly inverse correlated in 35 HCC patients. In HCC cell line, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-367, while miR-367 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-367 mimics significantly promoted the migration and invasion of HCC cells, whereas miR-367 inhibitors significantly reduced cell migration and invasion. Luciferase assays confirmed that miR-367 directly bound to the 3'untranslated region of PTEN, and western blotting showed that miR-367 suppressed the expression of PTEN at the protein levels. This study indicated that miR-367 negatively regulates PTEN and promotes proliferation and invasion of HCC cells. Thus, miR-367 may represent a potential therapeutic target for HCC intervention. - Highlights: • miR-367 mimics promote the proliferation and invasion of HCC cells. • miR-367 inhibitors inhibit the proliferation and invasion of HCC cells. • miR-367 targets 3′UTR of PTEN in HCC cells. • miR-367 negatively regulates PTEN in HCC cells.

  11. Correlations of matrix metalloproteinase content and expression with invasion and metastasis of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zhang Zhichao; Jia Mingku; Sun Yaxin

    2006-01-01

    Objective: To investigate the correlations of serum matrix metalloproteinase-2, -9 (MMP-2, MMP-9) contents and tissue expressions in hepatocellular carcinoma with tumor invasion and metastasis. Methods: Serum MMP-2, MMP-9 contents were detected in 40 patient with hepatocellular carcinoma and 20 healthy controls by ELISA; the expressions and distributions of MMP-2 and MMP-9 in 40 patients and 10 normal tissues were detected by immunohistochemical method. Results: Serum MMP-2, MMP-9 contents were significantly elevated in cancer samples compared with normal serum (P<0.01), the significant difference was found between contents in the presence and the absence of lymph node metastasis (P<0.05). In hepatocellular carcinoma, the expressions of MMP-2, MMP-9 were increased significantly compared with normal tissue. The expressions of MMP-2, MMP-9 were correlated with histological grade and lymph node metastasis (P<0.05). Conclusion: The serum of MMP-2 and MMP-9 contents and their expressions may provide reliable information for hepatocellular carcinoma prognosis. (authors)

  12. Low-grade appendiceal mucinous neoplasm mimicking an adnexal mass.

    Science.gov (United States)

    Cristian, Daniel Alin; Grama, Florin Andrei; Becheanu, Gabriel; Pop, Anamaria; Popa, Ileana; Şurlin, Valeriu; Stănilescu, Sorin; Bratu, Ana Magdalena; Burcoş, Traean

    2015-01-01

    We present a rare case of malignant epithelial neoplasm of the appendix, an uncommon disorder encountered in clinical practice, which poses a variety of diagnostic and therapeutic challenges. We report a particular case in which the appendix was abnormally located in the pelvis, mimicking an adnexal mass. Therefore, it was difficult to make the preoperative diagnosis on clinical examination, imaging studies and laboratory tests and we discovered the lesion during the diagnostic laparoscopy. No lymphadenopathy or mucinous ascites were found. The case was completely handled via the laparoscopic approach keeping the appendix intact during the operation. The frozen section, the detailed histopathology overview as well as multiple immunostaining with a complex panel of markers report diagnosed a low-grade appendiceal mucinous neoplasm (LAMN) with no invasion of the wall. No adjuvant therapy was considered needed. At a one-year follow-up oncological assessment, the patient was free of disease. In women with cystic mass in the right iliac fossa an appendiceal mucocele should be considered in the differential diagnosis. Laparoscopic appendectomy can represent an adequate operation for the appendiceal mucinous neoplasm if the histological report is clear and surgical precautionary measures are taken.

  13. Cell surface heparan sulfate proteoglycans control adhesion and invasion of breast carcinoma cells

    DEFF Research Database (Denmark)

    Lim, Hooi Ching; Multhaupt, Hinke A. B.; Couchman, John R.

    2015-01-01

    breast carcinoma. This may derive from their regulation of cell adhesion, but roles for specific syndecans are unresolved. Methods: The MDA-MB231 human breast carcinoma cell line was exposed to exogenous glycosaminoglycans and changes in cell behavior monitored by western blotting, immunocytochemistry......, invasion and collagen degradation assays. Selected receptors including PAR-1 and syndecans were depleted by siRNA treatments to assess cell morphology and behavior. Immunohistochemistry for syndecan-2 and its interacting partner, caveolin-2 was performed on human breast tumor tissue arrays. Two......-tailed paired t-test and one-way ANOVA with Tukey¿s post-hoc test were used in the analysis of data. Results: MDA-MB231 cells were shown to be highly sensitive to exogenous heparan sulfate or heparin, promoting increased spreading, focal adhesion and adherens junction formation with concomitantly reduced...

  14. 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.

  15. Low-Grade Appendiceal Mucinous Neoplasm Involving the Endometrium and Presenting with Mucinous Vaginal Discharge

    OpenAIRE

    Vavinskaya, Vera; Baumgartner, Joel M.; Ko, Albert; Saenz, Cheryl C.; Valasek, Mark A.

    2016-01-01

    Primary appendiceal mucinous lesions are uncommon and represent a spectrum from nonneoplastic mucous retention cysts to invasive adenocarcinoma. Low-grade appendiceal mucinous neoplasms (LAMNs) represent an intermediate category on this spectrum and can be classified according to whether or not they are confined to the appendix. Although LAMNs are frequently confined to the appendix, they can also spread to the peritoneum and clinically progress as pseudomyxoma peritonei (i.e., mucinous ascit...

  16. Downregulation of Connective Tissue Growth Factor by Three-Dimensional Matrix Enhances Ovarian Carcinoma Cell Invasion

    Science.gov (United States)

    Barbolina, Maria V.; Adley, Brian P.; Kelly, David L.; Shepard, Jaclyn; Fought, Angela J.; Scholtens, Denise; Penzes, Peter; Shea, Lonnie D.; Sharon Stack, M

    2010-01-01

    Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic malignancy, due mainly to the prevalence of undetected metastatic disease. The process of cell invasion during intra-peritoneal anchoring of metastatic lesions requires concerted regulation of many processes, including modulation of adhesion to the extracellular matrix and localized invasion. Exploratory cDNA microarray analysis of early response genes (altered after 4 hours of 3-dimensional collagen culture) coupled with confirmatory real-time RT-PCR, multiple three-dimensional cell culture matrices, Western blot, immunostaining, adhesion, migration, and invasion assays were used to identify modulators of adhesion pertinent to EOC progression and metastasis. cDNA microarray analysis indicated a dramatic downregulation of connective tissue growth factor (CTGF) in EOC cells placed in invasion-mimicking conditions (3-dimensional type I collagen). Examination of human EOC specimens revealed that CTGF expression was absent in 46% of the tested samples (n=41), but was present in 100% of normal ovarian epithelium samples (n=7). Reduced CTGF expression occurs in many types of cells and may be a general phenomenon displayed by cells encountering a 3D environment. CTGF levels were inversely correlated with invasion such that downregulation of CTGF increased, while its upregulation reduced, collagen invasion. Cells adhered preferentially to a surface comprised of both collagen I and CTGF relative to either component alone using α6β1 and α3β1 integrins. Together these data suggest that downregulation of CTGF in EOC cells may be important for cell invasion through modulation of cell-matrix adhesion. PMID:19382180

  17. 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...

  18. 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.

  19. Intratumoral androgen metabolism and actions in invasive lobular carcinoma of the breast.

    Science.gov (United States)

    Yoda, Tomomi; McNamara, Keely May; Miki, Yasuhiro; Takagi, Mayu; Rai, Yoshiaki; Ohi, Yasuyo; Sagara, Yasuaki; Tamaki, Kentaro; Hirakawa, Hisashi; Ishida, Takanori; Suzuki, Takashi; Ohuchi, Noriaki; Sasano, Hironobu

    2014-11-01

    Invasive lobular carcinoma (ILC) accounts for approximately 10% of all breast carcinomas and is characterized by higher levels of androgen receptor (AR) compared to invasive ductal carcinoma (IDC). Despite this potentially androgen-responsive environment, the combined importance of AR and androgen metabolism in non-neoplastic lobules and lobular carcinoma remains unknown. Therefore, in this study, we evaluated the status of pivotal androgen-producing enzymes 17β-hydroxysteroid dehydrogenase type 5 (17βHSD5) and 5α-reductase type 1 (5αRed1) in 178 cases of ILC and surrounding histologically non-neoplastic lobular tissue using immunohistochemistry. Androgen receptor prevalence was higher but androgenic enzymes lower in ILC than non-neoplastic lobules. In ILC cases the status of 5αRed1 and 17βHSD5 was inversely correlated with tumor size (P = 0.0053) and nuclear grade (P = 0.0290), and significantly associated with better overall survival of the patients (P = 0.0059). Based on these findings, we hypothesized that androgen signaling could act as a tumor suppressor. As previous studies suggested that androgens might partially act by increasing levels of the estrogen inactivating enzyme 17β-hydroxysteroid dehydrogenase type 2 (17βHSD2) in IDC tissues, this was reasonably considered a potential mechanism of androgen actions. Significantly positive correlation was detected between the status of androgenic enzymes and 17βHSD2 (P Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  20. Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade

    Directory of Open Access Journals (Sweden)

    Kanika Gupta

    2018-01-01

    Full Text Available Context: Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Aims: Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. Settings and Design: A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Materials and Methods: Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR Breast Imaging Reporting and Data System (BI-RADS Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Statistical Analysis Used: Chi square test, ordinal regression, and Goodman and Kruskal tau test. Results: Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor ( β 1.566, P 0.0001. The masses with abrupt interface boundary are more likely grade 3 ( β 1.524, P 0.001 in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs with complex solid and cystic echotexture are more likely to be of high histological grade ( β 1.146, P 0.04 as compared to masses with hypoechoic echotexture. Conclusions: Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited.

  1. Sonographic features of invasive ductal breast carcinomas predictive of malignancy grade.

    Science.gov (United States)

    Gupta, Kanika; Kumaresan, Meenakshisundaram; Venkatesan, Bhuvaneswari; Chandra, Tushar; Patil, Aruna; Menon, Maya

    2018-01-01

    Assessment of individual sonographic features provides vital clues about the biological behavior of breast masses and can assist in determining histological grade of malignancy and thereby prognosis. Assessment of individual sonographic features of biopsy proven invasive ductal breast carcinomas as predictors of malignancy grade. A retrospective analysis of sonographic findings of 103 biopsy proven invasive ductal breast carcinomas. Tumor characteristics on gray-scale ultrasound and color flow were assessed using American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) Atlas Fifth Edition. The sonographic findings of masses were individually correlated with their histopathologic grades. Chi square test, ordinal regression, and Goodman and Kruskal tau test. Breast mass showing reversal/lack of diastolic flow has a high probability of belonging to histological high grade tumor ( β 1.566, P 0.0001 ). The masses with abrupt interface boundary are more likely grade 3 ( β 1.524, P 0.001 ) in comparison to masses with echogenic halos. The suspicious calcifications present in and outside the mass is a finding associated with histologically high grade tumors. The invasive ductal carcinomas (IDCs) with complex solid and cystic echotexture are more likely to be of high histological grade ( β 1.146, P 0.04 ) as compared to masses with hypoechoic echotexture. Certain ultrasound features are associated with tumor grade on histopathology. If the radiologist is cognizant of these sonographic features, ultrasound can be a potent modality for predicting histopathological grade of IDCs of the breast, especially in settings where advanced tests such as receptor and molecular analyses are limited.

  2. 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.

  3. Intradermal invasive lobular carcinoma presenting: Not everything in the skin is benign.

    Science.gov (United States)

    Eaton, Jennifer Wells; Drotman, Michele B; Sales, Rachel M; Arleo, Elizabeth Kagan

    In this case report, the history and imaging of two patients with invasive lobular carcinoma (ILC) in the skin are presented, followed by a discussion of both benign and malignant intradermal findings on breast ultrasound. Although the majority of dermal findings are benign, these cases are a reminder that malignancy can manifest within the skin. The purpose of presenting these cases together is to remind breast imagers of the importance of considering malignancy in the differential diagnosis of intradermal lesions on breast ultrasound, especially in special circumstances such as a personal history of breast cancer or associated clinical findings. Copyright © 2017. Published by Elsevier Inc.

  4. Mucinous urothelial carcinoma of the renal pelvis

    Directory of Open Access Journals (Sweden)

    Kemal Behzatoğlu

    2014-12-01

    Full Text Available Urothelial carcinoma with abundant myxoid stroma is a newly-described and extremely rare entity. Since only very few cases have been reported, there is no consensus on its nomenclature. Microscopic examination revealed invasive urothelial carcinoma with widespread low-grade noninvasive areas. There were focal invasive areas in the neighborhood of the renal parenchyma. Malignant urothelial tumor/cell groups localized in the stroma had abundant myxoid/mucinous background in the invasive areas. The cytoplasm of the tumoral cells was more eosinophilic in these areas and the cells formed small groups and cords. Histochemically, PAS and Alcian Blue were positive in the cytoplasm of the tumoral cells and in the stroma while negative in the non-mucinous areas. Immunohistochemically, the tumoral cells of the mucinous invasive areas diffusely expressed MUC1 and MUC2. We discuss the origin of the mucinous/myxoid stroma, the tumor’s nature and its nomenclature with histochemical and immunohistochemical features.

  5. A comparison of pelvic retroperitoneal pneumography and computed tomography in the assessment of extramural invasion of rectal carcinoma

    International Nuclear Information System (INIS)

    Kaibara, Nobuaki; Kimura, Osamu; Nishidoi, Hideaki; Ikeguchi, Masahide; Sugezawa, Akira; Sumi, Kenichi; Ohta, Michio; Koga, Shigemasa

    1988-01-01

    Pelvic retroperitoneal pneumography (PRP) and pelvic computed tomography (CT) were performed on 33 patients with rectal carcinoma in order to compare the usefulness of the two diagnostic procedures in the preoperative assessment of local malignant extramural invasion. Six PRP-negative patients in whom no free air was visualized in the retroperitoneal space surrounding the mass, were all assessed as having extramural invasion by CT scan and all had histologic evidence of invasion. Of 27 PRP-positive patients in whom free air was seen surrounding the mass, 18 were diagnosed as having extramural invasion on CT, 15 of whom had histologic proof of invasion. In the remaining 9 PRP-positive patients, there was no evidence of extramural invasion on the CT scans, but 5 patients showed evidence of invasion histologically. PRP, when positive, had an unacceptably high rate of being false positive and was therefore unreliable in assessing extramural invasion, whereas CT was able to detect, to some extent, extramural invasion which PRP failed to demonstrate. Based on these findings, we conclude that CT is more useful than PRP in the preoperative assessment of extramural invasion of rectal carcinoma, but is of limited diagnostic value when negative. (author)

  6. Role of fascin in the proliferation and invasiveness of esophageal carcinoma cells

    International Nuclear Information System (INIS)

    Xie, J.J.; Xu, L.Y.; Zhang, H.H.; Cai, W.J.; Mai, R.Q.; Xie, Y.M.; Yang, Z.M.; Niu, Y.D.; Shen, Z.Y.; Li, E.M.

    2005-01-01

    Fascin, an actin-bundling protein, induces membrane protrusions and increases cell motility in various transformed cells. The overexpression of fascin in esophageal squamous cell carcinoma (ESCC) has been described only recently, but the roles and mechanism still remained unclear. Here, by using RNA interference (RNAi), we have stably silenced the expression of the fascin in EC109 cells, an ESCC cell line. Down-regulation of fascin resulted in a suppression of cell proliferation and as well as a decrease in cell invasiveness. Furthermore, we revealed that fascin might have functions in regulating tumor growth in vivo. The effect of fascin on cell invasiveness correlated with the activation of matrix metalloproteases such as MMP-2 and MMP-9. We examined that fascin down-expression also led to a decrease of c-erbB-2 and β-catenin at the protein level. These results suggested that fascin might play crucial roles in regulating neoplasm progression of ESCC

  7. Positive enhancement integral values in dynamic contrast enhanced magnetic resonance imaging of breast carcinoma: Ductal carcinoma in situ vs. invasive ductal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nadrljanski, Mirjan, E-mail: dr.m.nadrljanski@gmail.com [Clinic for Radiology and Radiation Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia); Maksimović, Ružica [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia); Plešinac-Karapandžić, Vesna; Nikitović, Marina [Clinic for Radiology and Radiation Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia); Marković-Vasiljković, Biljana [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia); Milošević, Zorica [Clinic for Radiology and Radiation Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia)

    2014-08-15

    Objectives: The aim of this study was to contribute to the standardization of the numeric positive enhancement integral (PEI) values in breast parenchyma, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to evaluate the significance of the difference in PEI values between IDC and parenchyma, DCIS and parenchyma and IDC and DCIS. Materials and Methods: In the prospective trial, we analyzed the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of 60 consecutive patients with histologically confirmed unilateral DCIS (n = 30) and IDC (n = 30) and defined the PEI values (range; mean ± SD) for the lesions and the breast parenchyma. Tumor-to-non-tumor (T/NT) ratios were calculated for DCIS and IDC and compared. PEI color maps (PEICM) were created. The differences in PEI values between IDC and parenchyma and between DCIS and parenchyma were tested according to t-test. Analysis of variance (ANOVA) was used to test the differences between the mean PEI values of parenchyma, DCIS and IDC. Results: IDC showed highly statistically different PEI numeric values compared to breast parenchyma (748.7 ± 32.2 vs. 74.6 ± 17.0; p < 0.0001). The same applied to the differences in the group of patients with DCIS (428.0 ± 25.0 vs. 66.0 ± 10.6; p < 0.0001). The difference between IDC, DCIS and parenchyma were also considered highly statistically significant (p < 0.0001) and so were the T/NT ratios for IDC and DCIS (10.1 ± 2.4 vs. 6.6 ± 1.4; p < 0.0001). Conclusions: PEI numeric values may contribute to differentiation between invasive and in situ breast carcinoma.

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

    International Nuclear Information System (INIS)

    Wu, Bin; Li, Ji; Huang, Damao; Wang, Weiwei; Chen, Yu; Liao, Youxiang; Tang, Xiaowei; Xie, Hongfu; Tang, Faqing

    2011-01-01

    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

  9. Linc-POU3F3 is overexpressed in hepatocellular carcinoma and regulates cell proliferation, migration and invasion.

    Science.gov (United States)

    Li, Yichun; Li, Yannan; Wang, Dan; Meng, Qingdong

    2018-06-12

    Linc-POU3F3 showed an up-regulated tendency and functioned as tumor promoter in glioma, esophageal cancer and colorectal cancer. There was no report about the expression pattern and clinical value of linc-POU3F3 in hepatocellular carcinoma. Thus, the purpose of our study is to explore the clinical significance and biological role of linc-POU3F3 in hepatocellular carcinoma. Our results suggested that levels of linc-POU3F3 were dramatically increased in hepatocellular carcinoma tissues and cell lines compared with paired normal hepatic tissues and normal hepatic cell line, respectively. Levels of linc-POU3F3 were positively correlated with clinical stage, tumor size, vascular invasion and metastasis. Moreover, high-expression of linc-POU3F3 was an independent prognostic factor for hepatocellular carcinoma patients. The gain- and loss-of-function experiments showed that linc-POU3F3 expression significantly promoted tumor cell proliferation, migration and invasion. In addition, linc-POU3F3 expression was negatively correlated with POU3F3 mRNA and protein expressions in hepatocellular carcinoma tissues, and negatively regulated POU3F3 mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, our study supports the first evidence that linc-POU3F3 plays an oncogenic role in hepatocellular carcinoma, and represents a potential therapeutic strategy for hepatocellular carcinoma patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  10. Single-incision laparoscopic cecectomy for low-grade appendiceal mucinous neoplasm after laparoscopic rectectomy

    Science.gov (United States)

    Fujino, Shiki; Miyoshi, Norikatsu; Noura, Shingo; Shingai, Tatsushi; Tomita, Yasuhiko; Ohue, Masayuki; Yano, Masahiko

    2014-01-01

    In this case report, we discuss single-incision laparoscopic cecectomy for low-grade appendiceal neoplasm after laparoscopic anterior resection for rectal cancer. The optimal surgical therapy for low-grade appendiceal neoplasm is controversial; currently, the options include appendectomy, cecectomy, right hemicolectomy, and open or laparoscopic surgery. Due to the risk of pseudomyxoma peritonei, complete resection without rupture is necessary. We have encountered 5 cases of low-grade appendiceal neoplasm and all 5 patients had no lymph node metastasis. We chose the appendectomy or cecectomy without lymph node dissection if preoperative imaging studies did not suspect malignancy. In the present case, we performed cecectomy without lymph node dissection by single-incision laparoscopic surgery (SILS), which is reported to be a reduced port surgery associated with decreased invasiveness and patient stress compared with conventional laparoscopic surgery. We are confident that SILS is a feasible alternative to traditional surgical procedures for borderline tumors, such as low-grade appendiceal neoplasms. PMID:24868331

  11. Clinical features and outcomes of patients with hepatocellular carcinoma complicated with bile duct invasion

    Directory of Open Access Journals (Sweden)

    Jihyun An

    2017-06-01

    Full Text Available Background/Aims Little is known about the treatment or outcomes of hepatocellular carcinoma (HCC complicated with bile duct invasion. Methods A total of 247 consecutive HCC patients with bile duct invasion at initial diagnosis were retrospectively included. Results The majority of patients had Barcelona Clinic Liver Cancer (BCLC stage C HCC (66.8%. Portal vein tumor thrombosis was present in 166 (67.2% patients. Median survival was 4.1 months. Various modalities of treatment were initially employed including surgical resection (10.9%, repeated transarterial chemoembolization (TACE (42.5%, and conservative management (42.9%. Among the patients with obstructive jaundice (n=88, successful biliary drainage was associated with better overall survival rate. Among the patients with BCLC stage C, overall survival differed depending on the initial treatment for HCC; surgical resection, TACE, systemic chemotherapy, and conservative management showed overall survival rates of 11.5, 6.0 ,2.4, and 1.6 months, respectively. After adjusting for confounders, surgical resection and repeated TACE were significant prognostic factors for HCC patients with bile duct invasion (hazard ratios 0.47 and 0.39, Ps <0.001, respectively. Conclusions The survival of HCC patients with bile duct invasion at initial diagnosis is generally poor. However, aggressive treatments for HCC such as resection or biliary drainage may be beneficial therapeutic options for patients with preserved liver function.

  12. Silencing cathepsin S gene expression inhibits growth, invasion and angiogenesis of human hepatocellular carcinoma in vitro

    International Nuclear Information System (INIS)

    Fan, Qi; Wang, Xuedi; Zhang, Hanguang; Li, Chuanwei; Fan, Junhua; Xu, Jing

    2012-01-01

    Highlights: ► Cat S is highly expressed in HCC cells with high metastatic potential. ► Knockdown of Cat S inhibits growth and invasion of HCC cells. ► Knockdown of Cat S inhibits HCC-associated angiogenesis. ► Cat S might be a potential target for HCC therapy. -- Abstract: Cathepsin S (Cat S) plays an important role in tumor invasion and metastasis by its ability to degrade extracellular matrix (ECM). Our previous study suggested there could be a potential association between Cat S and hepatocellular carcinoma (HCC) metastasis. The present study was designed to determine the role of Cat S in HCC cell growth, invasion and angiogenesis, using RNA interference technology. Small interfering RNA (siRNA) sequences for the Cat S gene were synthesized and transfected into human HCC cell line MHCC97-H. The Cat S gene targeted siRNA-mediated knockdown of Cat S expression, leading to potent suppression of MHCC97-H cell proliferation, invasion and angiogenesis. These data suggest that Cat S might be a potential target for HCC therapy.

  13. Desalination using low grade heat sources

    Science.gov (United States)

    Gude, Veera Gnaneswar

    A new, low temperature, energy-efficient and sustainable desalination system has been developed in this research. This system operates under near-vacuum conditions created by exploiting natural means of gravity and barometric pressure head. The system can be driven by low grade heat sources such as solar energy or waste heat streams. Both theoretical and experimental studies were conducted under this research to evaluate and demonstrate the feasibility of the proposed process. Theoretical studies included thermodynamic analysis and process modeling to evaluate the performance of the process using the following alternate energy sources for driving the process: solar thermal energy, solar photovoltaic/thermal energy, geothermal energy, and process waste heat emissions. Experimental studies included prototype scale demonstration of the process using grid power as well as solar photovoltaic/thermal sources. Finally, the feasibility of the process in reclaiming potable-quality water from the effluent of the city wastewater treatment plant was studied. The following results have been obtained from theoretical analysis and modeling: (1) The proposed process can produce up to 8 L/d of freshwater for 1 m2 area of solar collector and evaporation chamber respectively with a specific energy requirement of 3122 kJ for 1 kg of freshwater production. (2) Photovoltaic/thermal (PV/T) energy can produce up to 200 L/d of freshwater with a 25 m2 PV/T module which meets the electricity needs of 21 kWh/d of a typical household as well. This configuration requires a specific energy of 3122 kJ for 1 kg of freshwater production. (3) 100 kg/hr of geothermal water at 60°C as heat source can produce up to 60 L/d of freshwater with a specific energy requirement of 3078 kJ for 1 kg of freshwater production. (4) Waste heat released from an air conditioning system rated at 3.25 kW cooling, can produce up to 125 L/d of freshwater. This configuration requires an additional energy of 208 kJ/kg of

  14. Identification of Prognostic Biomarkers for Progression of Invasive Squamous Cell Carcinoma

    Science.gov (United States)

    2017-10-09

    Carcinoma, Squamous Cell; Carcinoma, Squamous; Squamous Cell Carcinoma; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Lung Cancer; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms

  15. 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.

  16. Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents.

    Science.gov (United States)

    Iliadou, Paschalia K; Effraimidis, Grigoris; Konstantinos, Michalakis; Grigorios, Panagiotou; Mitsakis, Periklis; Patakiouta, Frideriki; Pazaitou-Panayiotou, Kalliopi

    2015-12-01

    The association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer is an interesting topic. The aim of the present study was to evaluate if demographic and histological characteristics as well as the long-term outcome of thyroid cancer was different in children and adolescents with and without CLT. The medical records of children and adolescents (≤21 years old) were reviewed. The following data were recorded: gender, year and age at diagnosis, family history of thyroid cancer, history of external radiation therapy, histological type (papillary and variants, follicular and variants), tumour size, multifocality, infiltration of thyroid parenchyma or surrounding soft tissues, vascular invasion, presence of lymph node and distant metastases. Information about the presence of TgAb and TPOAb was also collected. One hundred eight children and adolescents (median age 19.0, interquartile range 4.0 years) were diagnosed with differentiated thyroid carcinoma (DTC); 31 patients (28.7%) presented histological characteristics compatible with CLT. Infiltration of thyroid parenchyma was more frequent in patients with CLT compared to patients without (74.2% vs 48.1% respectively, P=0.024). Familial papillary thyroid carcinoma (PTC) was more frequent in patients with CLT compared to those without CLT (20.7% vs 2.8% respectively, P=0.009). There was no better outcome with respect to the presence of CLT or not. Children and adolescents with CLT present more frequently familial PTC as well as thyroid cancer with invasive characteristics. © 2015 European Society of Endocrinology.

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

    Directory of Open Access Journals (Sweden)

    Park In

    2010-12-01

    Full Text Available Abstract Background 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. Methods 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. Results 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 P P P P P 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. Conclusions ILC, a rare histologic type of breast cancer in Korea, has distinctive clinicopathological characteristics similar to those of LA-IDC.

  18. p120-Catenin Is Critical for the Development of Invasive Lobular Carcinoma in Mice.

    Science.gov (United States)

    Tenhagen, Milou; Klarenbeek, Sjoerd; Braumuller, Tanya M; Hofmann, Ilse; van der Groep, Petra; Ter Hoeve, Natalie; van der Wall, Elsken; Jonkers, Jos; Derksen, Patrick W B

    2016-12-01

    Loss of E-cadherin expression is causal to the development of invasive lobular breast carcinoma (ILC). E-cadherin loss leads to dismantling of the adherens junction and subsequent translocation of p120-catenin (p120) to the cytosol and nucleus. Although p120 is critical for the metastatic potential of ILC through the regulation of Rock-dependent anoikis resistance, it remains unknown whether p120 also contributes to ILC development. Using genetically engineered mouse models with mammary gland-specific inactivation of E-cadherin, p120 and p53, we demonstrate that ILC formation induced by E-cadherin and p53 loss is severely impaired upon concomitant inactivation of p120. Tumors that developed in the triple-knockout mice were mostly basal sarcomatoid carcinomas that displayed overt nuclear atypia and multinucleation. In line with the strong reduction in ILC incidence in triple-knockout mice compared to E-cadherin and p53 double-knockout mice, no functional redundancy of p120 family members was observed in mouse ILC development, as expression and localization of ARVCF, p0071 or δ-catenin was unaltered in ILCs from triple-knockout mice. In conclusion, we show that loss of p120 in the context of the p53-deficient mouse models is dominant over E-cadherin inactivation and its inactivation promotes the development of basal, epithelial-to-mesenchymal-transition (EMT)-type invasive mammary tumors.

  19. Metastatic pattern of invasive lobular carcinoma of the breast-Emphasis on gastric metastases.

    Science.gov (United States)

    El-Hage, Ali; Ruel, Carolanne; Afif, Wahiba; Wissanji, Hussein; Hogue, Jean-Charles; Desbiens, Christine; Leblanc, Guy; Poirier, Éric

    2016-10-01

    Breast invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) have different metastatic patterns, but the exact pattern of metastases from ILC is poorly known. This study aimed to determine the frequency of ILC metastases in atypical locations, with an emphasis on gastric metastases. Patients with ILC treated at the Saint-Sacrement Hospital (Quebec City, Canada) and the Maisonneuve-Rosemont Hospital (Montreal, Canada) between January 2003 and December 2009 were retrospectively reviewed. Demographic, clinical, and follow-up data were retrieved from the medical charts. Metastases that were diagnosed during follow-up were recorded. Among the 481 patients with ILC, 74 (15.4%) were diagnosed with metastases after a median follow-up of 46 months. Among these 74 patients, 41.9% had metastases in atypical sites. Five patients were diagnosed with histologically confirmed gastric metastases of ILC. Metastases of breast ILC to atypical sites might be more frequent than previously reported. Clinicians should keep a high level of suspicion when a patient with a history of ILC develops digestive symptoms. It is important to differentiate metastases from a primary GI tumor by using immunohistochemical markers. J. Surg. Oncol. 2016;114:543-547. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Expression of CPEB4 in invasive ductal breast carcinoma and its prognostic significance

    Directory of Open Access Journals (Sweden)

    Sun HT

    2015-11-01

    Full Text Available Hao-Ting Sun,1,2,* Xin Wen,3,* Tian Han,4,* Zhen-Hua Liu,5 Shao-Bo Li,1 Ji-Gang Wang,1 Xiu-Ping Liu61Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, 2Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 3Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Canton, Guangdong Province, 4Key Lab of Myopia, Ministry of Health, Department of Ophthalmology, Eye & ENT Hospital of Fudan University, Shanghai, 5Urology Department and Institute of Urology, Peking University First Hospital, Peking University, Beijing, 6Department of Pathology, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workAims: Cytoplasmic polyadenylation element binding proteins (CPEBs are RNA-binding proteins that regulate translation by inducing cytoplasmic polyadenylation. CPEB4 has been reported in association with tumor growth, vascularization, and invasion in several cancers. To date, the expression of CPEB4 with clinical prognosis of breast cancer was never reported before. We aim to investigate the expression of CPEB4 and its prognostic significance in invasive ductal breast carcinoma.Methods: Immunohistochemical staining of CPEB4 and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor was performed in 107 invasive ductal carcinoma (IDC samples, and prognostic significance was evaluated.Results: High expression of CPEB4 was observed in 48.6% of IDC samples. Elevated CPEB4 expression was possibly related to increased histological grading (P=0.037 and N stage (P<0.001. Patients with high expression of CPEB4 showed shorter overall survival (P=0.001. High CPEB4 expression was an independent prognostic factor for overall survival (P=0.022, hazard ratio =4.344, 95% confidence interval =1.235–15

  1. Predicting microscopic extrauterine spread of endometrial carcinoma with MRI to support less invasive therapy

    Energy Technology Data Exchange (ETDEWEB)

    Oishi Tanaka, Yumiko; Nishida, Masato; Minami, Rie; Yamaguchi, Masayuki; Itai, Yuji [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Yoshizako, Takeshi

    2000-06-01

    Magnetic resonance imaging (MRI) provides precise staging of endometrial carcinoma. However, we have sometimes experienced patients with microscopic extrauterine extension in whom MRI showed the disease as being limited to the uterus. We studied indirect MRI signs for microscopic extrauterine spread of endometrial carcinoma which outwardly seemed to be limited to within the uterus. MRI studies and the clinical records of 100 patients with surgically proven endometrial carcinoma were retrospectively reviewed. We evaluated: MRI staging, tumor growing at the orifices of the fallopian tube in the uterine fundus, hydrosalpinx, and ascites, in each MRI study. Surgical specimens showed that 12 of the 100 patients had extrauterine spread, with 1 patient showing both ovarian extension and omental metastasis; there ovarian extension in 3, extension to the fallopian tubes in 3, omental metastasis in 1, and positive peritoneal cytology in 4. Tumor growing at the orifices of the fallopian tubes with deep myometrial invasion showed higher accuracy for predicting microscopic intrauterine spread (82.0%) although it was not significantly different from the accuracy of deep myometrial invasion anywhere within the uterus (75.0%). However, tumor growing at the orifices of the fallopian tubes in patients with stage Ia disease showed a high negative predictive value (89.7%). Hydrosalpinx had the highest specificity (98.9%) and accuracy (88.0%); however, it did not seem to be practical because it was observed in only 2 patients. Ascites in postmenopausal patients showed higher specificity (93.5%), although it was not considered to be useful in the premenopausal patients. Tumor extension at the orifices of the fallopian tubes in patients with stage Ia disease, and ascites in postmenopausal patients on MRI seemed to be predictive factors for microscopic extrauterine spread. (author)

  2. 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 Plobular 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 between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.

  3. Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas.

    Science.gov (United States)

    Takagi, Mayu; Miki, Yasuhiro; Miyashita, Minoru; Hata, Shuko; Yoda, Tomomi; Hirakawa, Hisashi; Sagara, Yasuaki; Rai, Yoshiaki; Ohi, Yasuyo; Tamaki, Kentaro; Ishida, Takanori; Suzuki, Takashi; Ouchi, Noriaki; Sasano, Hironobu

    2016-02-01

    The great majority of invasive lobular carcinoma (ILC) is estrogen-dependent luminal A type carcinoma but the details of estrogen actions and its intratumoral metabolism have not been well studied compared to invasive ductal carcinoma (IDC). We first immunolocalized estrogen-related enzymes including estrogen sulfotransferase (EST), estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase (HSD) 1/2, and aromatase. We then evaluated the tissue concentrations of estrogens in ILC and IDC and subsequently estrogen-responsive gene profiles in these tumors in order to explore the possible differences and/or similarity of intratumoral estrogen environment of these two breast cancer subtypes. The status of STS and 17βHSD1 was significantly lower in ILCs than IDCs (p = 0.022 and p < 0.0001), but that of EST and 17βHSD2 vice versa (p < 0.0001 and p = 0.0106). In ILCs, tissue concentrations of estrone and estradiol were lower than those in IDCs (p = 0.0709 and 0.069). In addition, the great majority of estrogen response genes tended to be lower in ILCs. Among those genes above, FOXP1 was significantly higher in ILCs than in IDCs (p = 0.002). FOXP1 expression was reported to be significantly higher in relapse-free IDC patients treated with tamoxifen. Therefore, tamoxifen may be considered an option of endocrine therapy for luminal A type ILC patients. This is the first study to demonstrate the detailed and comprehensive status of intratumoral production and metabolism of estrogens and the status of estrogen response genes in luminal A-like ILC with comparison to those in luminal A-like IDCs.

  4. Knockdown of long noncoding RNA linc-ITGB1 suppresses migration, invasion of hepatocellular carcinoma via regulating ZEB1.

    Science.gov (United States)

    Yu, W-W; Wang, K; Liao, G-J

    2017-11-01

    This research focuses on the influence of linc-ITGB1 on the metastasis of hepatocellular carcinoma and further explores its underlying mechanism. A total of 70 hepatocellular carcinoma patients were chosen for our study. RT-qPCR was used for detecting the expression level of linc-ITGB1 in their cancer tissues. Moreover, the expression level of linc-ITGB1 was also detected in hepatocellular carcinoma cell lines. Furthermore, whether linc-ITGB1 could affect the migrated and invaded ability of hepatocellular carcinoma cells was determined by wound healing assay and transwell assay. We further explored the potential mechanism by RT-qPCR and Western blot assay. Linc-ITGB1 expression level in hepatocellular carcinoma tissues was remarkably higher than that in adjacent tissues. Moreover, migrated and invaded ability of hepatocellular carcinoma cells was inhibited through knockdown of linc-ITGB1. Further study revealed that silenced linc-ITGB1 inhibited the expression of ZEB1 and then suppressed epithelial to mesenchymal transition (EMT), which was important during the metastasis of hepatocellular carcinoma. Moreover, the inhibition of cell invasion by silenced linc-ITGB1 could be rescued through overexpression of ZEB1 in hepatocellular carcinoma. The results indicate that linc-ITGB1, a novel oncogene in tumorigenesis, could promote the metastasis and EMT via ZEB1, which may offer a possible therapeutic target in hepatocellular carcinoma.

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

    International Nuclear Information System (INIS)

    Zheng, Jin; Guo, Hang; Tao, Yurong; Xue, Yan; Jiang, Ning; Yao, Libo; Liu, Wenchao; Li, Yan; Yang, Jiandong; Liu, Qiang; Shi, Ming; Zhang, Rui; Shi, Hengjun; Ren, Qinyou; Ma, Ji

    2011-01-01

    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

  6. Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.

    Science.gov (United States)

    Arosarena, Oneida A; Barr, Eric W; Thorpe, Ryan; Yankey, Hilary; Tarr, Joseph T; Safadi, Fayez F

    2018-01-01

    Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p = 0.0001), and MMP-3 (p = 0.0005) and -9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p = 0.0408) and MMP-9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP-2 (p = 0.0023) and -9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion. © 2017 Wiley Periodicals, Inc.

  7. Loss of RUNX3 expression inhibits bone invasion of oral squamous cell carcinoma.

    Science.gov (United States)

    Park, Junhee; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Kim, Hyungkeun; Park, Kwang-Kyun; Chung, Won-Yoon

    2017-02-07

    High recurrence and lower survival rates in patients with oral squamous cell carcinoma (OSCC) are associated with its bone invasion. We identified the oncogenic role of RUNX3 during bone invasion by OSCC. Tumor growth and the generation of osteolytic lesions were significantly inhibited in mice that were subcutaneously inoculated with RUNX3-knockdown human OSCC cells. RUNX3 knockdown enhanced TGF-β-induced growth arrest and inhibited OSCC cell migration and invasion in the absence or presence of transforming growth factor-β (TGF-β), a major growth factor abundant in the bone microenvironment. RUNX3 knockdown induced cell cycle arrest at the G1 and G2 phases and promoted G2 arrest by TGF-β in Ca9.22 OSCC cells. RUNX3 knockdown also inhibited both the basal and TGF-β-induced epithelial-to-mesenchymal transition by increasing E-cadherin expression and suppressing the nuclear translocation of β-catenin. In addition, the expression and TGF-β-mediated induction of parathyroid hormone-related protein (PTHrP), one of key osteolytic factors, was blocked in RUNX3-knockdown OSCC cells. Furthermore, treating human osteoblastic cells with conditioned medium derived from RUNX3-knockdown OSCC cells reduced the receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin ratio compared with treatment with conditioned medium from RUNX3-expressing cells. These findings indicate that RUNX3 expression in OSCC cells contributes to their bone invasion and the resulting osteolysis by inducing their malignant behaviors and production of osteolytic factors. RUNX3 alone or in combination with TGF-β and PTHrP may be a useful predictive biomarker and therapeutic target for bone invasion by oral cancer.

  8. PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Shi, Guo-Zhen; Yuan, Yang; Jiang, Guo-Jun; Ge, Zhi-Jun; Zhou, Jian; Gong, De-Jun; Tao, Jing; Tan, Yong-Fei; Huang, Sheng-Dong

    2012-01-01

    Prenylated Rab acceptor 1 domain family member 3 (PRAF3) is involved in the regulation of many cellular processes including apoptosis, migration and invasion. This study was conducted to investigate the effect of PRAF3 on apoptosis, migration and invasion in human esophageal squamous cell carcinoma (ESCC). The expression of PRAF3 mRNA and protein in primary ESCC and the matched normal tissues (57cases) was determined by quantitative RT-PCR and Western blot. Immunohistochemical analysis of PRAF3 expression was carried out in paraffin-embedded sections of ESCC and correlated with clinical features. The role of PRAF3 in apoptosis, migration and invasion was studied in ESCC cell lines of Eca109 and TE-1 through the adenovirus mediated PRAF3 gene transfer. The effect of PRAF3 on apoptosis was analyzed by annexin V-FITC assay. The regulation of PRAF3 on migration was determined by transwell and wounding healing assay, while the cellular invasion was analyzed by matrigel-coated transwell assay. We found that the expression of PRAF3 was significantly down-regulated in ESCC tissue compared with the matched normal tissue and was correlated with the clinical features of pathological grade, tumor stage and lymph node metastasis. Moreover, overexpression of PRAF3 induced cell apoptosis through both caspase-8 and caspase-9 dependent pathways, and inhibited cell migration and invasion by suppressing the activity of both MMP-2 and MMP-9 in human ESCC cell lines. Our data suggest that PRAF3 plays an important role in the regulation of tumor progression and metastasis and serves as a tumor suppressor in human ESCC. We propose that PRAF3 might be used as a potential therapeutic agent for human ESCC

  9. 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.

  10. Results of salvage radiotherapy after inadequate surgery in invasive cervical carcinoma patients: A retrospective analysis

    International Nuclear Information System (INIS)

    Saibishkumar, Elantholi P.; Patel, Firuza D.; Ghoshal, Sushmita; Kumar, Vinay; Karunanidhi, Gunaseelan; Sharma, Suresh C.

    2005-01-01

    Purpose: To evaluate the results of salvage radiotherapy (RT) after inadequate surgery in patients with invasive carcinoma of the cervix. Methods and Materials: Between 1996 and 2001, 105 invasive cervical carcinoma patients were treated at our center with external beam RT with or without intracavitary RT after having undergone total/subtotal hysterectomy at outside institutions. Results: The median follow-up was 34 months. The gap between surgery and RT was 23-198 days (median, 80). Clinically visible residual disease was present in 81 patients (77.1%). Total hysterectomy had been done in 82 patients (78%) and subtotal hysterectomy in 23 patients (22%). The 5-year overall survival, disease-free survival, and pelvic control rates of all patients were 55.2%, 53.3%, and 72.4%, respectively. On univariate analysis, older age, total hysterectomy, hemoglobin level >10 g% before RT, nonsquamous histologic type, use of intracavitary RT, a shorter gap between surgery and RT, and the absence of, or a small volume of, residual disease favorably affected the outcome. The 5-year actuarial rate of late toxicity (Radiation Therapy Oncology Group Criteria) was 19% in the rectum, 4.8% in the bladder, 24.8% in the skin, and 14.3% in the small intestine. Conclusions: Inadequate and inappropriate surgery in invasive cervical cancer with resulting gross residual disease is common in India. Factors such as the use of intracavitary RT, the correction of anemia, and a shorter gap between surgery and RT will enable postoperative RT to achieve acceptable results with minimal morbidity

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

    Directory of Open Access Journals (Sweden)

    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

  12. Petrographic and Geochemical Study of Low Grade Metamorphic ...

    African Journals Online (AJOL)

    Key words: Low grade metamorphic rocks, Base metal mineralization, Petrography,. Hydrogeochemistry, Negash ... Use of mineral deposit genetic models has become an important ..... The clasts show elongation due to deformation, parallel.

  13. Diagnosis of the depth of invasion of esophageal carcinoma using digital radiography

    International Nuclear Information System (INIS)

    Ito, Bunichi; Niwa, Yasumasa; Ando, Nobuhiro; Ohmiya, Naoki; Miyahara, Ryoji; Ohashi, Akira; Itoh, Akihiro; Hirooka, Yoshiki; Goto, Hidemi

    2005-01-01

    Objective: The purpose of our investigation was to determine the usefulness of digital radiography (DR) for diagnosing the depth of invasion of esophageal carcinoma. Methods: We evaluated 59 patients with esophageal carcinomas who underwent DR. During continuous DR in tangential views, the most distended image of the esophagus was chosen. Percent esophageal stenosis (PES) was based on the diameter across the lesion of maximal narrowing and the average of the normal oral and anal side diameters. The maximal thickness of the tumor was measured on sequentially prepared specimens. We evaluated whether the percent of esophageal stenosis correlated with the maximal thickness of the tumor on histologic findings. Receiver-operating characteristic (ROC) curves were constructed to establish the cut-off level for PES in diagnosing the depth of tumor invasion. Accuracies for the depth of the invasion were calculated based on PES using DR. For the accuracy rate, DR was compared with endoscopy and endoscopic ultrasonography (EUS). Results: There was a close correlation between PES and pathological thickness of the tumor. PES values (mean ± S.D.) were 2.45 ± 0.75% in Tis and T1a tumors, 13.3 ± 10.9% in T1b tumors, 35.2 ± 11.1% in T2 tumors, 55.2 ± 18.1% in T3 tumors, and 86.1 ± 7.5% in T4 tumors. Using the ROC analysis, 12.5, 37.5, and 44.4% were the highest cut-off values of PES for differentiating ≤T1a, ≤T1b, and ≤T2 tumors. Regarding T staging, 45 (76%) of 59 lesions were staged correctly with EUS, whereas 47 (80%) were staged correctly with DR. Conclusion: DR is useful for diagnosing the depth of the invasion because esophageal stenosis calculated using DR is an objective index of tumor infiltration. The accuracy rate of the depth of invasion with DR was as good as that of EUS

  14. Uranium mobilization from low-grade ore by cyanobacteria

    International Nuclear Information System (INIS)

    Lorenz, M.G.; Krumbein, W.E.

    1985-01-01

    Three cyanobacterial isolates (two LPP-B forms and one Anabaena or Nostoc species) from different environments could mobilize uranium from low-grade ores. After 80 days, up to 18% uranium had been extracted from coal and 51% from a carbonate rock by the filamentous cyanobacterium OL3, a LPP-B form. Low growth requirements with regard to light and temperature optima make this strain a possible candidate for leaching neutral and alkaline low-grade uranium ores. (orig.)

  15. Uranium mobilization from low-grade ore by cyanobacteria

    Energy Technology Data Exchange (ETDEWEB)

    Lorenz, M.G.; Krumbein, W.E.

    1985-04-01

    Three cyanobacterial isolates (two LPP-B forms and one Anabaena or Nostoc species) from different environments could mobilize uranium from low-grade ores. After 80 days, up to 18% uranium had been extracted from coal and 51% from a carbonate rock by the filamentous cyanobacterium OL3, a LPP-B form. Low growth requirements with regard to light and temperature optima make this strain a possible candidate for leaching neutral and alkaline low-grade uranium ores.

  16. Significance of lymph node capsular invasion in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Sakai, Makoto; Suzuki, Shigemasa; Sano, Akihiko; Tanaka, Naritaka; Inose, Takanori; Sohda, Makoto; Nakajima, Masanobu; Miyazaki, Tatsuya; Kuwano, Hiroyuki

    2012-06-01

    Extranodal invasion (ENI) has been reported to be associated with a poor prognosis in several malignancies. However, previous studies have included perinodal fat tissue tumor deposits in their definitions of ENI. To investigate the precise nature of ENI in esophageal squamous cell carcinoma (ESCC), we excluded these tumor deposits from our definition of ENI and defined tumor cell invasion through the lymph node capsule and into the perinodal tissues as lymph node capsular invasion (LNCI). The aim of the current study was to elucidate the significance of LNCI in ESCC. We investigated the associations between LNCI and other clinicopathologic features in 139 surgically resected ESCC. We also investigated the prognostic significance of LNCI in ESCC. LNCI was detected in 35 (25.2%) of 139 patients. The overall survival rate of the ESCC patients with LNCI was significantly lower than that of the ESCC patients with lymph node metastasis who were negative for LNCI. The survival difference between the patients with 1–3 lymph node metastases without LNCI and those with no lymph node metastasis was not significant. LNCI was significantly associated with distant organ recurrence. LNCI was also found to be an independent predictor of overall survival in addition to the number of lymph node metastases. LNCI in ESCC patients is an indicator of distant organ recurrence and a worse prognosis. LNCI could be used as a candidate marker for designing more precise staging and therapeutic strategies for ESCC.

  17. Prognostic significance of morphometric parameters of nucleoli and nuclei of invasive ductal breast carcinomas.

    Science.gov (United States)

    Karpińska-Kaczmarczyk, Katarzyna; Kram, Andrzej; Kaczmarczyk, Mariusz; Domagała, Wenancjusz

    2009-01-01

    The aim of this study was to evaluate associations between seven morphometric parameters of the nucleoli and nuclei of methyl green and pyronin Y (MG-PY) stained tumour cells of invasive ductal breast carcinoma with relapse-free survival (RFS) and overall survival (OS) time. Histological sections from 150 invasive ductal breast cancers were stained with MG-PY and the following parameters were evaluated by computer image analysis: the nucleolar area, long to short nucleolar axis ratio, nucleolar shape parameter assessing the degree of nucleolar roundness, long to short nuclear axis ratio, number of nucleoli in the nucleus and the percentage of the nuclear cross-section surface area occupied by the nucleoli. A statistically significant association between a nucleolar shape polymorphism and the number of nucleoli in the nuclei of tumour cells and the RFS but not OS was found in the entire group of patients as well as patients with axillary lymph node metastases. A higher polymorphism of nucleolar shape and a higher number of nucleoli in the nuclei of breast cancer cells were associated with decreased relapse-free survival (p nucleoli in MG-PY stained histological sections can be useful in the analysis of associations between nucleolar parameters and prognosis of patients with invasive breast cancer.

  18. An epithelial to mesenchymal transition programme does not usually drive the phenotype of invasive lobular carcinomas.

    Science.gov (United States)

    McCart Reed, Amy E; Kutasovic, Jamie R; Vargas, Ana C; Jayanthan, Janani; Al-Murrani, Amel; Reid, Lynne E; Chambers, Rachael; Da Silva, Leonard; Melville, Lewis; Evans, Elizabeth; Porter, Alan; Papadimos, David; Thompson, Erik W; Lakhani, Sunil R; Simpson, Peter T

    2016-03-01

    Epithelial to mesenchymal transition (EMT) is a cellular phenotype switching phenomenon which occurs during normal development and is proposed to promote tumour cell invasive capabilities during tumour progression. Invasive lobular carcinoma (ILC) is a histological special type of breast cancer with a peculiar aetiology - the tumour cells display an invasive growth pattern, with detached, single cells or single files of cells, and a canonical feature is the loss of E-cadherin expression. These characteristics are indicative of an EMT or at the very least that they represent some plasticity between phenotypes. While some gene expression profiling data support this view, the tumour cells remain epithelial and limited immunohistochemistry data suggest that EMT markers may not feature prominently in ILC. We assessed the expression of a panel of EMT markers (fibronectin, vimentin, N-cadherin, smooth muscle actin, osteonectin, Snail, Twist) in 148 ILCs and performed a meta-analysis of publically available molecular data from 154 ILCs. Three out of 148 (2%) ILCs demonstrated an early and coordinated alteration of multiple EMT markers (down-regulation of E-cadherin, nuclear TWIST, and up-regulation of vimentin, osteonectin, and smooth muscle actin). However, the data overall do not support a role for EMT in defining the phenotypic peculiarities of the majority of ILCs. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  19. The value of intraoperative sonography in low grade glioma surgery.

    Science.gov (United States)

    Petridis, Athanasios K; Anokhin, Maxim; Vavruska, Jan; Mahvash, Mehran; Scholz, Martin

    2015-04-01

    There is a number of different methods to localize a glioma intraoperatively. Neuronavigation, intraoperative MRI, 5-aminolevulinic acid, as well as intraoperative sonography. Every method has its advantages and disadvantages. Low grade gliomas do not show a specific signal with 5-aminolevulinic acid and are difficult to distinguish macroscopically from normal tissue. In the present study we stress out the importance of intraoperative diagnostic ultrasound for localization of low grade gliomas. We retrospectively evaluated the charts and MRIs of 34 patients with low grade gliomas operated in our department from 2011 until December 2014. The efficacy of ultrasound as an intraoperative navigational tool was assessed. In 15 patients ultrasound was used and in 19 not. Only histologically proven low grades gliomas (astrocytomas grade II) were evaluated. In none of the patients where ultrasound (combined with neuronavigation) was used (N=15) to find the tumors, the target was missed, whereas the exclusive use of neuronavigation missed the target in 5 of 19 cases of small subcortical low grade gliomas. Intraoperative ultrasound is an excellent tool in localizing low grade gliomas intraoperatively. It is an inexpensive, real time neuronavigational tool, which overcomes brain shift. Even when identifying the tumors with ultrasound is very reliable, the extend of resection and the decision to remove any residual tumor with the help of ultrasound is at the moment unreliable. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Low-Grade Appendiceal Mucinous Neoplasm Involving the Endometrium and Presenting with Mucinous Vaginal Discharge.

    Science.gov (United States)

    Vavinskaya, Vera; Baumgartner, Joel M; Ko, Albert; Saenz, Cheryl C; Valasek, Mark A

    2016-01-01

    Primary appendiceal mucinous lesions are uncommon and represent a spectrum from nonneoplastic mucous retention cysts to invasive adenocarcinoma. Low-grade appendiceal mucinous neoplasms (LAMNs) represent an intermediate category on this spectrum and can be classified according to whether or not they are confined to the appendix. Although LAMNs are frequently confined to the appendix, they can also spread to the peritoneum and clinically progress as pseudomyxoma peritonei (i.e., mucinous ascites). Thus, the appropriate classification of appendiceal primary neoplasia is essential for prognosis and influences clinical management. In addition, the precise classification, management, and clinical outcome of patients with disseminated peritoneal disease remain controversial. Here, we report an unusual case of LAMN with pseudomyxoma peritonei that initially presented with mucinous and bloody vaginal discharge. Pathological evaluation revealed low-grade appendiceal mucinous neoplasm with secondary involvement of the peritoneum, ovaries, and endometrial surface. Therefore, LAMN should be considered in the differential diagnosis of mucinous vaginal discharge.

  1. Low-Grade Appendiceal Mucinous Neoplasm Involving the Endometrium and Presenting with Mucinous Vaginal Discharge

    Directory of Open Access Journals (Sweden)

    Vera Vavinskaya

    2016-01-01

    Full Text Available Primary appendiceal mucinous lesions are uncommon and represent a spectrum from nonneoplastic mucous retention cysts to invasive adenocarcinoma. Low-grade appendiceal mucinous neoplasms (LAMNs represent an intermediate category on this spectrum and can be classified according to whether or not they are confined to the appendix. Although LAMNs are frequently confined to the appendix, they can also spread to the peritoneum and clinically progress as pseudomyxoma peritonei (i.e., mucinous ascites. Thus, the appropriate classification of appendiceal primary neoplasia is essential for prognosis and influences clinical management. In addition, the precise classification, management, and clinical outcome of patients with disseminated peritoneal disease remain controversial. Here, we report an unusual case of LAMN with pseudomyxoma peritonei that initially presented with mucinous and bloody vaginal discharge. Pathological evaluation revealed low-grade appendiceal mucinous neoplasm with secondary involvement of the peritoneum, ovaries, and endometrial surface. Therefore, LAMN should be considered in the differential diagnosis of mucinous vaginal discharge.

  2. Elevated expression of MMP-13 and TIMP-1 in head and neck squamous cell carcinomas may reflect increased tumor invasiveness

    International Nuclear Information System (INIS)

    Culhaci, Nil; Metin, Kubilay; Copcu, Eray; Dikicioglu, Emel

    2004-01-01

    Matrix metalloproteinases [MMPs], which degrade the extracellular matrix, play an important role in the invasion and metastasis of squamous cell carcinomas. One MMP, MMP-13, is thought to play a central role in MMP activation. The purpose of this study was to investigate MMP-13 and TIMP-1 expression in squamous cell carcinomas of the head and neck and to relate these levels of expression to histologic patterns of invasion. This study included T1 lesions obtained via biopsy from the larynx, tongue, and skin/mucosa of 78 patients with head and neck squamous cell carcinomas. The relationship between expression of MMP-13 and TIMP-1 and the mode of tumor invasion [MI] was evaluated immunohistochemically, using breast carcinoma tissue as a positive control. Increased expression was observed in highly invasive tumors, as reflected by the significant correlation between the degree of staining for MMP-13 or TIMP-1 and MI grade [p < 0.05]. There was no significant relationship between the degree of staining for MMP-13 or TIMP-1 and patient age, sex, tumor site, or tumor histologic grade. In addition, levels of staining for MMP-13 did not correlate with levels of staining for TIMP-1. The expression of MMP-13 and TIMP-1 appears to play an important role in determining the invasive capacity of squamous cell carcinomas of the head and neck. Whereas additional studies are needed to confirm these findings, evaluating expression of these MMPs in small biopsy samples may be useful in determining the invasive capacity of these tumors at an earlier stage

  3. Successful treatment of low-grade endometrial cancer in premenopausal women with an aromatase inhibitor after failure with oral or intrauterine progesterone

    Directory of Open Access Journals (Sweden)

    Alli Straubhar

    2017-08-01

    Full Text Available Introduction: Young women with endometrial intraepithelial hyperplasia or low-grade endometrial carcinoma are potential candidates for conservative fertility sparing therapy utilizing progesterone rather than hysterectomy. High-dose progesterone treatment is associated with 55–80% initial response but high relapse rates. Using aromatase inhibitors in conjunction with high-dose progesterone has largely been unstudied. Case descriptions: Three obese premenopausal women with endometrial cancer failed to respond to oral or intrauterine progesterone as first line therapy. Due to their desire to continue to pursue fertility sparing treatment options, an aromatase inhibitor was added to their treatment regimen. This resulted in resolution of their malignancy in each case. Discussion: In obese premenopausal women, the mechanism of malignant transformation in endometrial carcinoma is considered to be an association with relatively high levels of serum estrogen from peripheral conversion of androgens to estrone in adipose tissue with a deficiency in progesterone exposure due to chronic anovulation. Using aromatase inhibitors seems reasonable as an adjunct to progesterone given the high likelihood that this population has a significant proportion of their estrogen production coming from peripheral conversion in adipose tissue. This case series is unique in that each woman initially failed to respond to progesterone but had resolution when an aromatase inhibitor was added to their treatment regimen. This would suggest that obese women with low grade malignancy or hyperplasia who have no radiographic evidence of deep myometrial invasion, ovarian or retroperitoneal metastases and who wish to retain their fertility may be treated with intrauterine progesterone and an aromatase inhibitor.

  4. Molecular and immunohistochemical profiling of invasive micropapillary carcinoma of the breast

    Directory of Open Access Journals (Sweden)

    Thomas A

    2014-10-01

    Full Text Available Alexandra Thomas,1 Ryan W Askeland,2 Natalya V Guseva,2 Ramakrishna Sompallae,2,3 Deqin Ma2 1Department of Internal Medicine, 2Department of Pathology, 3Bioinformatics Division, Iowa Institute of Human Genetics, University of Iowa Hospitals and Clinics, Iowa City, IA, USABackground: In this study, molecular and immunohistochemical profiling of invasive micropapillary carcinoma of the breast was used to identify potentially useful markers for targeted therapies with a focus on BRAF V600E mutation.Methods: Formalin-fixed, paraffin-embedded tumor blocks from seven patients were identified from the archives at our institution and tumor registry from 1997 to 2012. Massively parallel (Next-generation sequencing was performed using the Ion AmpliSeq™ Cancer Hotspot Panel version 2 (Life Technologies, Carlsbad, CA, USA. Mutation analysis for BRAF V600E was performed using a single nucleotide primer extension assay. Immunohistochemistry studies for estrogen receptor (ER, progesterone receptor (PR, Her2/Neu, phosphatase and tensin homolog (PTEN, and non-metastatic protein 23 homologue 1 (NM23H1 were performed using the same tumor blocks. Staining for ER, PR, and Her2/Neu was scored according to American Society of Clinical Oncology/College of American Pathologists guidelines, and a four-tier system, ie, strong homogenous, heterogeneous, positive with negative foci, reduced in more than 50%, and lost in all or majority was used for PTEN and NM23H1 staining.Results: No pathogenic mutations were identified in the tumors by next-generation sequencing. The lack of BRAF V600E mutation was confirmed by single nucleotide primer extension assay. All tumors were positive for ER and PR, and showed no overexpression of Her2/Neu. Loss of or reduced PTEN expression was observed in six of seven cases and was associated with lymph node metastasis. Reduced NM23H1 expression was observed in three of seven cases, all of which had concurrent PTEN loss.Conclusion: No somatic

  5. Loss of p53 promotes anaplasia and local invasion in ret/PTC1-induced thyroid carcinomas.

    Science.gov (United States)

    La Perle, K M; Jhiang, S M; Capen, C C

    2000-08-01

    Papillary thyroid carcinomas in humans are associated with the ret/PTC oncogene and, following loss of p53 function, may progress to anaplastic carcinomas. Mice with thyroid-targeted expression of ret/PTC1 developed papillary thyroid carcinomas that were minimally invasive and did not metastasize. These mice were crossed with p53-/- mice to investigate whether loss of p53 would promote anaplasia and metastasis of ret/PTC1-induced thyroid tumors. The majority of p53-/- mice died or were euthanized by 17 weeks of age due to the development of thymic lymphomas, soft tissue sarcomas, and testicular teratomas. All ret/PTC1 mice developed thyroid carcinomas, but tumors in p53-/- mice were more anaplastic, larger in diameter, more invasive, and had a higher mitotic index than tumors in p53+/+ and p53+/- mice. Thyroid tumors did not metastasize in any of the experimental p53+/+ and p53+/- mice anaplasia and invasiveness of thyroid carcinomas.

  6. The expression of prostate-specific antigen in invasive breast carcinoma and its relationship with routine clinicopathologic parameters

    Directory of Open Access Journals (Sweden)

    Fereshteh Mohammadizadeh

    2012-01-01

    Full Text Available Background: Invasive breast carcinoma is one of the most common cancers of women. Parameters such as lymph node status, tumor grade, and the status of hormone receptors are among the main prognostic determinants of this cancer. Immunohistochemical detection of prostate-specific antigen (PSA is widely used to identify metastatic prostatic adenocarcinoma. However, its immunoreactivity has been found in some non-prostatic tissues. This study was conducted to assess PSA expression in invasive breast carcinoma and its relationship with routine clinicopathologic parameters. Materials and Methods: 100 formalin-fixed and paraffin-embedded invasive breast carcinoma tissue specimens from the pathology archive of Alzahra hospital (Isfahan, Iran were studied for the expression of estrogen receptor (ER, progesterone receptor (PR, HER2/neu, and PSA by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of cells showing PSA staining. The relationship between PSA expression and other markers, age, lymph node status, tumor subtype, and tumor grade was then studied. Results: No association was found between PSA expression on one hand and PR, Her2/neu, age, lymph node status, tumor grade, and tumor subtype on the other. PSA score was reversely correlated with ER expression (P = 0.015. Conclusion: Despite the reverse relationship between PSA expression and the immunoreactivity of ER, PSA expression was not correlated with other prognostic factors. Therefore, the detection of PSA by immunohistochemistry does not seem to be a significant prognostic parameter in patients with invasive breast carcinoma.

  7. Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ

    NARCIS (Netherlands)

    de Leeuw, W. J.; Berx, G.; Vos, C. B.; Peterse, J. L.; van de Vijver, M. J.; Litvinov, S.; van Roy, F.; Cornelisse, C. J.; Cleton-Jansen, A. M.

    1997-01-01

    Loss of expression of the intercellular adhesion molecule E-cadherin frequently occurs in invasive lobular breast carcinomas as a result of mutational inactivation. Expression patterns of E-cadherin and the molecules comprising the cytoplasmic complex of adherens junctions, alpha-, beta- and

  8. Prognostic significance of cyclin D1 protein expression and gene amplification in invasive breast carcinoma.

    Directory of Open Access Journals (Sweden)

    Angela B Ortiz

    Full Text Available The oncogenic capacity of cyclin D1 has long been established in breast cancer. CCND1 amplification has been identified in a subset of patients with poor prognosis, but there are conflicting data regarding the predictive value of cyclin D1 protein overexpression. This study was designed to analyze the expression of cyclin D1 and its correlation with CCND1 amplification and their prognostic implications in invasive breast cancer. By using the tissue microarray technique, we performed an immunohistochemical study of ER, PR, HER2, p53, cyclin D1, Ki67 and p16 in 179 invasive breast carcinoma cases. The FISH method was performed to detect HER2/Neu and CCND1 amplification. High cyclin D1 expression was identified in 94/179 (52% of invasive breast cancers. Cyclin D1 overexpression and CCND1 amplification were significantly associated (p = 0.010. Overexpression of cyclin D1 correlated with ER expression, PR expression and Luminal subtypes (p<0.001, with a favorable impact on overall survival in the whole series. However, in the Luminal A group, high expression of cyclin D1 correlated with shorter disease-free survival, suggesting that the prognostic role of cyclin D1 depends on the molecular subtype. CCND1 gene amplification was detected in 17 cases (9% and correlated significantly with high tumor grade (p = 0.038, high Ki-67 protein expression (p = 0.002, and the Luminal B subtype (p = 0.002. Patients with tumors with high amplification of CCND1 had an increased risk of recurrence (HR = 2.5; 95% CI, 1.2-4.9, p = 0.01. These findings suggest that CCND1 amplification could be useful for predicting recurrence in invasive breast cancer.

  9. β-Catenin promotes cell proliferation, migration, and invasion but induces apoptosis in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yang CM

    2017-02-01

    Full Text Available Chun-ming Yang,1 Shan Ji,2 Yan Li,3 Li-ye Fu,3 Tao Jiang,3 Fan-dong Meng31Department of Urology, The First Affiliated Hospital, China Medical University, 2Department of Endocrinology, The Fifth People’s Hospital of Shenyang, 3Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital, China Medical University, Shenyang, ChinaAbstract: β-Catenin (CTNNB1 gene coding protein is a component of the Wnt signaling pathway that has been shown to play an important role in the formation of certain cancers. Abnormal accumulation of CTNNB1 contributes to most cancers. This research studied the involvement of β-catenin in renal cell carcinoma (RCC cell proliferation, apoptosis, migration, and invasion. Proliferation, cell cycle, and apoptosis were analyzed by using Cell Counting Kit-8 and by flow cytometry. Migration and invasion assays were measured by transwell analysis. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of CTNNB1, ICAM-1, VCAM-1, CXCR4, and CCL18 in RCC cell lines. It was found that CTNNB1 knockdown inhibited cell proliferation, migration, and invasion and induced apoptosis of A-498 cells. CTNNB1 overexpression promoted cell proliferation, migration, and invasion and inhibited apoptosis of 786-O cells. Moreover, knockdown of CTNNB1 decreased the levels of ICAM-1, VCAM-1, CXCR4, and CCL18 expression, but CTNNB1 overexpression increased the expression of ICAM-1, VCAM-1, CXCR4, and CCL18. Further in vivo tumor formation study in nude mice indicated that inhibition of CTNNB1 delayed the progress of tumor formation through inhibiting PCNA and Ki67 expression. These results indicate that CTNNB1 could act as an oncogene and may serve as a promising therapeutic strategy for RCC.Keywords: kidney cancer, oncogene, β-catenin, survival time, tumor migration-related protein

  10. Estrogen switches pure mucinous breast cancer to invasive lobular carcinoma with mucinous features.

    Science.gov (United States)

    Jambal, Purevsuren; Badtke, Melanie M; Harrell, J Chuck; Borges, Virginia F; Post, Miriam D; Sollender, Grace E; Spillman, Monique A; Horwitz, Kathryn B; Jacobsen, Britta M

    2013-01-01

    Mucinous breast cancer (MBC) is mainly a disease of postmenopausal women. Pure MBC is rare and augurs a good prognosis. In contrast, MBC mixed with other histological subtypes of invasive disease loses the more favorable prognosis. Because of the relative rarity of pure MBC, little is known about its cell and tumor biology and relationship to invasive disease of other subtypes. We have now developed a human breast cancer cell line called BCK4, in which we can control the behavior of MBC. BCK4 cells were derived from a patient whose poorly differentiated primary tumor was treated with chemotherapy, radiation and tamoxifen. Malignant cells from a recurrent pleural effusion were xenografted in mammary glands of a nude mouse. Cells from the solid tumor xenograft were propagated in culture to generate the BCK4 cell line. Multiple marker and chromosome analyses demonstrate that BCK4 cells are human, near diploid and luminal, expressing functional estrogen, androgen, and progesterone receptors. When xenografted back into immunocompromised cycling mice, BCK4 cells grow into small pure MBC. However, if mice are supplemented with continuous estradiol, tumors switch to invasive lobular carcinoma (ILC) with mucinous features (mixed MBC), and growth is markedly accelerated. Tamoxifen prevents the expansion of this more invasive component. The unexpected ability of estrogens to convert pure MBC into mixed MBC with ILC may explain the rarity of the pure disease in premenopausal women. These studies show that MBC can be derived from lobular precursors and that BCK4 cells are new, unique models to study the phenotypic plasticity, hormonal regulation, optimal therapeutic interventions, and metastatic patterns of MBC.

  11. Prediction of Occult Invasive Disease in Ductal Carcinoma in Situ Using Deep Learning Features.

    Science.gov (United States)

    Shi, Bibo; Grimm, Lars J; Mazurowski, Maciej A; Baker, Jay A; Marks, Jeffrey R; King, Lorraine M; Maley, Carlo C; Hwang, E Shelley; Lo, Joseph Y

    2018-03-01

    The aim of this study was to determine whether deep features extracted from digital mammograms using a pretrained deep convolutional neural network are prognostic of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. In this retrospective study, digital mammographic magnification views were collected for 99 subjects with DCIS at biopsy, 25 of which were subsequently upstaged to invasive cancer. A deep convolutional neural network model that was pretrained on nonmedical images (eg, animals, plants, instruments) was used as the feature extractor. Through a statistical pooling strategy, deep features were extracted at different levels of convolutional layers from the lesion areas, without sacrificing the original resolution or distorting the underlying topology. A multivariate classifier was then trained to predict which tumors contain occult invasive disease. This was compared with the performance of traditional "handcrafted" computer vision (CV) features previously developed specifically to assess mammographic calcifications. The generalization performance was assessed using Monte Carlo cross-validation and receiver operating characteristic curve analysis. Deep features were able to distinguish DCIS with occult invasion from pure DCIS, with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval, 0.68-0.73). This performance was comparable with the handcrafted CV features (area under the curve = 0.68; 95% confidence interval, 0.66-0.71) that were designed with prior domain knowledge. Despite being pretrained on only nonmedical images, the deep features extracted from digital mammograms demonstrated comparable performance with handcrafted CV features for the challenging task of predicting DCIS upstaging. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  12. Diagnostic Accuracy of Diffusion Weighted Magnetic Resonance Imaging in the Detection of Myometrial Invasion in Endometrial Carcinoma

    International Nuclear Information System (INIS)

    Masroor, I.; Hussain, Z.; Taufiq, M.

    2016-01-01

    Objective: To determine the diagnostic accuracy of Diffusion-Weighted Magnetic Resonance Imaging (DWMRI) in the detection of myometrial invasion in endometrial cancer taking histopathology as gold standard. Study Design: Cross-sectional validation study. Place and Duration of Study: Department of Radiology, The Aga Khan University Hospital, Karachi, from January to December 2012. Methodology: DWMRI (b-value = 50,400 and 800 s/mm2) was performed in 85 patients of biopsy-proven endometrial carcinoma before hysterectomy using body and spine coil at 1.5 Tesla. DWI was evaluated for presence of myometrial invasion by tumor with histopathology as gold standard. Sensitivity, specificity, the negative predictive value and positive predictive value and accuracy of DWI were assessed against the gold standard. Results: On DWI, superficial myometrial invasion was found in 42 patients and deep myometrial invasion in 43. On histopathology, superficial myometrial invasion was found in 53 patients and deep myometrial invasion in 32. Hence sensitivity, specificity, positive predictive value, negative predictive value and accuracy for the assessment of myometrial invasion by endometrial tumor on DW images was 90 percentage, 73 percentage, 67 percentage, 92 percentage and 80 percentage, respectively. Diagnostic accuracy of diffusion-weighted magnetic resonance imaging in detection of myometrial invasion in endometrial cancer was 80 percentage. Conclusion: DWI is highly accurate in assessing myometrial invasion and can be used as an adjunct to routine MRI for pre-operative evaluation of myometrial invasion of endometrial cancer. (author)

  13. Clinical Outcomes Using Accelerated Partial Breast Irradiation in Patients With Invasive Lobular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Chirag; Wilkinson, J. Ben; Shaitelman, Simona; Grills, Inga; Wallace, Michelle; Mitchell, Christina [Department of Radiation Oncology, Beaumont Cancer Institute, Oakland University William Beaumont School of Medicine, Royal Oak, MI (United States); Vicini, Frank, E-mail: fvicini@beaumont.edu [Department of Radiation Oncology, Beaumont Cancer Institute, Oakland University William Beaumont School of Medicine, Royal Oak, MI (United States)

    2011-11-15

    Purpose: We compared clinical outcomes of women diagnosed with either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC) treated with accelerated partial breast irradiation (APBI). Methods and Materials: A total of 16 patients with ILC received APBI as part of their breast-conservation therapy (BCT) and were compared with 410 patients with IDC that received APBI as part of their BCT. Clinical, pathologic, and treatment related variables were analyzed including age, tumor size, hormone receptor status, surgical margins, lymph node status, adjuvant hormonal therapy, adjuvant chemotherapy, and APBI modality. Clinical outcomes including local recurrence (LR), regional recurrence (RR), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed. Results: Median follow-up was 3.8 years for the ILC patients and 6.0 years for the IDC patients. ILC patients were more likely to have positive margins (20.0% vs. 3.9%, p = 0.006), larger tumors (14.1 mm vs. 10.9 mm, p = 0.03) and less likely to be node positive (0% vs. 9.5%, p < 0.001) when compared with patients diagnosed with IDC. The 5-year rate of LR was 0% for the ILC cohort and 2.5% for the IDC cohort (p = 0.59). No differences were seen in the rates of RR (0% vs. 0.7%, p = 0.80), distant metastases (0% vs. 3.5%, p = 0.54), DFS (100% vs. 94%, p = 0.43), CSS (100% vs. 97%, p = 0.59), or OS (92% vs. 89%, p = 0.88) between the ILC and IDC patients, respectively. Additionally, when node-positive patients were excluded from the IDC cohort, no differences in the rates of LR (0% vs. 2.2%, p = 0.62), RR (0% vs. 0%), DFS (100% vs. 95%, p = 0.46), CSS (100% vs. 98%, p = 0.63), or OS (92% vs. 89%, p = 0.91) were noted between the ILC and IDC patients. Conclusion: Women with ILC had excellent clinical outcomes after APBI. No difference in local control was seen between patients with invasive lobular versus invasive ductal histology.

  14. Clinical Outcomes Using Accelerated Partial Breast Irradiation in Patients With Invasive Lobular Carcinoma

    International Nuclear Information System (INIS)

    Shah, Chirag; Wilkinson, J. Ben; Shaitelman, Simona; Grills, Inga; Wallace, Michelle; Mitchell, Christina; Vicini, Frank

    2011-01-01

    Purpose: We compared clinical outcomes of women diagnosed with either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC) treated with accelerated partial breast irradiation (APBI). Methods and Materials: A total of 16 patients with ILC received APBI as part of their breast-conservation therapy (BCT) and were compared with 410 patients with IDC that received APBI as part of their BCT. Clinical, pathologic, and treatment related variables were analyzed including age, tumor size, hormone receptor status, surgical margins, lymph node status, adjuvant hormonal therapy, adjuvant chemotherapy, and APBI modality. Clinical outcomes including local recurrence (LR), regional recurrence (RR), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed. Results: Median follow-up was 3.8 years for the ILC patients and 6.0 years for the IDC patients. ILC patients were more likely to have positive margins (20.0% vs. 3.9%, p = 0.006), larger tumors (14.1 mm vs. 10.9 mm, p = 0.03) and less likely to be node positive (0% vs. 9.5%, p < 0.001) when compared with patients diagnosed with IDC. The 5-year rate of LR was 0% for the ILC cohort and 2.5% for the IDC cohort (p = 0.59). No differences were seen in the rates of RR (0% vs. 0.7%, p = 0.80), distant metastases (0% vs. 3.5%, p = 0.54), DFS (100% vs. 94%, p = 0.43), CSS (100% vs. 97%, p = 0.59), or OS (92% vs. 89%, p = 0.88) between the ILC and IDC patients, respectively. Additionally, when node-positive patients were excluded from the IDC cohort, no differences in the rates of LR (0% vs. 2.2%, p = 0.62), RR (0% vs. 0%), DFS (100% vs. 95%, p = 0.46), CSS (100% vs. 98%, p = 0.63), or OS (92% vs. 89%, p = 0.91) were noted between the ILC and IDC patients. Conclusion: Women with ILC had excellent clinical outcomes after APBI. No difference in local control was seen between patients with invasive lobular versus invasive ductal histology.

  15. The diacylglycerol kinase α/atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness.

    Directory of Open Access Journals (Sweden)

    Elena Rainero

    Full Text Available Diacylglycerol kinase α (DGKα, by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of β1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and β1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - β1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells.

  16. The pattern of invasive lobular carcinoma in the patients diagnosed with breast cancer from Balochistan.

    Science.gov (United States)

    Baloch, A H; Khosa, A N; Bangulzai, N; Sadia, H; Ahmed, M; Khan, F; Jan, M; Tareen, M; Kakar, M H; Shuja, J; Naseeb, H K; Ahmad, J

    2016-01-01

    Invasive lobular carcinoma (ILC) is the second most common type of breast cancer accounting for 5%-15% of all the breast cancer cases. The present study was performed on 171 breast cancer patients from Balochistan registered in CENAR (Center for Nuclear Medicine and Radiotherapy), Quetta. Written consent was obtained from the patients. The history of the disease was taken from the patients, and the patients' enrollment files were retrieved. Of the 171 patients, 5 (2.96%) were diagnosed with ILC with tumor Grade II, and stage of the cancer reported was Grade III in all the 5 patients affected with ILC. ILC is the second most common type of breast cancer diagnosed with comparatively lower grade but almost reported infiltrating.

  17. Automated image analysis of cyclin D1 protein expression in invasive lobular breast carcinoma provides independent prognostic information.

    Science.gov (United States)

    Tobin, Nicholas P; Lundgren, Katja L; Conway, Catherine; Anagnostaki, Lola; Costello, Sean; Landberg, Göran

    2012-11-01

    The emergence of automated image analysis algorithms has aided the enumeration, quantification, and immunohistochemical analyses of tumor cells in both whole section and tissue microarray samples. To date, the focus of such algorithms in the breast cancer setting has been on traditional markers in the common invasive ductal carcinoma subtype. Here, we aimed to optimize and validate an automated analysis of the cell cycle regulator cyclin D1 in a large collection of invasive lobular carcinoma and relate its expression to clinicopathologic data. The image analysis algorithm was trained to optimally match manual scoring of cyclin D1 protein expression in a subset of invasive lobular carcinoma tissue microarray cores. The algorithm was capable of distinguishing cyclin D1-positive cells and illustrated high correlation with traditional manual scoring (κ=0.63). It was then applied to our entire cohort of 483 patients, with subsequent statistical comparisons to clinical data. We found no correlation between cyclin D1 expression and tumor size, grade, and lymph node status. However, overexpression of the protein was associated with reduced recurrence-free survival (P=.029), as was positive nodal status (Pinvasive lobular carcinoma. Finally, high cyclin D1 expression was associated with increased hazard ratio in multivariate analysis (hazard ratio, 1.75; 95% confidence interval, 1.05-2.89). In conclusion, we describe an image analysis algorithm capable of reliably analyzing cyclin D1 staining in invasive lobular carcinoma and have linked overexpression of the protein to increased recurrence risk. Our findings support the use of cyclin D1 as a clinically informative biomarker for invasive lobular breast cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Invasive lobular carcinoma of the breast: MRI pathological correlation following bilateral total mastectomy

    International Nuclear Information System (INIS)

    Stivalet, Aude; Pigneur, Frederic; Luciani, Alain

    2012-01-01

    Background: Invasive lobular carcinoma (ILC) is more often multifocal and bilateral than invasive ductal carcinoma. MRI is usually recommended for detection of all ILC sites. The performance of known diagnostic breast MRI criteria for ILC characterization has not been evaluated to date using bilateral mastectomy specimens as gold standard. Purpose: To determine the value of BI-RADS 2006 MRI criteria for ILC detection and characterization, using pathological examination of bilateral mastectomy specimens as the reference standard. Material and Methods: Between 2004 and 2007, we retrospectively included all patients with pathologically documented ILC referred to our institution for bilateral mastectomy and preoperative bilateral breast MRI. The location, diameter, and characteristics (BI-RADS) of all lesions were compared with pathological findings. The sensitivity and positive predictive value of bilateral breast MRI for the diagnosis of ILC were calculated. Association of MRI BI-RADS categorical variables and characterization of ILC were assessed (Fisher exact test). Results: Among 360 patients treated for ILC in 2004-2007, 15 patients qualified for this study. Thirty-one ILC foci were found on pathological examination (30 ipsilateral and 1 contralateral tumor; mean diameter 23 mm; range 2-60 mm) and all were identified on MRI, with 90% of masses and 10% non-mass-like enhancements; MRI features significantly associated with ILC included absence of smooth margins (P = 0.02) and rim-shaped enhancement (P = 0.039). Enhancement kinetics of the 31 foci were evenly distributed among wash-out, plateau, and persistent profiles. Eleven additional lesions were seen on MRI, mainly corresponding to fibrocystic disease; 91% presented as masses and 9% had a wash-out profile. Conclusion: Based on the 2006 BI-RADS criteria, breast MRI shows a high sensitivity for ILC detection, at the expense of a 26% false-positive rate, suggesting that a pathological proof by US- or MR

  19. Invasive lobular carcinoma of the breast: MRI pathological correlation following bilateral total mastectomy

    Energy Technology Data Exchange (ETDEWEB)

    Stivalet, Aude; Pigneur, Frederic (AP-HP, Groupe Henri Mondor Albert Chenevier, Imagerie Medicale, Creteil (France)); Luciani, Alain (AP-HP, Groupe Henri Mondor Albert Chenevier, Imagerie Medicale, Creteil (France); INSERM Unite U 955, Equipe 17, Univ. Paris Est Creteil, Creteil (France)), email: alain.luciani@hmn.aphp.fr (and others)

    2012-05-15

    Background: Invasive lobular carcinoma (ILC) is more often multifocal and bilateral than invasive ductal carcinoma. MRI is usually recommended for detection of all ILC sites. The performance of known diagnostic breast MRI criteria for ILC characterization has not been evaluated to date using bilateral mastectomy specimens as gold standard. Purpose: To determine the value of BI-RADS 2006 MRI criteria for ILC detection and characterization, using pathological examination of bilateral mastectomy specimens as the reference standard. Material and Methods: Between 2004 and 2007, we retrospectively included all patients with pathologically documented ILC referred to our institution for bilateral mastectomy and preoperative bilateral breast MRI. The location, diameter, and characteristics (BI-RADS) of all lesions were compared with pathological findings. The sensitivity and positive predictive value of bilateral breast MRI for the diagnosis of ILC were calculated. Association of MRI BI-RADS categorical variables and characterization of ILC were assessed (Fisher exact test). Results: Among 360 patients treated for ILC in 2004-2007, 15 patients qualified for this study. Thirty-one ILC foci were found on pathological examination (30 ipsilateral and 1 contralateral tumor; mean diameter 23 mm; range 2-60 mm) and all were identified on MRI, with 90% of masses and 10% non-mass-like enhancements; MRI features significantly associated with ILC included absence of smooth margins (P = 0.02) and rim-shaped enhancement (P = 0.039). Enhancement kinetics of the 31 foci were evenly distributed among wash-out, plateau, and persistent profiles. Eleven additional lesions were seen on MRI, mainly corresponding to fibrocystic disease; 91% presented as masses and 9% had a wash-out profile. Conclusion: Based on the 2006 BI-RADS criteria, breast MRI shows a high sensitivity for ILC detection, at the expense of a 26% false-positive rate, suggesting that a pathological proof by US- or MR

  20. Post-Mastectomy Radiation Therapy for Invasive Lobular Carcinoma: A Comparative Utilization and Outcomes Study.

    Science.gov (United States)

    Stecklein, Shane R; Shen, Xinglei; Mitchell, Melissa P

    2016-08-01

    To date, there have been no analyses to assess factors that influence post-mastectomy radiation therapy (PMRT) utilization in invasive lobular carcinoma (ILC) or to quantify the benefit of PMRT in ILC as compared with invasive ductal carcinoma (IDC). We compared histology-specific utilization of PMRT by tumor and patient characteristics and estimated the effect of PMRT on overall and breast cancer-specific survival in ILC and IDC patients meeting American College of Radiology (ACR) criteria for PMRT. We used the Surveillance, Epidemiology, and End Results database to identify women diagnosed with ILC or IDC from 2004 to 2009 who underwent mastectomy. We assessed utilization of PMRT by T and N stage, analyzed factors associated with PMRT use, and quantified the histology-specific survival benefit of PMRT using log-rank tests and multivariate Cox regression analysis. We identified 86,098 IDC and 12,703 ILC patients. Within this cohort, 18.7% of IDC patients and 26.1% of ILC met ACR criteria for PMRT. Among patients with a definite indication, PMRT was more commonly employed in ILC than in IDC (59.6% vs. 56.3%; P = .0004). Among patients with a definite indication for PMRT, radiation improved 5-year breast cancer-specific survival from 71.4% to 77.0% for IDC (P cancer-specific survival for ILC patients to a degree comparable with that seen in IDC. Moreover, among ILC and IDC patients who meet ACR criteria, PMRT appears to be significantly underutilized. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma?

    Science.gov (United States)

    Conlon, Niamh; Ross, Dara S; Howard, Jane; Catalano, Jeffrey P; Dickler, Maura N; Tan, Lee K

    2015-01-01

    Oncotype Dx Breast Cancer Assay is a 21-gene assay used in estrogen receptor (ER)-positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score (RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma (ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER-2) negative by immunohistochemistry. Sixty three percent of cases were low risk (LR), 35.5% were intermediate risk (IR) and 1.5% were high risk (HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision-making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions. © 2015 Wiley Periodicals, Inc.

  2. Clinical Significance of 18F-FDG-PET in Invasive Lobular Carcinoma.

    Science.gov (United States)

    Fujii, Takaaki; Yajima, Reina; Kurozumi, Sasagu; Higuchi, Toru; Obayashi, Sayaka; Tokiniwa, Hideaki; Nagaoka, Rin; Takata, Daisuke; Horiguchi, Jun; Kuwano, Hiroyuki

    2016-10-01

    The diagnostic utility of 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for breast cancer is controversial. The histological type or tumor size of breast cancer has been reported to be associated with a greater likelihood of positive FDG uptake. Compared to invasive ductal carcinomas (IDCs), invasive lobular carcinomas (ILCs) have a lower level of FDG uptake and are detected at a significantly lower sensitivity. The role of preoperative FDG-PET for ILCs may, thus, be limited. Few data evaluating the significance of FDG-PET in ILCs are available. Here, we evaluated the clinical significance of FDG-PET for ILC patients. We retrospectively investigated the cases of 196 consecutive patients with primary breast cancer who were diagnosed as having ILC (n=15) or IDC (n=181) and underwent FDG-PET preoperatively. Fifteen (7.7%) of patients were histopathologically diagnosed as ILC. A univariate analysis revealed that tumor size, extent of tumor, estrogen receptor (ER) expression and progesterone receptor (PgR) expression were significantly different between the ILC and IDC groups. The maximum standardized uptake value (SUV max ) values of the primary tumors were not significantly different between the two groups but, regardless of the larger size of tumor or ductal spread, the SUV max was relatively lower in the ILC group compared to the IDC group. The tumors in two ILC cases showed no FDG uptake. Among the ILC cases, there were linear associations between SUV max and tumor size and between SUV max and the nuclear grade by Pearson correlation (r=0.447, p=0.048 and r=0.519, p=0.024, respectively). Our findings imply that the preoperative FDG uptake in ILC may be reflective of the tumor size and the nuclear grade of the tumor. FDG uptake may be useful and predictive of aggressive features or prognosis in ILC patients. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. Medical and surgical treatment of idiopathic granulomatous lobular mastitis: a benign inflammatory disease mimicking invasive carcinoma.

    Science.gov (United States)

    Gurleyik, Gunay; Aktekin, Ali; Aker, Fugen; Karagulle, Hikmet; Saglamc, Abdullah

    2012-03-01

    Idiopathic granulomatous lobular mastitis (IGLM) is a rare chronic inflammatory disease of the breast with obscure etiology that mimics invasive carcinoma both clinically and radiologically. The treatment of IGLM remains controversial. The aim of proper management is to use a combination of medical and surgical treatment of this benign condition to achieve a good cosmetic result and low recurrence rate. A retrospective analysis of 19 patients with IGLM is performed based on the findings of clinical, radiological, and pathological examinations. The results of two treatments are presented: medical treatment with oral corticosteroids, and consecutive surgical excision after a follow-up period of 20 months (range, 6-75 months). The majority of patients treated in this paper were young (mean, 34 years) parous women with a history of hormonal medication use. The main clinical finding is large, irregular, and painful mass. Hypoechoic lobulated, irregular tubular or oval shaped masses had been imaged by ultrasound. Mammographic findings were an ill-defined mass, enlarged axillary lymph nodes, asymmetric density, and architectural distortion. Diagnoses of IGLM had been established by cytological or histological examination. Symptoms subside and inflammatory changes regressed with medical treatment. The remaining lesions were excised by consecutive breast conserving surgery. The disease recurred in one patient during the follow-up period. IGLM is an inflammatory breast disease found in young women who present with a large painful irregular mass, which mimics carcinoma, as a physical change. Breast imaging modalities are not helpful to differentiate IGLM from invasive cancer. The correct diagnosis is established by cytological or histological examination. Medical treatment with corticosteroids provides significant regression of the inflammatory disease, allowing more conservative surgery. Consecutive surgical excision of the remaining lesions with good cosmetic results

  4. Computer-aided-detection marker value and breast density in the detection of invasive lobular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Destounis, Stamatia; Hanson, Sarah [The Elizabeth Wende Breast Clinic, Rochester, NY (United States); Roehrig, Jimmy [R2/Hologic, Inc., Santa Clara, CA (United States)

    2007-08-15

    Invasive Lobular Carcinoma (ILC) is frequently a mammographic and diagnostic dilemma; thus any additional information that CAD (Computer-Aided Detection) systems can give radiologists may be helpful. Our study was to evaluate the role of CAD numeric values as indicators of malignancy and the effect of breast density in the diagnosis of ILC. Eighty consecutive biopsy-proven ILC cases with CAD (ImageChecker {sup registered}, Hologic vertical stroke R2, Santa Clara, CA, versions 2.3, 3.1, 3.2, 5.0, 5.2) diagnosed between June 2002 and December 2004 were retrospectively reviewed. Data included: BIRADS {sup registered} breast density, whether CAD marked the cancer at diagnosis year or years prior, and lesion type. Study mammograms underwent additional CAD scans (Image Checker {sup registered} V5.3, V8.0, V8.1) to obtain a numeric value associated with each marker, low values represent increasingly suspicious features. CAD correctly marked 65% (52/80) of ILC cases, detection was found to decrease with increased breast density. Numeric values of CAD marks at sites of carcinoma showed median score of 171 (range 0 - 1121). The CAD marker may potentially be used as an additional indicator of suspicious lesion features in all breast densities and higher likelihood that an area on the mammogram requires further investigation. (orig.)

  5. Computer-aided-detection marker value and breast density in the detection of invasive lobular carcinoma

    International Nuclear Information System (INIS)

    Destounis, Stamatia; Hanson, Sarah; Roehrig, Jimmy

    2007-01-01

    Invasive Lobular Carcinoma (ILC) is frequently a mammographic and diagnostic dilemma; thus any additional information that CAD (Computer-Aided Detection) systems can give radiologists may be helpful. Our study was to evaluate the role of CAD numeric values as indicators of malignancy and the effect of breast density in the diagnosis of ILC. Eighty consecutive biopsy-proven ILC cases with CAD (ImageChecker registered , Hologic vertical stroke R2, Santa Clara, CA, versions 2.3, 3.1, 3.2, 5.0, 5.2) diagnosed between June 2002 and December 2004 were retrospectively reviewed. Data included: BIRADS registered breast density, whether CAD marked the cancer at diagnosis year or years prior, and lesion type. Study mammograms underwent additional CAD scans (Image Checker registered V5.3, V8.0, V8.1) to obtain a numeric value associated with each marker, low values represent increasingly suspicious features. CAD correctly marked 65% (52/80) of ILC cases, detection was found to decrease with increased breast density. Numeric values of CAD marks at sites of carcinoma showed median score of 171 (range 0 - 1121). The CAD marker may potentially be used as an additional indicator of suspicious lesion features in all breast densities and higher likelihood that an area on the mammogram requires further investigation. (orig.)

  6. 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.

  7. 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.

  8. TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

    International Nuclear Information System (INIS)

    Sanlioglu, Ahter D.; Korcum, Aylin F.; Pestereli, Elif; Erdogan, Gulgun; Karaveli, Seyda; Savas, Burhan; Griffith, Thomas S.; Sanlioglu, Salih V.

    2007-01-01

    Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma

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

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    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

  10. Hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity in oral squamous cell carcinoma derived cells.

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    Chaudhari, Pratik Rajeev; Charles, Silvania Emlit; D'Souza, Zinia Charlotte; Vaidya, Milind Murlidhar

    2017-11-15

    BPAG1e and Plectin are hemidesmosomal linker proteins which anchor intermediate filament proteins to the cell surface through β4 integrin. Recent reports indicate that these proteins play a role in various cellular processes apart from their known anchoring function. However, the available literature is inconsistent. Further, the previous study from our laboratory suggested that Keratin8/18 pair promotes cell motility and tumor progression by deregulating β4 integrin signaling in oral squamous cell carcinoma (OSCC) derived cells. Based on these findings, we hypothesized that linker proteins may have a role in neoplastic progression of OSCC. Downregulation of hemidesmosomal linker proteins in OSCC derived cells resulted in reduced cell migration accompanied by alterations in actin organization. Further, decreased MMP9 activity led to reduced cell invasion in linker proteins knockdown cells. Moreover, loss of these proteins resulted in reduced tumorigenic potential. SWATH analysis demonstrated upregulation of N-Myc downstream regulated gene 1 (NDRG1) in linker proteins downregulated cells as compared to vector control cells. Further, the defects in phenotype upon linker proteins ablation were rescued upon loss of NDRG1 in linker proteins knockdown background. These data together indicate that hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity possibly through NDRG1 in OSCC derived cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Verification of hyperthermia treatment planning in cervix carcinoma patients using invasive thermometry

    International Nuclear Information System (INIS)

    Haaren Van, P.M.A.; Kok, H.P.; Zum Voerde Sive Voerding, P.J.; Oldenborg, S.; Stalpers, L.J.A.; Crezee, J.; Berg Van den, C.A.T; Leeuw De, A.A.C.

    2005-01-01

    Full text: Hyperthermia treatment planning (HTP) is a useful tool for improvement of clinical hyperthermia treatments. Aim of this study was to determine the correlation between HTP and measurements during hyperthermia treatments. We compared the calculated specific absorption rate (SAR) with clinically measured SAR-values, from ΔT-measurements, in cervix carcinoma patients. General difficulties for such clinical verifications are changes in the anatomy during the different steps and possible movement of the catheters. We used one fixed invasive catheter in the tumor additional to the usual non-invasive catheters in the vagina, bladder and rectum, for insertion of multisensor thermocouple probes. A special CT-scan with the patient in treatment position and the catheters in situ was made for the HTP. We performed these verifications in a total of 11 treatments in 7 patients. The main difficulties for accurate verification were of clinical nature: difficulties arising from the use of gynaecological tampon and the limited number of measurements in tissue. Remaining air in the vagina and sub-optimal tissue contact of the catheters resulted in bad thermal contact between thermocouples and tissue, causing measurement artefacts that are difficult to correlate with calculations. These artefacts are probably not specific for thermocouple measurements, but more general for intraluminal temperature and SAR measurements. (author)

  12. Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder

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    Mameghan, Hedy; Fisher, Richard; Mameghan, Jill; Brook, Susan

    1995-01-15

    Purpose: To assess prognostic factors for bladder relapse and distant failure following definitive radiotherapy for invasive transitional cell carcinoma (TCC) of the bladder. Methods and Materials: Retrospective review of patients treated in the period 1977 to 1990 by definitive radiotherapy. The factors studied included age, sex, T stage, histological grade, tumor multiplicity, ureteric obstruction, total radiation dose, and use of neoadjuvant chemotherapy. The endpoints studied were bladder relapse and distant failure. Results: There were 342 patients with a mean follow-up time of 7.9 years. Bladder relapse was observed in 159 patients. The overall actuarial bladder relapse rate at 5 years was 55% (SE = 3%). Prognostic factors for a higher bladder relapse rate were: tumor multiplicity (p < 0.001), presence of ureteric obstruction (p = 0.001), and higher T stage (p 0.044). Distant failure occurred in 39 patients. The overall actuarial distant failure rate at 5 years was 28% (SE = 3%). Prognostic factors for a higher distant failure rate were: ureteric obstruction (p = 0.003) and higher T stage (p = 0.030). Conclusion: In our study, patients with invasive bladder TCC fell into distinct prognostic groups determined by the three independent factors, ureteric obstruction, tumor multiplicity, and T stage. These factors provided estimated risks of bladder relapse by 5 years which ranged from 34% to 91%. Knowledge of these prognostic factors can help in the selection of patients more suited for bladder preservation by definitive radiotherapy.

  13. Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder

    International Nuclear Information System (INIS)

    Mameghan, Hedy; Fisher, Richard; Mameghan, Jill; Brook, Susan

    1995-01-01

    Purpose: To assess prognostic factors for bladder relapse and distant failure following definitive radiotherapy for invasive transitional cell carcinoma (TCC) of the bladder. Methods and Materials: Retrospective review of patients treated in the period 1977 to 1990 by definitive radiotherapy. The factors studied included age, sex, T stage, histological grade, tumor multiplicity, ureteric obstruction, total radiation dose, and use of neoadjuvant chemotherapy. The endpoints studied were bladder relapse and distant failure. Results: There were 342 patients with a mean follow-up time of 7.9 years. Bladder relapse was observed in 159 patients. The overall actuarial bladder relapse rate at 5 years was 55% (SE = 3%). Prognostic factors for a higher bladder relapse rate were: tumor multiplicity (p < 0.001), presence of ureteric obstruction (p = 0.001), and higher T stage (p 0.044). Distant failure occurred in 39 patients. The overall actuarial distant failure rate at 5 years was 28% (SE = 3%). Prognostic factors for a higher distant failure rate were: ureteric obstruction (p = 0.003) and higher T stage (p = 0.030). Conclusion: In our study, patients with invasive bladder TCC fell into distinct prognostic groups determined by the three independent factors, ureteric obstruction, tumor multiplicity, and T stage. These factors provided estimated risks of bladder relapse by 5 years which ranged from 34% to 91%. Knowledge of these prognostic factors can help in the selection of patients more suited for bladder preservation by definitive radiotherapy

  14. SREBP-1 Has a Prognostic Role and Contributes to Invasion and Metastasis in Human Hepatocellular Carcinoma

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    Chao Li

    2014-04-01

    Full Text Available Sterol regulatory element-binding protein 1 (SREBP-1 is a well-known nuclear transcription factor involved in lipid synthesis. Recent studies have focused on its functions in tumor cell proliferation and apoptosis, but its role in cell migration and invasion, especially in hepatocellular carcinoma (HCC, is still unclear. In this study, we found that the expression of SREBP-1 in HCC tissues was significantly higher than those in matched tumor-adjacent tissues (p < 0.05. SREBP-1 was expressed at significantly higher levels in patients with large tumor size, high histological grade and advanced tumor-node-metastasis (TNM stage (p < 0.05. The positive expression of SREBP-1 correlated with a worse 3-year overall and disease-free survival of HCC patients (p < 0.05. Additionally, SREBP-1 was an independent factor for predicting both 3-year overall and disease-free survival of HCC patients (p < 0.05. In vitro studies revealed that downregulation of SREBP-1 inhibited cell proliferation and induced apoptosis in both HepG2 and MHCC97L cells (p < 0.05. Furthermore, wound healing and transwell assays showed that SREBP-1 knockdown prominently inhibited cell migration and invasion in both HepG2 and MHCC97L cells (p < 0.05. These results suggest that SREBP-1 may serve as a prognostic marker in HCC and may promote tumor progression by promoting cell growth and metastasis.

  15. ERBB2 mutations associated with solid variant of high-grade invasive lobular breast carcinomas.

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    Deniziaut, Gabrielle; Tille, Jean Christophe; Bidard, François-Clément; Vacher, Sophie; Schnitzler, Anne; Chemlali, Walid; Trémoulet, Laurence; Fuhrmann, Laetitia; Cottu, Paul; Rouzier, Roman; Bièche, Ivan; Vincent-Salomon, Anne

    2016-11-08

    ERBB2 and ERBB3 somatic gain-of-function mutations, which may be targeted by anti-ERBB2 therapies, were reported by high-throughput sequencing studies in 1% and 2% of invasive breast cancers respectively. Our study aims to determine ERBB2 and ERBB3 mutations frequencies in grade 3 and/or ERBB2-positive invasive lobular breast carcinomas (ILC). All the 529 ILC surgically-excised registered at Institut Curie in the years 2005 to 2008 were reviewed. Thirty-nine grade 3 ERBB2-negative ILC and 16 ERBB2-positive ILC were retrieved and subjected to Sanger sequencing of the ERBB2 and ERBB3 activation mutation hotspots (ERBB2: exons 8, 17, 19, 20, 21; ERBB3: exons 3, 6, 7, 8). Among the 39 grade 3 ERBB2-negative ILC, six tumors were found to have at least one detectable ERBB2 activating mutation (incidence rate: 15%, 95%CI [4%-27%]). No ERBB2 mutation was found among the 16 ERBB2-positive ILC. No ERBB3 mutation was found in any of the 55 ILC. ERBB2 mutations were statistically associated with solid ILC features (p=0.01). Survival analyses showed no significant prognostic impact of ERBB2 mutations. Our study demonstrates that high grade ERBB2-negative ILC display a high frequency of ERBB2 mutations, and should be subjected to systematic genetic screening.

  16. Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

    Science.gov (United States)

    Korhan, Peyda; Erdal, Esra; Kandemiş, Emine; Cokaklı, Murat; Nart, Deniz; Yılmaz, Funda; Can, Alp; Atabey, Neşe

    2014-01-01

    c-Met, the receptor for Hepatocyte Growth Factor (HGF), overexpressed and deregulated in Hepatocellular Carcinoma (HCC). Caveolin 1 (CAV1), a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

  17. Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Peyda Korhan

    Full Text Available c-Met, the receptor for Hepatocyte Growth Factor (HGF, overexpressed and deregulated in Hepatocellular Carcinoma (HCC. Caveolin 1 (CAV1, a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

  18. PD-L1 expression and the immune microenvironment in primary invasive lobular carcinomas of the breast.

    Science.gov (United States)

    Thompson, Elizabeth D; Taube, Janis M; Asch-Kendrick, Rebecca J; Ogurtsova, Aleksandra; Xu, Haiying; Sharma, Rajni; Meeker, Alan; Argani, Pedram; Emens, Leisha A; Cimino-Mathews, Ashley

    2017-11-01

    Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (50%). The average immune cell subtype per high-power field was quantitatively scored. The percentage PD-L1 labeling on tumor-infiltrating lymphocytes was scored as none, focal (lobular carcinomas contained PD-L1 + tumor-infiltrating lymphocytes with the majority showing 1+ immune infiltrates with focal-moderate PD-L1 labeling. PD-L1 was expressed by tumor cells in 17% of lobular carcinomas. In contrast to ductal carcinomas, there was no correlation between the immune infiltrate density, the PD-L1 expression by lobular carcinoma cells, tumor grade, or the expression of estrogen receptor or human epidermal growth factor receptor-2. However, both the tumor-infiltrating lymphocyte density and the average CD8 + T-cell counts correlated with immune cell PD-L1 status (P=0.004 and 0.03, respectively). Similar to breast ductal carcinomas, PD-L1 + lobular breast carcinomas had higher numbers of PD-L1 + tumor-infiltrating lymphocytes (63%) than PD-L1 - lobular carcinomas (23%; P=0.04). These data show that a subset of primary breast lobular carcinomas both express PD-L1 on tumor cells and contain PD-L1 + tumor-infiltrating lymphocytes, suggesting the possibility of both constitutive and adaptive PD-L1 expression. Together, these results support immunotherapy as a potential treatment for a subset of patients with primary invasive lobular breast carcinomas.

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

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    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

  20. Skull-base invasion of nasopharyngeal carcinoma: magnetic resonance imaging findings and therapeutic implications

    International Nuclear Information System (INIS)

    Nishioka, Takeshi; Shirato, Hiroki; Kagei, Kenji; Abe, Satoru; Hashimoto, Seiko; Ohmori, Keiichi; Yamazaki, Akira; Fukuda, Satoshi; Miyasaka, Kazuo

    2000-01-01

    Purpose: To evaluate the value of skull-base abnormality on MRI for predicting local recurrence in nasopharyngeal carcinoma. Materials and Methods: Between November 1988 and February 1997, 48 patients with NPC were examined with both MRI (1.5 T) and CT prior to radiation therapy. T classification (1987 UICC) based on physical examination and CT findings were T1 in 3 cases, T2 in 22, T3 in 9, and T4 in 14. On MRI, low-intensity tissue with Gd enhancement in the marrow of the skull was considered to be a suspicious finding of skull-base invasion. CT simulation was performed in all patients. The total dose to the primary tumor was 60-75 Gy (mean, 67 Gy). The mean follow-up period was 42 months. Results: All 14 T4 patients had abnormal tissue in the marrow of the skull base on MRI. Thirty-eight percent (13 of 34) of T1-3 patients were suspected to have skull-base invasion based on MRI (0% for T1, 27% [6 of 22] for T2, and 78% [7 of 9] for T3). The 5-year local control rate was significantly different between T1-3 and T4 tumors (97% vs. 69%, p < 0.025) but was not different by the presence of the MRI abnormality in the skull base. Conclusion: Skull-base invasion suspected solely by MRI does not relate to local recurrence provided that careful treatment planning is performed with the aid of MRI and CT simulator

  1. Suppression of actopaxin impairs hepatocellular carcinoma metastasis through modulation of cell migration and invasion.

    Science.gov (United States)

    Ng, Lui; Tung-Ping Poon, Ronnie; Yau, Simon; Chow, Ariel; Lam, Colin; Li, Hung-Sing; Chung-Cheung Yau, Thomas; Law, Wai-Lun; Pang, Roberta

    2013-08-01

    Early reports suggested that actopaxin, a member of the focal adhesion proteins, regulates cell migration. Here we investigated whether actopaxin is involved in hepatocellular carcinoma (HCC) progression and metastasis. We examined actopaxin expression in human HCC samples using immunohistochemistry and western blotting. The functional and molecular effect of actopaxin was studied in vitro by overexpression in a nonmetastatic HCC cell line, as well as repression in a metastatic cell line. The in vivo effect of actopaxin repression was studied in nonobese diabetic and severe combined immunodeficient mice. We found that actopaxin was frequently overexpressed in human HCC patients and its overexpression positively correlated with tumor size, stage, and metastasis. Actopaxin expression also correlated with the metastatic potential of HCC cell lines. Actopaxin overexpression induced the invasion and migration ability of nonmetastatic HCC cells, whereas down-regulation of actopaxin reverted the invasive phenotypes and metastatic potential of metastatic HCC cells through regulating the protein expression of certain focal adhesion proteins including ILK, PINCH, paxillin, and cdc42, as well as regulating the epithelial-mesenchymal transition pathway. Furthermore, there was a close association between actopaxin and CD29. HCC cells with stronger CD29 expression showed a higher actopaxin level, whereas actopaxin repression attenuated CD29 activity. Finally, actopaxin down-regulation enhanced the chemosensitivity of HCC cells towards oxaliplatin treatment by way of a collective result of suppression of survivin protein, β-catenin, and mammalian target of rapamycin pathways and up-regulation of p53. This study provides concrete evidence of a significant role of actopaxin in HCC progression and metastasis, by way of regulation of cell invasiveness and motility, an epithelial-mesenchymal transition process, and chemosensitivity to cytotoxic drugs. Copyright © 2013 by the

  2. Comparison of SPECT/CT, MRI and CT in diagnosis of skull base bone invasion in nasopharyngeal carcinoma.

    Science.gov (United States)

    Zhang, Shu-xu; Han, Peng-hui; Zhang, Guo-qian; Wang, Rui-hao; Ge, Yong-bin; Ren, Zhi-gang; Li, Jian-sheng; Fu, Wen-hai

    2014-01-01

    Early detection of skull base invasion in nasopharyngeal carcinoma (NPC) is crucial for correct staging, assessing treatment response and contouring the tumor target in radiotherapy planning, as well as improving the patient's prognosis. To compare the diagnostic efficacy of single photon emission computed tomography/computed tomography (SPECT/CT) imaging, magnetic resonance imaging (MRI) and computed tomography (CT) for the detection of skull base invasion in NPC. Sixty untreated patients with histologically proven NPC underwent SPECT/CT imaging, contrast-enhanced MRI and CT. Of the 60 patients, 30 had skull base invasion confirmed by the final results of contrast-enhanced MRI, CT and six-month follow-up imaging (MRI and CT). The diagnostic efficacy of the three imaging modalities in detecting skull base invasion was evaluated. The rates of positive findings of skull base invasion for SPECT/CT, MRI and CT were 53.3%, 48.3% and 33.3%, respectively. The sensitivity, specificity and accuracy were 93.3%, 86.7% and 90.0% for SPECT/CT fusion imaging, 96.7%, 100.0% and 98.3% for contrast-enhanced MRI, and 66.7%, 100.0% and 83.3% for contrast-enhanced CT. MRI showed the best performance for the diagnosis of skull base invasion in nasopharyngeal carcinoma, followed closely by SPECT/CT. SPECT/CT had poorer specificity than that of both MRI and CT, while CT had the lowest sensitivity.

  3. 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. © 2016 UICC.

  4. microRNA-188 is downregulated in oral squamous cell carcinoma and inhibits proliferation and invasion by targeting SIX1.

    Science.gov (United States)

    Wang, Lili; Liu, Hongchen

    2016-03-01

    microRNA-188 expression is downregulated in several tumors. However, its function and mechanism in human oral squamous cell carcinoma (OSCC) remains obscure. The present study aims to identify the expression pattern, biological roles, and potential mechanism by which miR-188 dysregulation is associated with oral squamous cell carcinoma. Significant downregulation of miR-188 was observed in OSCC tissues compared with paired normal tissues. In vitro, gain-of-function, loss-of-function experiments were performed to examine the impact of miR-188 on cancer cell proliferation, invasion, and cell cycle progression. Transfection of miR-188 mimics suppressed Detroit 562 cell proliferation, cell cycle progression and invasion, with downregulation of cyclin D1, MMP9, and p-ERK. Transfection of miR-188 inhibitor in FaDu cell line with high endogenous expression exhibited the opposite effects. Using fluorescence reporter assays, we confirmed that SIX1 was a direct target of miR-188 in OSCC cells. Transfection of miR-188 mimics downregulated SIX1 expression. SIX1 siRNA treatment abrogated miR-188 inhibitor-induced cyclin D1 and MMP9 upregulation. In addition, we found that SIX1 was overexpressed in 32 of 80 OSCC tissues. In conclusion, this study indicates that miR-188 downregulation might be associated with oral squamous cell carcinoma progression. miR-188 suppresses proliferation and invasion by targeting SIX1 in oral squamous cell carcinoma cells.

  5. Use of Ulex europaeus agglutinin I (UEAI) to distinguish vascular and "pseudovascular" invasion in transitional cell carcinoma of bladder with lamina propria invasion.

    Science.gov (United States)

    Larsen, M P; Steinberg, G D; Brendler, C B; Epstein, J I

    1990-01-01

    We used Ulex europaeus agglutinin I (UEAI)-immunoperoxidase staining of endothelium to study the accuracy of hematoxylin and eosin (H&E) diagnosis, occurrence, and significance of lymphvascular invasion in transitional cell carcinoma (TCC) of the bladder invading the lamina propria (Stage T1). Original histologic slides from cases (1967 to 1985) with and without vascular invasion were destained and restained with UEAI-immunoperoxidase. Only 5 of 36 biopsies originally diagnosed with lymphvascular invasion had tumor nests within endothelium-lined spaces. The 31 negative biopsies had extensive retraction artifacts lined by connective tissue and fibroblasts around tumor nests. Thirty-five control biopsies remained negative for lymphvascular invasion. Clinical follow-up of the five patients with proven lymphvascular invasion found three without progression of disease 3 to 10 yr postbiopsy, one dead of a local recurrence of TCC 1.67 yr postbiopsy, and one lost to follow-up. Based on this study, we feel that lymphvascular invasion by TCC in Stage T1 tumors is unusual, is frequently misdiagnosed on H&E stain, and does not necessarily portend a poor prognosis.

  6. Assessment of mural invasion depth of gastric carcinoma with high-resolution compound sonographic imaging in vitro

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    Park, Seong Hoon; Kim, Eun A; Yoon, Kwon Ha; Yun, Ki Jung; Kim, Jeong Ho; Won, Jong Jin [Wonkwang University School of Medicine, Iksan (Korea, Republic of)

    2002-11-01

    To evaluate whether the accuracy of invasion depth assessment in gastric carcinoma in vitro can be improved with high-resolution spatial compound sonographic imaging. In sixteen fresh gastric specimens obtained from patients with preoperatively biopsy proven gastric carcinoma, normal and lesional areas were scanned using conventional and compound imaging technique with a 15-MHz linear transducer. Two radiologists independently compared the sharpness and the contrast of images obtained with two different modes and determined the layers invaded by cancer with consensus. The invasion depths by images were compared with histopathologic results. The sharpness and the contrast in normal and lesional areas were significantly higher in compound imaging (p<0.01) than those in conventional imaging and interobserver agreement was over moderate, with k-value of 0.41 to 0.86. But the accuracy in invasion depth assessment was 68.8% (11/16) on conventional imaging and 75% (12/16) on compound imaging and non different significantly between two modes (p>0305). High-resolution spatial compound sonographic imaging has improved image quality, compared with conventional imaging, but the accuracy of invasion depth assessment in gastric carcinoma was not significantly different.

  7. Primary invasive carcinoma of the vagina after Le Fort partial colpocleisis for stage IV pelvic organ prolapse: a case report.

    Science.gov (United States)

    Cho, Moon Kyoung; Kim, Chul Hong; Kim, Yoon Ha

    2011-11-01

    We present here the case report of a postmenopausal woman who complained of recurrent pus-like vaginal discharge and perianal pain 1 year after Le Fort colpocleisis, which was subsequently identified as a primary invasive carcinoma of the vagina. Biopsy confirmed a squamous cell carcinoma in the vagina, and the disease was classified as stage III according to FIGO staging. The patient received pelvic radiotherapy. This case emphasizes that differential diagnosis of recurrent vaginal discharge that presents remote from obliterative procedure for pelvic organ prolapse should consider not only pyometra, but also other causes.

  8. Impact of mandibular invasion on prognosis in oral squamous cell carcinoma four centimeters or less in size.

    Science.gov (United States)

    Fives, Cassie; Nae, Andreea; Roche, Phoebe; O'Leary, Gerard; Fitzgerald, Brendan; Feeley, Linda; Sheahan, Patrick

    2017-04-01

    Previous studies have reported variable results for the impact of bone invasion on survival in oral cancer. It is unclear whether bone invasion in small (≤4 cm) squamous cell carcinomas (SCC) of the oral cavity is an independent adverse prognosticator. Our objective was to investigate impact on survival of bone invasion in SCC of floor of mouth (FOM), lower alveolus (LA), and retromolar trigone (RMT) ≤4 cm in size. Retrospective study of 96 patients with SCC of the FOM, LA, and RMT undergoing primary surgical treatment. Original pathology reports and slides were reviewed by three pathologists. Level of bone invasion was categorized as cortical or medullary. Main outcome measures were local control (LC) and overall survival (OS). Bone invasion was present in 31 cases (32%). On review of pathology slides, all cases of bone invasion demonstrated medullary involvement. Median follow-up was 36 months for all patients, and 53 months for patients not dying from cancer. Among tumors ≤4 cm, bone invasion was associated with significantly worse LC (P =.04) and OS (P =.0005). Medullary invasion (hazard ratio: 2.2, 95% confidence interval: 1.1-4.4, P =.03), postoperative radiotherapy (hazard ratio: 0.3, 95% confidence interval: 0.1-0.5, P oral cancers, irrespective of small size of primary tumor. Such cases should be considered for postoperative radiotherapy. 4. Laryngoscope, 127:849-854, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  9. Invasive lobular carcinoma of the male breast: A rare histology of an uncommon disease

    International Nuclear Information System (INIS)

    Upadhyay, R.; Kumar, P.; Sharma, D.N.; Haresh, K.P.; Gupta, S.; Julka, P.K.; Rath, G.K.; Bhankar, H.

    2016-01-01

    Male breast carcinoma is a rare malignancy comprising less than 1% of all breast cancers. It is a serious disease with most patients presenting in advanced stages. Infiltrating ductal carcinoma is the most common histology while lobular carcinoma represents less than 1% of all these tumors. We report a case of locally advanced lobular carcinoma of breast in a 60 year old male

  10. Method of dry distillation of low-grade fuels

    Energy Technology Data Exchange (ETDEWEB)

    Hellsing, G H; Wengstrom, R O.A.

    1920-05-20

    A method of dry distillation of low-grade fuels is characterized by having the process take place in a furnace that is charged alternately by partly cooled, red-hot, and fresh raw materials. The patent has one more claim.

  11. Low-grade hardwood lumber production, markets, and issues

    Science.gov (United States)

    Dan Cumbo; Robert Smith; Philip A. Araman

    2003-01-01

    Due to recent downturn in the economy and changes in traditional hardwood markets. U.S. hardwood manufacturers are facing significant difficulties. In particular, markets for low-grade lumber have been diminishing, while increased levels of the material are being produced at hardwood sawmills in the United States. A nationwide survey of hardwood lumber manufacturers...

  12. Rheology and extrusion of low-grade paper and sludge

    Science.gov (United States)

    C. Tim Scott; Stefan Zauscher; Daniel J. Klingenberg

    1999-01-01

    This paper discusses efforts to characterize the rheological properties of pulps that include low-grade wastepapers and papermill sludges to determine their potential for extrusion and conversion into useful products. We investigated apparent changes in viscosity associated with the addition of typical inorganic paper fillers (calcium carbonate, kaolin clay, and...

  13. An unusual cystic appearance of disseminated low-grade gliomas

    International Nuclear Information System (INIS)

    Huang, T.; Zimmerman, R.A.; Perilongo, G.; Kaufman, B.A.; Holden, K.R.; Carollo, C.; Kling Chong, W.K.

    2001-01-01

    We report five cases of pediatric disseminated low-grade gliomas of the brainstem or spinal cord that exhibited an unusual, cystic pattern. Leptomeningeal disease was present in three of these at diagnosis, and was detected shortly afterwards in the other two. Four patients are alive up to 5 years later, following minimal to no intervention, while one is dead. (orig.)

  14. CLINICAL RELEVANCE OF COEXISTENCE OF DUCTAL CA IN SITU AND INVASIVE DUCTAL CARCINOMA OF BREAST

    Directory of Open Access Journals (Sweden)

    Kirithiga Ramalingam

    2017-06-01

    Full Text Available BACKGROUND There are many studies reported in the literature with respect to the Ductal Carcinoma in Situ (DCIS progressing into Invasive Ductal Carcinoma (IDC of the breast. However, there is hardly any study on the coexistence of both and its clinical significance. The aim of the study is to analyse the clinical and pathological parameters of synchronous DCIS and IDC to predict the prognostic factors. MATERIALS AND METHODS 42 patients with a final pathological diagnosis of synchronous DCIS and IDC diagnosed in 2009-11 were included in the study. Statistical analysis was done using SPSS software utilising the appropriate analytical methods. RESULTS Majority of the patients in this study group presented with early breast cancer (64.3%. Forty eight percent were Her2 subtype (ER, PR negative and HER2/neu-positive and 31% were triple negative. Eighty one percent of the IDC associated histology was Not Otherwise Specified (NOS type. Grade 3 lesions were more common (57%. Recurrence of the disease occurred in 66% of patients during a mean duration of follow up of 3.6 years with predominance of visceral metastasis (51.5%. Recurrence was more common in node positive disease (59.5%, those with lymphovascular emboli (59.5% and perinodal spread (76% on histopathological examination. CONCLUSION Synchronous DCIS and IDC disease entity appears to have an aggressive nature compared to the course of IDC alone entity. Prognostic factors relating to IDC appears to correlate well with recurrence than that of the prognostic factors of DCIS component in such synchronous setting.

  15. Prognostic Value of Perineural Invasion in Esophageal and Esophagogastric Junction Carcinoma: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Aiqin Gao

    2016-01-01

    Full Text Available Objective. Here we aimed to clarify the prognostic significance of perineural invasion (PNI in esophageal and esophagogastric junction (EGJ carcinoma. Methods. A comprehensive literature search for relevant reports published up to July 2015 was performed using Pubmed and Embase databases. The pooled HR and 95% CI for overall survival (OS and disease-free survival (DFS were used to assess the prognostic value. The association of PNI with pathological characteristics was evaluated by OR and 95% CI. Results. A total of 13 cohorts were retrieved, covering 2770 patients treated by surgery. The cumulative analysis revealed a statistical correlation between PNI and poor OS (HR = 1.76, 95% CI: 1.54–2.20, and P<0.00001, as well as poor DFS (HR = 1.96, 95% CI: 1.42–2.71, and P<0.001. Moreover, analysis of 1475 patients showed improved PNI in T3 + T4 (OR = 0.39, 95% CI: 0.21–0.70, and P=0.002, N+ (OR = 0.52, 95% CI: 0.40–0.69, and P<0.00001, and G3 + G4 (OR = 0.66, 95% CI: 0.48–0.90, and P=0.008 patients compared with T1 + T2, N−, and G1 + G2 ones, respectively. No significant heterogeneity was found between the studies. Conclusions. PNI is an adverse prognostic biomarker in esophageal and EGJ carcinoma. Moreover, PNI implies advanced T, N stage and poor cell differentiation.

  16. 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.

  17. Confocal fluorescence microscopy for rapid evaluation of invasive tumor cellularity of inflammatory breast carcinoma core needle biopsies.

    Science.gov (United States)

    Dobbs, Jessica; Krishnamurthy, Savitri; Kyrish, Matthew; Benveniste, Ana Paula; Yang, Wei; Richards-Kortum, Rebecca

    2015-01-01

    Tissue sampling is a problematic issue for inflammatory breast carcinoma, and immediate evaluation following core needle biopsy is needed to evaluate specimen adequacy. We sought to determine if confocal fluorescence microscopy provides sufficient resolution to evaluate specimen adequacy by comparing invasive tumor cellularity estimated from standard histologic images to invasive tumor cellularity estimated from confocal images of breast core needle biopsy specimens. Grayscale confocal fluorescence images of breast core needle biopsy specimens were acquired following proflavine application. A breast-dedicated pathologist evaluated invasive tumor cellularity in histologic images with hematoxylin and eosin staining and in grayscale and false-colored confocal images of cores. Agreement between cellularity estimates was quantified using a kappa coefficient. 23 cores from 23 patients with suspected inflammatory breast carcinoma were imaged. Confocal images were acquired in an average of less than 2 min per core. Invasive tumor cellularity estimated from histologic and grayscale confocal images showed moderate agreement by kappa coefficient: κ = 0.48 ± 0.09 (p confocal images require less than 2 min for acquisition and allow for evaluation of invasive tumor cellularity in breast core needle biopsy specimens with moderate agreement to histologic images. We show that confocal fluorescence microscopy can be performed immediately following specimen acquisition and could indicate the need for additional biopsies at the initial visit.

  18. Gamma Knife treatment of low-grade gliomas in children.

    Science.gov (United States)

    Ekşi, Murat Şakir; Yılmaz, Baran; Akakın, Akın; Toktaş, Zafer Orkun; Kaur, Ahmet Cemil; Demir, Mustafa Kemal; Kılıç, Türker

    2015-11-01

    Low-grade gliomas have good overall survival rates in pediatric patients compared to adults. There are some case series that reported the effectiveness and safety of Gamma Knife radiosurgery, yet they are limited in number of patients. We aimed to review the relevant literature for pediatric low-grade glial tumors treated with stereotactic radiosurgery, specifically Gamma Knife radiosurgery, and to present an exemplary case. A 6-year-old boy was admitted to clinic due to head trauma. He was alert, cooperative, and had no obvious motor or sensorial deficit. A head CT scan depicted a hypodense zone at the right caudate nucleus. The brain magnetic resonance imaging (MRI) depicted a mass lesion at the same location. A stereotactic biopsy was performed. Histopathological diagnosis was low-grade astrocytoma (grade II, World Health Organization (WHO) classification, 2007). Gamma Knife radiosurgery was applied to the tumor bed. Tumor volume was 21.85 cm(3). Fourteen gray was given to 50% isodose segment of the lesion (maximal dose of 28 Gy). The tumor has disappeared totally in 4 months, and the patient was tumor-free 21 months after the initial treatment. The presented literature review represents mostly single-center experiences with different patient and treatment characteristics. Accordingly, a mean/median margin dose of 11.3-15 Gy with Gamma Knife radiosurgery (GKRS) is successful in treatment of pediatric and adult low-grade glial tumor patients. However, prospective studies with a large cohort of pediatric patients should be conducted to make a more comprehensive conclusion for effectiveness and safety of GKRS in pediatric low-grade glial tumors.

  19. ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

    Directory of Open Access Journals (Sweden)

    de Souza Emanuel M

    2009-03-01

    Full Text Available Abstract Background ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer. Methods First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP. Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test. Results The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM; tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC was 76.2% compared with 25.5% in invasive ductal carcinoma

  20. ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

    International Nuclear Information System (INIS)

    Seniski, Gerusa G; Zanata, Silvio M; Costa, Fabrício F; Klassen, Giseli; Camargo, Anamaria A; Ierardi, Daniela F; Ramos, Edneia AS; Grochoski, Mariana; Ribeiro, Enilze SF; Cavalli, Iglenir J; Pedrosa, Fabio O; Souza, Emanuel M de

    2009-01-01

    ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer. First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR) treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP). Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test. The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR) demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM); tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC) was 76.2% compared with 25.5% in invasive ductal carcinoma (IDC), and this difference was

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

    International Nuclear Information System (INIS)

    Jung, So-Youn; Lee, Seeyoun; Kim, Seok Won; Kang, Han-Sung; Ro, Jungsil; Jeong, Junsoo; Shin, Seung-Ho; Kwon, Youngmee; Kim, Eun-A; Ko, Kyoung Lan; Shin, Kyung Hwan; Lee, Keun Seok; Park, In Hae

    2010-01-01

    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

  2. Specific sites of metastases in invasive lobular carcinoma: a retrospective cohort study of metastatic breast cancer.

    Science.gov (United States)

    Inoue, Masayuki; Nakagomi, Hiroshi; Nakada, Haruka; Furuya, Kazushige; Ikegame, Kou; Watanabe, Hideki; Omata, Masao; Oyama, Toshio

    2017-09-01

    Invasive lobular carcinoma (ILC) is known to be the second most common histological type following invasive ductal carcinoma (IDC). Definitive clinical features of ILC are controversial. We retrospectively analyzed a cohort of 330 patients with metastatic breast cancer, 303 of IDC, 19 of ILC, and 8 of others. We compared the patient age and tumor-node-metastasis factors, disease-free survival (DFS), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression at the primary site between ILC and IDC. We then selected the patients in the ER + or PR + /HER2 - subtype specifically and compared sites of recurrence, and the survival curve starting from the point of development of metastatic disease. The clinical stage was significantly higher in the ILC patients than in the IDC (p = 0.001). The mean (±SD) of DFS for the ILC and IDC patients was 2.6 ± 0.6 and 2.4 ± 0.3 years, respectively, with no significant difference (p = 0.18). However, the hormone receptor status was same between both groups; the rate of HER2 positivity was significantly lower in the ILC group (0%) than in the IDC group (16.2%) (p = 0.05). In ER + or PR + /HER2 - subtype, the mean DFS for the ILC and IDC was 2.9 ± 0.6 and 3.1 ± 0.3 years, and the median survival time after the recurrence for ILC and IDC patients was 4.2 ± 0.7 and 5.6 ± 0.7 years, respectively, with no significant difference (p = 0.77). The frequency of lung metastases was significantly lower in the ILC group (6.3%) than in the IDC group (53.7%) (p cancer patients with ILC. We need to reveal the definitive feature of ILC and develop new therapeutic strategies to prevent the dissemination of ILCs.

  3. Slug silencing inhibited perineural invasion through regulation of EMMPRIN expression in human salivary adenoid cystic carcinoma.

    Science.gov (United States)

    Wu, Baolei; Wei, Jianhua; Hu, Zhiqiang; Shan, Chun; Wang, Lei; Zhang, Chenping; Yang, Xi; Yang, Xinjie; Lei, Delin

    2016-02-01

    Salivary adenoid cystic carcinoma (SACC) is the most frequent salivary gland malignancy with a unique characteristic that has been named perineural invasion (PNI). EMMPRIN is a transmembrane glycoprotein that has been demonstrated to promote PNI in SACC. Slug, one of the most effective promoters of the epithelial-to-mesenchymal transition (EMT), has been found to be associated with PNI in SACC. The aim of the present study was to investigate the roles and relationships of Slug, EMMPRIN, and E-cadherin in the PNI process of SACC. The expression levels of Slug, EMMPRIN, and E-cadherin in 115 primary SACC cases were statistically analyzed by immunohistochemistry. Simultaneously, the SACC cell line SACC-83 was transfected with recombinant plasmids of silencing Slug (si-Slug) and/or silencing EMMPRIN (si-EMMPRIN). The functions of Slug and EMMPRIN in the EMT and PNI process were assessed by reverse transcription PCR (RT-PCR), western blotting, morphological observation, scratch test, migration assay, and in vitro perineural invasion assay. The immunohistochemical statistics revealed that the high expression of Slug and EMMPRIN and the low expression of E-cadherin were significantly associated with the PNI of SACC (P EMMPRIN expression (P EMMPRIN expression were both significantly negatively associated with E-cadherin expression (P EMMPRIN silencing both significantly inhibited EMMPRIN expression but promoted E-cadherin expression in SACC-83 cells (P EMMPRIN, or both induced cell morphology changes and inhibited tumor cell motility and PNI ability in SACC-83 cells (P EMMPRIN and then upregulating E-cadherin in the PNI process of SACC. The present study indicated that Slug and EMMPRIN are potential biomarkers and therapeutic targets for the diagnosis and treatment of PNI in human SACC.

  4. Gene expression signatures predict outcome in non-muscle invasive bladder carcinoma - a multi-center validation study

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, Karsten; Real, Francisco X.

    2007-01-01

    and carcinoma in situ (CIS) and for predicting disease recurrence and progression. EXPERIMENTAL DESIGN: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic....... CONCLUSION: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non-muscle-invasive bladder cancer. This information may be useful to better guide patient treatment....

  5. The diagnosis and management of pre-invasive breast disease: Pathology of atypical lobular hyperplasia and lobular carcinoma in situ

    International Nuclear Information System (INIS)

    Simpson, Peter T; Gale, Theodora; Fulford, Laura G; Reis-Filho, Jorge S; Lakhani, Sunil R

    2003-01-01

    The term lobular neoplasia refers to a spectrum of lesions featuring atypical lobular hyperplasia and lobular carcinoma in situ (LCIS). The histopathological characteristics of these lesions are well documented. What is less well understood is the management implications of a patient diagnosed with LCIS; treatment regimes vary and are somewhat controversial. LCIS is now considered a risk factor and a non-obligate precursor for the subsequent development of invasive cancer

  6. Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

    Energy Technology Data Exchange (ETDEWEB)

    Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J

    1998-06-29

    Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

  7. Multifocal manifestation does not affect vascular invasion of hepatocellular carcinoma: implications for patient selection in liver transplantation.

    Science.gov (United States)

    Löhe, Florian; Angele, Martin K; Rentsch, Markus; Graeb, Christian; Gerbes, Alexander; Löhrs, Udo; Beuers, Ulrich; Jauch, Karl-Walter

    2007-01-01

    Liver transplantation (OLT) for hepatocellular carcinoma (HCC) improves patient survival when tumor size and number are limited according to the Milan criteria. However, the impact of tumor size vs. the number of lesions for tumor recurrence after OLT is unclear. Microvascular invasion appears to be a significant risk factor for tumor recurrence. Therefore, it was the aim of this study to investigate tumor differentiation and microvascular invasion in relation to tumor number and size and their impact on survival after transplantation. In 97 adult HCC patients who underwent OLT between June 1985 and December 2005 the incidence of microvascular invasion, tumor differentiation, and the number and size of tumor lesions were analyzed retrospectively. Their impact on survival was studied by multivariate analysis. Microvascular invasion was the only independent negative predictor of survival after OLT for HCC (p = 0.025). Tumor size > 5 cm was predictive for microvascular invasion (p = 0.007). In contrast, tumor number did not affect the incidence of microvascular invasion or cumulative survival. The size of the largest HCC lesion, but not the number of tumors, determined microvascular invasion, a predictor of the outcome following OLT for HCC. Thus, the number of HCC lesions should not be applied to patient selection prior to OLT. These data support the extension of the Milan criteria for the selection of HCC patients for OLT with regard to tumor number, but not tumor size.

  8. Accessory Breast Cancer Occurring Concurrently with Bilateral Primary Invasive Breast Carcinomas: A Report of Two Cases and Literature Review

    International Nuclear Information System (INIS)

    Hao, Jin-yan; Yang, Cui-cui; Liu, Fang-fang; Yang, Yi-ling; Li, Shuai; Li, Wei-dong; Li, Ya-qing; Lang, Rong-gang; Fan, Yu; Paulos, Estifanos; Zhang, Xin-min; Fu, Li

    2012-01-01

    The development of accessory breast tissue, which is found anywhere along the milk line, is attributed to the failure of milk line remnants to regress during embryogenesis. Primary tumors may arise from any ectopic breast tissue. Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare. Two such cases were reported in this article. One was a 43-year-old Chinese female who exhibited bilateral breast cancer (invasive ductal carcinoma, not otherwise specified, IDC-NOS) and an accessory breast carcinoma (IDC-NOS) incidentally identified in her left axilla. The ectopic breast tissue in her right axilla presented with adenosis. The patient was surgically treated, followed by postoperative docetaxel epirubicin (TE) chemotherapy. The second case was a 53-year-old Chinese female with bilateral breast cancer (apocrine carcinoma) accompanied by an accessory breast carcinoma (IDC-NOS) in her right axilla that was also incidentally identified. The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel (CET) neoadjuvant chemotherapy, followed by adjuvant chemotherapy of the same regimen

  9. 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.

  10. Advanced Tracheal Adenoid Cystic Carcinoma with Thyroid Invasion Mimicking Thyroid Cancer Treated with Definitive Radiation: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sondos Al Khatib

    2017-08-01

    Full Text Available A 54-year-old female patient, a breast cancer survivor and a case of unresectable adenoid cystic carcinoma of the trachea, with thyroid invasion, presented with suprasternal neck swelling mimicking thyroid primary. A literature search was undertaken to highlight this rare presentation. There have been few reports in the literature describing tracheal adenoid cystic carcinoma involving the thyroid.

  11. Invasive lobular carcinoma with extracellular mucin production-a novel pattern of lobular carcinomas of the breast. Clinico-pathological description of eight cases.

    Science.gov (United States)

    Cserni, Gábor; Floris, Giuseppe; Koufopoulos, Nektarios; Kovács, Anikó; Nonni, Afroditi; Regitnig, Peter; Stahls, Anders; Varga, Zsuzsanna

    2017-07-01

    Invasive lobular carcinoma of the breast is known to produce intracellular mucin and has been recognized in single-case reports to show extracellular mucin production, as well. This latter morphology is not only rare but must also be under- or misdiagnosed. The aim was to better characterize this entity. Cases of lobular cancers demonstrating extracellular mucin formation were identified in a multi-institutional effort and their clinical and morphologic features were assessed. Immunohistochemistry was used to characterize the E-cadherin-membrane complex, neuroendocrine differentiation, and to some extent, mucin formation. All but one of the eight cases occurred in postmenopausal patients. Extracellular mucin production was present in 5 to 50% of the tumour samples and rarely also appeared in nodal and distant metastases. The tumours were completely E-cadherin negative and showed cytoplasmic p120 positivity. The majority (n = 6/8) was also completely negative for β-catenin, but two tumours displayed focal β-catenin positivity in the mucinous area. MUC1 and MUC2 expression was observed in all and 7/8 tumours, respectively; neuroendocrine differentiation was present in only one. Invasive lobular carcinoma with extracellular mucin formation is a rare morphologic variant of lobular carcinoma prone to be misdiagnosed and warranting further studies.

  12. Three-dimensional visualization and quantification for the growth and invasion of oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yoshihito Shimazu

    2010-02-01

    Full Text Available Recent advance in three-dimensional (3D imaging technology allows us to inspect visually and quantitatively the architecture of complex biological tissues and pathological lesions. We initiated histology-based 3D reconstruction of oral squamous cell carcinoma (SCC in order to collect quantitative information of diagnostic value regarding cancer invasion and prognosis. The basic procedures for 3D reconstruction are: preparation of serial histological sections in combination with immunostaining of cell/tissue constituents of interest, alignment and superposition of digitized images, computer-assisted color segmentation of labeled targets, and finally viewing and morphometric analysis of the reconstruct. Our past experience showed that cytokeratin-positive tumor parenchyma can be segmented readily from the surrounding stroma with the aid of Image-J and RATOC TRI-SRF2 software. Cytoplasm/nucleus segmentation of individual SCC cells was also feasible at higher magnifications, leading to quantitative analysis of several histological parameters in tissue space, e.g., parenchyma and stroma volume, nuclear numbers and nuclear/cytoplasm volume ratio, as well as proliferation activity of cancer cells by counting separately the number of Ki-67 positive and negative nuclei in the parenchyma. The results support the wide potential usage and advantage of histology-based 3D reconstruction in cancer biology understanding and pathological diagnosis.

  13. The influence of aging on pathologic and immunobiologic parameters of invasive ductal breast carcinoma

    Directory of Open Access Journals (Sweden)

    Ivković-Kapicl Tatjana

    2006-01-01

    Full Text Available Background/Aim. Most human cancers, including breast one, increase in frequency with aging. The aim of this study was to explore the hypothesis that aging also alters breast cancer biology. Methods. The study included 120 women with primary invasive ductal carcinoma of the breast. We correlated the patients age and diagnosis with the commonly used clinical, pathological factors and newer tumor biomarkers. Immunohistochemical staining was conducted for p53, c-erbB-2, Ki-67, estrogen (ER, progesterone (PR receptors, and angiogenesis. Results. In our study, the patients with axillary lymph node metastases and negative steroid hormone receptors (ER and PR were significantly younger than the patients with nodal involvement and positive hormone receptors. There was also a significant association between the patients age, diagnosis and angiogenesis. No association was found between the patients age and tumor size, histological grade, p53, c-erbB-2, and Ki-67. Conclusion. The results of our study supported only partially the hypothesis that the breast cancer biology is significantly affected by a patient's age.

  14. Value of MR histogram analyses for prediction of microvascular invasion of hepatocellular carcinoma.

    Science.gov (United States)

    Huang, Ya-Qin; Liang, He-Yue; Yang, Zhao-Xia; Ding, Ying; Zeng, Meng-Su; Rao, Sheng-Xiang

    2016-06-01

    The objective is to explore the value of preoperative magnetic resonance (MR) histogram analyses in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC).Fifty-one patients with histologically confirmed HCC who underwent diffusion-weighted and contrast-enhanced MR imaging were included. Histogram analyses were performed and mean, variance, skewness, kurtosis, 1th, 10th, 50th, 90th, and 99th percentiles were derived. Quantitative histogram parameters were compared between HCCs with and without MVI. Receiver operating characteristics (ROC) analyses were generated to compare the diagnostic performance of tumor size, histogram analyses of apparent diffusion coefficient (ADC) maps, and MR enhancement.The mean, 1th, 10th, and 50th percentiles of ADC maps, and the mean, variance. 1th, 10th, 50th, 90th, and 99th percentiles of the portal venous phase (PVP) images were significantly different between the groups with and without MVI (P histogram analyses-in particular for 1th percentile for PVP images-held promise for prediction of MVI of HCC.

  15. 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.

  16. Lycopene inhibits the cell proliferation and invasion of human head and neck squamous cell carcinoma.

    Science.gov (United States)

    Ye, Min; Wu, Qundan; Zhang, Min; Huang, Jinbei

    2016-10-01

    Lycopene has been shown to be associated with anticancer effects in numerous tumor types. However, the underlying mechanisms of lycopene in human head and neck squamous cell carcinoma (HNSCC) remain to be determined. The present study aimed to investigate the involvement of lycopene overload and the cytotoxic effects of lycopene on HNSCC cells, and to determine the possible mechanisms involved. Treatment with lycopene at a dose of >10 µM for >24 h inhibited the growth of FaDu and Cal27 cells in a time‑ and dose‑dependent manner. The clearest increase in growth inhibition was due to the apoptotic population being significantly increased. The invasion abilities decreased with 25 µM lycopene exerting significant inhibitory effects (Plycopene induced the upregulation of the pro‑apoptotic protein, B‑cell lymphoma‑associated X protein, and therefore, resulted in the inhibition of the protein kinase B and mitogen‑activated protein kinase signaling pathway. These data provided insights into the antitumor activity of lycopene in HNSCC cells.

  17. The Expression of BTS-2 Enhances Cell Growth and Invasiveness in Renal Cell Carcinoma.

    Science.gov (United States)

    Pham, Quoc Thang; Oue, Naohide; Yamamoto, Yuji; Shigematsu, Yoshinori; Sekino, Yohei; Sakamoto, Naoya; Sentani, Kazuhiro; Uraoka, Naohiro; Tiwari, Mamata; Yasui, Wataru

    2017-06-01

    Renal cell carcinoma (RCC) is one of the most common types of cancer in developed countries. Bone marrow stromal cell antigen 2 (BST2) gene, which encodes BST2 transmembrane glycoprotein, is overexpressed in several cancer types. In the present study, we analyzed the expression and function of BST2 in RCC. BST2 expression was analyzed by immunohistochemistry in 123 RCC cases. RNA interference was used to inhibit BST2 expression in a RCC cell line. Immunohistochemical analysis showed that 32% of the 123 RCC cases were positive for BST2. BST2 expression was positively associated with tumour stage. Furthermore, BST2 expression was an independent predictor of survival in patients with RCC. BST2 siRNA-transfected Caki-1 cells displayed significantly reduced cell growth and invasive activity relative to negative control siRNA-transfected cells. These results suggest that BST2 plays an important role in the progression of RCC. Because BST2 is expressed on the cell membrane, BST2 is a good therapeutic target for RCC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Diagnostic and prognostic relevance of Cullin1 expression in invasive ductal carcinoma of the breast.

    Science.gov (United States)

    Min, Kyueng-Whan; Kim, Dong-Hoon; Do, Sung-Im; Sohn, Jin Hee; Chae, Seoung Wan; Pyo, Jung-Soo; Park, Chan Heun; Oh, Young-Ha; Jang, Ki-Seok; Kim, Hack-Lyoung; Kim, Min

    2012-10-01

    Cullin1 (Cul1) is a matrix degrading enzyme known to be involved in the remodelling of extracellular matrix proteins. This enzyme has recently been reported to play a key role in tumour progression and its presence is associated with poor clinical outcome for several different types of tumours. 159 patients diagnosed with invasive ductal carcinoma between 2000 and 2005 were studied. Cul1 expression was analysed by immunohistochemical staining on a tissue microarray. The relationship between Cul1 expression and clinicopathological parameters was evaluated. Tumour expression of Cul1 was correlated with prognostic factors such as high histological grade and p53 expression, and was also linked to negative ER and positive HER2 as therapeutic markers (all pCul1 expression in both univariate and multivariate analyses (all pCul1 expression was significantly associated with high-grade tumours and poor prognosis, suggesting that it may play a role in breast tumour progression. Cul1 expression may therefore be crucial for the prediction of disease outcome in breast cancer patients.

  19. 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

  20. HDAC 1 and 6 modulate cell invasion and migration in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Ramakrishnan, Swathi; Ku, ShengYu; Ciamporcero, Eric; Miles, Kiersten Marie; Attwood, Kris; Chintala, Sreenivasulu; Shen, Li; Ellis, Leigh; Sotomayor, Paula; Swetzig, Wendy; Huang, Ray; Conroy, Dylan; Orillion, Ashley; Das, Gokul; Pili, Roberto

    2016-01-01

    Class I histone deacetylases (HDACs) have been reported to be overexpressed in clear cell renal cell carcinoma (ccRCC), whereas the expression of class II HDACs is unknown. Four isogenic cell lines C2/C2VHL and 786-O/786-OVHL with differential VHL expression are used in our studies. Cobalt chloride is used to mimic hypoxia in vitro. HIF-2α knockdowns in C2 and 786-O cells is used to evaluate the effect on HDAC 1 expression and activity. Invasion and migration assays are used to investigate the role of HDAC 1 and HDAC 6 expression in ccRCC cells. Comparisons are made between experimental groups using the paired T-test, the two-sample Student’s T-test or one-way ANOVA, as appropriate. ccRCC and the TCGA dataset are used to observe the clinical correlation between HDAC 1 and HDAC 6 overexpression and overall and progression free survival. Our analysis of tumor and matched non-tumor tissues from radical nephrectomies showed overexpression of class I and II HDACs (HDAC6 only in a subset of patients). In vitro, both HDAC1 and HDAC6 over-expression increased cell invasion and motility, respectively, in ccRCC cells. HDAC1 regulated invasiveness by increasing matrix metalloproteinase (MMP) expression. Furthermore, hypoxia stimulation in VHL-reconstituted cell lines increased HIF isoforms and HDAC1 expression. Presence of hypoxia response elements in the HDAC1 promoter along with chromatin immunoprecipitation data suggests that HIF-2α is a transcriptional regulator of HDAC1 gene. Conversely, HDAC6 and estrogen receptor alpha (ERα) were co-localized in cytoplasm of ccRCC cells and HDAC6 enhanced cell motility by decreasing acetylated α-tubulin expression, and this biological effect was attenuated by either biochemical or pharmacological inhibition. Finally, analysis of human ccRCC specimens revealed positive correlation between HIF isoforms and HDAC. HDAC1 mRNA upregulation was associated with worse overall survival in the TCGA dataset. Taking together, these results

  1. Adjuvant Chemoradiotherapy After Pancreatic Resection for Invasive Carcinoma Associated With Intraductal Papillary Mucinous Neoplasm of the Pancreas

    International Nuclear Information System (INIS)

    Swartz, Michael J.; Hsu, Charles C.; Pawlik, Timothy M.; Winter, Jordan; Hruban, Ralph H.; Guler, Mehmet; Schulick, Richard D.; Cameron, John L.; Laheru, Daniel A.; Wolfgang, Christopher L.; Herman, Joseph M.

    2010-01-01

    Purpose: Intraductal papillary mucinous neoplasms are mucin-producing cystic neoplasms of the pancreas. One-third are associated with invasive carcinoma. We examined the benefit of adjuvant chemoradiotherapy (CRT) for this cohort. Methods and Materials: Patients who had undergone pancreatic resection at Johns Hopkins Hospital between 1999 and 2004 were reviewed. Of these patients, 83 with a resected pancreatic mass were found to have an intraductal papillary mucinous neoplasm with invasive carcinoma, 70 of whom met inclusion criteria for the present analysis. Results: The median age at surgery was 68 years. The median tumor size was 3.3 cm, and invasive carcinoma was present at the margin in 16% of the patients. Of the 70 patients, 50% had metastases to the lymph nodes and 64% had Stage II disease. The median survival was 28.0 months, and 2- and 5-year survival rate was 57% and 45%, respectively. Of the 70 patients, 40 had undergone adjuvant CRT. Those receiving CRT were more likely to have lymph node metastases, perineural invasion, and Stage II-III disease. The 2-year survival rate after surgery with vs. without CRT was 55.8% vs. 59.3%, respectively (p = NS). Patients with lymph node metastases or positive surgical margins benefited significantly from CRT (p = .047 and p = .042, respectively). On multivariate analysis, adjuvant CRT was associated with improved survival, with a relative risk of 0.43 (95% confidence interval, 0.19-0.95; p = .044) after adjusting for major confounders. Conclusion: Adjuvant CRT conferred a 57% decrease in the relative risk of mortality after pancreaticoduodenectomy for intraductal papillary mucinous neoplasms with an associated invasive component after adjusting for major confounders. Patients with lymph node metastases or positive margins appeared to particularly benefit from CRT after definitive surgery.

  2. Low grade uranium deposits of India - a bane or boon

    International Nuclear Information System (INIS)

    Chaki, Anjan

    2010-01-01

    Uranium resources of the world is estimated to be 5.5 million tonnes and the proven resources in India forms 3% of the world resources. The biggest uranium deposit is the Olympic dam deposit in Australia, which contains nearly one million tonnes of 0.04% U 3 O 8 , while the highest grade of nearly 20% is established in the McArthur river deposit, Canada. Another very high grade deposit, the Cigar lake deposit, is established in Canada with an average grade of nearly 18%. Most of the uranium deposits established in India so far falls under the category of low grade. These low grade uranium deposits are distributed mainly in Singhbhum Shear Zone, eastern India; in parts of Chhattisgarh; Southern parts of Meghalaya; Cuddapah Basin, Andhra Pradesh; in parts of Karnataka and Aravalli- and Delhi Supergroups, Rajasthan and Haryana. These deposits are mainly hydrothermal vein type, stratabound type and unconformity related. The Singhbhum Shear Zone, Jharkhand hosts a seventeen low grade uranium deposits, aggregating about 30% of Indian uranium resources. The uranium mineralisation hosted by Vempalle dolostone extends over 160 km belt along southwestern margin of Cuddapah Basin in Andhra Pradesh and accounts 23% of the Indian resources. Though the dolostone hosted Tummalapalle uranium deposit was established in the early nineties, because of techno-economic constraints, the deposit remained dormant. As a consequence of the development of an innovative pressure alkali beneficiation process, the deposit became economically viable and a mine and mill are being constructed here. Recent exploration inputs are leading to prove a number of low grade uranium deposits in the extension areas of Tummalapalle. Nearly 10 blocks have been identified within a 30 km belt which are being actively explored and a large uranium deposit has already been proved in this province. The deposit at Tummalapalle and adjoining areas is likely to become the second biggest deposit in the world. The

  3. Actinide recovery from waste and low-grade sources

    International Nuclear Information System (INIS)

    Navratil, J.D.; Schulz, W.W.

    1982-01-01

    Actinide and nuclear fuel cycle operations generate a variety of process waste streams. New methods are needed to remove and recover actinides. More interest is also being expressed in recovering uranium from oceans, phosphoric acid, and other low grade sources. To meet the need for an up-to-date status report in the area of actinide recovery from waste and low grade sources, these papers were brought together. The papers provide an authoritative, in-depth coverage of an important area of nuclear and industrial and engineering chemistry which cover the following topics: uranium recovery from oceans and phosphoric acid; recovery of actinides from solids and liquid wastes; plutonium scrap recovery technology; and other new developments in actinide recovery processes

  4. Underground bioleaching: extracting from low-grade ore

    International Nuclear Information System (INIS)

    McCready, R.G.L.

    1986-01-01

    In 1984, Denison Mines began a research and demonstration project on the engineering aspects of bacterial leaching of low-grade uranium ore at Elliot Lake. The leaching solution was acidic mine water enriched in bacterial nutrients and innoculated with Thiobacillus ferrooxidans. Leaching of one stope was found to be impeded by fungi of the genus penicillium. Although fungal growth on leaching stopes must be prevented, research is proceeding on the potential use of the fungi to concentrate uranium from bioleaching solutions

  5. Properties of concrete blocks prepared with low grade recycled aggregates.

    Science.gov (United States)

    Poon, Chi-Sun; Kou, Shi-cong; Wan, Hui-wen; Etxeberria, Miren

    2009-08-01

    Low grade recycled aggregates obtained from a construction waste sorting facility were tested to assess the feasibility of using these in the production of concrete blocks. The characteristics of the sorted construction waste are significantly different from that of crushed concrete rubbles that are mostly derived from demolition waste streams. This is due to the presence of higher percentages of non-concrete components (e.g. >10% soil, brick, tiles etc.) in the sorted construction waste. In the study reported in this paper, three series of concrete block mixtures were prepared by using the low grade recycled aggregates to replace (i) natural coarse granite (10mm), and (ii) 0, 25, 50, 75 and 100% replacement levels of crushed stone fine (crushed natural granite concrete blocks. Test results on properties such as density, compressive strength, transverse strength and drying shrinkage as well as strength reduction after exposure to 800 degrees C are presented below. The results show that the soil content in the recycled fine aggregate was an important factor in affecting the properties of the blocks produced and the mechanical strength deceased with increasing low grade recycled fine aggregate content. But the higher soil content in the recycled aggregates reduced the reduction of compressive strength of the blocks after exposure to high temperature due probably to the formation of a new crystalline phase. The results show that the low grade recycled aggregates obtained from the construction waste sorting facility has potential to be used as aggregates for making non-structural pre-cast concrete blocks.

  6. Polymorphous low-grade adenocarcinoma of the nasopharynx. Case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Lengyel, E.; Somogyi, A.; Nemeth, G. [National Institute of Oncology, Budapest (Hungary). Dept. of Radiation Oncology; Godeny, M. [National Institute of Oncology, Budapest (Hungary). Dept. of Radiology; Szerdahelyi, A. [National Institute of Oncology, Budapest (Hungary). Dept. of Pathology

    2000-01-01

    Background: The polymorphous low-grade adenocarcinoma of the nasopharynx is a rare disease. Polymorphous low-grade adenocarcinoma is a minor salivary gland neoplasm which occurs frequently in the mucosa of the soft and hard palates, in the buccal mucosa and in the upper lip. To date this entity has been identified within the oral cavity and only one case within the nasopharynx and some cases in the parotid gland. It has a slow infiltrating growing pattern with frequent perineural invasion and low metastatic potential. Case Report: We report on a patient with non-papillary polymorphous low-grade adenocarcinoma in the nasopharynx which extended intracranially. The patient underwent primary radiotherapy. The CT showed partial response to radiotherapy and the patient is alive 51 months after the diagnosis his state being unchanged. Conclusion: The treatment for minor salivary gland tumor is primarily surgical. It is reported that the polymorphous low-grade adenocarcinoma has been known to have poor response to radiotherapy. However, we believe that in addition to its favorable biological behavior, the radiotherapy in this localization may result in longer survival. (orig.) [German] Hintergrund: Das polymorphe Adenokarzinom des Nasopharynx mit niedrigem Malignitaetsgrad ist eine seltene Krankheit. Es handelt sich um eine Geschwulst der kleinen Speicheldruesen, die oft in der Schleimhaut des harten und weichen Gaumens, in der Mundschleimhaut und in der oberen Lippe vorkommt. Diese Krankheitsform wurde bisher in der Mundhoehle, nur in einem Fall im Nasenrachenraum und in einigen Faellen in der Ohrspeicheldruese nachgewiesen. Sie zeigt ein langsam infiltrierendes Wachstum, oft mit perineuraler Invasion und geringem metastatischen Potential. Fallbeschreibung: Wir berichten ueber einen Patienten mit intrakranial ausgedehntem nichtpapillaeren polymorphen Adenokarzinom des Nasopharynx. Der Patient erhielt eine primaere Strahlenbehandlung. Durch CT wurde danach eine partielle

  7. Low grade uranium ores as potential sources of raw material

    International Nuclear Information System (INIS)

    Venzlaff, H.

    1976-01-01

    Reports on the uranium requirement and the uranium reserves show that, even if the demand were to be stretched out slightly, the rate of new discoveries of uranium would have to be doubled or even tripled within a few years in order to ensure supply. Despite some spectacular discoveries of large scale deposits in Australia it must be said that only very few truly new uranium provinces have been discovered over the past twenty years. In this situation more attention is now being devoted to low grade uranium depositis, to findings whose concentration does not exceed 1,000 ppm. These deposits contain quantities of uranium many times larger than the deposits that can now be mined at prices up to 30/lb of U 3 O 8 . Even now low grade uranium ore is being mined as a byproduct, with the actual valuable mineral producing most of the income from mining activities. However, if one strikes a balance in this situation, one finds that only part of the requirement can be met in this way. Hence, all possibilities must be exhausted to mine uranium as a byproduct, new techniques of uranium production from low grade ores must be developed, and also conventional prospection must be intensified, if the continuity of supply of the nuclear power stations in the eighties and nineties is to be guaranteed. (orig.) [de

  8. Recovery of Tungsten and Molybdenum from Low-Grade Scheelite

    Science.gov (United States)

    Li, Yongli; Yang, Jinhong; Zhao, Zhongwei

    2017-10-01

    With most high-quality tungsten ores being exhausted, the enhancement of low-grade scheelite concentrates processing has attracted a great deal of attention. The objective of this study is to develop a method to maximize the recovery tungsten and molybdenum from a low-grade scheelite via a new acid leaching process followed by solvent extraction. Under optimal conditions (350 g/L H2SO4, 95°C, and 2 h), approximately 99.8% of tungsten and 98% of molybdenum were leached out. In the subsequent solvent extraction process, more than 99% of the tungsten and molybdenum were extracted with a co-extraction system (50% TBP, 30% HDEHP, and 10% 2-octanol in kerosene) using a three-stage cross-flow extraction. The raffinate can be recycled for the next leaching process after replenishing the H2SO4 to the initial value (approximately 350 g/L). Based on these results, a conceptual flowsheet is presented to recover tungsten and molybdenum from the low-grade scheelite.

  9. Fibronectin Modulates Cell Adhesion and Signaling to Promote Single Cell Migration of Highly Invasive Oral Squamous Cell Carcinoma

    Science.gov (United States)

    Ramos, Grasieli de Oliveira; Bernardi, Lisiane; Lauxen, Isabel; Sant’Ana Filho, Manoel; Horwitz, Alan Rick; Lamers, Marcelo Lazzaron

    2016-01-01

    Cell migration is regulated by adhesion to the extracellular matrix (ECM) through integrins and activation of small RhoGTPases, such as RhoA and Rac1, resulting in changes to actomyosin organization. During invasion, epithelial-derived tumor cells switch from laminin-enriched basal membrane to collagen and fibronectin-enriched connective tissue. How this switch affects the tumor migration is still unclear. We tested the hypothesis that ECM dictates the invasiveness of Oral Squamous Cell Carcinoma (OSCC). We analyzed the migratory properties of two OSCC lines, a low invasive cell line with high e-cadherin levels (Linv/HE-cad) or a highly invasive cell line with low e-cadherin levels (Hinv/LE-cad), plated on different ECM components. Compared to laminin, fibronectin induced non-directional collective migration and decreased RhoA activity in Linv/HE-cad OSCC. For Hinv/LE-cad OSCC, fibronectin increased Rac1 activity and induced smaller adhesions, resulting in a fast single cell migration in both 2D and 3D environments. Consistent with these observations, human OSCC biopsies exhibited similar changes in cell-ECM adhesion distribution at the invasive front of the tumor, where cells encounter fibronectin. Our results indicate that ECM composition might induce a switch from collective to single cell migration according to tumor invasiveness due to changes in cell-ECM adhesion and the resulting signaling pathways that alter actomyosin organization. PMID:26978651

  10. Fibronectin Modulates Cell Adhesion and Signaling to Promote Single Cell Migration of Highly Invasive Oral Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Grasieli de Oliveira Ramos

    Full Text Available Cell migration is regulated by adhesion to the extracellular matrix (ECM through integrins and activation of small RhoGTPases, such as RhoA and Rac1, resulting in changes to actomyosin organization. During invasion, epithelial-derived tumor cells switch from laminin-enriched basal membrane to collagen and fibronectin-enriched connective tissue. How this switch affects the tumor migration is still unclear. We tested the hypothesis that ECM dictates the invasiveness of Oral Squamous Cell Carcinoma (OSCC. We analyzed the migratory properties of two OSCC lines, a low invasive cell line with high e-cadherin levels (Linv/HE-cad or a highly invasive cell line with low e-cadherin levels (Hinv/LE-cad, plated on different ECM components. Compared to laminin, fibronectin induced non-directional collective migration and decreased RhoA activity in Linv/HE-cad OSCC. For Hinv/LE-cad OSCC, fibronectin increased Rac1 activity and induced smaller adhesions, resulting in a fast single cell migration in both 2D and 3D environments. Consistent with these observations, human OSCC biopsies exhibited similar changes in cell-ECM adhesion distribution at the invasive front of the tumor, where cells encounter fibronectin. Our results indicate that ECM composition might induce a switch from collective to single cell migration according to tumor invasiveness due to changes in cell-ECM adhesion and the resulting signaling pathways that alter actomyosin organization.

  11. HPV types, HIV and invasive cervical carcinoma risk in Kampala, Uganda: a case-control study

    Directory of Open Access Journals (Sweden)

    Kleter Bernhard

    2011-06-01

    Full Text Available Abstract Background While the association of human papillomavirus (HPV with cervical cancer is well established, the influence of HIV on the risk of this disease in sub-Saharan Africa remains unclear. To assess the risk of invasive cervical carcinoma (ICC associated with HIV and HPV types, a hospital-based case-control study was performed between September 2004 and December 2006 in Kampala, Uganda. Incident cases of histologically-confirmed ICC (N=316 and control women (N=314, who were visitors or care-takers of ICC cases in the hospital, were recruited. Blood samples were obtained for HIV serology and CD4 count, as well as cervical samples for HPV testing. HPV DNA detection and genotyping was performed using the SPF10/DEIA/LiPA25 technique which detects all mucosal HPV types by DEIA and identifies 25 HPV genotypes by LiPA version 1. Samples that tested positive but could not be genotyped were designated HPVX. Odds ratios (OR and 95% confidence intervals (CI were calculated by logistic regression, adjusting for possible confounding factors. Results For both squamous cell carcinoma (SCC and adenocarcinoma of the cervix, statistically significantly increased ORs were found among women infected with HPV, in particular single HPV infections, infections with HPV16-related types and high-risk HPV types, in particular HPV16, 18 and 45. For other HPV types the ORs for both SCC and adenocarcinoma were not statistically significantly elevated. HIV infection and CD4 count were not associated with SCC or adenocarcinoma risk in our study population. Among women infected with high-risk HPV types, no association between HIV and SCC emerged. However, an inverse association with adenocarcinoma was observed, while decrease in CD4 count was not associated with ICC risk. Conclusions The ORs for SCC and adenocarcinoma were increased in women infected with HPV, in particular single HPV infections, infections with HPV16- and 18-related types, and high-risk HPV types

  12. [Low grade renal trauma (Part II): diagnostic validity of ultrasonography].

    Science.gov (United States)

    Grill, R; Báca, V; Otcenásek, M; Zátura, F

    2010-04-01

    The aim of the study was to verify whether ultrasonography can be considered a reliable method for the diagnosis of low-grade renal trauma. The group investigated included patients with grade I or grade II blunt renal trauma, as classified by the AAST grading system, in whom ultrasonography alone or in conjunction with computed tomography was used as a primary diagnostic method. B-mode ultrasound with a transabdominal probe working at frequencies of 2.5 to 5.0 MHz was used. Every finding of post-traumatic changes in the renal tissues, i.e., post-contusion hypotonic infiltration of the renal parenchyma or subcapsular haematoma, was included. The results were statistically evaluated by the Chi-square test with the level of significance set at 5%, using Epi Info Version 6 CZ software. The group comprised 112 patients (43 women, 69 men) aged between 17 and 82 years (average, 38 years). It was possible to diagnose grade I or grade II renal injury by ultrasonography in only 60 (54%) of them. The statistical significance of ultrasonography as the only imaging method for the diagnosis of low-grade renal injury was not confirmed (p=0.543) Low-grade renal trauma is a problem from the diagnostic point of view. It usually does not require revision surgery and, if found during repeat surgery for more serious injury of another organ, it usually does not receive attention. Therefore, the macroscopic presentation of grade I and grade II renal injury is poorly understood, nor are their microscopic findings known, because during revision surgery these the traumatised kidneys are not usually removed and their injuries at autopsy on the patients who died of multiple trauma are not recorded either. The results of this study demonstrated that the validity of ultrasonography for the diagnosis of low-grade renal injury is not significant, because this examination can reveal only some of the renal injuries such as perirenal haematoma. An injury to the renal parenchyma is also indicated by

  13. Low Grade Peritoneal Mucinous Carcinomatosis Associated with Human Papilloma Virus Infection: Case Report

    Science.gov (United States)

    Gatalica, Zoran; Foster, Jason M.; Loggie, Brian W.

    2008-01-01

    Pseudomyxoma peritonei is a clinical syndrome characterized by peritoneal dissemination of a mucinous tumor with mucinous ascites. The vast majority of the pseudomyxoma peritoneis are associated with mucinous neoplasms of the appendix. We describe a case of pseudomyxoma peritonei associated with mucinous adenocarcinoma of the cervix in a 60-year-old woman. The patient developed low grade mucinous peritoneal carcinomatosis 8 years after hysterectomy for cervical adenocarcinoma. No other primary mucinous tumor was identified and peritoneal carcinomatosis tested positive for high-risk human papilloma virus (HPV), showing both integrated and episomal pattern. HPV has been previously associated with development of cervical carcinomas (both squamous and mucinous) but neither has cervical adenocarcinoma nor HPV been implicated in development of pseudomyxoma peritonei. To the best of our knowledge, this is the first description of HPV-associated malignancy presenting as pseudomyxoma peritonei. PMID:18925701

  14. 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.

  15. The prognostic effect of perineural invasion in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Chen, Jie-Wei; Cai, Mu-Yan; Xie, Jing-Dun; Ling, Yi-Hong; Li, Peng; Yan, Shu-Mei; Xi, Shao-Yan; Luo, Rong-Zhen; Yun, Jing-Ping; Xie, Dan

    2014-01-01

    Perineural invasion (PNI) is correlated with adverse survival in several malignancies, but its significance in esophageal squamous cell carcinoma (ESCC) remains to be clearly defined. The objective of this study was to determine the association between PNI status and clinical outcomes. We retrospectively evaluated the PNI of 433 patients with ESCC treated with surgery between 2000 and 2007 at a single academic center. The resulting data were analyzed using Spearman’s rank correlation, the Kaplan-Meier method, Cox proportional hazards regression modeling and Harrell’s concordance index (C-index). PNI was identified in 209 of the 433 (47.7%) cases of ESCC. The correlation analysis demonstrated that PNI in ESCC was significantly correlated with tumor differentiation, infiltration depth, pN classification and stage (P < 0.05). The five-year overall survival rate was 0.570 for PNI-negative tumors versus 0.326 for PNI-positive tumors. Patients with PNI-negative tumors exhibited a 1.7-fold increase in five-year recurrence-free survival compared with patients with PNI-positive tumors (0.531 v 0.305, respectively; P < 0.0001). In the subset of patients with node-negative disease, PNI was evaluated as a prognostic predictor as well (P < 0.05). In the multivariate analysis, PNI was an independent prognostic factor for overall survival (P = 0.027). The C-index estimate for the combined model (PNI, gender and pN status) was a significant improvement on the C-index estimate of the clinicopathologic model alone (0.739 v 0.706, respectively). PNI can function as an independent prognostic factor of outcomes in ESCC patients, and the PNI status in primary ESCC specimens should be considered for therapy stratification

  16. SIRT1 Regulates the Chemoresistance and Invasiveness of Ovarian Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    David Hamisi Mvunta

    2017-08-01

    Full Text Available BACKGROUND: SIRT1 is a longevity gene that forestalls aging and age-related diseases including cancer, and has recently attracted widespread attention due to its overexpression in some cancers. We previously identified the overexpression of SIRT1 in ovarian carcinoma (OvCa as a poor prognostic factor. However, mechanistic insights into the function of SIRT1 in OvCa have yet to be elucidated. METHODS: Quantitative real-time reverse PCR (qRT-PCR and Western blotting were employed to examine the expression of SIRT1 in a panel of human OvCa cell lines. si-RNA or sh-RNA and cDNA technologies were utilized to knockdown or overexpress SIRT1, respectively. The effects of SIRT1 on proliferation and chemoresistance were examined using a WST-1 assay, and the underlying mechanisms were confirmed using an apoptotic assay, and the quantification of glutathione (GSH, and reactive oxygen species (ROS. The aggressiveness of SIRT1 was analyzed using in vitro invasion and migration assays. RESULTS: SIRT1 was more strongly expressed in OvCa cell lines than in the immortalized ovarian epithelium at the gene and protein levels. Stress up-regulated the expression of SIRT1 in dose- and time-dependent manners. SIRT1 significantly enhanced the proliferation (P < .05, chemoresistance (P < .05, and aggressiveness of OvCa cells by up-regulating multiple antioxidant pathways to inhibit oxidative stress. Further study into the overexpression of SIRT1 demonstrated the up-regulation of several stemness-associated genes and enrichment of CD44v9 via an as-yet-unidentified pathway. CONCLUSIONS: Our results suggest that SIRT1 plays a role in the acquisition of aggressiveness and chemoresistance by OvCa, and has potential as a therapeutic target for OvCa.

  17. Expression of melatonin receptor MT1 in cells of human invasive ductal breast carcinoma.

    Science.gov (United States)

    Jablonska, Karolina; Pula, Bartosz; Zemla, Agata; Owczarek, Tomasz; Wojnar, Andrzej; Rys, Janusz; Ambicka, Aleksandra; Podhorska-Okolow, Marzena; Ugorski, Maciej; Dziegiel, Piotr

    2013-04-01

    In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  18. Real time elastography - a non-invasive diagnostic method of small hepatocellular carcinoma in cirrhosis.

    Science.gov (United States)

    Gheorghe, Liana; Iacob, Speranta; Iacob, Razvan; Dumbrava, Mona; Becheanu, Gabriel; Herlea, Vlad; Gheorghe, Cristian; Lupescu, Ioana; Popescu, Irinel

    2009-12-01

    Small nodules (under 3 cm) detected on ultrasound (US) in cirrhotics represent the most challenging category for noninvasive diagnosis of hepatocellular carcinoma (HCC). To evaluate real-time sonoelastography as a noninvasive tool for the diagnosis of small HCC nodules in cirrhotic patients. 42 cirrhotic patients with 58 nodules (1-3 cm) were evaluated with real-time elastography (Hitachi EUB-6500); the mean intensity of colors red, blue, green were measured using a semi-quantitative method. Analysis of histograms for each color of the sonoelastography images was performed for quantifying the elasticity of nodule tissue in comparison with the cirrhotic liver tissue. AUROC curves were constructed to define the best cut-off points to distinguish malignant features of the nodules. Univariate and multivariate logistic regression analysis was performed. 595 sonoelastography images from 42 patients (25 men; 17 women) were analyzed. The mean age was 56.4 +/- 0.7 years and 69% patients were in Child-Pugh class A, 19% class B, 11% class C. For the mean intensity of green color AUROC=0.81, a cut-off value under 108.7 being diagnostic for HCC with a Sp=91.1%, Se=50%, PPV=92.1%, NPV=47.1%. Mean intensity of blue color proved to be an excellent diagnostic tool for HCC (AUROC=0.94); for a cut-off value greater than 128.9, Sp=92.2%, Se=78.9%, PPV=95.4%, NPV=68%. Independent predictive factors of HCC for a small nodule in cirrhotic patients were: blue color over 128.9 at sonoelastography and hypervascular appearance at Doppler US. US elastography is a promising method for the non-invasive diagnosis of early HCC. Blue color at elastography and hypervascular aspects are independent predictors of HCC.

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

    International Nuclear Information System (INIS)

    Safaverdi, S.; Roshani, F.; Lamehi Rashti, M.; Golkhoo, Sh.; Hassan, Z. M.; Langroudi, L.

    2009-01-01

    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.

  20. Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis

    Directory of Open Access Journals (Sweden)

    Lucio Dell’Atti

    2015-03-01

    Full Text Available Objectives: We retrospectively reviewed data of patients with incidental prostate cancer (PCa who underwent radical cystoprostatectomy (RCP for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Material and Methods: Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. Results: 11 out of 64 patients (17.2% who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3% were diagnosed as significant PCa, while 8 cases (72.7% were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79. During the follow-up, biochemical recurrence occurred in 1 patient (9%. Concernig the cancer specific survival there was no statistical significance (P = 0.326 between the clinically significant and clinical insignificant cancer group. Conclusions: In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

  1. Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants.

    Science.gov (United States)

    Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

    2016-01-01

    Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.

  2. Scutellarin suppresses migration and invasion of human hepatocellular carcinoma by inhibiting the STAT3/Girdin/Akt activity.

    Science.gov (United States)

    Ke, Yang; Bao, Tianhao; Wu, Xuesong; Tang, Haoran; Wang, Yan; Ge, Jiayun; Fu, Bimang; Meng, Xu; Chen, Li; Zhang, Cheng; Tan, Yuqi; Chen, Haotian; Guo, Zhitang; Ni, Fan; Lei, Xuefen; Shi, Zhitian; Wei, Dong; Wang, Lin

    2017-01-29

    Scutellarin is an active flavone from Erigeron breviscapine (vant) Hand Mass. This study aimed to investigate the potential role of scutellarin in migration and invasion of human hepatocellular carcinoma (HCC) cells and its possible mechanism. In comparison with the vehicle-treated controls, treatment with scutellarin (50 mg/kg/day) for 35 days significantly mitigated the lung and intrahepatic metastasis of HCC tumors in vivo. Scutellarin treatment significantly reduced HepG2 cell viability in a dose-dependent manner, and inhibited migration and invasion of HCC cells in vitro. Scutellarin treatment significantly reduced STAT3 and Girders of actin filaments (Girdin) expression, STAT3 and Akt phosphorylation in HCC cells. Introduction of STAT3 overexpression restored the scutellarin-downregulated Girdin expression, Akt activation, migration and invasion of HCC cells. Furthermore, induction of Girdin overexpression completely abrogated the inhibition of scutellarin on the Akt phosphorylation, migration and invasion of HCC cells. Scutellarin can inhibit HCC cell metastasis in vivo, and migration and invasion in vitro by down-regulating the STAT3/Girdin/Akt signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Accuracy of imaging methods for detection of bone tissue invasion in patients with oral squamous cell carcinoma

    Science.gov (United States)

    Uribe, S; Rojas, LA; Rosas, CF

    2013-01-01

    The objective of this review is to evaluate the diagnostic accuracy of imaging methods for detection of mandibular bone tissue invasion by squamous cell carcinoma (SCC). A systematic review was carried out of studies in MEDLINE, SciELO and ScienceDirect, published between 1960 and 2012, in English, Spanish or German, which compared detection of mandibular bone tissue invasion via different imaging tests against a histopathology reference standard. Sensitivity and specificity data were extracted from each study. The outcome measure was diagnostic accuracy. We found 338 articles, of which 5 fulfilled the inclusion criteria. Tests included were: CT (four articles), MRI (four articles), panoramic radiography (one article), positron emission tomography (PET)/CT (one article) and cone beam CT (CBCT) (one article). The quality of articles was low to moderate and the evidence showed that all tests have a high diagnostic accuracy for detection of mandibular bone tissue invasion by SCC, with sensitivity values of 94% (MRI), 91% (CBCT), 83% (CT) and 55% (panoramic radiography), and specificity values of 100% (CT, MRI, CBCT), 97% (PET/CT) and 91.7% (panoramic radiography). Available evidence is scarce and of only low to moderate quality. However, it is consistently shown that current imaging methods give a moderate to high diagnostic accuracy for the detection of mandibular bone tissue invasion by SCC. Recommendations are given for improving the quality of future reports, in particular provision of a detailed description of the patients' conditions, the imaging instrument and both imaging and histopathological invasion criteria. PMID:23420854

  4. RNAi Knockdown of Hypoxia-Inducible Factor-1α Decreased the Proliferation, Migration, and Invasion of Hypoxic Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Chen, ChengShi; Liu, Rong; Wang, JianHua; Yan, ZhiPing; Qian, Sheng; Zhang, Wei

    2015-04-01

    The obstruction of hepatic arterial blood flow results in tumor tissue hypoxia and elevated expression of hypoxia-inducible factor-1alpha (HIF-1α). Our study evaluated whether lentivirus-mediated short interference RNA against HIF-1α inhibits proliferation, invasion, and migration of hepatocellular carcinoma (HCC) cells under hypoxia. RNA interference knockdown of HIF-1α was achieved by HIF-1α-directed lentiviral shRNA, in a rat HCC cell line cultured under hypoxia condition for varying length of times. The expression levels of HIF-1α and vascular endothelial growth factor were examined using reverse transcription polymerase chain reaction and western blot analyses. Cell proliferation, migration, and invasion were measured by cell viability, transwell migration, and invasion assays, respectively. Inhibition of HIF-1α expression by shRNA suppressed vascular endothelial growth factor mRNA and protein levels under both normoxia and hypoxia. It also suppressed cell migration and invasion, which were enhanced under hypoxic conditions. RNAi knockdown of HIF-1α further suppressed hypoxia-mediated inhibition of the cell proliferation. These data suggest that shRNA of HIF-1α could antagonize the hypoxia-mediated increase in hepatic cancer cell migration and invasion, and synergize with hypoxia to inhibit the cell proliferation in HCC cells.

  5. Inhibition of IGF-1-Mediated Cellular Migration and Invasion by Migracin A in Ovarian Clear Cell Carcinoma Cells.

    Science.gov (United States)

    Ukaji, Tamami; Lin, Yinzhi; Banno, Kouji; Okada, Shoshiro; Umezawa, Kazuo

    2015-01-01

    Previously we isolated migracin A from a Streptomyces culture filtrate as an inhibitor of cancer cell migration. In the present research, we found that migracin A inhibited migration and invasion of ovarian clear cell carcinoma ES-2 cells. In the course of our mechanistic study, migracin A was shown to enhance vasohibin-1 expression in an angiogenesis array. We also confirmed that it increased the mRNA expression of this protein. Moreover, overexpression of vasohibin-1 lowered the migration but not the invasion of ES-2 cells. Then, we looked for another target protein employing a motility array, and found that migracin A lowered the IGF-1 expression. Knockdown of IGF-1 by siRNA decreased the migration and invasion of ES-2 cells. Migracin A also decreased Akt phosphorylation involved in the downstream signaling. Crosstalk analysis indicated that overexpression of vasohibin-1 decreased the IGF-1 expression. On the other hand, it showed no direct anticancer activity in terms of the ES-2 growth in agar. Migracin A inhibited the migration and IGF-1 expression in not only ES-2 but also another ovarian clear cell carcinoma JHOC-5 cells. In addition, it also inhibited capillary tube formation of human umbilical vein endothelial cells. Since its cytotoxicity is very low, migracin A may be a candidate for an anti-metastasis agent not exhibiting prominent toxicity.

  6. Lobular carcinoma in situ and invasive lobular breast cancer are characterized by enhanced expression of transcription factor AP-2β.

    Science.gov (United States)

    Raap, Mieke; Gronewold, Malte; Christgen, Henriette; Glage, Silke; Bentires-Alj, Mohammad; Koren, Shany; Derksen, Patrick W; Boelens, Mirjam; Jonkers, Jos; Lehmann, Ulrich; Feuerhake, Friedrich; Kuehnle, Elna; Gluz, Oleg; Kates, Ronald; Nitz, Ulrike; Harbeck, Nadia; Kreipe, Hans H; Christgen, Matthias

    2018-01-01

    Transcription factor AP-2β (TFAP2B) regulates embryonic organ development and is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene expression profiling has implicated AP-2β in breast cancer (BC). This study characterizes AP-2β expression in the mammary gland and in BC. AP-2β protein expression was assessed in the normal mammary gland epithelium, in various reactive, metaplastic and pre-invasive neoplastic lesions and in two clinical BC cohorts comprising >2000 patients. BCs from various genetically engineered mouse (GEM) models were also evaluated. Human BC cell lines served as functional models to study siRNA-mediated inhibition of AP-2β. The normal mammary gland epithelium showed scattered AP-2β-positive cells in the luminal cell layer. Various reactive and pre-invasive neoplastic lesions, including apocrine metaplasia, usual ductal hyperplasia and lobular carcinoma in situ (LCIS) showed enhanced AP-2β expression. Cases of ductal carcinoma in situ (DCIS) were more often AP-2β-negative (Pinvasive BC cohorts, AP-2β-positivity was associated with the lobular BC subtype (Plobular BC cell lines in vitro. In summary, AP-2β is a new mammary epithelial differentiation marker. Its expression is preferentially retained and enhanced in LCIS and invasive lobular BC and has prognostic implications. Our findings indicate that AP-2β controls tumor cell proliferation in this slow-growing BC subtype.

  7. 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

  8. Low-grade myofibroblastic sarcoma arising in fibroadenoma of the breast-A case report.

    Science.gov (United States)

    Myong, Na-Hye; Min, Jun-Won

    2016-03-25

    Myofibroblastic sarcoma or myofibrosarcoma is a malignant tumor of myofibroblasts and known to develop rarely in the breast, but its underlying lesion and tumor cell origin have never been reported yet. A 61-year-old female presented with a gradually growing breast mass with well-demarcated ovoid nodular shape. The tumor was histologically characterized by fascicular-growing spindle cell proliferation with large areas of hyalinized fibrosis and focally ductal epithelial remnants embedded in myxoid stroma, mimicking a fibroadenomatous lesion. It had frequent mitoses of 5-16/10 high-power fields, hemorrhagic necrosis, and focally pericapsular invasion. The spindle cells were diffusely immunoreactive for fibronectin, smooth muscle actin, and calponin, which suggest a myofibroblastic origin. Multiple irregularly thickened vessels with medial or pericytic cell proliferation were found to be merged with the intrinsic tumor cells. The tumor could be diagnosed low-grade myofibroblastic sarcoma arising in an old fibroadenoma. We report a case of a low-grade mammary myofibrosarcoma that showed a background lesion of fibroadenoma first in the worldwide literature and suggest the pericytes or medial muscle cells of the intratumoral vessels as the cell origin of the myofibroblastic sarcoma.

  9. Human papillomavirus genotypes in invasive cervical squamous cell carcinoma in Trinidad Genotipos de virus de los papilomas humanos en carcinoma cervicouterino escamocelular invasor en Trinidad

    Directory of Open Access Journals (Sweden)

    Felicia Hosein

    2013-04-01

    Full Text Available OBJECTIVE: To determine the relative contribution of known high-risk human papillomavirus (HPV genotypes to the occurrence of cervical cancers in Trinidad. METHODS: The distribution of HPV genotypes in cases of invasive cervical squamous cell carcinoma in Trinidad was investigated. This study was a follow-up to an investigation of HPV genotypes in 310 nonsymptomatic women in Trinidad. The latter study showed that cervical HPV prevalence and heterogeneity of genotypes were high in the study population; notably, the genotypes targeted by the available HPV prophylactic vaccines were not the most common types. RESULTS: The current study of 85 cases of invasive cervical squamous cell carcinomas demonstrated that the previously observed heterogeneity in HPV genotype distribution is lost in cases of invasive cervical cancer, with the vaccine-targeted HPV types HPV 16 and HPV 18 becoming the most prevalent. CONCLUSIONS: HPV 16 and HPV 18 were the primary HPV genotypes associated with cases of invasive squamous cell carcinoma in the current Trinidad study. This strong association leads us to conclude that the HPV vaccines targeting HPV 16 and HPV 18 may contribute to reducing the cervical cancer burden in Trinidad.OBJETIVO: Determinar la contribución relativa de los diferentes genotipos de virus de los papilomas humanos (VPH conocidos como de alto riesgo para la aparición de cáncer cervicouterino en Trinidad. MÉTODOS: Se investigó la distribución de los genotipos de VPH en casos de carcinoma cervicouterino escamocelular invasor en Trinidad. Este estudio fue la continuación de una investigación de los genotipos de VPH presentes en 310 mujeres asintomáticas en Trinidad. Este último estudio reveló altas prevalencia de VPH en el cuello uterino y heterogeneidad de los genotipos en la población del estudio; cabe destacar que los genotipos a los que se dirigen las vacunas preventivas de la infección por VPH disponibles no fueron los tipos m

  10. Seizure prognosis of patients with low-grade tumors.

    Science.gov (United States)

    Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C

    2012-09-01

    Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and

  11. Persistent low-grade inflammation and regular exercise

    DEFF Research Database (Denmark)

    Astrom, Maj-Briit; Feigh, Michael; Pedersen, Bente Klarlund

    2010-01-01

    Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection ...... diabetes and dementia. We suggest that the anti-inflammatory effects of exercise may be mediated via a long-term effect of exercise leading to a reduction in visceral fat mass and/or by induction of anti-inflammatory cytokines with each bout of exercise....

  12. Selective recovery of titanium dioxide from low grade sources

    CSIR Research Space (South Africa)

    Van Vuuren, DS

    2006-09-01

    Full Text Available that is too fine for use in the chloride process  Perovskite (CaTiO3) resources in Colorado3. The main problem with utilizing a low-grade resource is the amount of chemical wastes produced per unit of pigment of produced. If a TiO2 bearing feedstock... The mineralogical form of the titanium oxide species affects the thermodynamic equilibrium of the reaction. Calcium titanate, CaTiO3 (Perovskite) is more stable than magnesium titanate MgTiO3, (Geikilite) which is more stable than titanium dioxide or ilmenite (Fe...

  13. Postoperative radiotherapy for low grade glioma of the brain

    International Nuclear Information System (INIS)

    Chun, Ha Chung; Lee, Myung Za

    2000-01-01

    To evaluate the effectiveness and tolerance of postoperative external beam radiotherapy for patients with low grade glioma of the brain and define the optimal radiotherapeutic regimen. Between June, 1985 and May, 1998, 72 patients with low grade gliomas were treated with postoperative radiotherapy immediately following surgery. Median age was 37 years with range of 11 to 76 years. Forty one patients were male and 31 patients were female with male to female ratio of 1.3:1. Of those patients, 15 underwent biopsy alone and remaining 57 did subtotal resection. The distribution of the patients according to histologic type was as follows: astrocytomas-42 patients (58%), mixed oligodendrogliomas-19 patients (27%), oligodendrogliomas-11 patients (15%). Two patients were treated with whole brain irradiation followed by cone down boost and remaining 70 patients were treated with localized field with appropriate margin. All of the patients were treated with conventional once a day fractionation. Most of patients received total tumor dose of 5000-5500 cGy. The overall 5 and 7 year survival rates for entire group of 72 patients were 61% and 50%. Corresponding disease free survival rates for entire patients were 53% and 45%, respectively. The 5 and 7 year overall survival rates for astrocytomas, mixed oligodendrogliomas, and oligodendrogliomas were 48% and 45%, 76% and 56%, and 80% and 52%, respectively. Patients who underwent subtotal resection showed better survival rates than those who did biopsy alone. The overall 5 year survival rates for subtotal resection patients and biopsy alone patients were 67% and 43%, respectively. Forty six patients who were 40 years or younger survived better than 26 patients who were 41 years or older (overall survival rate at 5 years, 69% vs 45%). Although one patient was not able to complete the treatment because of neurological deterioration, there was no significant treatment related acute toxicities. Postoperative radiotherapy was safe and

  14. Experimental Study on Purification of Low Grade Diatomite

    Science.gov (United States)

    Xiao, Liguang; Pang, Bo

    2017-04-01

    This paper presented an innovation for purification of low grade diatomite(DE) by grinding, ultrasonic pretreatment, acid leaching of closed stirring and calcination. The optimum process parameters of DE purification were obtained, the characterizations of original and purified DE were determined by SEM and BET. The results showed that the specific surface area of DE increased from 12.65m2/g to 23.23m2/g, which increased by 45.54%. SEM analysis revealed that the pore structure of purified DE was dredged highly.

  15. Parathyroid hormone-related protein (PTHrP) expression and bone invasion by oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Tsuchimochi, Makoto; Kameta, Ayako; Harada, Mikiko; Okada, Yasuo; Katagiri, Masataka

    1999-01-01

    Parathyroid hormone-related protein (PTHrP) indirectly stimulates osteoclastic bone resorption through osteoblasts in humoral hypercalcemia of malignancy. We reported that the serum concentration of PTHrP elevated in terminal stage patients with oral squamous cell carcinoma (SCC) in 1996. Therefore, PTHrP is a candidate for direct bone resorption factor released from the tumor tissue. The purpose of this study was to elucidate the correlation between the direct bone invasion by oral SCC and PTHrP expression. The serum C-PTHrP concentration was measured in 53 patients with oral SCC. The immunohistochemical study using PTHrP (labeled streptoavidin-biotin method, 38-64 monoclonal and 1-34 polyclonal antibody) was performed in 53 biopsy specimens. The bone invasion was assessed by using panoramic radiographs and bone scintigrams ( 99m Tc-MDP). The mean serum C-PTHrP concentration in the bone invasion identified group was 43.1±17.2 pmol/1. In the non-bone invasion group it was 42.0±18.0 pmol/1. No significant correlation was found between serum C-PTHrP levels and bone invasion or between PTHrP (1-34) and (38-64) expression in tumors and bone invasion. These results showed that there is no relationship between PTHrP expression in the biopsy specimen and direct bone invasion. Since the expression of PTHrP in the tumor tissue attached to the bone or surgical specimens has not been investigated, it is still unclear if PTHrP plays a role in direct bone resorption by oral SCC. (author)

  16. Prognostic Value of Cavernous Sinus Invasion in Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiotherapy.

    Directory of Open Access Journals (Sweden)

    Jun-Fang Liao

    Full Text Available To investigate the prognostic value of cavernoussinus invasion (CSI in patients with nasopharyngeal carcinoma (NPC treated with intensity-modulated radiotherapy (IMRT.Retrospective review of data from 1,087 patients with biopsy-proven, non-metastatic NPC. All patients were diagnosed using magnetic resonance imaging (MRI scans and received IMRT as the primary treatment.The incidence of cavernoussinus invasion in this cohort was 12.1%. In univariate analysis, 5-year overall survival (OS (70.6% vs. 88.5%, P < 0.001 and distant metastasis-free survival (DMFS (71.4% vs. 87.7%, P < 0.001, but not locoregional relapse-free survival (LRFS (93.9% vs. 93.7%, P = 0.341, were significantly different between patients with and without cavernoussinus invasion. In the T4 subgroup, the 5-year OS, DMFS, and LRFS of patients with and without cavernoussinus extension were 70.6% vs. 81.9% (P = 0.011, 71.4% vs. 84.1% (P = 0.011, and 91.2% vs. 89.7% (P = 0.501, respectively. In multivariate analysis, cavernoussinus invasion was an independent prognostic factor for poorer OS (HR = 1.782; P = 0.013 and DMFS (HR = 1.771; P = 0.016, but not LRFS (HR = 0.632; P = 0.294. In patients with lymph node metastasis, the DMFS rates of patients with and without cavernoussinus invasion were significantly different (P < 0.001. Preliminaryanalysis indicated that neoadjuvant chemotherapy led to better DMFS and OS in patients with cavernoussinus invasion than concurrent chemotherapy or radiotherapy alone; however, the differences were not significant.In the IMRT era, cavernoussinus invasion remains a prognostic factor for poor DMFS and OS in NPC, even in patients with T4 disease.

  17. Examining the sensitivity of ultrasound-guided large core biopsy for invasive breast carcinoma in a population screening programme

    International Nuclear Information System (INIS)

    Rouse, Hannah C.; Ussher, Simon; Cawson, Jennifer N.; Kavanagh, Anne M.

    2013-01-01

    To evaluate the sensitivity of ultrasound-guided core-needle biopsy (UCB) in invasive breast carcinoma and to establish causes of false-negative biopsy in a population screening programme. We identified 571 consecutive women diagnosed with surgically proven invasive breast cancer. Histology from 14-gauge UCB was compared with surgical histology to identify true-positive and false-negative ultrasound core biopsies. True-positive and false-negative groups were compared for tumour size and histology. On blinded review of UCB images and pathology reports from false negative (n=20) and a random sample of true-positive cases (n=80), we compared core sample number and needle visualisation in the lesion. Of 571 carcinomas sampled with UCB, 551 (96.5%) were true positive and 20 (3.5%) were false negative. The mean core number was 2.0 (range 1–3) for false negatives and 2.25 (range 1–4) for true positives (P=0.27). Mean tumour sizes were 13.3 and 16.2mm for the false-negative and true-positive groups, respectively (P=0.25). Tubular carcinomas represented 30% (6/20) of false-negative cases compared with 5.1% (28/551) of the true-positive cases (P<0.001). On blinded review, needle visualisation within the lesion was demonstrated in 47.4% (9/19) of false-negative cases and 76.3% (61/80) of true-positive cases (P=0.02).We demonstrated a sensitivity of 96.5% with a mean of 2.21 cores. False-negative results were more likely in the absence of post-fire needle position verification and with tubular carcinomas. Neither tumour size nor core number predicted diagnostic accuracy.

  18. Diagnostic value of computed tomography for invasion toward the caudate bile duct branch in carcinoma of the hepatic hilum

    International Nuclear Information System (INIS)

    Nagino, Masato; Nimura, Yuji; Hayakawa, Naokazu; Kamiya, Junichi; Kondoh, Satoshi; Shionoya, Shigehiko

    1988-01-01

    The visualization of the caudate bile duct branch (B 1 ) in computed tomography (CT-scan) with a high dose of contrast medium was evaluated in 71 patients with carcinoma of the liver, biliary tract and pancreas, preoperatively. The patients were classified into four groups: Group A, 22 patients (twelve hepatomas, six gall bladder cancers and four cancers of the pancreas body or tail) without abnormal findings in the biliary tract ; Group B, two patients (cancer of the pancreas head and the common bile duct) with obstructive jaundice whose CT-scans were taken before percutaneous transhepatic cholangiodrainage (PTCD) ; Group C, 22 patients (16 cancers of the pancreas head and six common bile duct cancers) whose CT-scans were taken after release of jaundice by PTCD ; Group D, 25 patients with carcinoma of the hepatic hilum whose CT-scans were taken after release of jaundice by PTCD. The results were as follows. 1) In Group A, B 1 was invisible in all the patients. 2) In Group B, B 1 was clearly visible in all the patients. But in Group C, B 1 was visible only in one patient. 3) In Group D, B 1 was visible in 19 out of 25 patients and in 18 patients out of these 19 patients, cancer invasion toward B 1 was histopathologically confirmed. In contrast, invasion was revealed only in one out of six patients whose B 1 s were invisible. From these results, it is concluded that in carcinoma of the hepatic hilum the visualization of B 1 in CT-scan after release of jaundice by PTCD strongly suggests the cancer invasion on B 1 , and requests the caudate lobe resection. (author)

  19. Urine and bladder washing cytology for detection of urothelial carcinoma: standard test with new possibilities

    International Nuclear Information System (INIS)

    Flezar, Margareta Strojan

    2010-01-01

    Light microscopic evaluation of cell morphology in preparations from urine or bladder washing containing exfoliated cells is a standard and primary method for the detection of bladder cancer and also malignancy from other parts of the urinary tract. The cytopathologic examination is a valuable method to detect an early recurrence of malignancy or new primary carcinoma during the follow-up of patients after the treatment of bladder cancer. Characteristic cellular and nuclear signs of malignancy indicate invasive or in situ urothelial carcinoma or high-grade papillary urothelial carcinoma. However, low sensitivity of the method reflects the unreliable cytopathologic diagnosis of low-grade urothelial neoplasms as cellular and nuclear signs of malignancy in these neoplasms are poorly manifested. Many different markers were developed to improve the diagnosis of bladder carcinoma on urinary samples. UroVysion™ test is among the newest and most promising tests. By the method of in situ hybridization one can detect specific cytogenetic changes of urothelial carcinoma

  20. The long non-coding RNA MALAT1 promotes the migration and invasion of hepatocellular carcinoma by sponging miR-204 and releasing SIRT1.

    Science.gov (United States)

    Hou, Zhouhua; Xu, Xuwen; Zhou, Ledu; Fu, Xiaoyu; Tao, Shuhui; Zhou, Jiebin; Tan, Deming; Liu, Shuiping

    2017-07-01

    Increasing evidence supports the significance of long non-coding RNA in cancer development. Several recent studies suggest the oncogenic activity of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in hepatocellular carcinoma. In this study, we explored the molecular mechanisms by which MALAT1 modulates hepatocellular carcinoma biological behaviors. We found that microRNA-204 was significantly downregulated in sh-MALAT1 HepG2 cell and 15 hepatocellular carcinoma tissues by quantitative real-time polymerase chain reaction analysis. Through bioinformatic screening, luciferase reporter assay, RNA-binding protein immunoprecipitation, and RNA pull-down assay, we identified microRNA-204 as a potential interacting partner for MALAT1. Functionally, wound-healing and transwell assays revealed that microRNA-204 significantly inhibited the migration and invasion of hepatocellular carcinoma cells. Notably, sirtuin 1 was recognized as a direct downstream target of microRNA-204 in HepG2 cells. Moreover, si-SIRT1 significantly inhibited cell invasion and migration process. These data elucidated, by sponging and competitive binding to microRNA-204, MALAT1 releases the suppression on sirtuin 1, which in turn promotes hepatocellular carcinoma migration and invasion. This study reveals a novel mechanism by which MALAT1 stimulates hepatocellular carcinoma progression and justifies targeting metastasis-associated lung adenocarcinoma transcript 1 as a potential therapy for hepatocellular carcinoma.

  1. Analysis of DTI-Derived Tensor Metrics in Differential Diagnosis between Low-grade and High-grade Gliomas.

    Science.gov (United States)

    Jiang, Liang; Xiao, Chao-Yong; Xu, Quan; Sun, Jun; Chen, Huiyou; Chen, Yu-Chen; Yin, Xindao

    2017-01-01

    Purpose: It is critical and difficult to accurately discriminate between high- and low-grade gliomas preoperatively. This study aimed to ascertain the role of several scalar measures in distinguishing high-grade from low-grade gliomas, especially the axial diffusivity (AD), radial diffusivity (RD), planar tensor (Cp), spherical tensor (Cs), and linear tensor (Cl) derived from diffusion tensor imaging (DTI). Materials and Methods: Fifty-three patients with pathologically confirmed brain gliomas (21 low-grade and 32 high-grade) were included. Contrast-enhanced T1-weighted images and DTI were performed in all patients. The AD, RD, Cp, Cs, and Cl values in the tumor zone, peritumoral edema zone, white matter (WM) adjacent to edema and contralateral normal-appearing white matter (NAWM) were calculated. The DTI parameters and tumor grades were statistically analyzed, and receiver operating characteristic (ROC) curve analysis was also performed. Results: The DTI metrics in the affected hemisphere showed significant differences from those in the NAWM, except for the AD values in the tumor zone and the RD values in WM adjacent to edema in the low-grade groups, as well as the Cp values in WM adjacent to edema in the high-grade groups. AD in the tumor zone as well as Cs and Cl in WM adjacent to edema revealed significant differences between the low- and high-grade gliomas. The areas under the curve (Az) of all three metrics were greater than 0.5 in distinguishing low-grade from high-grade gliomas by ROC curve analysis, and the best DTI metric was Cs in WM adjacent to edema (Az: 0.692). Conclusion: AD in the tumor zone as well as Cs and Cl in WM adjacent to edema will provide additional information to better classify gliomas and can be used as non-invasive reliable biomarkers in glioma grading.

  2. Magnetic resonance imaging of low-grade fibromyxoid sarcoma

    International Nuclear Information System (INIS)

    Torriani, Martin; Ouellette, Hugue; Etchebehere, Mauricio; Amstalden, Eliane M.I.

    2006-01-01

    Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue tumor with a deceptively benign histologic appearance affecting predominantly young adults during the fourth decade of life. (MR) imaging features of a surgically confirmed case of LGFMS, affecting the shoulder is presented. A 30-year-old man presented with a 20-year history of a painless slow-growing mass in the right shoulder. Magnetic resonance images were obtained on a 2.0T scanner (Elscint, Haifa, Israel), demonstrating a well-defined soft tissue mass measuring 12.0 x 7.0 x 9.0 cm located between the deltoid muscle, rotator-cuff muscles, and proximal humerus. The differential diagnosis of LGFMS includes several benign and malignant neoplasms containing variable amounts of myxoid and fibrous tissue. Histologically, the most important differential diagnosis is with myxofibrosarcoma. Low-grade fibromyxoid sarcoma is a rare soft tissue tumor with slow growth and deceptively benign histologic appearance. The possibility of LGFMS must be considered when elaborating differential diagnostic possibilities for young adults with a large soft tissue mass exhibiting MR imaging characteristics of intermixed fibrous and myxoid tissue

  3. Low-grade energy of the ground for civil engineering

    Directory of Open Access Journals (Sweden)

    Potienko Natalia

    2017-01-01

    Full Text Available The article researches issues related to the relevance of applying renewable energy sources for civil engineering. The aim of the work is the study of modern approaches to designing buildings, using low-grade energy of the ground. The research methodology is based on the complex analysis of international design experience and on identifying the strengths and weaknesses of objects that use low-grade heat. We have identified the prospects of applying it for domestic construction practice. The state policy in the field of the efficient use of energy resources has been analyzed, and the vector of energy-saving programs development for the Samara Region has been defined. The research describes the impact of using geothermal energy on the architectural and planning solutions of buildings, as well as the peculiar features of the latter’s design, which are related primarily to the increase of energy efficiency. As a result, in the article a conclusion is made that the objects under investigation may be considered as one of the vectors of sustainable architecture development.

  4. Magnetic resonance imaging of low-grade fibromyxoid sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Torriani, Martin; Ouellette, Hugue [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States). Dept. of Radiology. Div. of Musculoskeletal Radiology; Etchebehere, Mauricio [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Ciencias Medicas. Dept. de Ortopedia; Amstalden, Eliane M.I. [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Ciencias Medicas. Dept. de Patologia

    2006-06-15

    Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue tumor with a deceptively benign histologic appearance affecting predominantly young adults during the fourth decade of life. (MR) imaging features of a surgically confirmed case of LGFMS, affecting the shoulder is presented. A 30-year-old man presented with a 20-year history of a painless slow-growing mass in the right shoulder. Magnetic resonance images were obtained on a 2.0T scanner (Elscint, Haifa, Israel), demonstrating a well-defined soft tissue mass measuring 12.0 x 7.0 x 9.0 cm located between the deltoid muscle, rotator-cuff muscles, and proximal humerus. The differential diagnosis of LGFMS includes several benign and malignant neoplasms containing variable amounts of myxoid and fibrous tissue. Histologically, the most important differential diagnosis is with myxofibrosarcoma. Low-grade fibromyxoid sarcoma is a rare soft tissue tumor with slow growth and deceptively benign histologic appearance. The possibility of LGFMS must be considered when elaborating differential diagnostic possibilities for young adults with a large soft tissue mass exhibiting MR imaging characteristics of intermixed fibrous and myxoid tissue.

  5. A comparison of two low grade heat recovery options

    International Nuclear Information System (INIS)

    Walsh, Conor; Thornley, Patricia

    2013-01-01

    Low grade heat (LGH) recovery is one way of increasing industrial energy efficiency and reducing associated greenhouse gas emissions. The organic Rankine cycle (ORC) and condensing boiler are two options that can be used to recover low grade heat ( 2 annually, but the high carbon intensity of the coking process means this has a negligible influence (<1%) on the overall process lifecycle impacts. However, if the electricity generated offsets the external purchasing of electricity this results in favourable economic payback periods of between 3 and 6 years. The operation of a condensing boiler within a woodchip boiler reduces the fuel required to achieve an increased thermal output. The thermal efficiency gains reduce the lifecycle impacts by between 11 and 21%, and reflect payback periods as low as 1.5–2 years, depending on the condenser type and wood supply chain. The two case studies are used to highlight the difficulty in identifying LGH recovery solutions that satisfy multiple environmental, economic and wider objectives

  6. Ethanol and other oxygenateds from low grade carbonaceous resources

    Energy Technology Data Exchange (ETDEWEB)

    Joo, O.S.; Jung, K.D.; Han, S.H. [Korea Institute of Science and Technology, Seoul (Korea, Democratic People`s Republic of)] [and others

    1995-12-31

    Anhydrous ethanol and other oxygenates of C2 up can be produced quite competitively from low grade carbonaceous resources in high yield via gasification, methanol synthesis, carbonylation of methanol an hydrogenation consecutively. Gas phase carbonylation of methanol to form methyl acetate is the key step for the whole process. Methyl acetate can be produced very selectively in one step gas phase reaction on a fixed bed column reactor with GHSV over 5,000. The consecutive hydrogenation of methyl or ethyl acetate produce anhydrous ethanol in high purity. It is also attempted to co-produce methanol and DME in IGCC, in which low grade carbonaceous resources are used as energy sources, and the surplus power and pre-power gas can be stored in liquid form of methanol and DME during base load time. Further integration of C2 up oxygenate production with IGCC can improve its economics. The attempt of above extensive technology integration can generate significant industrial profitability as well as reduce the environmental complication related with massive energy consumption.

  7. Polymorphous Low Grade Adenocarcinoma of the Parotid in a Teenager

    Directory of Open Access Journals (Sweden)

    Divya Khosla

    2017-09-01

    Full Text Available Abstract Introduction: Polymorphous low grade adenocarcinoma (PLGA is a rare salivary gland neoplasm with an indolent course. It occurs primarily in the minor salivary glands but can rarely occur in the major salivary glands. It usually occurs in the fifth to seventh decades of life with female preponderance.   Case Report: A 16-year-old male presented with recurrent painless swelling in the right preauricular region and with a history of surgical intervention at the same site in the past. His histopathology report was suggestive of pleomorphic adenoma. The swelling recurred after one year of excision and a superficial parotidectomy was performed. The detailed histopathological examination was suggestive of Polymorphous low grade adenocarcinoma. In view of close margins, the patient was given adjuvant radiotherapy. Thirty-three months post-surgery, he is alive and disease-free. We describe a rare case of PLGA of the parotid gland in a teenager with its clinical characteristics, histopathological features, and treatment.   Conclusion: The occurrence of PLGA in the parotid gland is rare with only a few cases reported in literature. The diagnosis of PLGA is challenging due to morphological diversity.

  8. NMR characteristics of low-grade glioma. Comparison with CT

    Energy Technology Data Exchange (ETDEWEB)

    Asato, Reinin; Tokuriki, Yasuhiko; Nakano, Yoshihisa; Itoh, Harumi; Torizuka, Kanji; Ueda, Tohru; Yamashita, Junkoh; Handa, Hajime

    1985-08-01

    Sixteen low-grade gliomas were evaluated both with nuclear magnetic resonance (NMR) imaging and with computed tomography (CT). In 13 cases (81%), the NMR images were much better in tissue contrast than the contrast-enhanced CT images. The tumors were shown as well-circumscribed oval lesions in the NMR, though they appeared as ill-defined, irregular, low-attenuation areas in the CT. The extent of the lesion, which was supposed to represent the active tumor tissue, was greater in the NMR than in the CT, because NMR tissue parameters (T/sub 1/, T/sub 2/) are more sensitive to pathological changes in brain tissue than is the X-ray attenuation coefficient. Though, in an optic glioma and a brain-stem astrocytoma, the CT with contrast enhancement displayed the contour of the mass as well as did NMR, it was inferior to the NMR in showing the cephalocaudal extension of the tumors. Calcification does not give a proton NMR signal under the present measuring conditions; thus the calcified cystic wall of a hypothalamic astrocytoma was displayed only in the CT images. In conclusion, the NMR imaging was apparently superior to contrast-enhanced CT in demonstrating the lesions due to low-grade glioma.

  9. Arsenite-loaded nanoparticles inhibit the invasion and metastasis of a hepatocellular carcinoma: in vitro and in vivo study

    Science.gov (United States)

    Chi, Xiaoqin; Yin, Zhenyu; Jin, Jianbin; Li, Hui; Zhou, Jian; Zhao, Zhenghuan; Zhang, Sheng; Zhao, Wenxiu; Xie, Chengrong; Li, Jie; Feng, Min; Lin, Hongyu; Wang, Xiaomin; Gao, Jinhao

    2017-11-01

    Postoperative recurrence and metastasis are the major problems for the current treatment of hepatocellular carcinomas (HCC) in the clinic, including hepatectomy and liver transplantation. Here, we report that arsentic-loaded nanoparticles (ALNPs) are able to reduce the invasion of HCC cells in vitro, and, more importantly, can strongly suppress the invasion and metastasis of HCC in vivo without adverse side effects. Compared to free drug arsenic trioxide , ALNPs can deliver the drug into cancer cells more efficiently, destroy the structure of microtubules and reduce the aggregation of microfilaments in cell membranes more significantly. Furthermore, our results also reveal that tumor cells in murine blood were reduced remarkably after intravenous injection of ALNPs, indicating that this nano-drug may efficiently kill circulating tumor cells in vivo. In conclusion, our nano-drug ALNPs have great potential for the suppression of metastasis of HCC, which may open up a new avenue for the effective treatment of HCC without metastasis and recurrence.

  10. 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)

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    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 < 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).

  12. 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

  13. Breast MRI in Invasive Lobular Carcinoma: A Useful Investigation in Surgical Planning?

    Science.gov (United States)

    Parvaiz, Muhammad Asad; Yang, Peiming; Razia, Eisha; Mascarenhas, Margaret; Deacon, Caroline; Matey, Pilar; Isgar, Brian; Sircar, Tapan

    2016-01-01

    Magnetic resonance imaging (MRI) is highly sensitive in detecting invasive lobular carcinoma (ILC) of the breast. In our institution, patients who are deemed to be suitable for breast conserving surgery (BCS) with unifocal small ILC on standard imaging are offered breast MRI to exclude multifocal and larger ILC. Our study investigates the usefulness of breast MRI in ILC. A prospective cohort study over a 58-month period, including all consecutive patients with ILC having breast MRI. Primary objective was to find out the proportion of ILC patients where preoperative MRI caused a change in the surgical treatment. Secondary objectives included finding mastectomy rate (initial & final), re-operation rate, cancer size correlation with different imaging modalities and final histopathology, loco-regional recurrence and disease-free survival. A total of 334 bilateral breast MRI were performed including 72 (21.5%) MRI for ILC patients. All these MRI were carried out within 2 week of patients given the diagnosis (median 5.5 days). Age range was 24-83 (median 56.5) years. Nineteen of 72 ILC patients (26.4%) had a change in their planned operation from BCS to a different operation owing to MRI findings (seven patients with multifocal cancers, 10 with significantly larger size of the cancer and two with contralateral malignancy). Initial mastectomy rate was 31.9%, final mastectomy rate was 36.1% and re-operation rate in BCS group was 18.3%. MRI correlated better with ILC histopathology cancer size than mammogram and ultrasound scans. There was no statistically significant difference (p = 0.999) between the cancer size on histology (median 23 mm) and MRI (median 25 mm). However, mammogram (median 17 mm) and ultrasound (median 14.5 mm) scans showed cancer sizes significantly different to final histology cancer size (p = 0.0008 and p = 0.0021 respectively). Over a 44 months median follow-up (range 27-85), 95.8% disease-free survival and 98.6% overall survival have been observed

  14. Clinicopathological characteristics and survival outcomes of invasive lobular carcinoma in different races

    Science.gov (United States)

    Yang, Li-Yuan; Yang, Li-Peng; Zhu, Biao

    2017-01-01

    To investigate the clinicopathological characteristics and to determine whether there is a differential effect of race and examine survival outcomes according to race, 18,295 breast invasive lobular carcinoma (ILC) patients were identified in the Surveillance, Epidemiology, and End Result (SEER) database, which includes White patients (n=15,936), Black patients (n=1,451) and patients of other races (including American Indians/Alaskan Natives and Asian/Pacific Islanders) (n=908). The Black ILC patients presented a higher rate of advanced histological grades and American Joint Committee on Cancer (AJCC) stages, a higher rate of lymph node (LN) involvement and a lower rate of progesterone receptors (PR)-positivity than the White patients and other races. The five-year overall survival (OS) and five-year breast cancer specific survival (BCSS) were worst in the Black patients among these patients (85.5%, 76.0% and 87.7%, P<0.01; 91.1%, 84.4% and 91.6%, P<0.01). Multivariate regression analyses were performed to determine the risk hazards ratios (HR) of death for patients of the White, Black and other races. Among these patients, the Black patients had the worst survival outcomes in five-year OS and BCSS outcomes (HR=1.35, 95% confidence interval (CI) :1.20-1.51, P<0.01; HR=1.39, 95%CI:1.21-1.61, P<0.01, respectively). After a 1:1:1 matching of the three groups, the Black patients still presented worse survival outcomes in BCSS compared to White patients (HR=1.88, 95%CI: 1.14-3.10, P=0.013), however, there was no difference in OS (HR=1.35, 95%CI: 0.93-1.96, P=0.111). Difference in outcomes may partially explained by difference in histological grades, AJCC stage, LN and PR status among the three groups. In conclusion, this study revealed that the Black patients had worse five-year OS and BCSS than White and other race patients. PMID:29088785

  15. WNT4 mediates estrogen receptor signaling and endocrine resistance in invasive lobular carcinoma cell lines.

    Science.gov (United States)

    Sikora, Matthew J; Jacobsen, Britta M; Levine, Kevin; Chen, Jian; Davidson, Nancy E; Lee, Adrian V; Alexander, Caroline M; Oesterreich, Steffi

    2016-09-20

    Invasive lobular carcinoma (ILC) of the breast typically presents with clinical biomarkers consistent with a favorable response to endocrine therapies, and over 90 % of ILC cases express the estrogen receptor (ER). However, a subset of ILC cases may be resistant to endocrine therapies, suggesting that ER biology is unique in ILC. Using ILC cell lines, we previously demonstrated that ER regulates a distinct gene expression program in ILC cells, and we hypothesized that these ER-driven pathways modulate the endocrine response in ILC. One potential novel pathway is via the Wnt ligand WNT4, a critical signaling molecule in mammary gland development regulated by the progesterone receptor. The ILC cell lines MDA-MB-134-VI, SUM44PE, and BCK4 were used to assess WNT4 gene expression and regulation, as well as the role of WNT4 in estrogen-regulated proliferation. To assess these mechanisms in the context of endocrine resistance, we developed novel ILC endocrine-resistant long-term estrogen-deprived (ILC-LTED) models. ILC and ILC-LTED cell lines were used to identify upstream regulators and downstream signaling effectors of WNT4 signaling. ILC cells co-opted WNT4 signaling by placing it under direct ER control. We observed that ER regulation of WNT4 correlated with use of an ER binding site at the WNT4 locus, specifically in ILC cells. Further, WNT4 was required for endocrine response in ILC cells, as WNT4 knockdown blocked estrogen-induced proliferation. ILC-LTED cells remained dependent on WNT4 for proliferation, by either maintaining ER function and WNT4 regulation or uncoupling WNT4 from ER and upregulating WNT4 expression. In the latter case, WNT4 expression was driven by activated nuclear factor kappa-B signaling in ILC-LTED cells. In ILC and ILC-LTED cells, WNT4 led to suppression of CDKN1A/p21, which is critical for ILC cell proliferation. CDKN1A knockdown partially reversed the effects of WNT4 knockdown. WNT4 drives a novel signaling pathway in ILC cells, with a

  16. Stand-Alone Lateral Interbody Fusion for the Treatment of Low-Grade Degenerative Spondylolisthesis

    Directory of Open Access Journals (Sweden)

    Luis Marchi

    2012-01-01

    Full Text Available The purpose of this paper was to investigate the stand-alone lateral interbody fusion as a minimally invasive option for the treatment of low-grade degenerative spondylolisthesis with a minimum 24-month followup. Prospective nonrandomized observational single-center study. 52 consecutive patients (67.6±10 y/o; 73.1% female; 27.4±3.4 BMI with single-level grade I/II single-level degenerative spondylolisthesis without significant spine instability were included. Fusion procedures were performed as retroperitoneal lateral transpsoas interbody fusions without screw supplementation. The procedures were performed in average 73.2 minutes and with less than 50cc blood loss. VAS and Oswestry scores showed lasting improvements in clinical outcomes (60% and 54.5% change, resp.. The vertebral slippage was reduced in 90.4% of cases from mean values of 15.1% preoperatively to 7.4% at 6-week followup (P<0.001 and was maintained through 24 months (7.1%, P<0.001. Segmental lordosis (P<0.001 and disc height (P<0.001 were improved in postop evaluations. Cage subsidence occurred in 9/52 cases (17% and 7/52 cases (13% spine levels needed revision surgery. At the 24-month evaluation, solid fusion was observed in 86.5% of the levels treated. The minimally invasive lateral approach has been shown to be a safe and reproducible technique to treat low-grade degenerative spondylolisthesis.

  17. 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

    2015-04-07

    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.

  18. Assessment of Myometrial Invasion in Premenopausal Grade 1 Endometrial Carcinoma: Is Magnetic Resonance Imaging a Reliable Tool in Selecting Patients for Fertility-Preserving Therapy?

    Science.gov (United States)

    Sakane, Makoto; Hori, Masatoshi; Onishi, Hiromitsu; Tsuboyama, Takahiro; Ota, Takashi; Tatsumi, Mitsuaki; Ueda, Yutaka; Kimura, Toshihiro; Kimura, Tadashi; Tomiyama, Noriyuki

    The aim of this study was to evaluate the diagnostic ability of magnetic resonance imaging (MRI) in premenopausal women with G1 endometrial carcinoma. Twenty-six patients underwent T2W, diffusion weighted, and dynamic contrast-enhanced 3-T MRI. The degree of myometrial invasion was pathologically classified into no invasion, shallow (3 mm or less), and more. Two radiologists assessed myometrial invasion on MRI. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values, AUC, and interobserver agreement were analyzed. For assessing myometrial invasion, mean accuracy, sensitivity, specificity, positive predictive values, negative predictive values, and AUC, respectively, were as follows: 63%, 42%, 85%, 79%, 47%, and 0.75. Mean interobserver agreement was fair (k = 0.36). Shallow invasions were underestimated as no invasion on MRI in all 6 cases. Magnetic resonance imaging produced false-negative result on half of patients. The misjudgments tended to happen in patients with shallow invasion.

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

    International Nuclear Information System (INIS)

    Zhou, X.Q.; Huang, S.Y.; Zhang, D.S.; Zhang, S.Z.; Li, W.G.; Chen, Z.W.; Wu, H.W.

    2014-01-01

    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

  20. Arterial spin labelling MRI for detecting pseudocapsule defects and predicting renal capsule invasion in renal cell carcinoma.

    Science.gov (United States)

    Zhang, H; Wu, Y; Xue, W; Zuo, P; Oesingmann, N; Gan, Q; Huang, Z; Wu, M; Hu, F; Kuang, M; Song, B

    2017-11-01

    To evaluate prospectively the performance of combining morphological and arterial spin labelling (ASL) magnetic resonance imaging (MRI) for detecting pseudocapsule defects in renal cell carcinoma (RCC), and to predict renal capsule invasion confirmed histopathologically. Twenty consecutive patients with suspicious renal tumours underwent MRI. Renal ASL imaging was performed and renal blood flow was measured quantitatively. The diagnostic performance of T2-weighted images alone, and a combination of T2-weighted and ASL images for predicting renal capsule invasion were assessed. Twenty renal lesions were evaluated in 20 patients. All lesions were clear cell RCCs (ccRCCs) confirmed at post-surgical histopathology. Fifteen ccRCCs showed pseudocapsule defects on T2-weighted images, of which 12 cases showed existing blood flow in defect areas on perfusion images. To predict renal capsule invasion, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 71.4%, 86.7%, 100%, respectively, for T2-weighted images alone, and 92.3%, 100%, 100%, 87.5%, respectively, for the combination of T2-weighted and ASL images. ASL images can reflect the perfusion of pseudocapsule defects and as such, the combination of T2-weighted and ASL images produces promising diagnostic accuracy for predicting renal capsule invasion. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  1. 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.

  2. MicroRNA-199 suppresses cell proliferation, migration and invasion by downregulating RGS17 in hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Wei; Qian, Sheng; Yang, Guowei; Zhu, Liang; Zhou, Bo; Wang, Jianhua; Liu, Rong; Yan, Zhiping; Qu, Xudong

    2018-06-15

    Hepatocellular carcinoma (HCC), the most common primary tumor of the liver, has a poor prognosis and shows rapid progression. MicroRNAs (miRNAs) play important roles in carcinogenesis and tumor progression. Regulators of G-protein signaling (RGS) are critical for defining G-protein-dependent signal fidelity. RGS17 plays an important role in the regulation of cancer cell proliferation, migration and invasion. Here, we showed that miR-199 was downregulated in a hepatocarcinoma cell line. Overexpression of miR-199 significantly suppressed HCC cell proliferation, migration, and invasion in vitro. RGS17 overexpression promoted HCC cell proliferation, migration, and invasion, and reversed the miR-199 mediated inhibition of proliferation, migration, and invasion. Dual-fluorescence reporter experiments confirmed that miR-199 downregulated RGS17 by direct interaction with the 3'-UTR of RGS17 mRNA. In vivo studies showed that miR-199 overexpression significantly inhibited the growth of tumors. Taken together, the results suggested that miR-199 inhibited tumor growth and metastasis by targeting RGS17. Published by Elsevier B.V.

  3. 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.

  4. MAML1 and TWIST1 co-overexpression promote invasion of head and neck squamous cell carcinoma.

    Science.gov (United States)

    Ardalan Khales, Sima; Ebrahimi, Ehsan; Jahanzad, Eisa; Ardalan Khales, Sahar; Forghanifard, Mohammad Mahdi

    2018-01-15

    Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with considerable morbidity and mortality. Invasion and metastasis of HNSCC is a complex process involving multiple molecules and signaling pathways. Twist Family BHLH Transcription Factor 1 (TWIST1) and Mastermind-like 1 (MAML1) are essential in induction of epithelial-mesenchymal transition through direct regulation of implicated molecules in cellular adhesion, migration and invasion. Our aim in this study was to assess the clinical significance of MAML1 and TWIST1 expression in HNSCC, and elucidate the probable correlation between these genes to exhibit their possible associations with progression and metastasis of the disease. The gene expression profile of MAML1 and TWIST1 was assessed in fresh tumoral compared to distant tumor-free tissues of 55 HNSCC patients using quantitative real-time Polymerase chain reaction (PCR). Significant overexpression of MAML1 and TWIST1 mRNA was observed in 49.1% and 38.2% (P ˂ 0.05) of tumor specimens, respectively. Overexpression of MAML1 was associated with vascular invasion (P = 0.048). Concomitant overexpression of MAML1 and TWIST1 was significantly correlated to each other (P = 0.004). Co-overexpression of the genes was significantly correlated to the various clinicopathological indices of poor prognosis including depth of tumor invasion (P < 0.01), lymphatic invasion and grade of tumor cell differentiation (P < 0.05). Significant correlation between MAML1 and TWIST1 in HNSCC was revealed. This study was the first report elucidating MAML1 clinical relevance in HNSCC. These new findings suggest an oncogenic role for concomitant expression of MAML1 and TWIST1 genes in HNSCC invasion and metastasis. © 2018 John Wiley & Sons Australia, Ltd.

  5. Characterizing the adoption of low-grade hardwood lumber by the secondary wood processing industry

    Science.gov (United States)

    Robert L. Smith; Wibke Pohle; Philip Araman; Dan Cumbo

    2004-01-01

    This study investigated the adoption of low-grade lumber in the secondary hardwood industry. Factors influencing decisions regarding the utilization of low-grade lumber were identified and value-added opportunities to increase the use of low-grade lumber among manufacturers currently using higher grades were evaluated. Data were collected via a nationwide mail survey...

  6. Conformal proton radiation therapy for pediatric low-grade astrocytomas

    International Nuclear Information System (INIS)

    Hug, E.B.; Loma Linda Univ. Medical Center, Loma Linda, CA; Darthmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Muenter, M.W.; Archambeau, J.O.; DeVries, A.; Loredo, L.N.; Grove, R.I.; Slater, J.D.; Liwnicz, B.

    2002-01-01

    Background: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). Patients and Method: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephatic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (cobalt gray equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. Results: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. Conclusions: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment

  7. Integrin αβ1, αvβ, α6β effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

    International Nuclear Information System (INIS)

    Sansing, Hope A.; Sarkeshik, Ali; Yates, John R.; Patel, Vyomesh; Gutkind, J. Silvio; Yamada, Kenneth M.; Berrier, Allison L.

    2011-01-01

    Research highlights: → Proteomics of clustered integrin αβ1, α v β, α 6 β receptors in oral carcinoma. → p130Cas, Dek, Src and talin regulate oral carcinoma invasion. → 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 αβ1, α v β or α 6 β 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.

  8. 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.

  9. 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.

  10. 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.

  11. Is there an association between invasive lobular carcinoma of the breast and a family history of gastric cancer?

    Science.gov (United States)

    Chikman, Bar; Davidson, Tima; Kais, Hasan; Jeroukhimov, Igor; Leshno, Ari; Sandbank, Judith; Halevy, Ariel; Lavy, Ron

    2016-01-01

    CDH1 gene mutations have been found to be associated with diffuse type gastric cancer and invasive lobular carcinoma (ILC) of the breast. To the best of our knowledge, this is the only study relating a family history of gastric cancer to ILC of the breast. We conducted a retrospective study comparing the family history of malignancies in patients with invasive ductal carcinoma (IDC) of the breast and ILC treated in our Medical Center. The comparison was evaluated in both types of breast cancer groups, dividing the patients into two age groups, cancer was reported in 7.2 % in the ILC group as compared to 2.3 % in the IDC group, P cancer was more common in the ILC group as opposed to the IDC group, 18 versus 8.1 % respectively, P = 0.002 and persisted in both age groups. We conclude that a family history of malignancies in first degree relatives is more common in patients with ILC than IDC and that there is a significant association between a family history of gastric cancer and ILC.

  12. 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.

  13. 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. © 2016 Annunziato et al.; Published by Cold Spring Harbor Laboratory Press.

  14. Immunohistochemical analysis of stromal fibrocytes and myofibroblasts to envision the invasion and lymph node metastasis in oral squamous cell carcinoma.

    Science.gov (United States)

    Rao, Sowmya J; Rao, Jyothi Bellur Madhava; Rao, Pp Jagadish

    2017-01-01

    Tumor cells work in close coordination with stromal elements from its stage of emergence to metastasis. The study was designed to assess the presence and distribution pattern of stromal fibrocytes and myofibroblasts in oral squamous cell carcinoma (OSCC). Possibility of using these stromal cells as a marker for invasion and lymphnode metastasis was evaluated. A total of 40 cases of OSCC consisting twenty cases of each lymph node positive (pN+) and lymph node negative (pN0) samples and ten normal oral mucosa (NOM) tissues were subjected to double immunostaining using CD34 and alpha-smooth muscle actin (α-SMA) antibodies. Stained sections were evaluated semiquantitatively. CD34 fibrocytes were seen in 70% of NOM and none of OSCC samples. α-SMA myofibroblasts were seen in 80% of OSCC and none of NOM samples. A statistically significant difference was found in fibrocyte values ( P < 0.001) and myofibroblast values ( P < 0.001) between NOM and OSCC study samples. No statistical significance in myofibroblast values between pN0 and pN+ study groups; however, their distribution pattern appreciably varied. This study suggested that fibrocytes could be used as one of the markers for early invasion. Abrupt loss of fibrocytes at the transition zone toward carcinoma and statistical significance in their values supported this inference. Heterogeneity in the distribution pattern of myofibroblasts in tumor stroma indicates that this variability may predict the tumor behavior toward nodal metastasis rather than their mere presence or absence.

  15. Prognostic value of a novel risk classification of microvascular invasion in patients with hepatocellular carcinoma after resection.

    Science.gov (United States)

    Zhao, Hui; Chen, Chuang; Fu, Xu; Yan, Xiaopeng; Jia, Wenjun; Mao, Liang; Jin, Huihan; Qiu, Yudong

    2017-01-17

    The present research aimed to evaluate the prognostic value of a novel risk classification of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) after resection. A total of 295 consecutive HCC patients underwent hepatectomy were included in our study. We evaluated the degree of MVI according to the following three features: the number of invaded microvessels (≤5 vs >5), the number of invading carcinoma cells (≤ 50 vs >50), the distance of invasion from tumor edge (≤1 cm vs >1 cm). All patients were divided into three groups according to the three risk factors of MVI: non-MVI group (n=180), low-MVI group (n=60) and high-MVI group (n=55). The overall survival (OS) and recurrence-free survival (RFS) rates of high-MVI group were significantly poorer than those of low-MVI and non-MVI groups (Prisk factors for OS after hepatectomy. High-MVI, type of resection and tumor size were risk factors for RFS. In subgroup analyses, the OS and RFS rates of low-MVI and non-MVI groups were better than high-MVI group regardless of tumor size. In high-MVI group, anatomical liver resection (n=28) showed better OS and RFS rates compared with non-anatomical liver resection (n=29) (P=0.012 and P=0.002). The novel risk classification of MVI based on histopathological features is valuable for predicting prognosis of HCC patients after hepatectomy.

  16. Neoadjuvant intra-arterial chemotherapy with a combination of radiotherapy for the treatment of invasive bladder carcinoma

    International Nuclear Information System (INIS)

    Sumiyoshi, Yoshiteru; Uyama, Takeshi.

    1992-01-01

    Fifty patients with invasive bladder carcinoma were treated with neoadjuvant intra-arterial chemotherapy using doxorubicin or pirarubicin, and this was combined with low dose radiotherapy. All of 50 patients were evaluated for clinical and histological efficacy. Twenty-nine of 50 (58%) patients achieved a clinically complete remission (CR) and 17 of 50 (34%) achieved a clinically partial remission (PR). Twenty-eight of 50 (56%) achieved a histological CR and 13 of 50 (26%) achieved a histological PR. The patients who underwent bladder preservation operations after this treatment and were followed up for longer than 3 years were evaluated for long-term results. The 5-year survival for 35 patients in this group was 74.1%. The 5-year survival for patients with a clinical CR was 93.3%, and for patients with a clinical PR it was 45.3%. The survival for patients with a histological CR was 93.3%, and for patients with a histological PR, it was 85.7%. This study suggests that neoadjuvant intra-arterial chemotherapy plus radiotherapy is a useful regimen that could become the treatment of first choice for patients with invasive bladder carcinoma. Patients who achieved a histological CR or PR with this regimen, might be able to retain the function of their bladders. (author)

  17. Economics and the question of low-grade heat

    International Nuclear Information System (INIS)

    Gorbet, F.W.

    1976-01-01

    This paper examines, from the viewpoint of an economist, the issues involved in the increased waste heat production generated by the rapid acceleration of electrical production and nuclear generation. It reviews some of the literature on low-grade heat - its economic considerations and ecological impact - and examines the applicability of the traditional type of analytical decision tool (cost/benefit analysis) to the efficient design of heat rejection systems. It is recognized that decisions should be made on the basis of social costs and benefits as well as purely monetary considerations. The validity and shortcomings of cost/benefit analysis are presented. It is concluded that, for energy policy planning and waste heat management, economic feasibility studies should lay out the options together with the costs and risks. (author)

  18. Intracardiac Low-grade Sarcoma Following Treatment for Ewing Sarcoma.

    Science.gov (United States)

    Ortiz, Michael V; Magnan, Heather; Slotkin, Emily K; Ambati, Srikanth R; Chou, Alexander J; Wexler, Leonard H; Meyers, Paul A; Walsh, Michael F; Heaton, Todd; Girardi, Leonard N; Wolden, Suzanne L; Price, Anita P; Kennedy, Jennifer A; Zehir, Ahmet; Hameed, Meera; Berger, Michael F; Kentsis, Alex; Shukla, Neerav

    2017-11-01

    A 16-year-old male was diagnosed with Ewing sarcoma of the ribcage with pulmonary metastases. Six months after completion of scheduled therapy, he was found to have a new intracardiac mass, presumed recurrent Ewing sarcoma. EWSR1 fusion was not detected by droplet digital polymerase chain reaction from blood plasma. After no improvement with salvage chemotherapy, he underwent surgical resection that identified a low-grade spindle cell sarcoma. Despite the near-synchronous presentation of 2 unrelated sarcomas, extensive genomic analyses did not reveal any unifying somatic or germline mutations nor any apparent cancer predisposition. This case also highlights the potential role of utilizing plasma cell-free DNA for diagnosing tumors in locations where biopsy confers high morbidity.

  19. Persistent low-grade inflammation and regular exercise

    DEFF Research Database (Denmark)

    Åström, Maj-brit; Feigh, Michael; Pedersen, Bente Klarlund

    2010-01-01

    against all of these diseases and recent evidence suggests that the protective effect of exercise may to some extent be ascribed to an anti-inflammatory effect of regular exercise. Visceral adiposity contributes to systemic inflammation and is independently associated with the occurrence of CVD, type 2...... diabetes and dementia. We suggest that the anti-inflammatory effects of exercise may be mediated via a long-term effect of exercise leading to a reduction in visceral fat mass and/or by induction of anti-inflammatory cytokines with each bout of exercise.......Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection...

  20. Holocord low grade astrocytoma - Role of radical irradiation and chemotherapy

    International Nuclear Information System (INIS)

    Goyal, S.; Puri, T.; Julka, R.K.

    2015-01-01

    Spinal intradural tumors, especially those extending along the entire length of the spinal cord, termed as ‘holocord’ tumors are uncommon. Most of these are gliomas, with astrocytomas (low grade) predominating in children and ependymomas in adults. Other histologies, though reported, are even rarer. Management is debatable, with both surgery and radiotherapy of such extensive tumors posing challenges. We describe a case of a 14-year-old girl with holocord astrocytoma extending from cervicomedullary junction till lumbar spine, who recovered full neurological function following radical irradiation of entire spine followed by temozolomide-based chemotherapy. No grade 3/4 bone marrow morbidity was seen. Five years following treatment, she maintained normal neurological function and apparently normal pubertal and skeletal growth despite residual disease visible on imaging. Literature review of existing reports of holocord astrocytomas highlighting management and outcome is presented.

  1. Novel minimally invasive chemoradiation therapy combined with biliary stenting for multidisciplinary approach to unresectable bile duct carcinoma

    International Nuclear Information System (INIS)

    Suzuki, Masanori; Sato, Takeaki; Umino, Noriaki

    2001-01-01

    Multidisciplinary treatment is a useful approach to unresectable non-metastatic bile duct carcinoma with invasion of the hepatic artery and portal vein. The authors developed a multidisciplinary treatment consisting of chemoradiation therapy combined with intraluminal bile duct irradiation plus external irradiation and systemic or local chemotherapy. The aim of this regimen was to improve the ability to locally control bile duct carcinoma by intraluminal irradiation and to shorten the treatment period compared to external irradiation therapy alone. According to the treatment schedule whole-body irradiation is performed first and followed by systemic administration of 5-fluorouracil (5-FU, 600 mg/m 2 /day) and cisplatin (CDDP, 10 mg/m 2 /day) after biliary stenting plus simultaneously intraluminal irradiation (8 Gy/week x 3, total 24 Gy) administered with 192 Ir-RALS (Remote After Loading System). Two novel types of applicators specifically designed by the authors for intraluminal radiation of the bile duct were improved. The authors have used this multidisciplinary approach to treat 3 patients with bile duct carcinoma. Its application has shortened the course of multidisciplinary therapy to about 6 weeks, and the patients have surviveed more than 6-8 months without recurrence. (K.H.)

  2. 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.

  3. Development of low grade waste heat thermoelectric power generator

    Directory of Open Access Journals (Sweden)

    Suvit Punnachaiya

    2010-07-01

    Full Text Available This research aimed to develop a 50 watt thermoelectric power generator using low grade waste heat as a heat source,in order to recover and utilize the excess heat in cooling systems of industrial processes and high activity radioisotope sources. Electricity generation was based on the reverse operation of a thermoelectric cooling (TEC device. The TEC devices weremodified and assembled into a set of thermal cell modules operating at a temperature less than 100°C. The developed powergenerator consisted of 4 modules, each generating 15 watts. Two cascade modules were connected in parallel. Each modulecomprised of 96 TEC devices, which were connected in series. The hot side of each module was mounted on an aluminumheat transfer pipe with dimensions 12.212.250 cm. Heat sinks were installed on the cold side with cooling fans to provideforced air cooling.To test electricity generation in the experiment, water steam was used as a heat source instead of low grade waste heat.The open-circuit direct current (DC of 250 V and the short-circuit current of 1.2 A was achieved with the following operatingconditions: a hot side temperature of 96°C and a temperature difference between the hot and cold sides of 25°C. The DC poweroutput was inverted to an AC power source of 220 V with 50 Hz frequency, which can continuously supply more than 50 wattsof power to a resistive load as long as the heat source was applied to the system. The system achieved an electrical conversionefficiency of about 0.47 percent with the capital cost of 70 US$/W.

  4. Age-related modifications of type I collagen impair DDR1-induced apoptosis in non-invasive breast carcinoma cells.

    Science.gov (United States)

    Charles, Saby; Hassan, Rammal; Kevin, Magnien; Emilie, Buache; Sylvie, Brassart-Pasco; Laurence, Van-Gulick; Pierre, Jeannesson; Erik, Maquoi; Hamid, Morjani

    2018-05-07

    Type I collagen and DDR1 axis has been described to decrease cell proliferation and to initiate apoptosis in non-invasive breast carcinoma in three-dimensional cell culture matrices. Moreover, MT1-MMP down-regulates these effects. Here, we address the effect of type I collagen aging and MT1-MMP expression on cell proliferation suppression and induced-apoptosis in non-invasive MCF-7 and ZR-75-1 breast carcinoma. We provide evidence for a decrease in cell growth and an increase in apoptosis in the presence of adult collagen when compared to old collagen. This effect involves a differential activation of DDR1, as evidenced by a higher DDR1 phosphorylation level in adult collagen. In adult collagen, inhibition of DDR1 expression and kinase function induced an increase in cell growth to a level similar to that observed in old collagen. The impact of aging on the sensitivity of collagen to MT1-MMP has been reported recently. We used the MT1-MMP expression strategy to verify whether, by degrading adult type I collagen, it could lead to the same phenotype observed in old collagen 3D matrix. MT1-MMP overexpression abrogated the proliferation suppression and induced-apoptosis effects only in the presence of adult collagen. This suggests that differential collagen degradation by MT1-MMP induced a structural disorganization of adult collagen and inhibits DDR1 activation. This could in turn impair DDR1-induced cell growth suppression and apoptosis. Taken together, our data suggest that modifications of collagen structural organization, due to aging, contribute to the loss of the growth suppression and induced apoptosis effect of collagen in luminal breast carcinoma. MT1-MMP-dependent degradation and aging of collagen have no additive effects on these processes.

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

    International Nuclear Information System (INIS)

    Shao, Mingchen; Geng, Yiwei; Lu, Peng; Xi, Ying; Wei, Sidong; Wang, Liuxing; Fan, Qingxia; Ma, Wang

    2015-01-01

    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

  6. Development and validation of algorithms to differentiate ductal carcinoma in situ from invasive breast cancer within administrative claims data.

    Science.gov (United States)

    Hirth, Jacqueline M; Hatch, Sandra S; Lin, Yu-Li; Giordano, Sharon H; Silva, H Colleen; Kuo, Yong-Fang

    2018-04-18

    Overtreatment is a common concern for patients with ductal carcinoma in situ (DCIS), but this entity is difficult to distinguish from invasive breast cancers in administrative claims data sets because DCIS often is coded as invasive breast cancer. Therefore, the authors developed and validated algorithms to select DCIS cases from administrative claims data to enable outcomes research in this type of data. This retrospective cohort using invasive breast cancer and DCIS cases included women aged 66 to 70 years in the 2004 through 2011 Texas Cancer Registry (TCR) data linked to Medicare administrative claims data. TCR records were used as "gold" standards to evaluate the sensitivity, specificity, and positive predictive value (PPV) of 2 algorithms. Women with a biopsy enrolled in Medicare parts A and B at 12 months before and 6 months after their first biopsy without a second incident diagnosis of DCIS or invasive breast cancer within 12 months in the TCR were included. Women in 2010 Medicare data were selected to test the algorithms in a general sample. In the TCR data set, a total of 6907 cases met inclusion criteria, with 1244 DCIS cases. The first algorithm had a sensitivity of 79%, a specificity of 89%, and a PPV of 62%. The second algorithm had a sensitivity of 50%, a specificity of 97%. and a PPV of 77%. Among women in the general sample, the specificity was high and the sensitivity was similar for both algorithms. However, the PPV was approximately 6% to 7% lower. DCIS frequently is miscoded as invasive breast cancer, and thus the proposed algorithms are useful to examine DCIS outcomes using data sets not linked to cancer registries. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

  7. The role of long noncoding RNA-LET in cell proliferation and invasion of nasopharyngeal carcinoma and its mechanism

    Directory of Open Access Journals (Sweden)

    Chen L

    2017-05-01

    Full Text Available Lei Chen,1,* Lingling Sun,1,* Lei Dong,2 Peng Cui,3 Ziwei Xia,4 Chao Li,1 Yu Zhu5 1Department of Otolaryngology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Pediatrics, Division of Hematology/Oncology, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, USA; 3Department of Multidisciplinary Consultation Center of TCM and Western Medicine, The Affiliated Qingdao Hiser Hospital of Qingdao University, Qingdao, 4Department of Clinical Medicine, The Second Clinical Medical School of Tianjin Medical University, 5Department of Clinical Laboratory, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: LncRNA-LET, a recently identified long noncoding RNA, has been shown to act as a tumor suppressor; however, its biological function and mechanism have not been fully investigated. Our research found that there was less expression of LET in nasopharyngeal carcinoma (NPC tissues than normal tissues and that LET might inhibit proliferation, adhesion and invasion of NPC in vitro by enhancing its expression. By contrast, decreased LET expression could promote the proliferation, adhesion and invasion of NPC. In addition, the expression profiles of related genes and MAPK/ERK pathway were also regulated effectively via overexpression or silencing of LET. This result provides comprehensive evidence of LET’s antitumor effect on NPC in vitro, which might provide a new approach for clinical treatment. Keywords: LncRNA-LET, proliferation, invasion, nasopharyngeal carcinoma, MAPK/ERK pathway

  8. 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.

  9. Human papillomavirus type 16 variants in cervical intraepithelial neoplasia and invasive carcinoma in San Luis Potosí City, Mexico

    Science.gov (United States)

    López-Revilla, Rubén; Pineda, Marco A; Ortiz-Valdez, Julio; Sánchez-Garza, Mireya; Riego, Lina

    2009-01-01

    Background In San Luis Potosí City cervical infection by human papillomavirus type 16 (HPV16) associated to dysplastic lesions is more prevalent in younger women. In this work HPV16 subtypes and variants associated to low-grade intraepithelial lesions (LSIL), high-grade intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) of 38 women residing in San Luis Potosí City were identified by comparing their E6 open reading frame sequences. Results Three European (E) variants (E-P, n = 27; E-T350G, n = 7; E-C188G, n = 2) and one AA-a variant (n = 2) were identified among the 38 HPV16 sequences analyzed. E-P variant sequences contained 23 single nucleotide changes, two of which (A334G, A404T) had not been described before and allowed the phylogenetic separation from the other variants. E-P A334G sequences were the most prevalent (22 cases, 57.9%), followed by the E-P Ref prototype (8 cases, 21.1%) and E-P A404T (1 case, 2.6%) sequences. The HSIL + ICC fraction was 0.21 for the E-P A334G variants and 0.00 for the E-P Ref variants. Conclusion We conclude that in the women included in this study the HPV16 E subtype is 19 times more frequent than the AA subtype; that the circulating E variants are E-P (71.1%) > E-T350G (18.4%) > E-C188G (5.3%); that 71.0% of the E-P sequences carry the A334G single nucleotide change and appear to correspond to a HPV16 variant characteristic of San Luis Potosi City more oncogenic than the E-P Ref prototype. PMID:19216802

  10. IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of invasive ductal breast carcinoma via canonical Wnt pathway.

    Science.gov (United States)

    Zhao, Huan-Yu; Han, Yang; Wang, Jian; Yang, Lian-He; Zheng, Xiao-Ying; Du, Jiang; Wu, Guang-Ping; Wang, En-Hua

    2017-06-01

    IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.

  11. 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)

    Shamloula, M.M.; El-Shorbagy, S.H.; Saied, E.M.E.

    2007-01-01

    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

  12. 17β-estradiol-induced ACSL4 protein expression promotes an invasive phenotype in estrogen receptor positive mammary carcinoma cells.

    Science.gov (United States)

    Belkaid, Anissa; Ouellette, Rodney J; Surette, Marc E

    2017-04-01

    Long chain acyl-CoA synthase-4 (ACSL4) expression has been associated with an aggressive phenotype in breast carcinoma cells, whereas its role in ERα-positive breast cancer has not been studied. ACSL4 prefers 20-carbon polyunsaturated fatty acid (PUFA) substrates, and along with other ACSLs has been associated with cellular uptake of exogenous fatty acids. 17β-estradiol induces proliferation and invasive capacities in ERα+ve breast carcinoma that is associated with modifications of cellular lipid metabolism. In this study, treatment of steroid-starved ERα-positive MCF-7 and T47D mammary carcinoma cells with 17β-estradiol resulted in increased cellular uptake of the PUFA arachidonic acid (AA) and eicosapentaenoic acid (EPA), important building blocks for cellular membranes, and increased ACSL4 protein levels. There was no change in the expression of the ACSL1, ACSL3 and ACSL6 protein isotypes. Increased ACSL4 protein expression was not accompanied by changes in ACSL4 mRNA expression, but was associated with a significant increase in the protein half-life compared to untreated cells. ERα silencing reversed the impact of 17β-estradiol on ACSL4 protein levels and half-life. Silencing of ACSL4 eliminated the 17β-estradiol-induced increase in AA and EPA uptake, as well as the 17β-estradiol-induced cell migration, proliferation and invasion capacities. ASCL4 silencing also prevented the 17β-estradiol induced increases in p-Akt and p-GSK3β, and decrease in E-cadherin expression, important events in epithelial to mesenchymal transition. Taken together, these results demonstrate that ACSL4 is a target of 17β-estradiol-stimulated ERα and is required for the cellular uptake of exogenous PUFA and the manifestation of a more malignant phenotype in ERα+ve breast carcinoma cells. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Expression of COX-2, CD44v6 and CD147 and relationship with invasion and lymph node metastasis in hypopharyngeal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Qing Yang

    Full Text Available To assess the expression of COX-2,CD44v6 and CD147 in hypopharyngeal squamous cell carcinomas and the three biomarkers correlation with tumor invasion and lymph node metastasis of Chinese people. 101 cases of surgically excised primary tumor were included in this study, and 40 tissues of epithelium adjacent to carcinoma were used as controls. We characterized the immunohistochemical expression of COX-2, CD44v6, and CD147 in 141 formalin-fixed, paraffin-embedded tissues, and measured the mean optical density (OD of the positive area to identify the expression of the three bio-markers and relationship with tumor invasion and lymph node metastasis. Our study demonstrates that the expression of the COX-2 and CD147 were significantly increased in carcinoma tissues compared to the epithelium adjacent to carcinoma. We also observed that the expression of COX-2, CD44v6, and CD147 were significantly associated with T classification, lymph node metastasis and clinical stage. There was strong significant correlation among the three biomarkers as well. Additionally, we indicated that recurrence and ≥ P50 level of COX-2 expression had an independent prognostic effect on prognosis. In conclusion, the three biomarkers play important roles in tumor invasion and lymph node metastases and might be valuable indicators of tumor metastasis in hypopharyngeal squamous cell carcinoma.

  14. Invasive micropapillary carcinoma of the breast has a better long-term survival than invasive ductal carcinoma of the breast in spite of its aggressive clinical presentations: a comparison based on large population database and case-control analysis.

    Science.gov (United States)

    Chen, Hongliang; Wu, Kejin; Wang, Maoli; Wang, Fuwen; Zhang, Mingdi; Zhang, Peng

    2017-12-01

    There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  15. MicroRNA-214-5p Inhibits the Invasion and Migration of Hepatocellular Carcinoma Cells by Targeting Wiskott-Aldrich Syndrome Like.

    Science.gov (United States)

    Li, Hongdan; Wang, Haoqi; Ren, Zhen

    2018-01-01

    This study aims to explore the effects of microRNA-214-5p (miR-214-5p) on the invasion and migration of Hepatocellular Carcinoma cells (HCC). Hepatocellular Carcinoma tissues and adjacent normal tissues from 44 hepatocellular carcinoma patients were prepared for this study. The HepG2 and BEL-7402 cells were transfected with miR-214-5p mimic and inhibitor. qRT-PCR was performed to detect the expressions of miR-214-5p. Transwell assays were used to detect the invasion and migration assays in HepG2 and BEL-7402 cells. A dual-luciferase reporter assay was conducted to examine the effect of miR-214-5p on Wiskott-Aldrich Syndrome Like (WASL/ N-WASP). Western blot and qRT-PCR were used to measure the expressions of the E-cadherin, N-cadherin and Vimentin proteins. Transwell chamber assays were performed to detect cell invasion and migration. Compared with normal tissues, HCC tissues demonstrated significantly lower expression of miR-214-5p. Overexpression of miR-214-5p significantly inhibited the migration and invasion of HCC cells and inhibition of miR-214-5p promoted the migration and invasion. Additionally, miR-214-5p suppressed the epithelial-mesenchymal transition (EMT). Further study showed WASL was a putative target gene of miR-214-5p. Up-regulating the expression of WASL could reverse the inhibition effect of miR-214-5p on invasion and migration. Our data suggested that miR-214-5p inhibited the invasion and migration of HepG2 and BEL-7402 by targeting WASL in Hepatocellular carcinoma. © 2018 The Author(s). Published by S. Karger AG, Basel.

  16. Transplantation of colon carcinoma into granulation tissue induces an invasive morphotype

    NARCIS (Netherlands)

    Dingemans, K. P.; Zeeman-Boeschoten, I. M.; Keep, R. F.; Das, P. K.

    1993-01-01

    The stroma surrounding many malignant tumors resembles granulation tissue. To test the hypothesis that such stroma stimulates tumor invasiveness, we compared, by electron microscopy and immunohistochemistry, the growth patterns of CC531 rat colon adenocarcinoma in 2 experimental situations: (i)

  17. 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.

  18. PTEN Loss in E-Cadherin-Deficient Mouse Mammary Epithelial Cells Rescues Apoptosis and Results in Development of Classical Invasive Lobular Carcinoma

    NARCIS (Netherlands)

    Boelens, M.C.; Nethe, M.; Klarenbeek, S.; de Ruiter, J.R.; Schut, E.; Bonzanni, N.; Zeeman, A.L.; Wientjens, E.; van der Burg, E.; Wessels, L.; van Amerongen, R.; Jonkers, J.

    2016-01-01

    Invasive lobular carcinoma (ILC) is an aggressive breast cancer subtype with poor response to chemotherapy. Besides loss of E-cadherin, a hallmark of ILC, genetic inactivation of PTEN is frequently observed in patients. Through concomitant Cre-mediated inactivation of E-cadherin and PTEN in mammary

  19. 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.

  20. Gallic Acid Inhibited Matrix Invasion and AP-1/ETS-1-Mediated MMP-1 Transcription in Human Nasopharyngeal Carcinoma Cells.

    Science.gov (United States)

    Pang, Jong-Hwei S; Yen, Jia-Hau; Wu, Hsiao-Ting; Huang, Sheng-Teng

    2017-06-24

    Gallic acid is a trihydroxybenzoic acid found in natural herbal plants. Gallic acid has been reported to inhibit the migration and invasive capability of various cancers. Little is known about the underlying mechanisms of invasion responsible for cancer metastasis via gallic acid. The present study was intended to investigate the anti-invasive effect of gallic acid on human nasopharyngeal carcinoma cells (NPC-BM1) and its related mechanism. Gallic acid inhibited the invasion of NPC-BM1 cells dose- and time-dependently without significant cytotoxic effect. Affymetrix oligonucleotide microarray analysis revealed matrix metalloproteinase-1 (MMP-1) as the most down-regulated gene in NPC-BM1 cells by gallic acid. The cytosolic and secreted MMP-1 levels were both found to be inhibited by gallic acid as demonstrated by western blot analysis and ELISA respectively. The mRNA expression and transcription of MMP-1 gene was also down-regulated as determined by RT/real-time PCR and promoter activity assay. The expression of two major transcription binding factors in the MMP-1 promoter, AP-1 and ETS-1, were demonstrated to be reduced by gallic acid in NPC-BM1 cells. The effect of gallic acid was associated with the inhibition of p38 MAPK signaling pathway. In addition, gallic acid enhanced the gene expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) which further suppressed the MMP-1 activity. These findings may be useful to develop a novel chemotherapeutic agent to inhibit the metastasis of nasopharyngeal cancer.

  1. Learning better deep features for the prediction of occult invasive disease in ductal carcinoma in situ through transfer learning

    Science.gov (United States)

    Shi, Bibo; Hou, Rui; Mazurowski, Maciej A.; Grimm, Lars J.; Ren, Yinhao; Marks, Jeffrey R.; King, Lorraine M.; Maley, Carlo C.; Hwang, E. Shelley; Lo, Joseph Y.

    2018-02-01

    Purpose: To determine whether domain transfer learning can improve the performance of deep features extracted from digital mammograms using a pre-trained deep convolutional neural network (CNN) in the prediction of occult invasive disease for patients with ductal carcinoma in situ (DCIS) on core needle biopsy. Method: In this study, we collected digital mammography magnification views for 140 patients with DCIS at biopsy, 35 of which were subsequently upstaged to invasive cancer. We utilized a deep CNN model that was pre-trained on two natural image data sets (ImageNet and DTD) and one mammographic data set (INbreast) as the feature extractor, hypothesizing that these data sets are increasingly more similar to our target task and will lead to better representations of deep features to describe DCIS lesions. Through a statistical pooling strategy, three sets of deep features were extracted using the CNNs at different levels of convolutional layers from the lesion areas. A logistic regression classifier was then trained to predict which tumors contain occult invasive disease. The generalization performance was assessed and compared using repeated random sub-sampling validation and receiver operating characteristic (ROC) curve analysis. Result: The best performance of deep features was from CNN model pre-trained on INbreast, and the proposed classifier using this set of deep features was able to achieve a median classification performance of ROC-AUC equal to 0.75, which is significantly better (p<=0.05) than the performance of deep features extracted using ImageNet data set (ROCAUC = 0.68). Conclusion: Transfer learning is helpful for learning a better representation of deep features, and improves the prediction of occult invasive disease in DCIS.

  2. 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

  3. Bio-coal briquettes using low-grade coal

    Science.gov (United States)

    Estiaty, L. M.; Fatimah, D.; Widodo

    2018-02-01

    The technology in using briquettes for fuel has been widely used in many countries for both domestic and industrial purposes. Common types of briquette used are coal, peat, charcoal, and biomass. Several researches have been carried out in regards to the production and the use of briquettes. Recently, researches show that mixing coal and biomass will result in an environmentally friendly briquette with better combustion and physical characteristics. This type of briquette is known as bio-coal briquettes. Bio-coal briquettes are made from agriculture waste and coal, which are readily available, cheap and affordable. Researchers make these bio-coal briquettes with different aims and objectives, depending on the issues to address, e.g. utilizing agricultural waste as an alternative energy to replace fossil fuels that are depleting its reserves, adding coal to biomass in order to add calorific value to bio-coal briquette, and adding biomass to coal to improve its chemical and physical properties. In our research, biocoal briquettes are made to utilize low grade coal. The biomass we use, however, is different from the ones used in past researches because it has undergone fermentation. The benefits of using such biomass are 1. Fermentation turns the hemi cellulose into a simpler form, so that the burning activation energy decreases while the calorific value increases. 2. Enzym produced will bind to heavy metals from coal as co-factors, forming metals that are environmentally friendly.

  4. Second Surgery in Insular Low-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    Tamara Ius

    2015-01-01

    Full Text Available Background. Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR are poorly documented. Objective. The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs that subsequently underwent second surgery. Methods. A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR. Results. At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs. Univariate analysis showed that TR is influenced by the following: extent of resection (EOR (P<0.002, ΔVT2T1 value (P<0.001, histological diagnosis of oligodendroglioma (P=0.017, and mutation of IDH1 (P=0.022. The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P<0.001. Conclusions. In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery.

  5. Characterization and Beneficiation Studies of a Low Grade Bauxite Ore

    Science.gov (United States)

    Rao, D. S.; Das, B.

    2014-10-01

    A low grade bauxite sample of central India was thoroughly characterized with the help of stereomicroscope, reflected light microscope and electron microscope using QEMSCAN. A few hand picked samples were collected from different places of the mine and were subjected to geochemical characterization studies. The geochemical studies indicated that most of the samples contain high silica and low alumina, except a few which are high grade. Mineralogically the samples consist of bauxite (gibbsite and boehmite), ferruginous mineral phases (goethite and hematite), clay and silicate (quartz), and titanium bearing minerals like rutile and ilmenite. Majority of the gibbsite, boehmite and gibbsitic oolites contain clay, quartz and iron and titanium mineral phases within the sample as inclusions. The sample on an average contains 39.1 % Al2O3 and 12.3 % SiO2, and 20.08 % of Fe2O3. Beneficiation techniques like size classification, sorting, scrubbing, hydrocyclone and magnetic separation were employed to reduce the silica content suitable for Bayer process. The studies indicated that, 50 % by weight with 41 % Al2O3 containing less than 5 % SiO2 could be achieved. The finer sized sample after physical beneficiation still contains high silica due to complex mineralogical associations.

  6. Diagnosis and treatment of invasive squamous cell carcinoma of the skin

    DEFF Research Database (Denmark)

    Stratigos, Alexander; Garbe, Claus; Lebbe, Celeste

    2015-01-01

    Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in Caucasian populations, accounting for 20% of all cutaneous malignancies. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO...

  7. Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells.

    Science.gov (United States)

    Zhang, Wei; Liu, Yuan; Li, Yu Feng; Yue, Yun; Yang, Xinghua; Peng, Lin

    2016-01-01

    Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first "Survivin suppressant" but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. Survivin protein plays critical roles in oral squamous cell carcinoma (OSCC), suggesting that YM155 would be extremely valuable for OSCC. In this study, we tested our hypothesis whether YM155 could be an effective inhibitor of cell growth, invasion and angiogenesis in oral squamous cell carcinoma (OSCC) cells. SCC9 and SCC25 were treated with different concentration of YM155 for indicated time. Using MTT assay and flow cytometry analysis to detect cell growth and apoptosis; Using transwell and Wound healing assay to detect migration and invasion; Using reverse transcription-PCR, Western blotting and electrophoretic mobility shift assay for measuring gene and protein expression, and DNA binding activity of NF-x03BA;B. YM155 inhibited survivin-rich expressed SCC9 cell growth in a dose- and time dependent manner. This was accompanied by increased apoptosis and concomitant attenuation of NF-x03BA;B and downregulation of NF-x03BA;B downstream genes MMP-9, resulting in the inhibition of SCC9 cell migration and invasion in vitro and caused antitumor activity and anti metastasis in vivo. YM155 treatment did not affect cell growth, apoptosis and invasion of surviving-poor expressed SCC25 cells in vitro. YM155 is a potent inhibitor of progression of SCC9 cells, which could be due to attenuation of survivin signaling processes. Our findings provide evidence showing that YM155 could act as a small molecule survivin inhibitor on survivin-rich expressed SCC9 cells in culture as well as when grown as tumor in a xenograft model. We also suggest that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed

  8. Reoperation Rates in Ductal Carcinoma In Situ vs Invasive Breast Cancer After Wire-Guided Breast-Conserving Surgery

    DEFF Research Database (Denmark)

    Langhans, Linnea; Jensen, Maj-Britt; Talman, Maj-Lis M

    2017-01-01

    Importance: New techniques for preoperative localization of nonpalpable breast lesions may decrease the reoperation rate in breast-conserving surgery (BCS) compared with rates after surgery with the standard wire-guided localization. However, a valid reoperation rate for this procedure needs...... to be established for comparison, as previous studies on this procedure include a variety of malignant and benign breast lesions. Objectives: To determine the reoperation rate after wire-guided BCS in patients with histologically verified nonpalpable invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS......) and to examine whether the risk of reoperation is associated with DCIS or histologic type of the IBC. Design, Setting, and Participants: This nationwide study including women with histologically verified IBC or DCIS having wire-guided BCS performed between January 1, 2010, and December 31, 2013, used data from...

  9. Contrast-enhanced computed tomography of the primary tumor in muscle invasive carcinoma of the urinary bladder

    International Nuclear Information System (INIS)

    Sager, E.M.

    1991-01-01

    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

  10. Study on invadopodia formation for lung carcinoma invasion with a microfluidic 3D culture device.

    Science.gov (United States)

    Wang, Shanshan; Li, Encheng; Gao, Yanghui; Wang, Yan; Guo, Zhe; He, Jiarui; Zhang, Jianing; Gao, Zhancheng; Wang, Qi

    2013-01-01

    Invadopodia or invasive feet, which are actin-rich membrane protrusions with matrix degradation activity formed by invasive cancer cells, are a key determinant in the malignant invasive progression of tumors and represent an important target for cancer therapies. In this work, we presented a microfluidic 3D culture device with continuous supplement of fresh media via a syringe pump. The device mimicked tumor microenvironment in vivo and could be used to assay invadopodia formation and to study the mechanism of human lung cancer invasion. With this device, we investigated the effects of epidermal growth factor (EGF) and matrix metalloproteinase (MMP) inhibitor, GM6001 on invadopodia formation by human non-small cell lung cancer cell line A549 in 3D matrix model. This device was composed of three units that were capable of achieving the assays on one control group and two experimental groups' cells, which were simultaneously pretreated with EGF or GM6001 in parallel. Immunofluorescence analysis of invadopodia formation and extracellular matrix degradation was conducted using confocal imaging system. We observed that EGF promoted invadopodia formation by A549 cells in 3D matrix and that GM6001 inhibited the process. These results demonstrated that epidermal growth factor receptor (EGFR) signaling played a significant role in invadopodia formation and related ECM degradation activity. Meanwhile, it was suggested that MMP inhibitor (GM6001) might be a powerful therapeutic agent targeting invadopodia formation in tumor invasion. This work clearly demonstrated that the microfluidic-based 3D culture device provided an applicable platform for elucidating the mechanism of cancer invasion and could be used in testing other anti-invasion agents.

  11. Use of Artificial Intelligence and Machine Learning Algorithms with Gene Expression Profiling to Predict Recurrent Nonmuscle Invasive Urothelial Carcinoma of the Bladder.

    Science.gov (United States)

    Bartsch, Georg; Mitra, Anirban P; Mitra, Sheetal A; Almal, Arpit A; Steven, Kenneth E; Skinner, Donald G; Fry, David W; Lenehan, Peter F; Worzel, William P; Cote, Richard J

    2016-02-01

    Due to the high recurrence risk of nonmuscle invasive urothelial carcinoma it is crucial to distinguish patients at high risk from those with indolent disease. In this study we used a machine learning algorithm to identify the genes in patients with nonmuscle invasive urothelial carcinoma at initial presentation that were most predictive of recurrence. We used the genes in a molecular signature to predict recurrence risk within 5 years after transurethral resection of bladder tumor. Whole genome profiling was performed on 112 frozen nonmuscle invasive urothelial carcinoma specimens obtained at first presentation on Human WG-6 BeadChips (Illumina®). A genetic programming algorithm was applied to evolve classifier mathematical models for outcome prediction. Cross-validation based resampling and gene use frequencies were used to identify the most prognostic genes, which were combined into rules used in a voting algorithm to predict the sample target class. Key genes were validated by quantitative polymerase chain reaction. The classifier set included 21 genes that predicted recurrence. Quantitative polymerase chain reaction was done for these genes in a subset of 100 patients. A 5-gene combined rule incorporating a voting algorithm yielded 77% sensitivity and 85% specificity to predict recurrence in the training set, and 69% and 62%, respectively, in the test set. A singular 3-gene rule was constructed that predicted recurrence with 80% sensitivity and 90% specificity in the training set, and 71% and 67%, respectively, in the test set. Using primary nonmuscle invasive urothelial carcinoma from initial occurrences genetic programming identified transcripts in reproducible fashion, which were predictive of recurrence. These findings could potentially impact nonmuscle invasive urothelial carcinoma management. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Brinkman, David; Misra, Subhasis; Aydin, Nail

    2016-01-01

    Invasive lobular carcinoma is the second most common type of breast cancer, responsible for 5-15 percent of all cases. Peritoneal carcinomatosis secondary to breast cancer is a rare event, frequently resulting in morbidity and mortality. Symptomatic gallbladder disease in the setting of peritoneal carcinomatosis originating from invasive lobular carcinoma of the breast is a very rare event and is not well covered in literature. A 44year old female patient previously diagnosed with stage IV invasive lobular carcinoma of the left breast with widespread systemic metastases and peritoneal carcinomatosis presented with a three week history of right upper quadrant pain trigged by food intake only, greatly diminishing her quality of life. She had spent almost a year in a progression free disease status but was now suffering from debilitating symptomatic gallbladder disease. Despite the extent of her peritoneal carcinomatosis, she elected to undergo a laparoscopic cholecystectomy. We are presenting a rare case of symptomatic gallbladder disease in the setting of peritoneal carcinomatosis secondary to invasive lobular carcinoma. A major concern is tumor load within nearby portal structures. Even though laparoscopic cholecystectomy could be a viable option to treat the condition, it needs to be applied selectively and very cautiously in the respective patient population. 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. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. EMMPRIN promotes angiogenesis, proliferation, invasion and resistance to sunitinib in renal cell carcinoma, and its level predicts patient outcome.

    Science.gov (United States)

    Sato, Mototaka; Nakai, Yasutomo; Nakata, Wataru; Yoshida, Takahiro; Hatano, Koji; Kawashima, Atsunari; Fujita, Kazutoshi; Uemura, Motohide; Takayama, Hitoshi; Nonomura, Norio

    2013-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to play crucial roles, including in angiogenesis, in several carcinomas. However, the correlation between EMMPRIN levels and angiogenesis expression profile has not been reported, and the role of EMMPRIN in renal cell carcinoma (RCC) is unclear. In the present study, we evaluated the association of EMMPRIN with angiogenesis, its value in prognosis, and its roles in RCC. EMMPRIN expression was examined in 50 RCC patients treated with radical nephrectomy. Angiogenesis, proliferation, and invasion activity were evaluated using EMMPRIN knockdown RCC cell lines. The size of EMMPRIN-overexpressing xenografts was measured and the degree of angiogenesis was quantified. EMMPRIN expression was evaluated in RCC patients who received sunitinib therapy and in sunitinib-resistant cells. Further, the relation between EMMPRIN expression and sensitivity to sunitinib was examined. EMMPRIN score was significantly associated with clinicopathological parameters in RCC patients, as well as being significantly correlated with microvessel area (MVA) in immature vessels and with prognosis. Down-regulation of EMMPRIN by siRNA led to decreased VEGF and bFGF expression, cell proliferation, and invasive potential. EMMPRIN over-expressing xenografts showed accelerated growth and MVA of immature vessels. EMMPRIN expression was significantly increased in patients who received sunitinib therapy as well as in sunitinib-resistant 786-O cells (786-suni). EMMPRIN-overexpressing RCC cells were resistant to sunitinib. Our findings indicate that high expression of EMMPRIN in RCC plays important roles in tumor progression and sunitinib resistance. Therefore, EMMPRIN could be a novel target for the treatment of RCC.

  14. EMMPRIN promotes angiogenesis, proliferation, invasion and resistance to sunitinib in renal cell carcinoma, and its level predicts patient outcome.

    Directory of Open Access Journals (Sweden)

    Mototaka Sato

    Full Text Available Extracellular matrix metalloproteinase inducer (EMMPRIN has been reported to play crucial roles, including in angiogenesis, in several carcinomas. However, the correlation between EMMPRIN levels and angiogenesis expression profile has not been reported, and the role of EMMPRIN in renal cell carcinoma (RCC is unclear. In the present study, we evaluated the association of EMMPRIN with angiogenesis, its value in prognosis, and its roles in RCC.EMMPRIN expression was examined in 50 RCC patients treated with radical nephrectomy. Angiogenesis, proliferation, and invasion activity were evaluated using EMMPRIN knockdown RCC cell lines. The size of EMMPRIN-overexpressing xenografts was measured and the degree of angiogenesis was quantified. EMMPRIN expression was evaluated in RCC patients who received sunitinib therapy and in sunitinib-resistant cells. Further, the relation between EMMPRIN expression and sensitivity to sunitinib was examined.EMMPRIN score was significantly associated with clinicopathological parameters in RCC patients, as well as being significantly correlated with microvessel area (MVA in immature vessels and with prognosis. Down-regulation of EMMPRIN by siRNA led to decreased VEGF and bFGF expression, cell proliferation, and invasive potential. EMMPRIN over-expressing xenografts showed accelerated growth and MVA of immature vessels. EMMPRIN expression was significantly increased in patients who received sunitinib therapy as well as in sunitinib-resistant 786-O cells (786-suni. EMMPRIN-overexpressing RCC cells were resistant to sunitinib.Our findings indicate that high expression of EMMPRIN in RCC plays important roles in tumor progression and sunitinib resistance. Therefore, EMMPRIN could be a novel target for the treatment of RCC.

  15. Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain

    International Nuclear Information System (INIS)

    García-Espinosa, Benjamín; Moro-Rodríguez, Ernesto; Álvarez-Fernández, Emilio

    2012-01-01

    Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. A total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited

  16. 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.

  17. Clinicopathological study of response to preoperative chemoradiotherapy and applicability for minimum invasive surgery on advanced tongue carcinomas

    International Nuclear Information System (INIS)

    Ohgi, Kazuhiko; Kirita, Tadaaki; Sugimura, Masahito

    2000-01-01

    Forty patients who received chemoradiotherapy followed by surgery for advanced tongue carcinoma were studied clinically and histopathologically, and the minimally invasive treatment for advanced tongue carcinoma was evaluated. Clinical effects on the primary tumor were CR in 22 (55.0%), PR in 15 (37.5%), and NC in 3 (7.5%). The CR rate was nearly 60%, and the overall response rate was 92.5%; the treatment was highly effective. Histological effects on the primary tumor were Grade II b or above, i.e. effective, in 31 (8.6%), and Grade IV, i.e. pathological CR, in 18 (51.4%). The treatment was also very effective histologically, and a correlation was observed between clinical effects and histological effects. Concerning the relationship between histological effects and the regression rate, a regression rate of 85% or higher was needed to obtain a histological effect of Grade II b or above, and a regression rate of 95% or higher was needed to obtain a histological effect of Grade III or above. Investigation of residual tumors showed persistence of cancer cells primarily in the center of the tumor, but both the horizontal and vertical residual rates were low, and cancer cells tended to be limited to the superficial layer of the central area of the primary tumor in the patients who showed a regression rate of 85% or higher. Histopathological malignancy, tumor vessel density (CD31), and p53 were suggested to be potential predictive factors of the effectiveness of preoperative therapy. The residual tumor Grade (R Grade) in the resected specimen is considered to be useful as a prognostic factor after resection of the primary tumor. Histological effects were also satisfactory in patients who showed a clinical effect of 85% or higher on this preoperative therapy. In such patients, minimum invasive surgery is considered to be applicable even in advanced cases, and improvements in the postoperative QOL are expected by oral organ/function preservation. (author)

  18. Malignant phyllodes tumor in the right breast and invasive lobular carcinoma within fibroadenoma in the other: case report

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    Luiz Henrique Gebrim

    2000-03-01

    Full Text Available CONTEXT: The malignant variety of the phyllodes tumor is rare. The occurrence of invasive lobular carcinoma within fibroadenoma is rare as well. DESIGN: Case report. CASE REPORT: A 58-year-old black female patient was referred to the Mastology unit of the Department of Gynecology, Federal University of São Paulo / Escola Paulista de Medicina, in February 1990, presenting an ulcerated tumor in the right breast with fast growth over the preceding six months. She was a virgin, with meno-pause at the age of 45 years and had not undergone hormone replacement treatment. The physical examination showed, in her right breast, an ulcerated tumor of 20 x 30 cm which was not adher-ent to the muscle level, multilobular and with fibroelastic consistency. The axillary lymph nodes were not palpable. The left breast showed a 2 x 3 cm painless, movable nodule, with well-defined edges, and fibroelastic consistency. We performed left-breast mammography, which showed several nodules with well-defined edges, the largest being 2 x 3 cm and exhibiting rough calcification and grouped microcalcifications within it. The patient underwent a frozen biopsy that showed a malignant variant of the phyllodes tumor in the right breast and fibroadenoma in the left one. After that, we performed a total mastectomy in the right breast and an excision biopsy in the left one. Paraffin study confirmed the frozen biopsy result from the right breast, yet we observed that in the interior of the fibroadenoma that was removed on the left, there was a focal area of invasive lobular carcinoma measuring 0.4 cm. The patient then underwent a modi-fied radical mastectomy with total axillary lymphadenectomy. None of the 21 dissected lymph nodes showed evidence of metastasis. In the follow-up, the patient evolved asymptomatically and with normal physical and laboratory examination results up to July 1997.

  19. The sensitivity of pre-operative axillary staging in breast cancer: comparison of invasive lobular and ductal carcinoma.

    Science.gov (United States)

    Topps, A; Clay, V; Absar, M; Howe, M; Lim, Y; Johnson, R; Bundred, N

    2014-07-01

    Axillary ultrasound (AUS) with fine-needle aspiration (FNA) biopsy of abnormal lymph nodes is important for pre-operative staging and planning the surgical management of the axilla. Invasive lobular carcinoma (ILC) metastases are thought to be difficult to detect because the cells are small and on cytology resemble lymphocytes. To investigate this we directly compared the sensitivity of pre-operative axillary staging between ILC and invasive ductal carcinoma (IDC). Consecutive patients that presented in a single breast unit with pure IDC between April 2005 and December 2006 and pure ILC between January 2008 and December 2012 were retrospectively identified from pathology records. Pre-operative axillary ultrasound and FNA biopsy results were compared with post-operative histopathology from the sentinel node biopsy (SNB) or axillary lymph node dissection (ALND). A total of 275 and 142 axillae were identified in the IDC and ILC groups respectively. In the node positive patients there was no significant difference in the sensitivity of AUS (IDC vs. ILC; 58.7% vs. 52.8%). However, there was a significant difference in the sensitivity of ultrasound-guided FNA biopsy of abnormal nodes (IDC vs. ILC; 98.4% vs. 53.6%; p < 0.001). AUS has comparative sensitivities between IDC and ILC populations. In contrast, FNA biopsy of abnormal axillary nodes is clearly less sensitive in the ILC group. In these patients, who have abnormal AUS, we suggest that a core biopsy is required to improve the pre-operative staging and prevent unnecessary surgical procedures. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. SIPA1 promotes invasion and migration in human oral squamous cell carcinoma by ITGB1 and MMP7

    International Nuclear Information System (INIS)

    Takahara, Toshikazu; Kasamatsu, Atsushi; Yamatoji, Masanobu; Iyoda, Manabu; Kasama, Hiroki; Saito, Tomoaki; Takeuchi, Shin; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2017-01-01

    Signal-induced proliferation-associated protein 1 (SIPA1) is known to be a GTPase activating protein. Overexpressed SIPA1 is related to metastatic progression in breast and prostate cancers; however, the relevance of SIPA1 in oral squamous cell carcinoma (OSCC) is still unknown. The aim of this study was to examine SIPA1 expression and its functional mechanisms in OSCC. SIPA1 mRNA and protein expressions were analyzed by quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. The expressions of SIPA1 were up-regulated significantly in vitro and in vivo. Moreover, SIPA1 expression was correlated with regional lymph node metastasis. We next assessed the cellular functions associated with tumoral metastasis using SIPA1 knockdown (shSIPA1) cells and analyzed the downstream molecules of SIPA1, i.e., bromodomain containing protein 4(BRD4), integrin beta1 (ITGB1), and matrix metalloproteinase 7 (MMP7). The shSIPA1 cells showed decreased invasiveness and migratory activities, however cellular adhesion ability was maintained at a high level. In addition, ITGB1 expression was greater in shSIPA1 cells, whereas MMP7 expression was lower than in control cells. This research is the first to establish that SIPA1 promotes cancer metastasis by regulating the ITGB1 and MMP7. Therefore, SIPA1 might be a novel therapeutic target for patients with lymph node metastasis of OSCC. - Highlights: • SIPA1 expression was up-regulated in oral squamous cell carcinoma (OSCC). • SIPA1-positive OSCCs were correlated with regional lymph node metastasis. • SIPA1 controlled BRD4 and influenced transcription of ITGB1and MMP7. • SIPA1 induced cellular invasion and migration and decreased cellular adhesion. • SIPA1 might be a potential biomarker of cancer metastasis for OSCC.

  1. SIPA1 promotes invasion and migration in human oral squamous cell carcinoma by ITGB1 and MMP7

    Energy Technology Data Exchange (ETDEWEB)

    Takahara, Toshikazu [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba (Japan); Kasamatsu, Atsushi, E-mail: kasamatsua@faculty.chiba-u.jp [Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba (Japan); Yamatoji, Masanobu [Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba (Japan); Iyoda, Manabu; Kasama, Hiroki; Saito, Tomoaki [Division of Oral Surgery, Chiba Rosai Hospital, Chiba (Japan); Takeuchi, Shin [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba (Japan); Endo-Sakamoto, Yosuke [Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba (Japan); Shiiba, Masashi [Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan); Tanzawa, Hideki [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba (Japan); Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba (Japan); Uzawa, Katsuhiro, E-mail: uzawak@faculty.chiba-u.jp [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba (Japan); Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba (Japan)

    2017-03-15

    Signal-induced proliferation-associated protein 1 (SIPA1) is known to be a GTPase activating protein. Overexpressed SIPA1 is related to metastatic progression in breast and prostate cancers; however, the relevance of SIPA1 in oral squamous cell carcinoma (OSCC) is still unknown. The aim of this study was to examine SIPA1 expression and its functional mechanisms in OSCC. SIPA1 mRNA and protein expressions were analyzed by quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry. The expressions of SIPA1 were up-regulated significantly in vitro and in vivo. Moreover, SIPA1 expression was correlated with regional lymph node metastasis. We next assessed the cellular functions associated with tumoral metastasis using SIPA1 knockdown (shSIPA1) cells and analyzed the downstream molecules of SIPA1, i.e., bromodomain containing protein 4(BRD4), integrin beta1 (ITGB1), and matrix metalloproteinase 7 (MMP7). The shSIPA1 cells showed decreased invasiveness and migratory activities, however cellular adhesion ability was maintained at a high level. In addition, ITGB1 expression was greater in shSIPA1 cells, whereas MMP7 expression was lower than in control cells. This research is the first to establish that SIPA1 promotes cancer metastasis by regulating the ITGB1 and MMP7. Therefore, SIPA1 might be a novel therapeutic target for patients with lymph node metastasis of OSCC. - Highlights: • SIPA1 expression was up-regulated in oral squamous cell carcinoma (OSCC). • SIPA1-positive OSCCs were correlated with regional lymph node metastasis. • SIPA1 controlled BRD4 and influenced transcription of ITGB1and MMP7. • SIPA1 induced cellular invasion and migration and decreased cellular adhesion. • SIPA1 might be a potential biomarker of cancer metastasis for OSCC.

  2. Epstein-Barr virus infection and breast invasive ductal carcinoma in Egyptian women: A single center experience.

    Science.gov (United States)

    El-Naby, Noha Ed Hassab; Hassan Mohamed, Hameda; Mohamed Goda, Asmaa; El Sayed Mohamed, Ahmed

    2017-06-01

    A controversy of the role of Epstein-Barr virus (EBV) infection in breast carcinomas has been reported in the literature. We carried on this research to explore possible association between EBV infection and breast invasive ductal carcinoma (IDC) in Egyptian women attending our center. This study carried out at Sohag university hospital on 84 paraffin embedded samples of breast tissue, of them 42 breast IDC as the case group and 42 breast fibroadenomas as the control group. Nested PCRand immunohistochemistry (IHC) done separately for all samples to identify the Epstein-Barr nuclear antigen-1 (EBNA-1) gene and EBV latent membrane protein-1 (LMP-1) respectively, in breast cancer cells and controls. Specimen considered positive when both (EBNA-1) gene and LMP-1 were detected using PCR and IHC separately for the same sample, this was achieved by 10/42 (23.81%) of breast IDC (case group) and 6/42 (14.29%) of breast fibro-adenomas (control group) (P-value=0.4). Nodal involvement was the only parameter that demonstrated a significant statistical relationship with EBV presence in cancerous tissue with p-value=0.003. Our research could not find a significant statistical association between EBV infection and breast IDC in Egyptian women attending our center, but, there might be an association between the existence of EBV and tumor aggressiveness. Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  3. Repeated surgeries in invasive lobular breast cancer with preoperative MRI: Role of additional carcinoma in situ and background parenchymal enhancement.

    Science.gov (United States)

    Preibsch, H; Richter, V; Bahrs, S D; Hattermann, V; Wietek, B M; Bier, G; Kloth, C; Blumenstock, G; Hahn, M; Staebler, A; Nikolaou, K; Wiesinger, B

    2017-05-01

    Analysing the influence of additional carcinoma in situ (CIS) and background parenchymal enhancement (BPE) in preoperative MRI on repeated surgeries in patients with invasive lobular carcinoma (ILC) of the breast. Retrospective analysis of 106 patients (mean age 58.6±9.9years) with 108 ILC. Preoperative tumour size as assessed by MRI, mammography and sonography was recorded and compared to histopathology. In contrast-enhanced MRI, the degree of BPE was categorised by two readers. The influence of additionally detected CIS and BPE on the rate of repeated surgeries was analysed. Additional CIS was present in 45.4% of the cases (49/108). The degree of BPE was minimal or mild in 80% of the cases and moderate or marked in 20% of the cases. In 17 cases (15.7%) at least one repeated surgery was performed. In n=15 of these cases, repeated surgery was performed after BCT (n=9 re-excisions, n=6 conversions to mastectomy), in n=2 cases after initial mastectomy. The initial surgical procedure (p=0.008) and additional CIS (p=0.046) significantly influenced the rate of repeated surgeries, while tumour size, patient age and BPE did not (p=ns). Additional CIS was associated with a higher rate of repeated surgeries, whereas BPE had no influence. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Evaluation of T-lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin.

    Science.gov (United States)

    Stravodimou, Aristea; Tzelepi, Vassiliki; Papadaki, Helen; Mouzaki, Athanasia; Georgiou, Sophia; Melachrinou, Maria; Kourea, Eleni P

    2018-05-01

    Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T-cells (Tregs) in these lesions. Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup-Mäkinen (K-M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification. An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes. T-cells and cytotoxic T-cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K-M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal carcinomas of the breast and its clinicopathologic relationships

    International Nuclear Information System (INIS)

    Park, Kwang-Hwa; Choi, Sung-E; Eom, Minseob; Kang, Yup

    2005-01-01

    The anaphase-promoting complex (APC) is a multiprotein complex with E3 ubiquitin ligase activity, which is required for the ubiquitination of securin and cyclin-B. Moreover, the mitotic spindle checkpoint is activated if APC activation is prevented. In addition, several APC-targeting molecules such as securin, polo-like kinase, aurora kinase, and SnoN have been reported to be oncogenes. Therefore, dysregulation of APC may be associated with tumorigenesis. However, the clinical significance and the involvement of APC in tumorigenesis have not been investigated. The expression of APC7 was immunohistochemically investigated in 108 invasive ductal carcinomas of the breast and its relationship with clinicopathologic parameters was examined. The expression of APC7 was defined as positive when the summed scores of staining intensities (0 to 3+) and stained proportions (0 to 3+) exceeded 3+. Positive APC7 expression was less frequent than its negative expression when histologic (P = 0.009) or nuclear grade (P = 0.009), or mitotic number (P = 0.0016) was elevated. The frequency of APC7 negative expression was higher in high Ki-67 or aneuploid groups than in low Ki-67 or diploid groups. These data show that loss of APC7 expression is more common in breast carcinoma cases with poor prognostic parameters or malignant characteristics. They therefore suggest that dysregulation of APC activity, possibly through downregulation of APC7, may be associated with tumorigenesis in breast cancer

  6. 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.

  7. Non-Invasive Radiofrequency-Induced Targeted Hyperthermia for the Treatment of Hepatocellular Carcinoma

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    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.

  8. Stroke due to non-bacterial thrombotic endocarditis as initial presentation of breast invasive ductal carcinoma.

    Science.gov (United States)

    Detremerie, Celine; Timmermans, Frank; De Pauw, Michel; Gheeraert, Peter; Hemelsoet, Dimitri; Toeback, Jonas; Bové, Thierry; Vandecasteele, Els

    2017-08-01

    We present a case of a 71-year-old woman with recurrent stroke episodes due to non-bacterial thrombotic endocarditis (NBTE) leading to the diagnosis of an early-stage breast carcinoma. NBTE is associated with a variety of inflammatory states, including malignancy. NBTE presents itself with systemic embolization, mostly stroke. Treatment consists of treating the underlying condition and start of systemic anticoagulation therapy. Cardiac surgery is restricted to highly selected cases, since prognosis usually is limited by the neoplasm, which usually is in an advanced stage at time of diagnosis of NBTE. The malignancy usually is diagnosed prior to NBTE. Cases presenting with NBTE leading to the diagnosis of malignancy, however, are rarely reported. To our knowledge, we present the first case leading to the diagnosis of an early-stage breast carcinoma.

  9. Gut microbiota, low-grade inflammation, and metabolic syndrome.

    Science.gov (United States)

    Chassaing, Benoit; Gewirtz, Andrew T

    2014-01-01

    The intestinal tract is inhabited by a large diverse community of bacteria collectively referred to as the gut microbiota. Alterations in gut microbiota composition are associated with a variety of disease states including obesity, diabetes, and inflammatory bowel disease (IBD). Transplant of microbiota from diseased persons (or mice) to germfree mice transfers some aspects of disease phenotype, indicating that altered microbiota plays a role in disease establishment and manifestation. There are myriad potential mechanisms by which alterations in gut microbiota might promote disease, including increasing energy harvest, production of toxic metabolites, and molecular mimicry of host proteins. However, our research indicates that an overarching mechanism by which an aberrant microbiota negatively impacts health is by driving chronic inflammation. More specifically, we hypothesize that the histopathologically evident gut inflammation that defines IBD is a severe but relatively rare outcome of an altered host-microbiota relationship, while a much more common consequence of such disturbances is "low-grade" inflammation characterized by elevated proinflammatory gene expression that associates with, and may promote, metabolic syndrome. In this context, a variety of chronic inflammatory diseases may stem from inability of the mucosal immune system to properly manage a stable healthy relationship with the gut microbiota. While one's ability to manage their gut microbiota is dictated in part by genetics, it can be markedly influenced by the composition of the microbiota one inherits from their early environment. Moreover, the host-microbiota relationship can be perturbed by instigator bacteria or dietary components, which may prove to play a role in promoting chronic inflammatory disease states.

  10. Occult Invasive Lobular Carcinoma of Breast Detected by Stomach Metastasis: A Case Report

    International Nuclear Information System (INIS)

    KIm, So Jung; Jung, Hae Kyoung; Ko, Kyung Hee; Yoon, Jung Hyun

    2012-01-01

    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.

  11. 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.

  12. Conformal proton radiation therapy for pediatric low-grade astrocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Hug, E.B. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Radiation Medicine; Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Pediatrics and Dept. of Pathology; Darthmouth-Hitchcock Medical Center, Lebanon, New Hampshire (United States). Section of Radiation Oncology; Muenter, M.W.; Archambeau, J.O.; DeVries, A.; Loredo, L.N.; Grove, R.I.; Slater, J.D. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Radiation Medicine; Liwnicz, B. [Loma Linda Univ. Medical Center, Loma Linda, CA (United States). Dept. of Pathology

    2002-01-01

    Background: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). Patients and Method: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephatic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (cobalt gray equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. Results: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. Conclusions: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment

  13. Clinico-pathological pattern, classification and staging of urinary bladder carcinomas - a five years experience at a tertiary care hospital in central punjab

    International Nuclear Information System (INIS)

    Naeem, A.

    2015-01-01

    In Pakistan, urinary bladder carcinoma is the 8th commonest malignancy while being the fourth commonest cancer in men. The relative occurrence of a particular histological type of bladder carcinoma depends on the clinical setting. Both grade and stage of these cancers are highly correlated with recurrence, progression and patient survival rates. Methods: This cross-sectional study comprised of 122 patients with newly diagnosed operable primary bladder carcinomas who underwent cystoscopy associated transurethral resection of bladder tumour at the Urology Department of Punjab Employees Social Security Hospital, Lahore. All participants completed a detailed questionnaire and underwent an in-depth interview to obtain data. The surgical specimens were referred to the Pathology department. Gross observations of the tumour recorded. Result: A total of 114 cases, classified according to WHO/ISUP criteria, low-grade papillary lesions, comprising Papillary Urothelial Neoplasm of Low Malignant Potential (PUNLMP) and Papillary Low Grade carcinomas, accounted for 43% of tumours. Male to female ratio being 5.3:1 (74%). Lateral walls were involved in 44%, posterior wall in 25.3%, trigone in 10.7%, bladder neck in 7.2%, dome in 5.8%, ureteric orifice in 4.13%, anterior wall in 2% and left ureter in 0.87% cases. Tumour staging revealed an overall 11.5% of tumours with stage Ta and 31.5% with stage T3-4. About 29% tumours were non invasive. About n=13 of low-grade carcinomas and n=68 of high-grade carcinomas were invasive. For tumours classified by WHO/ISUP criteria, the percentage of women was larger for PUNLMP than for the other categories of urothelial tumours (p-value 0.006); no statistically significant difference was found by age or gender with respect to tumour stage (p-value 0.138 and 0.452). Conclusion: Transitional Cell Carcinoma (TCC) is the commonest among middle aged men. (author)

  14. Urinary collecting system invasion is associated with poor survival in patients with clear-cell renal cell carcinoma.

    Science.gov (United States)

    Bailey, George C; Boorjian, Stephen A; Ziegelmann, Matthew J; Westerman, Mary E; Lohse, Christine M; Leibovich, Bradley C; Cheville, John C; Thompson, R Houston

    2017-04-01

    To evaluate the prognostic significance of urinary collecting system invasion (UCSI) in a large series of patients with clear-cell renal cell carcinoma (RCC). Patients with clear-cell RCC treated with nephrectomy between 2001 and 2010 were reviewed from a prospectively maintained registry. One urological pathologist re-reviewed all slides. Cancer-specific survival was estimated using the Kaplan-Meier method, and associations of UCSI with death from RCC were evaluated using Cox models. Of the 859 patients with clear-cell RCC, 58 (6.8%) had UCSI. At last follow-up, 310 patients had died from RCC at a median of 1.8 years after surgery. The median follow-up for patients alive at last follow-up was 8.2 years. The estimated cancer-specific survival at 10 years after surgery for patients with UCSI was 17%, compared with 60% for patients without UCSI (P system invasion is associated with poor prognosis among patients with clear-cell RCC. If validated, consideration should be given to including UCSI in future staging systems. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

  15. Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Kanjoormana Aryan Manu

    Full Text Available Accumulating evidence(s indicate that CXCL12-CXCR4 signaling cascade plays an important role in the process of invasion and metastasis that accounts for more than 80% of deaths in hepatocellular carcinoma (HCC patients. Thus, identification of novel agents that can downregulate CXCR4 expression and its associated functions have a great potential in the treatment of metastatic HCC. In the present report, we investigated an anthraquinone derivative, emodin for its ability to affect CXCR4 expression as well as function in HCC cells. We observed that emodin downregulated the expression of CXCR4 in a dose-and time-dependent manner in HCC cells. Treatment with pharmacological proteasome and lysosomal inhibitors did not have substantial effect on emodin-induced decrease in CXCR4 expression. When investigated for the molecular mechanism(s, it was observed that the suppression of CXCR4 expression was due to downregulation of mRNA expression, inhibition of NF-κB activation, and abrogation of chromatin immunoprecipitation activity. Inhibition of CXCR4 expression by emodin further correlated with the suppression of CXCL12-induced migration and invasion in HCC cell lines. In addition, emodin treatment significantly suppressed metastasis to the lungs in an orthotopic HCC mice model and CXCR4 expression in tumor tissues. Overall, our results show that emodin exerts its anti-metastatic effect through the downregulation of CXCR4 expression and thus has the potential for the treatment of HCC.

  16. HER2 evaluation using the novel rabbit monoclonal antibody SP3 and CISH in tissue microarrays of invasive breast carcinomas.

    Science.gov (United States)

    Ricardo, Sara Alexandra Vinhas; Milanezi, Fernanda; Carvalho, Sílvia Teresa; Leitão, Dina Raquel Aguilera; Schmitt, Fernando Carlos Lander

    2007-09-01

    Laboratory methods for HER2 assessment currently include immunohistochemical (IHC) methods (measuring protein overexpression) and fluorescence in situ hybridisation (FISH) (measuring gene amplification). The measure of HER2 protein by IHC is usually assessed by the mouse monoclonal antibody CB11, and polyclonal antibodies (Herceptest) directed against the internal portion of the receptor. Recently, chromogenic in situ hybridisation (CISH), in which HER2 is detected by a peroxidase reaction and the gene amplification can be determined by regular bright-field microscopy, has emerged as an alternative to FISH. To evaluate the status of HER2 in tissue microarrays (TMAs) of invasive breast cancer using the novel rabbit monoclonal antibody SP3 directed against the external portion of HER2, and correlate the results with CB11 and CISH. IHC was performed with two antibodies (CB11 and SP3) and CISH for HER2 in 10 TMA blocks with 190 formalin-fixed paraffin-embedded cases of invasive breast carcinomas. The correlation between SP3 and CB11 was significant (pCISH (pCISH, shows that this novel antibody is a reliable candidate to evaluate the expression of HER2 in breast cancer.

  17. Correlation of primary tumor FDG uptake with clinicopathologic prognostic factors in invasive ductal carcinoma of the breast

    International Nuclear Information System (INIS)

    Jo, I; Kim, Sung Hoon; Kim, Hae Won; Kang, Sung Hee; Zeon, Seok Kil; Kim, Su Jin

    2015-01-01

    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 max ) of the primary breast tumor was measured and compared with hormonal receptor and HER2 overexpression status. The high SUV 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 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

  18. Factors Affecting Concordance between Radiological and Histological Findings in Invasive Lobular Carcinoma - Experience from a National Cancer Centre.

    Science.gov (United States)

    Abu-Sinn, Duaa; O'Driscoll, Donal; Murphy, Maurice

    2017-05-01

    Invasive lobular carcinoma (ILC) is characterized by an infiltrative discohesive growth pattern, making it difficult to accurately assess both clinically and by imaging studies. Despite favourable biological characteristics, challenges remain in the surgical treatment of ILC. We aimed to evaluate radiology/histology concordance and identify histological and biological parameters on core biopsies that may predict final tumour histology and guide surgical treatment decisions. The radiology and histology reports for all newly diagnosed cases of ILC were analysed. The biopsy and resection histological slides for all the surgical cases were reviewed. 75 new cases of ILC were diagnosed over a 2-year period. 48 patients underwent surgery of whom 25% had 2 or more operations. There was discordance between radiological and histological tumour focality and tumour size in 35 and 40%, respectively. The correlation between radiology/histology discordance and E-cadherin expression was statistically significant. However, the correlation between radiology/histology discordance and menopausal status, breast density, pattern of invasion, presence of lobular intraepithelial neoplasia (LIN), hormonal status, and Ki67 were not statistically significant. Histological and biological factors in ILC, with the exception of E-cadherin expression, do not seem to play a significant role in radiology/histology discordance. However, larger studies are needed to further corroborate these findings.

  19. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    Energy Technology Data Exchange (ETDEWEB)

    Ferramosca, Alessandra, E-mail: alessandra.ferramosca@unisalento.it [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Conte, Annalea; Guerra, Flora; Felline, Serena [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Rimoli, Maria Grazia [Dipartimento di Farmacia, Università di Napoli Federico II, Napoli (Italy); Mollo, Ernesto [Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli (Italy); Zara, Vincenzo [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Terlizzi, Antonio [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Stazione Zoologica Anton Dohrn, Napoli (Italy)

    2016-05-13

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  20. Evaluation of tumor invasion in gastric carcinoma with CT using water as an oral contrast agent in prone position

    International Nuclear Information System (INIS)

    Chung, Jin Il; Lee, Jong Tae; Yoo, Hyung Sik; Lee, Byung Hee; Bae, Jong Yup

    1994-01-01

    To evaluate the accuracy of CT using water as an oral contrast material in a prone position in determining the depth of tumor invasion in gastric cancer patients. Thirty three patients(19 male, 14 female) with surgically confirmed gastric cancer were studied. We performed CT in a prone position after ingestion of 1 liter of pure water. CT findings were classified into 4 groups by the morphologic appearance of infiltrates in the perigastric fat plane: normal perigastric fat(S0), fine mottled densities(S1), irregular aggregated or liner densities(S2) and direct extension and invasion of tumor into contiguous structures(S3). Also we prospectively compared the CT staging with pathologic T staging according to the TNM systems. The overall accuracy of CT staging in determining the pathologic T factor was 69.6%. As we regarded T1 and T2 lesions as one group on CT, the accuracy of CT staging was increased to 80.2% because of a limitation of CT for distinguishing T1 from T2 lesions. Prone position CT using water as an oral contrast agent is quite accurate in determining the T staging of gastric carcinoma

  1. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    International Nuclear Information System (INIS)

    Ferramosca, Alessandra; Conte, Annalea; Guerra, Flora; Felline, Serena; Rimoli, Maria Grazia; Mollo, Ernesto; Zara, Vincenzo; Terlizzi, Antonio

    2016-01-01

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  2. Massive and life-threatening upper gastrointestinal bleeding due to invasive hepatocellular carcinoma: A case report

    Directory of Open Access Journals (Sweden)

    Semih Hot, M.D.

    2016-01-01

    Conclusions: The incidence of patients with massive bleeding due to gastric invasion of HCC is low, and only a few cases have been reported in the literature. Our purpose while presenting this rare case is to increase the awareness about the issue.

  3. The Invasion and Metastasis Promotion Role of CD97 Small Isoform in Gastric Carcinoma

    DEFF Research Database (Denmark)

    Liu, Daren; Trojanowicz, Bogusz; Ye, Longyun

    2012-01-01

    CD97 is over-expressed in the majority of gastric adenocarcinomas and is associated with its dedifferentiation and aggressiveness. Our previous results demonstrated that out of three CD97 isoforms tested, only the small one was able to promote increased invasiveness in vitro. Based on these data ...

  4. Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion

    Directory of Open Access Journals (Sweden)

    Shen Qingli

    2010-08-01

    Full Text Available Abstract Background Micro-ribonucleic acid (miRNA-199a-5p has been reported to be decreased in hepatocellular carcinoma (HCC compared to normal tissue. Discoidin domain receptor-1 (DDR1 tyrosine kinase, involved in cell invasion-related signaling pathway, was predicted to be a potential target of miR-199a-5p by the use of miRNA target prediction algorithms. The aim of this study was to investigate the role of miR-199a-5p and DDR1 in HCC invasion. Methods Mature miR-199a-5p and DDR1 expression were evaluated in tumor and adjacent non-tumor liver tissues from 23 patients with HCC undergoing liver resection and five hepatoma cell lines by the use of real-time quantitative RT-PCR (qRT-PCR analysis. The effect of aberrant miR-199a-5p expression on cell invasion was assessed in vitro using HepG2 and SNU-182 hepatoma cell lines. Luciferase reporter assay was employed to validate DDR1 as a putative miR-199a-5p target gene. Regulation of DDR1 expression by miR-199a-5p was assessed by the use qRT-PCR and western blotting analysis. Results A significant down-regulation of miR-199a-5p was observed in 65.2% of HCC tissues and in four of five cell lines. In contrast, DDR1 expression was significantly increased in 52.2% of HCC samples and in two of five cell lines. Increased DDR1 expression in HCC was associated with advanced tumor stage. DDR1 was shown to be a direct target of miR-199a-5p by luciferase reporter assay. Transfection of miR-199a-5p inhibited invasion of HepG2 but not SNU-182 hepatoma cells. Conclusions Decreased expression of miR-199a-5p contributes to increased cell invasion by functional deregulation of DDR1 activity in HCC. However, the effect of miR-199a-5p on DDR1 varies among individuals and hepatoma cell lines. These findings may have significant translational relevance for development of new targeted therapies as well as prognostic prediction for patients with HCC.

  5. BCORL1 is an independent prognostic marker and contributes to cell migration and invasion in human hepatocellular carcinoma.

    Science.gov (United States)

    Yin, Guozhi; Liu, Zhikui; Wang, Yufeng; Dou, Changwei; Li, Chao; Yang, Wei; Yao, Yingmin; Liu, Qingguang; Tu, Kangsheng

    2016-02-15

    The deregulation of E-cadherin has been considered as a leading cause of hepatocellular carcinoma (HCC) metastasis. BCL6 corepressor-like 1 (BCORL1) is a transcriptional corepressor and contributes to the repression of E-cadherin. However, the clinical significance of BCORL1 and its role in the metastasis of HCC remain unknown. Differentially expressed BCORL1 between HCC and matched tumor-adjacent tissues, HCC cell lines and normal hepatic cell line were detected by Western blot. The expression of BCORL1 was altered by siRNAs or lentivirus-mediated vectors. Transwell assays were performed to determine HCC cell invasion and migration. Increased expression of BCORL1 protein was detected in HCC specimens and cell lines. Clinical association analysis showed that BCORL1 protein was expressed at significant higher levels in HCC patients with multiple tumor nodes, venous infiltration and advanced TNM tumor stage. Survival analysis indicated that high expression of BCORL1 protein conferred shorter overall survival (OS) and recurrence-free survival (RFS) of HCC patients. Multivariate Cox regression analysis disclosed that BCORL1 expression was an independent prognostic marker for predicting survival of HCC patients. Our in vitro studies demonstrated that BCORL1 prominently promoted HCC cell migration and invasion. Otherwise, an inverse correlation between BCORL1 and E-cadherin expression was observed in HCC tissues. BCORL1 inversely regulated E-cadherin abundance and subsequently facilitated epithelial-mesenchymal transition (EMT) in HCC cells. Notably, the effect of BCORL1 knockdown on HCC cells was abrogated by E-cadherin silencing. BCORL1 may be a novel prognostic factor and promotes cell migration and invasion through E-cadherin repression-induced EMT in HCC.

  6. A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells.

    Science.gov (United States)

    Fu, Zhi-guang; Wang, Li; Cui, Hong-yong; Peng, Jian-long; Wang, Shi-jie; Geng, Jie-jie; Liu, Ji-de; Feng, Fei; Song, Fei; Li, Ling; Zhu, Ping; Jiang, Jian-li; Chen, Zhi-nan

    2016-02-23

    CD147, a type I transmembrane glycoprotein, is highly expressed in various cancer types and plays important roles in tumor progression, especially by promoting the motility and invasion of hepatocellular carcinoma (HCC) cells. These crucial roles make CD147 an attractive target for therapeutic intervention in HCC, but no small-molecule inhibitors of CD147 have been developed to date. To identify a candidate inhibitor, we used a pharmacophore model derived from the structure of CD147 to virtually screen over 300,000 compounds. The 100 highest-ranked compounds were subjected to biological assays, and the most potent one, dubbed AC-73 (ID number: AN-465/42834501), was studied further. We confirmed that AC-73 targeted CD147 and further demonstrated it can specifically disrupt CD147 dimerization. Moreover, molecular docking and mutagenesis experiments showed that the possible binding sites of AC-73 on CD147 included Glu64 and Glu73 in the N-terminal IgC2 domain, which two residues are located in the dimer interface of CD147. Functional assays revealed that AC-73 inhibited the motility and invasion of typical HCC cells, but not HCC cells that lacked the CD147 gene, demonstrating on-target action. Further, AC-73 reduced HCC metastasis by suppressing matrix metalloproteinase (MMP)-2 via down-regulation of the CD147/ERK1/2/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, AC-73 attenuated progression in an orthotopic nude mouse model of liver metastasis, suggesting that AC-73 or its derivatives have potential for use in HCC intervention. We conclude that the novel small-molecule inhibitor AC-73 inhibits HCC mobility and invasion, probably by disrupting CD147 dimerization and thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways, which are crucial for cancer progression.

  7. Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival

    International Nuclear Information System (INIS)

    Tomita, Masaki; Ayabe, Takanori; Matsuzaki, Yasunori; Edagawa, Masao; Maeda, Masayuki; Shimizu, Tetsuya; Hara, Masaki; Onitsuka, Toshio

    2001-01-01

    We assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma. Formalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody. Expression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87). In patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion

  8. Distribution of myofibroblast cells and microvessels around invasive ductal carcinoma of the breast and comparing with the adjacent range of their normal-to-DCIS zones.

    Science.gov (United States)

    Dabiri, Shahriar; Talebi, Amin; Shahryari, Jahanbanoo; Meymandi, Manzoumeh Shamsi; Safizadeh, Hossein

    2013-02-01

    This study seeks to determine the relationships between manifestation of myofibroblasts in the stroma tissue of hyperplastic pre-invasive breast lesions to invasive cancer by investigating clinicopathological data of patients, their effect on steroid receptor expression and HER2, and angiogenesis according to CD34 antigen expression. 100 cases of invasive ductal carcinoma were immunohistochemically investigated for the presence of smooth muscle actin (SMA), ER/PR, HER2, anti-CD34 antibody and microvessel count (MVC). Patients were scored in four different zones of invasive areas: invasive cancer, DCIS, fibrocystic disease ± ductal intraepithelial neoplasia (FCD ± DIN), and normal tissue.  There was a significant difference in stromal myofibroblasts between all areas except for the stroma of DCIS and FCD ± DIN (P normal areas (P = 0.054). There