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Sample records for terminally differentiated malignant

  1. Non-teleological differentiation of malignancy (review).

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    Chigira, M; Watanabe, H

    1994-03-01

    So-called 'de-differentiation' of malignant tumors is not identical with 'retro-differentiation' of normal cells, although induction of differentiation of tumor cells seems to be successful. De-differentiation of tumor cells is a more stochastic process than the reversion of serial developmental lineage in normal differentiation. After retro-differentiation, re-differentiation of normal cells includes serial expression of negative regulators programmed a priori, and a teleological explanation of differentiation is possible. However, 'fragmented' gene expression is generally observed in tumor-cell differentiation. In tumor cells, it is more important that they cannot maintain a differentiated state under normal microenvironments than that they can be induced to differentiate by artificial agents. Induction of differentiation of tumor cells should be different from that of their normal counterparts since loss of regulatory mechanisms could not be restored by the inducers. Phenomenological homology between tumor cells and their normal counterparts in the differentiation may be only an experimental artifact, since the genetic information of development is generally damaged or lost in tumor cells. Loss of teleology in tumor cells is essentially correlated with their selfish behavior. Differentiation is not necessary for tumor cells, since they are 'selfish cells' in the altruistic somatic cell society. The differentiation program of tumor cells should be considered as a remnant of the normal one with loss of teleology.

  2. The role of tumor necrosis factor alpha in differentiation between malignant and non malignant pleural effusion

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    Heba M. Atef

    2016-07-01

    Conclusion: Pleural fluid level of TNF-α can be used in differentiating malignant from non malignant effusion. Also levels of TNF-α in the serum and pleural fluid could be useful as a complementary marker in the differential diagnosis of two most common types of exudates (tuberculous and malignant.

  3. Differentiating malignant vertebral tumours from non-malignancies with CT spectral imaging: a preliminary study

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    Yuan, Yuan; Zhang, Yan; Lang, Ning; Yuan, Huishu [Peking University Third Hospital, No.49 North Garden Street, Haidian District, Beijing (China); Li, Jianying [GE Healthcare, CT imaging Research Center, Beijing (China)

    2015-10-15

    To investigate the value of dual-energy spectral computed tomography (DESCT) for differentiating malignant vertebral tumours from non-malignancies during venous phase. This study was institutional review board-approved, and written informed consent was obtained from all patients. Thirty-seven patients were examined by DESCT during venous phase. Twenty patients had malignant vertebral tumours, 17 had non-malignant vertebral tumours. The iodine/water densities for the lesion, the lesion-to-muscle ratio, and lesion-to-artery ratio for iodine density measurements were calculated and compared between the two groups with the two-tailed Student t test. A p-value < 0.05 was considered statistically significant. Sensitivity and specificity were compared between the qualitative and quantitative studies. The iodine density, lesion-to-muscle ratio, and lesion-to-artery ratio of the iodine density measurement for malignant vertebral tumours were significantly different from the respective values for non-malignancies (all p < 0.05). Using 0.52 as the threshold value for the lesion-to-artery iodine density ratio, one could obtain sensitivity of 85 % and specificity of 100 % for differentiating malignant vertebral tumours from non-malignancies, significantly higher than the qualitative diagnosis. DESCT imaging enables analysis of a number of additional quantitative CT parameters to improve the accuracy for differentiating malignant vertebral tumours from non-malignancies during venous phase. (orig.)

  4. Palliative management of malignant bowel obstruction in terminally Ill patient

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    Darshit A Thaker

    2010-01-01

    Full Text Available Mr. P was a 57-year-old man who presented with symptoms of bowel obstruction in the setting of a known metastatic pancreatic cancer. Diagnosis of malignant bowel obstruction was made clinically and radiologically and he was treated conservatively (non-operativelywith octreotide, metoclopromide and dexamethasone, which provided good control over symptoms and allowed him to have quality time with family until he died few weeks later with liver failure. Bowel obstruction in patients with abdominal malignancy requires careful assessment. The patient and family should always be involved in decision making. The ultimate goals of palliative care (symptom management, quality of life and dignity of death should never be forgotten during decision making for any patient.

  5. Is the adult Sertoli cell terminally differentiated?

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    Tarulli, Gerard A; Stanton, Peter G; Meachem, Sarah J

    2012-07-01

    New data have challenged the convention that the adult Sertoli cell population is fixed and unmodifiable. The Sertoli cell has two distinct functions: 1) formation of the seminiferous cords and 2) provision of nutritional and structural support to developing germ cells. For these to occur successfully, Sertoli cells must undergo many maturational changes between fetal and adult life, the main switches occurring around puberty, including the loss of proliferative activity and the formation of the blood-testis barrier. Follicle-stimulating hormone plays a key role in promoting Sertoli cell proliferation, while thyroid hormone inhibits proliferative activity in early postnatal life. Together these regulate the Sertoli-germ cell complement and sperm output in adulthood. By puberty, the Sertoli cell population is considered to be stable and unmodifiable by hormones. But there is mounting evidence that the size of the adult Sertoli cell population and its maturational status is modifiable by hormones and that Sertoli cells can gain proliferative ability in the spermatogenically disrupted hamster and human model. This new information demonstrates that the adult Sertoli cell population, at least in the settings of testicular regression in the hamster and impaired fertility in humans in vivo and from mice and men in vitro, is not a terminally differentiated population. Data from the hamster now show that the adult Sertoli cell population size is regulated by hormones. This creates exciting prospects for basic and clinical research in testis biology. The potential to replenish an adult Sertoli-germ cell complement to normal in a setting of infertility may now be realized.

  6. Ensemble approach for differentiation of malignant melanoma

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    Rastgoo, Mojdeh; Morel, Olivier; Marzani, Franck; Garcia, Rafael

    2015-04-01

    Melanoma is the deadliest type of skin cancer, yet it is the most treatable kind depending on its early diagnosis. The early prognosis of melanoma is a challenging task for both clinicians and dermatologists. Due to the importance of early diagnosis and in order to assist the dermatologists, we propose an automated framework based on ensemble learning methods and dermoscopy images to differentiate melanoma from dysplastic and benign lesions. The evaluation of our framework on the recent and public dermoscopy benchmark (PH2 dataset) indicates the potential of proposed method. Our evaluation, using only global features, revealed that ensembles such as random forest perform better than single learner. Using random forest ensemble and combination of color and texture features, our framework achieved the highest sensitivity of 94% and specificity of 92%.

  7. COMPUTATION MODELING OF TCDD DISRUPTION OF B CELL TERMINAL DIFFERENTIATION

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    In this study, we established a computational model describing the molecular circuit underlying B cell terminal differentiation and how TCDD may affect this process by impinging upon various molecular targets.

  8. Perfusion MR imaging for differentiation of benign and malignant meningiomas

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    Zhang, Hao [University of Groningen, Department of Radiology, University Medical Center Groningen, Groningen (Netherlands); Shanghai Jiaotong University, Department of Radiology, First People' s Hospital, Shanghai (China); Roediger, Lars A.; Oudkerk, Matthijs [University of Groningen, Department of Radiology, University Medical Center Groningen, Groningen (Netherlands); Shen, Tianzhen [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Miao, Jingtao [Shanghai Jiaotong University, Department of Radiology, First People' s Hospital, Shanghai (China)

    2008-06-15

    Our purpose was to determine whether perfusion MR imaging can be used to differentiate benign and malignant meningiomas on the basis of the differences in perfusion of tumor parenchyma and/or peritumoral edema. A total of 33 patients with preoperative meningiomas (25 benign and 8 malignant) underwent conventional and dynamic susceptibility contrast perfusion MR imaging. Maximal relative cerebral blood volume (rCBV) and the corresponding relative mean time to enhance (rMTE) (relative to the contralateral normal white matter) in both tumor parenchyma and peritumoral edema were measured. The independent samples t-test was used to determine whether there was a statistically significant difference in the mean rCBV and rMTE ratios between benign and malignant meningiomas. The mean maximal rCBV values of benign and malignant meningiomas were 7.16{+-}4.08 (mean{+-}SD) and 5.89{+-}3.86, respectively, in the parenchyma, and 1.05{+-}0.96 and 3.82{+-}1.39, respectively, in the peritumoral edema. The mean rMTE values were 1.16{+-}0.24 and 1.30{+-}0.32, respectively, in the parenchyma, and 0.91{+-}0.25 and 1.24{+-}0.35, respectively, in the peritumoral edema. The differences in rCBV and rMTE values between benign and malignant meningiomas were not statistically significant (P>0.05) in the parenchyma, but both were statistically significant (P<0.05) in the peritumoral edema. Perfusion MR imaging can provide useful information on meningioma vascularity which is not available from conventional MRI. Measurement of maximal rCBV and corresponding rMTE values in the peritumoral edema is useful in the preoperative differentiation between benign and malignant meningiomas. (orig.)

  9. Terminal Cancer: Malignant Spinal Cord Compression and Full Code Status

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    Yaseen Ali

    2014-09-01

    Full Text Available Background: Malignant spinal cord compression has significantly increased hospitalization costs and even with best approach in treatment the disease course remains relatively stable with dire outcomes. Case presentation: The patient was an 80 years old male with the past medical history of hypertension, stroke with chronic right sided weakness, recently diagnosed with non-squamous cell lung carcinoma stage T4N0Mx presently undergoing chemotherapy as outpatient with carboplatin and taxol presented to the emergency room with the chief complaint of right leg pain with weakness and chest pain for 1~2 days. On d 4 of the admission patient complained of chest pain again and a CT angiogram was ordered as part of the work up for chest pain based on high probability for a pulmonary embolus per “Wells Score”. The CT angiogram revealed a large soft tissue mass centered at T5 vertebral body and probable spinal canal invasion. Conclusion: A more favorable outcome requires the input of both a surgeon and a radiation oncologist to find the most effective approach depending on the area involved and the extent of the lesion, and patient’s choice of treatment always must be respected as well. Despite aggressive treatment patient did not respond well and was deteriorating. Options were discussed with the patient, including the futility of care and lack of response. Patient opted to return home with hospice care and was subsequently discharged home with family.

  10. Differential diagnosis of cervical malignant lymphadenopathy among Iranian patients.

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    Naeimi, Mohammad; Sharifi, Amin; Erfanian, Youssef; Velayati, Arash; Izadian, Shahla; Golparvar, Sadegh

    2009-03-01

    To investigate the differential diagnosis in cases referred with neck lumps suspicious to malignant nodal masses and its relation to demographic variants. Individuals who entered in this cross-sectional study conducted at the Department of Otolaryngology, Ghaem Medical Center, Mashdad, Iran from May 1995 to April 2005 were re-evaluated by history taking, physical examination and imaging studies. Fine needle aspiration was applied to obtain tissue sampling. Among the patients, 232 cases had malignant disease confirmed by pathology reports. Cases with unknown primary tumor underwent investigations including pan-endoscopy, and further imaging studies were carried out to determine the primary tumor site. Demographic data as gender, age, location, size, and pathology of tumor were considered. The results of this study showed that 50% of patients which were referred with neck masses had malignant neoplasm. The most common pathology in patients younger than 40 years were lymphoma (55%) and thyroid cancer (26%), whereas, in patients older than 40 years squamous cell carcinoma (67%) was more common. The most involved lymph nodes were jugulodigastric chain. Larynx and hypopharynx are the most common sources of aerodigestive tract metastatic. According to high incidence malignancy (50%) among neck lesions, an asymmetrical neck mass in adults should be considered malignant until proven otherwise. It seems that age is an important predictor of tumor pathology, and determination of further diagnostic investigations would be helpful.

  11. Malignant Phyllodes Tumor with Chondrosarcomatous Differentiation: Radiological-Pathological Correlation

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    Kathyayini Paidipati Gopalkishna Murthy

    2014-01-01

    Full Text Available We present a case of a 63-year-old woman with malignant phyllodes tumor in her left breast. On imaging, a large, dumbbell-shaped, predominantly cystic mass with thin peripheral enhancement was noted. The lesion was causing rib destruction, chest wall invasion, and intrathoracic extension. These aggressive imaging features were considered highly suspicious of a malignant chest wall tumor. Subsequent chest wall resection of the tumor showed breast tissue with a biphasic lesion composed of proliferated spindle cells in loose sheets with extensive islands of atypical cartilage and a scanty epithelial component, including compressed ducts in the periphery of the lesion. A diagnosis of a malignant phyllodes tumor with stromal overgrowth and chondrosarcomatous differentiation was made in view of the presence of a benign epithelial component and negative reaction of the stromal component with a pancytokeratin. To the best of our knowledge, a phyllodes tumor with the radiological features of chest wall invasion and intrathoracic extension has not been described in the literature until now. Malignant phyllodes should be included in the list of differentials along with sarcomas on encountering lesions with such aggressive imaging features.

  12. Differential diagnosis of malignant ovarian tumors on CT findings

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    Kim, Young Chae; Yoon, Myung Hwan; Yang, Dal Mo; Chung, Hyo Sun; Kim, Hyung Sik; Song, Ik Hyun; Chung, Yoon Ho; Lee, Young Suk [Chungang Gil Hospital, Inchon (Korea, Republic of)

    1996-07-01

    To assess the value of CT for the differential diagnosis of malignant ovarian tumors. We reviewed CT scans of 31 patients with surgically confirmed 46 malignant ovarian tumors. (29 epithelial tumors, 9 Krukenberg tumors, 6 germ cell tumors, and 2 sex cord-stromal tumors.) CT scans were evaluated for the mass (bilaterality, size, internal component, and margin), peritoneal spread pattern, ascites, invasion of adjacent organ, and lymphadenopathy. Bilateral masses were seen in epithelial or Krukenberg tumor in 61.1%(11/18) and 80%(4/5) respectively. Epithelial tumors showed predominantly cystic mass(37.9%, 11/29), irregular margin(82.8%, 24/29) of mass, and accompanying peritoneal and omental spread (66.7%, 12/18), while Krukenberg tumor showed predominantly solid mass(55.5%, 5/9), smooth margin of mass(100%, 5/5), and no peritoneal and omental spread. All cases with germ cell tumor or sex cord-stromal tumor showed unilateral mass. Relatively young aged, unilateral solid (66.7%, 4/6) tumors were germ cell tumor. Of these cases, septa within solid portion of mass were prominent in all dysgerminoma. (3/3) CT may be a valuable tool for the differential diagnosis of malignant ovarian tumors.

  13. Coordinated control of terminal differentiation and restriction of cellular plasticity

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    Patel, Tulsi; Hobert, Oliver

    2017-01-01

    The acquisition of a specific cellular identity is usually paralleled by a restriction of cellular plasticity. Whether and how these two processes are coordinated is poorly understood. Transcription factors called terminal selectors activate identity-specific effector genes during neuronal differentiation to define the structural and functional properties of a neuron. To study restriction of plasticity, we ectopically expressed C. elegans CHE-1, a terminal selector of ASE sensory neuron identity. In undifferentiated cells, ectopic expression of CHE-1 results in activation of ASE neuron type-specific effector genes. Once cells differentiate, their plasticity is restricted and ectopic expression of CHE-1 no longer results in activation of ASE effector genes. In striking contrast, removal of the respective terminal selectors of other sensory, inter-, or motor neuron types now enables ectopically expressed CHE-1 to activate its ASE-specific effector genes, indicating that terminal selectors not only activate effector gene batteries but also control the restriction of cellular plasticity. Terminal selectors mediate this restriction at least partially by organizing chromatin. The chromatin structure of a CHE-1 target locus is less compact in neurons that lack their resident terminal selector and genetic epistasis studies with H3K9 methyltransferases suggest that this chromatin modification acts downstream of a terminal selector to restrict plasticity. Taken together, terminal selectors activate identity-specific genes and make non-identity-defining genes less accessible, thereby serving as a checkpoint to coordinate identity specification with restriction of cellular plasticity. DOI: http://dx.doi.org/10.7554/eLife.24100.001 PMID:28422646

  14. Cpeb4-mediated translational regulatory circuitry controls terminal erythroid differentiation.

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    Hu, Wenqian; Yuan, Bingbing; Lodish, Harvey F

    2014-09-29

    While we have considerable understanding of the transcriptional networks controlling mammalian cell differentiation, our knowledge of posttranscriptional regulatory events is very limited. Using differentiation of primary erythroid cells as a model, we show that the sequence-specific mRNA-binding protein Cpeb4 is strongly induced by the erythroid-important transcription factors Gata1 and Tal1 and is essential for terminal erythropoiesis. By interacting with the translation initiation factor eIF3, Cpeb4 represses the translation of a large set of mRNAs, including its own mRNA. Thus, transcriptional induction and translational repression combine to form a negative feedback loop to control Cpeb4 protein levels within a specific range that is required for terminal erythropoiesis. Our study provides an example of how translational control is integrated with transcriptional regulation to precisely control gene expression during mammalian cell differentiation. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Epigenetic heterochromatin markers distinguish terminally differentiated leukocytes from incompletely differentiated leukemia cells in human blood

    Czech Academy of Sciences Publication Activity Database

    Popova, Evgenya Y.; Claxton, David F.; Lukášová, Emilie; Bird, Philip I.; Grigoryev, Sergei A.

    2006-01-01

    Roč. 34, č. 4 (2006), s. 453-462 ISSN 0301-472X R&D Projects: GA AV ČR(CZ) 1QS500040508 Institutional research plan: CEZ:AV0Z50040507 Keywords : terminal cell differentiation * chromatin structure * chronic myeloid leukemia Subject RIV: BO - Biophysics Impact factor: 3.408, year: 2006

  16. Can magnetic resonance spectroscopy differentiate malignant and benign causes of lymphadenopathy? An in-vitro approach

    National Research Council Canada - National Science Library

    Lionel Buré; Louis-Martin Boucher; Miriam Blumenkrantz; Stefan Schob; Pierre Lafaye de Micheaux; Caroline Reinhold; Benoit Gallix

    2017-01-01

    .... The goal of our research was to assess whether magnetic resonance (MR) spectroscopy contains the necessary information to allow differentiation of benign from malignant lymph nodes in an in-vitro approach using a modern pattern recognition method...

  17. Mechanisms of dealing with DNA damage in terminally differentiated cells

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    Fortini, P. [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy); Dogliotti, E., E-mail: eugenia.dogliotti@iss.it [Department of Environment and Primary Prevention, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome (Italy)

    2010-03-01

    To protect genomic integrity living cells that are continuously exposed to DNA-damaging insults are equipped with an efficient defence mechanism termed the DNA damage response. Its function is to eliminate DNA damage through DNA repair and to remove damaged cells by apoptosis. The DNA damage response has been investigated mainly in proliferating cells, in which the cell cycle machinery is integrated with the DNA damage signalling. The current knowledge of the mechanisms of DNA repair, DNA damage signalling and cell death of post-mitotic cells that have undergone irreversible cell cycle withdrawal will be reviewed. Evidence will be provided that the protection of the genome integrity in terminally differentiated cells is achieved by different strategies than in proliferating cells.

  18. Can magnetic resonance spectroscopy differentiate malignant and benign causes of lymphadenopathy? An in-vitro approach.

    Science.gov (United States)

    Buré, Lionel; Boucher, Louis-Martin; Blumenkrantz, Miriam; Schob, Stefan; Lafaye de Micheaux, Pierre; Reinhold, Caroline; Gallix, Benoit

    2017-01-01

    Lymphadenopathy continues to be a common problem to radiologists and treating physicians because of the difficulty in confidently categorizing a node as being benign or malignant using standard diagnostic techniques. The goal of our research was to assess whether magnetic resonance (MR) spectroscopy contains the necessary information to allow differentiation of benign from malignant lymph nodes in an in-vitro approach using a modern pattern recognition method. Tissue samples from a tissue bank were analyzed on a nuclear magnetic resonance (NMR) spectrometer. A total of 69 samples were studied. The samples included a wide variety of malignant and benign etiologies. Using 45 samples, we initially created a model which was able to predict if a certain spectrum originates from benign or malignant lymph nodes using a pattern-recognition technique which takes into account the entire magnetic spectrum rather than single peaks alone. The remaining 24 samples were blindly loaded in the model to assess its performance. We obtained an excellent accuracy in differentiating benign and malignant lymphadenopathy using the model. It correctly differentiated as malignant or benign, in a blinded fashion, all of the malignant samples (13 of 13) and 10 out of the 11 benign samples. We thus showed that magnetic spectroscopy is able to differentiate benign from malignant causes of lymphadenopathy. Additional experiments were performed to verify that the differentiating abilities of our model were not due to differential tissue decay in between benign and malignant tissues. If future experiments demonstrate that a similar approach could be executed with standard MR imaging, this technique could be useful as a problem-solving tool when assessing lymphadenopathy in general. Alternatively, our in-vitro technique could also be useful to pathologists faced with indeterminate pathologies of the lymph nodes after validating our results with a larger sample size.

  19. Differentiation of malignant melanoma from benign nevus using a novel genomic microarray with low specimen requirements.

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    Chandler, Wells M; Rowe, Leslie R; Florell, Scott R; Jahromi, Mona S; Schiffman, Joshua D; South, Sarah T

    2012-08-01

    Histologic examination of clinically suspicious melanocytic lesions is very sensitive and specific for the detection of malignant melanoma. Yet, the malignant potential of a small percentage of melanocytic lesions remains histologically uncertain. Molecular testing offers the potential to detect the genetic alterations that lead to malignant behavior without overt histologic evidence of malignancy. To differentiate benign melanocytic nevi from malignant melanoma and to predict the clinical course of melanocytic lesions with ambiguous histology using a novel genomic microarray. We applied a newly developed single-nucleotide polymorphism genomic microarray to formalin-fixed, paraffin-embedded melanocytic lesions to differentiate benign nevi (n  =  23) from malignant melanoma (n  =  30) and to predict the clinical course of a set of histologically ambiguous melanocytic lesions (n  =  11). For cases with unambiguous histology, there was excellent sensitivity and specificity for identifying malignant melanoma with this genomic microarray (89% sensitivity, 100% specificity). For cases with ambiguous histology, the performance of this genomic microarray was less impressive. Without microdissection and with quantities of DNA one-tenth what is required for more commonly used microarrays, this microarray can differentiate between malignant melanoma and benign melanocytic nevi. For histologically ambiguous lesions, longer clinical follow-up is needed to confidently determine the sensitivity and specificity of this microarray. Some of the previous technical hurdles to the clinical application of genomic microarray technology are being overcome, and the advantages over targeted fluorescence in situ hybridization assays currently in clinical use are becoming apparent.

  20. A Case of Malignant Peripheral Nerve Sheath Tumor with Rhabdomyoblastic Differentiation: Malignant Triton Tumor

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    Kenichiro Mae

    2013-12-01

    Full Text Available Malignant peripheral nerve sheath tumors (MPNST constitute a rare variety of soft tissue sarcomas thought to originate from Schwann cells or pluripotent cells of the neural crest. Malignant triton tumor (MTT, a very rare, highly aggressive soft tissue tumor, is a subgroup of MPNST and is comprised of malignant Schwann cells coexisting with malignant rhabdomyoblasts. We herein report the case of a 24-year-old man who presented a subcutaneous mass in his right thigh. The mass was removed surgically in its entirety and radiation therapy was applied locally to prevent tumor regrowth. Nonetheless, the patient died 10 months after surgery from metastases to the lung and brain. He presented neither cafe-au-lait spots nor cutaneous neurofibromas. The histopathology showed a transition from a neurofibroma to an MTT, making this the second report of an MTT arising from a neurofibroma without neurofibromatosis type 1, an autosomal dominant disorder with which 50-70% of tumors reported in previous studies were associated. A histopathological examination using immunostaining with desmin confirmed this diagnosis. MTT has a poorer prognosis than MPNST and should therefore be regarded as a distinct clinical entity.

  1. [Regression in malignant melanoma. Definition, etiopathogenesis, morphology and differential diagnosis].

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    Paredes, B E

    2007-11-01

    Malignant melanoma is a neoplasm that more often tends to undergo regression. Clinically, variation in color is perhaps the most important hallmark of primary cutaneous melanoma. The change in color to white, off-white, blue-white and gray-white is a sign of (spontaneous) regression in malignant melanoma. Histopathologically the process starts with a dense lichenoid infiltrate of lymphocytes, and ends with fibrosis and/or melanosis within a thickened papillary dermis. The dense infiltrate of lymphocytes permeates the thin melanoma and destroys the atypical melanocytes in the epidermis and the papillary dermis. A key concern is how to define regression in a reproducible way. Using the following definition, a statistically significant risk of metastases can be demonstrated in thin melanomas (50%): "fibroplasia with an absence of epidermal and dermal involvement by melanoma cells, but allowing for (lentiginous) single-cell proliferation of atypical melanocytes along the dermo-epidermal junction".

  2. The efficacy of apparent diffusion coefficient value calculation in differentiation between malignant and benign thyroid nodules.

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    Dilli, Alper; Ayaz, Umit Yasar; Cakir, Evrim; Cakal, Erman; Gultekin, Salih Sinan; Hekimoglu, Baki

    2012-01-01

    To evaluate the efficacy of apparent diffusion coefficient (ADC) calculation in differentiation between malignant and benign thyroid nodules. A prospective study was conducted in 52 patients. Diffusion-weighted echoplanar imaging was performed and b factors were taken as 0 and 400 s/mm(2). The mean ADC value for malignant thyroid nodules was 0.829±0.179×10(-3) mm(2)/s and that for benign thyroid nodules was 1.984±0.482×10(-3) mm(2)/s. The mean ADC value for malignant nodules was significantly lower than that for benign nodules (P=.0001). ADC value calculation is an effective method in differentiation of malignant thyroid nodules from benign ones. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Direct lineage conversion of terminally differentiated hepatocytes to functional neurons.

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    Marro, Samuele; Pang, Zhiping P; Yang, Nan; Tsai, Miao-Chih; Qu, Kun; Chang, Howard Y; Südhof, Thomas C; Wernig, Marius

    2011-10-04

    Several recent studies have showed that mouse and human fibroblasts can be directly reprogrammed into induced neuronal (iN) cells, bypassing a pluripotent intermediate state. However, fibroblasts represent heterogeneous mesenchymal progenitor cells that potentially contain neural crest lineages, and the cell of origin remained undefined. This raises the fundamental question of whether lineage reprogramming is possible between cell types derived from different germ layers. Here, we demonstrate that terminally differentiated hepatocytes can be directly converted into functional iN cells. Importantly, single-cell and genome-wide expression analyses showed that fibroblast- and hepatocyte-derived iN cells not only induced a neuronal transcriptional program, but also silenced their donor transcriptome. The remaining donor signature decreased over time and could not support functional hepatocyte properties. Thus, the reprogramming factors lead to a binary lineage switch decision rather than an induction of hybrid phenotypes, but iN cells retain a small but detectable epigenetic memory of their donor cells. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. The usefulness of endoscopic ultrasonography in differentiation between benign and malignant gastric ulcer

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    Roganović Branka

    2016-01-01

    Full Text Available Background/Aim. Gastric ulcer may be benign or malignant. In terms of therapy and patient’s prognosis early detection of malignancy is very important. The aim of this study was to assess the usefulness of endoscopic ultrasound (EUS in differentiation between benign and malignant gastric ulcer. Methods. A prospective study included 20 consecutive adult patients with malignant gastric ulceration and 20 consecutive adult patients with benign gastric ulceration. All the patients underwent EUS. A total of 6 parameters were analyzed: ulcer width, ulcer depth, the thickness of the gastric wall along the edge of ulceration (T0, the thickness of the gastric wall 2 cm from the edge of ulceration (T2, loss of layering structure of the gastric wall, and the presence of regional lymph nodes. EUS criteria for malignancy and a point-score of malignancy were defined. The critical value of total point-score was also calculated showing the best reliability parameters. Results. There are 4 criteria for malignancy of gastric ulceration: T0 > 10 mm, T2 > 5 mm, EUS visualization of at least one lymph node, loss of layering structure of the gastric wall. Furthermore, T2 > 5 mm was the only EUS independent predictor of ulcer malignancy. The total point score of ≥ 4 was the cut-off pointscore value which gave the best reliability parameters in the assessment of malignant ulcers: sensitivity of 70%, specificity of 95%, positive predictive value of 93.3%, negative predictive value of 76% and accuracy of 82.5%. Conclusion. According to the results obtained in this study, we can conclude that EUS is usefull in differentiation between benign and malignant gastric ulcer.

  5. Role of strain elastography in differentiating malignant hypoechoic splenic lesions in dogs: Preliminary results

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    G. Barella

    2017-09-01

    Full Text Available This study aims to assess the repeatability and reproducibility of strain elastography in the evaluation of splenic nodules and to verify if it can differentiate benign from malignant splenic lesions in dogs. Twenty-four dogs with a single splenic hypoechoic lesion, underwent strain elastosonography. The strain ratio (SR and hardness value (HV were calculated. Repeatability and reproducibility were assessed by the coefficient of variability (CV and the K of Cohen respectively. ANOVA and Fisher exact test verified the differences between the SR values and HV of benign versus malignant lesions. The odds ratio was also calculated. The SR and HV of benign lesions were different from those of malignant lesions (P<0.05. Malignant lesions tended to have a SR≥1.5 (P=0.0003 and an HV ≥ 70% (P=0.001. The correlation between SR≥1.5 and malignancy was significant (OR, 80.6; P=0.0067 as the one between HV ≥ 70% and malignancy (OR, 47.22; P=0.013. This technique was repeatable and reproducible (CV 0.08±0.03 and K=1 for the SR; CV 0.08±0.05 and K=0.66 for the HV. Elastosonography can differentiate malignant from benign canine hypoechoic splenic lesions

  6. Malignant phyllodes tumor of the breast with liposarcomatous differentiation and intraductal hyperplasia.

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    Ayadi-Kaddour, Aïda; Zeddini, Abdelfatteh; Braham, Emna; Ismail, Olfa; Mlika, Mona; Guelmami, Karim; El Mezni, Faouzi

    2015-01-01

    Phyllodes tumor of the breast is a biphasic fibroepithelial neoplasm. 10 to 20% of phyllodes tumor show malignant transformation, often in the form of stroma, which usually shows fibrosarcomatous differentiation and rarely heterologous sarcomatous elements. Liposarcomatous differentiation is not common among phyllodes tumors. The correct diagnosis of heterologous liposarcomatous differentiation in a malignant PT requires identification of the biphasic component of the tumor. We reported a case of malignant phyllodes tumor which initially transformed into liposarcoma, in addition to a very rare intraductal hyperplasia and flat epithelial atypia. The patient was a 75-year-old woman, with a lump in the left breast without axillary lymphadenopathy. She also have a positive family history of breast carcinoma. She underwent surgery and still alive and disease free after one year.

  7. Functional Characterization of C-terminal Ryanodine Receptor 1 Variants Associated with Central Core Disease or Malignant Hyperthermia.

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    Parker, Remai; Schiemann, Anja H; Langton, Elaine; Bulger, Terasa; Pollock, Neil; Bjorksten, Andrew; Gillies, Robyn; Hutchinson, David; Roxburgh, Richard; Stowell, Kathryn M

    2017-01-01

    Central core disease and malignant hyperthermia are human disorders of skeletal muscle resulting from aberrant Ca2+ handling. Most malignant hyperthermia and central core disease cases are associated with amino acid changes in the type 1 ryanodine receptor (RyR1), the skeletal muscle Ca2+-release channel. Malignant hyperthermia exhibits a gain-of-function phenotype, and central core disease results from loss of channel function. For a variant to be classified as pathogenic, functional studies must demonstrate a correlation with the pathophysiology of malignant hyperthermia or central core disease. We assessed the pathogenicity of four C-terminal variants of the ryanodine receptor using functional analysis. The variants were identified in families affected by either malignant hyperthermia or central core disease. Four variants were introduced separately into human cDNA encoding the skeletal muscle ryanodine receptor. Following transient expression in HEK-293T cells, functional studies were carried out using calcium release assays in response to an agonist. Two previously characterized variants and wild-type skeletal muscle ryanodine receptor were used as controls. The p.Met4640Ile variant associated with central core disease showed no difference in calcium release compared to wild-type. The p.Val4849Ile variant associated with malignant hyperthermia was more sensitive to agonist than wild-type but did not reach statistical significance and two variants (p.Phe4857Ser and p.Asp4918Asn) associated with central core disease were completely inactive. The p.Val4849Ile variant should be considered a risk factor for malignant hyperthermia, while the p.Phe4857Ser and p.Asp4918Asn variants should be classified as pathogenic for central core disease.

  8. Computer tomographic differential diagnosis of benign and malignant lipoid masses in the mediastinum and their spread

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    Sinner, W.N.

    1980-06-01

    Details of the tissues in the mediastinum can nowadays be demonstrated by computer tomography (CT) pictorially and quantitative measurements of their density coefficient carried out. The diagnosis of a fat-containing tumour or of benign lipomatosis of the mediastinum and their differentiation from malignant lesions is important for treatment and prognosis. In the past this could only be done by surgery. CT permits this differentiation pre-operatively and by a non-invasive method. The extent of malignant tumours and their relationship to other mediastinal structures and their spread beyond the mediastinum can be determined.

  9. DNA replication is intrinsically hindered in terminally differentiated myotubes.

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    Deborah Pajalunga

    2010-07-01

    Full Text Available Terminally differentiated (TD cells permanently exit the mitotic cycle while acquiring specialized characteristics. Although TD cells can be forced to reenter the cell cycle by different means, they cannot be made to stably proliferate, as attempts to induce their replication constantly result in cell death or indefinite growth arrest. There is currently no biological explanation for this failure.Here we show that TD mouse myotubes, reactivated by depletion of the p21 and p27 cell cycle inhibitors, are unable to complete DNA replication and sustain heavy DNA damage, which triggers apoptosis or results in mitotic catastrophe. In striking contrast, quiescent, non-TD fibroblasts and myoblasts, reactivated in the same way, fully replicate their DNA, do not suffer DNA damage, and proliferate even in the absence of growth factors. Similar results are obtained when myotubes and fibroblasts are reactivated by forced expression of E1A or cyclin D1 and cdk4.We conclude that the inability of myotubes to complete DNA replication must be ascribed to peculiar features inherent in their TD state, rather than to the reactivation method. On reviewing the literature concerning reactivation of other TD cell types, we propose that similar mechanisms underlie the general inability of all kinds of TD cells to proliferate in response to otherwise mitogenic stimuli. These results define an unexpected basis for the well known incompetence of mammalian postmitotic cells to proliferate. Furthermore, this trait might contribute to explain the inability of these cells to play a role in tissue repair, unlike their counterparts in extensively regenerating species.

  10. Rhabdomyoblastic Differentiation in Head and Neck Malignancies Other Than Rhabdomyosarcoma

    NARCIS (Netherlands)

    Bishop, J.A.; Thompson, L.D.; Cardesa, A.; Barnes, L.; Lewis, J.S., Jr.; Triantafyllou, A.; Hellquist, H.; Stenman, G.; Hunt, J.L.; Williams, M.D.; Slootweg, P.J.; Devaney, K.O.; Gnepp, D.R.; Wenig, B.M.; Rinaldo, A.; Ferlito, A.

    2015-01-01

    Rhabdomyosarcoma is a relatively common soft tissue sarcoma that frequently affects children and adolescents and may involve the head and neck. Rhabdomyosarcoma is defined by skeletal muscle differentiation which can be suggested by routine histology and confirmed by immunohistochemistry for the

  11. MR diffusion imaging in mediastinal masses the differentiation between benign and malignant lesions

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    Youssriah Yahia Sabri

    2017-09-01

    Full Text Available Background: Diffusion-weighted imaging is a fundamental tool integrated in MR protocols useful in differentiating benign from malignant mediastinal masses, assessing mediastinal lymphadenopathy and investigating central bronchogenic carcinoma. This method is an excellent alternative to CT or PET/CT in the investigation of mediastinal masses. Current applications of diffusion MRI in malignancies include monitoring the treatment response and detecting recurrent cancer. Aim of the work: This study aims to assess the value of using MRI diffusion in differentiating benign and malignant mediastinal masses, differentiating central masses from post obstructive collapse and differentiating lymphoma versus sarcoidosis. Patients and methods: This study included 30 patients; 16 males and 14 females in the period from June 2013 to July 2014. The mean age was 49.3 ± 16.85 (range: 22–82 years.Cases were referred for MRI assessment and were approved by the ethical committee in our department.The complaints varied between dyspnea, chest pain, cough, hemoptysis, fatigue and loss of weight. A superconducting 1.5 T MRI machine with a four-channel body phased-array coil was used for the examination. Biopsy and histopathological assessment was done after that. Results: MRI examination with diffusion imaging was able to differentiate between benign and malignant mediastinal and hilar lesion confirmed by the biopsy and histopathology. Conclusion: MRI with diffusion weighted images can detect and stage lung cancer, differentiate benign from malignant mediastinal masses and differentiate lymphoma from sarcoidosis in mediastinal/hilar lymphadenopathy. Keywords: Magnetic resonance imaging, Diffusion, Sarcoidosis, Lymphoma, Bronchogenic carcinoma

  12. The effect of dexamethasone and triiodothyronine on terminal differentiation of primary bovine chondrocytes and chondrogenically differentiated mesenchymal stem cells.

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    Thomas M Randau

    Full Text Available The newly evolved field of regenerative medicine is offering solutions in the treatment of bone or cartilage loss and deficiency. Mesenchymal stem cells, as well as articular chondrocytes, are potential cells for the generation of bone or cartilage. The natural mechanism of bone formation is that of endochondral ossification, regulated, among other factors, through the hormones dexamethasone and triiodothyronine. We investigated the effects of these hormones on articular chondrocytes and chondrogenically differentiated mesenchymal stem cells, hypothesizing that these hormones would induce terminal differentiation, with chondrocytes and differentiated stem cells being similar in their response. Using a 3D-alginate cell culture model, bovine chondrocytes and chondrogenically differentiated stem cells were cultured in presence of triiodothyronine or dexamethasone, and cell proliferation and extracellular matrix production were investigated. Collagen mRNA expression was measured by real-time PCR. Col X mRNA and alkaline phosphatase were monitored as markers of terminal differentiation, a prerequisite of endochondral ossification. The alginate culture system worked well, both for the culture of chondrocytes and for the chondrogenic differentiation of mesenchymal stem cells. Dexamethasone led to an increase in glycosaminoglycan production. Triiodothyronine increased the total collagen production only in chondrocytes, where it also induced signs of terminal differentiation, increasing both collagen X mRNA and alkaline phosphatase activity. Dexamethasone induced terminal differentiation in the differentiated stem cells. The immature articular chondrocytes used in this study seem to be able to undergo terminal differentiation, pointing to their possible role in the onset of degenerative osteoarthritis, as well as their potential for a cell source in bone tissue engineering. When chondrocyte-like cells, after their differentiation, can indeed be moved on

  13. Imetelstat, a telomerase inhibitor, differentially affects normal and malignant megakaryopoiesis.

    Science.gov (United States)

    Mosoyan, G; Kraus, T; Ye, F; Eng, K; Crispino, J D; Hoffman, R; Iancu-Rubin, C

    2017-11-01

    Imetelstat (GRN163L) is a specific telomerase inhibitor that has demonstrated clinical activity in patients with myeloproliferative neoplasms (MPN) and in patients with solid tumors. The antitumor effects were associated with the development of thrombocytopenia, one of the common side effects observed in patients treated with imetelstat. The events underlying these adverse effects are not apparent. In this report, we investigated the potential mechanisms that account for imetelstat's beneficial effects in MPN patients and the manner by which imetelstat treatment leads to a reduction in platelet numbers. Using a well-established system of ex vivo megakaryopoiesis, we demonstrated that imetelestat treatment affects normal megakaryocyte (MK) development by exclusively delaying maturation of MK precursor cells. By contrast, additional stages along MPN MK development were affected by imetelstat resulting in reduced numbers of assayable colony-forming unit MK and impaired MK maturation. In addition, treatment with imetelstat inhibited the secretion of fibrogenic growth factors by malignant but not by normal MK. Our results indicate that the delay observed in normal MK maturation may account for imetelstat-induced thrombocytopenia, while the more global effects of imetelstat on several stages along the hierarchy of MPN megakaryopoiesis may be responsible for the favorable clinical outcomes reported in MPN patients.

  14. Renal Adenomas: Pathological Differential Diagnosis with Malignant Tumors

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    F. Algaba

    2008-01-01

    Full Text Available The renal adenomas can be confused by imaging diagnosis with malignant renal tumors, but there are also real biological dilemmas to determine their behavior. The consensus decisions are the following. (1 The adenoma of clear cells is not accepted, instead it is considered that all the clear-cell tumors are carcinomas, with greater or lesser aggressiveness. (2 Among the papillary neoplasms the WHO 2004 renal cell tumors classification are considered as papillary adenomas tumors with a maximum diameter of 5 mm and may represent a continuum biological process to papillary renal cell carcinoma. The papillary adenomas associated with End-kidney and/or acquired cystic disease may have a different pathogenesis. (3 To consider a tumor as an oncocytoma the size is not important, only the cytological features, microscopic, ultrastructural, and immunohistochemically can help, but some chromosomal observations introduce some questions about its relation with the chromophobe renal cell carcinoma. (4 Finally, the metanephric adenoma, a tumor with some morphological similarity with the nephroblastoma must be considered in the renal adenomas diagnosis.

  15. Role of Duplex Power Doppler Ultrasound in Differentiation between Malignant and Benign Thyroid Nodules

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    Algin, Oktay [Ataturk Training and Research Hospital Bilkent, Ankara (Turkmenistan); Algin, Efnan [Gazi University Medical Faculty, Ankara (Turkmenistan); Gokalp, Gokhan; Ocakog, Gokhan; Erdog an, Cuneyt; Saraydaroglu, Ozlem; Ercan Tuncel, Prof [Uludag University Medical Faculty, Bursa (Turkmenistan)

    2010-12-15

    To evaluate the usage of duplex power Doppler ultrasound (PDUS) for the differentiation of benign and malignant thyroid nodules. We prospectively examined 77 thyroid nodules in 60 patients undergoing ultrasound-guided fine needle aspiration biopsy (FNAB). Each nodule was described according to size, inner structure, borders, parenchymal echogenicity, peripheral halo formation, and the presence of calcification (Bmode ultrasound findings). Vascularity as determined by PDUS imaging was defined as non-vascular, peripheral, central, or of mixed type. For each nodule, the pulsatility index (PI) and resistive index (RI) values were obtained. Results of FNAB and surgical pathological examination (if available) were used as a proof of final diagnosis to categorize all nodules as benign or malignant. A receiver operating characteristic (ROC) curve analysis was performed to establish cut-off, sensitivity, and specificity values associated with RI-PI values. A significant relationship was observed between malignancy and irregular margins, microcalcifications, and hypoechogenicity on ultrasound examination (p < 0.05). The pattern of vascularity as determined by PDUS analysis was not a statistically significant criterion to suggest benign or malignant disease in this study (p > 0.05). The central, peripheral, and mean RI-PI values were higher in malignant nodules when compared to the other cytologies (p < 0.05). Vascularity is not a useful parameter for distinguishing malignant from benign thyroid nodules. However, RI and PI values are useful in distinguishing malignant from benign thyroid nodules

  16. Evaluating the reliability of ultrasonographic parameters in differentiating benign from malignant superficial lymphadenopathy

    Directory of Open Access Journals (Sweden)

    Sarir Nazemi

    2016-11-01

    Full Text Available Diagnosis of malignant lymphadenopathy is of particular importance for treatment planning, before treatment staging and also for prognosis determination. Currently various diagnostic procedures are used to differentiate benign and malignant lymphadenopathy which are invasive and costly. Ultrasonography as a noninvasive, low-cost and accessible method is proposed. The aim of this study was to evaluate the reliability of some ultrasonographic parameters in differentiating malignant from benign superficial lymphadenopathies. In this study ultrasonography was performed for lymph nodes of 100 patients who were eligible for pathological evaluation of superficial lymphadenopathy. The most accessible lymph nodes were marked and biopsied. Sonographic and pathologic results were compared. The sensitivity and specificity of the test and the appropriate cutoff point was determined based on the Receiver Operating Characteristics (ROC curve using SPSS Ver.17. From 100 evaluated lymph nodes 55 were benign and 45 were malignant. There was no significant difference between malignant and benign lymph nodes in terms of cortical and medullary thickness (p=0.055,but there was a significant difference between benign and malignant lymph nodes in terms of blood supply pattern and mean of Pulsatility Index (PI (P=.007 and Resistive Index (RI (P<0.001 . The cortex thickness of 7.95 mm with 62.2٪ sensitivity, 72.7٪ specificity and 70٪ accuracy was the appropriate cutoff point in differentiating malignant and benign lymphadenopathy. The color Doppler criteria in combination with gray scale ultrasonography could be helpful to select patients for biopsy or Fine Needle Aspiration (FNA, but cannot fully replace pathological evaluation.

  17. An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi.

    Science.gov (United States)

    Clarke, Loren E; Flake, Darl D; Busam, Klaus; Cockerell, Clay; Helm, Klaus; McNiff, Jennifer; Reed, Jon; Tschen, Jaime; Kim, Jinah; Barnhill, Raymond; Elenitsas, Rosalie; Prieto, Victor G; Nelson, Jonathan; Kimbrell, Hillary; Kolquist, Kathryn A; Brown, Krystal L; Warf, M Bryan; Roa, Benjamin B; Wenstrup, Richard J

    2017-02-15

    Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions. A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis. The gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%. These results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2017;123:617-628. © 2016 American Cancer Society. © 2016 Myriad Genetics, Inc. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  18. Tumor-Associated Macrophages Promote Malignant Progression of Breast Phyllodes Tumors by Inducing Myofibroblast Differentiation.

    Science.gov (United States)

    Nie, Yan; Chen, Jianing; Huang, Di; Yao, Yandan; Chen, Jiewen; Ding, Lin; Zeng, Jiayi; Su, Shicheng; Chao, Xue; Su, Fengxi; Yao, Herui; Hu, Hai; Song, Erwei

    2017-07-01

    Myofibroblast differentiation plays an important role in the malignant progression of phyllodes tumor, a fast-growing neoplasm derived from periductal stromal cells of the breast. Macrophages are frequently found in close proximity with myofibroblasts, but it is uncertain whether they are involved in the myofibroblast differentiation during phyllodes tumor progression. Here we show that increased density of tumor-associated macrophage (TAM) correlates with malignant progression of phyllodes tumor. We found that TAMs stimulated myofibroblast differentiation and promoted the proliferation and invasion of phyllodes tumor cells. Furthermore, we found that levels of the chemokine CCL18 in TAM was an independent prognostic factor of phyllodes tumor. Mechanistic investigations showed that CCL18 promoted expression of α-smooth muscle actin, a hallmark of myofibroblast, along with the proliferation and invasion of phyllodes tumor cells, and that CCL18-driven myofibroblast differentiation was mediated by an NF-κB/miR-21/PTEN/AKT signaling axis. In murine xenograft models of human phyllodes tumor, CCL18 accelerated tumor growth, induced myofibroblast differentiation, and promoted metastasis. Taken together, our findings indicated that TAM drives myofibroblast differentiation and malignant progression of phyllodes tumor through a CCL18-driven signaling cascade amenable to antibody disruption. Cancer Res; 77(13); 3605-18. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Soft tissue masses with myxoid stroma: Can conventional magnetic resonance imaging differentiate benign from malignant tumors?

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    Crombe, A., E-mail: amandine.crombe@ens-lyon.fr [Department of Radiology, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France); Alberti, N. [Department of Radiology, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France); Stoeckle, E. [Department of Surgery, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France); Brouste, V. [Clinical and Epidemiological Research Unit, Institut Bergonié, 33000 Bordeaux (France); Buy, X. [Department of Radiology, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France); Coindre, J-M. [Department of Pathology, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France); Kind, M. [Department of Radiology, Institut Bergonié, 229 cours de l’Argonne, 33076 Bordeaux Cedex (France)

    2016-10-15

    Objectives: To retrospectively evaluate the diagnostic performance of morphological signs observed on conventional magnetic resonance (MR) imaging to differentiate benign from malignant peripheral solid tumors of soft tissue with myxoid stroma. Methods: MR images from 95 consecutive histopathologically proven tumors (26 benign and 69 malignant) of soft tissues with myxoid components were evaluated in our tertiary referral center. Two radiologists, blind to pathology results, independently reviewed conventional MR sequences including at least a) one T2-weighted sequence with or without fat suppression; b) one T1-weighted sequence without fat suppression; and c) one T1-weighted sequence with gadolinium-complex contrast enhancement and fat suppression. Multiple criteria were defined to analyze morphology, margins, architecture and tumor periphery and evaluated for each lesion. Intra- and inter-observer reproducibility and Odds ratios were calculated for each criterion. Results: The most relevant and reproducible criteria to significantly predict malignancy were: (1) ill-defined tumor margins, (2) a hemorrhagic component, (3) intra-tumoral fat, (4) fibrosis and (5) the “tail sign”. A lesion is classified as malignant if any of these 5 criteria is present, and benign if none of them are observed. Therefore, this combination provides a sensitivity of 92.9% and a specificity of 93.3%. Conclusion: Conventional MR imaging provides reproducible criteria that can be combined to differentiate between benign and malignant solid tumors of soft tissue with myxoid stroma.

  20. Differentiation of malignant from benign focal splenic lesions: added value of diffusion-weighted MRI.

    Science.gov (United States)

    Jang, Kyung Mi; Kim, Seong Hyun; Hwang, Jiyoung; Lee, Soon Jin; Kang, Tae Wook; Lee, Min Woo; Choi, Dongil

    2014-10-01

    The objective of our study was to evaluate the added value of diffusion-weighted imaging (DWI) for distinguishing between malignant and benign focal splenic lesions. This study included 53 patients with 11 malignant and 42 benign splenic lesions who underwent gadoxetic acid-enhanced MRI and DWI. Qualitative and quantitative analyses were conducted for splenic lesions. Two blinded observers evaluated the two image sets--that is, the conventional MR images alone versus the combined conventional MR and DW images--and scored their confidence for malignancy of splenic lesions. The Fisher exact test and Mann-Whitney U test were performed, and diagnostic performance values (ROC curve analysis) were evaluated. All malignant lesions showed a progressive hypovascular enhancement pattern, whereas the hypervascular enhancement patterns were shown in only benign lesions (n = 20, 47.6%) (p improvement for predicting malignant splenic lesions (area under ROC curve [Az] without DW images vs with DW images: 0.774 vs 0.983 for observer 1 and 0.742 vs 0.986 for observer 2) (p value, and negative predictive value of combined conventional MR and DW images were higher than those of conventional MR images alone. The addition of DWI to conventional MRI improves differentiation of malignant from benign splenic lesions.

  1. Macrocystic pancreatic lesions: Differentiation of benign from premalignant and malignant cysts by CT

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    Kim, Seong Hyun [Department of Radiology and Center for Imaging Science and Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of)], E-mail: kshyun@skku.edu; Lim, Jae Hoon; Lee, Won Jae; Lim, Hyo K. [Department of Radiology and Center for Imaging Science and Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of)

    2009-07-15

    Objective: To assess useful CT features for differentiating benign from premalignant and malignant macrocystic pancreatic lesions. Methods: Seventy-four patients with pathologically proven macrocystic pancreatic lesions were enrolled: 17 benign cysts (macrocystic serous cystadenoma, n = 12; congenital cyst; n = 5) and 57 premalignant and malignant cysts (mucinous cystic neoplasm, n = 28; intraductal papillary mucinous neoplasm of branch duct type, n = 20; tumor with cystic change, n = 9). Size, location, shape (lobulated, round or oval, or complex cystic with tubular cyst), wall thickness (thin, {<=}1 mm; thick, >1 mm), internal surface (smooth or irregular), and other findings were analyzed with multiphasic CT with thin-section (2.5-3 mm) images. CT features between two groups were compared using univariate and multivariate stepwise logistic regression analyses. Results: On univariate analysis, the differences for the shape (p = 0.007), wall thickness (p = 0.011), and internal surface (p = 0.012) between benign and premalignant and malignant cysts were significant. A lobulated shape, a thin wall and a smooth internal surface were more frequent in benign cysts, whereas a round or oval shape or a complex cystic shape with tubular cyst, a thick wall and an irregular internal surface were more frequent in premalignant and malignant cysts. On multivariate analysis, the shape (p = 0.002) and wall thickness (p = 0.025) were significant CT features for differentiating benign from premalignant and malignant cysts. Conclusion: Shape and wall thickness are the main CT features for differentiating benign from premalignant and malignant macrocystic pancreatic lesions.

  2. FGF Signaling Prevents the Terminal Differentiation of Odontoblasts.

    Science.gov (United States)

    Sagomonyants, K; Kalajzic, I; Maye, P; Mina, M

    2017-06-01

    Members of the fibroblast growth factor (FGF) family play essential and important roles in primary and reparative dentinogenesis, with conflicting results regarding their effects on odontoblast differentiation. Our recent studies showed that the effects of FGF2 on cells in odontoblast lineage were stage-specific and depended on the stage of cell maturity. Continuous exposure of pulp cells to FGF2 inhibited odontoblast differentiation, whereas early and limited exposure of pulp cells to FGF2 resulted in marked increases in odontoblast differentiation. The purpose of this study was to evaluate the cellular and molecular mechanisms regulating the inhibitory effects of FGF2 on odontoblast differentiation. To do so, we examined the effects of the addition of FGF2 during the differentiation/mineralization phase of the in vitro growth of pulp cultures derived from a series of green fluorescent protein reporter transgenic mice that display stage-specific activation of transgenes during odontoblast differentiation. Our results showed that this treatment first stimulated the differentiation of remaining progenitors in pulp cultures into functional odontoblasts but prevented their differentiation into mature odontoblasts. In addition, this treatment inhibited expression of markers of osteogenesis. Furthermore, we demonstrated that the inhibitory effects of FGF2 on odontoblast differentiation were mediated through activation of FGFR/MEK/Erk1/2 signaling and downregulation of bone morphogenetic protein signaling, with negative and positive roles in the expression of Dmp1 and Dspp, respectively, during the advanced stage of odontoblast differentiation.

  3. Apparent Diffusion Coefficient Measurement in Mediastinal Lymphadenopathies: Differentiation between Benign and Malignant Lesions

    Directory of Open Access Journals (Sweden)

    Fethi Emre Ustabasioglu

    2017-01-01

    Full Text Available Objectives: We aimed to prospectively assess the diagnostic value of apparent diffusion coefficient (ADC measurement in the differentiation of benign and malignant mediastinal lymphadenopathies. Materials and Methods: The study included 63 consecutive patients (28 women, 35 men; mean age 59.3 years with 125 mediastinal lymphadenopathies. Echoplanar diffusion-weighted magnetic resonance imaging of the mediastinum was performed with b-factors of 0 and 600 mm2/s before mediastinoscopy and mediastinotomy, and ADC values were measured. The ADC values were compared with the histological results, and statistical analysis was done. P < 0.05 was considered statistically significant. Results: The mean ADC value of malignant mediastinal lymphadenopathy (1.030 ± 0.245 × 10−3 mm2/s was significantly lower (P < 0.05 when compared to benign lymphadenopathies (1.571 ± 0.559 × 10−3 mm2/s. For differentiating malignant from benign mediastinal lymphadenopathy, the best result was obtained when an ADC value of 1.334 × 10−3 mm2/s was used as a threshold value; area under the curve 0.848, accuracy 78.4%, sensitivity 66%, specificity of 86%, positive predictive value 76.7%, and negative predictive value of 79.2%. Interobserver agreement was excellent for ADC measurements. Conclusions: ADC measurements could be considered an important supportive method in differentiating benign from malignant mediastinal lymphadenopathies.

  4. Loss of H2B monoubiquitination is associated with poor-differentiation and enhanced malignancy of lung adenocarcinoma.

    Science.gov (United States)

    Zhang, Keqiang; Wang, Jinhui; Tong, Tommy R; Wu, Xiwei; Nelson, Rebecca; Yuan, Yate-Ching; Reno, Theresa; Liu, Zheng; Yun, Xinwei; Kim, Jae Y; Salgia, Ravi; Raz, Dan J

    2017-08-15

    Deregulated monoubiquitination of histone H2B (H2Bub1), mainly catalyzed by E3 ubiquitin-protein ligase RNF20/RNF40 complex, may play an important role in cancer. Here we investigate potential roles of H2Bub1 and the underlying mechanisms through which it contributes to cancer development and progression in lung adenocarcinoma. We show that downregulation of H2Bub1 through RNF20 knockdown dramatically decreases H3K79 and H3K4 trimethylation in both normal and malignant lung epithelial cell lines. Concurrently, global transcriptional profiling analysis reveals that multiple tumor-associated genes such as CCND3, E2F1/2, HOXA1, Bcl2 modifying factor (BMF), Met, and Myc; and signaling pathways of cellular dedifferentiation, proliferation, adhesion, survival including p53, cadherin, Myc, and anti-apoptotic pathways are differentially expressed or significantly altered in these lung epithelial cells upon downregulation of H2Bub1. Moreover, RNF20 knockdown dramatically suppresses terminal squamous differentiation of cultured bronchial epithelial cells, and significantly enhances proliferation, migration, invasion, and cisplatin resistance of lung cancer cells. Furthermore, immunohistochemistry analysis shows that H2Bub1 is extremely low or undetectable in >70% of 170 lung adenocarcinoma samples. Notably, statistical analysis demonstrates that loss of H2Bub1 is significantly correlated with poor differentiation in lung adenocarcinoma (p = 0.0134). In addition, patients with H2Bub1-negative cancers had a trend towards shorter survival compared with patients with H2Bub1-positive cancers. Taken together, our findings suggest that loss of H2Bub1 may enhance malignancy and promote disease progression in lung adenocarcinoma probably through modulating multiple cancer signaling pathways. © 2017 UICC.

  5. Contrast-enhanced ultrasonography in differential diagnosis of benign and malignant ovarian tumors.

    Directory of Open Access Journals (Sweden)

    Jing-Jing Qiao

    Full Text Available To evaluate the accuracy of contrast-enhanced ultrasonography (CEUS in differential diagnosis of benign and malignant ovarian tumors.The scientific literature databases PubMed, Cochrane Library and CNKI were comprehensively searched for studies relevant to the use of CEUS technique for differential diagnosis of benign and malignant ovarian cancer. Pooled summary statistics for specificity (Spe, sensitivity (Sen, positive and negative likelihood ratios (LR+/LR-, and diagnostic odds ratio (DOR and their 95%CIs were calculated. Software for statistical analysis included STATA version 12.0 (Stata Corp, College Station, TX, USA and Meta-Disc version 1.4 (Universidad Complutense, Madrid, Spain.Following a stringent selection process, seven high quality clinical trials were found suitable for inclusion in the present meta-analysis. The 7 studies contained a combined total of 375 ovarian cancer patients (198 malignant and 177 benign. Statistical analysis revealed that CEUS was associated with the following performance measures in differential diagnosis of ovarian tumors: pooled Sen was 0.96 (95%CI = 0.92∼0.98; the summary Spe was 0.91 (95%CI = 0.86∼0.94; the pooled LR+ was 10.63 (95%CI = 6.59∼17.17; the pooled LR- was 0.04 (95%CI = 0.02∼0.09; and the pooled DOR was 241.04 (95% CI = 92.61∼627.37. The area under the SROC curve was 0.98 (95% CI = 0.20∼1.00. Lastly, publication bias was not detected (t = -0.52, P = 0.626 in the meta-analysis.Our results revealed the high clinical value of CEUS in differential diagnosis of benign and malignant ovarian tumors. Further, CEUS may also prove to be useful in differential diagnosis at early stages of this disease.

  6. Differentiating benign from malignant bone tumors using fluid-fluid level features on magnetic resonance imaging

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    Yu, Hong; Cui, Jian Ling; Cui, Sheng Jie; Sun, Ying Cal; Cui, Feng Zhen [Dept. of Radiology, The Third Hospital of Hebei Medical University, Hebei Province Biomechanical Key Laborary of Orthopedics, Shijiazhuang, Hebei (China)

    2014-12-15

    To analyze different fluid-fluid level features between benign and malignant bone tumors on magnetic resonance imaging (MRI). This study was approved by the hospital ethics committee. We retrospectively analyzed 47 patients diagnosed with benign (n = 29) or malignant (n = 18) bone tumors demonstrated by biopsy/surgical resection and who showed the intratumoral fluid-fluid level on pre-surgical MRI. The maximum length of the largest fluid-fluid level and the ratio of the maximum length of the largest fluid-fluid level to the maximum length of a bone tumor in the sagittal plane were investigated for use in distinguishing benign from malignant tumors using the Mann-Whitney U-test and a receiver operating characteristic (ROC) analysis. Fluid-fluid level was categorized by quantity (multiple vs. single fluid-fluid level) and by T1-weighted image signal pattern (high/low, low/high, and undifferentiated), and the findings were compared between the benign and malignant groups using the chi2 test. The ratio of the maximum length of the largest fluid-fluid level to the maximum length of bone tumors in the sagittal plane that allowed statistically significant differentiation between benign and malignant bone tumors had an area under the ROC curve of 0.758 (95% confidence interval, 0.616-0.899). A cutoff value of 41.5% (higher value suggests a benign tumor) had sensitivity of 73% and specificity of 83%. The ratio of the maximum length of the largest fluid-fluid level to the maximum length of a bone tumor in the sagittal plane may be useful to differentiate benign from malignant bone tumors.

  7. Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation.

    Science.gov (United States)

    Gao, Xiaofei; Lee, Hsiang-Ying; Li, Wenbo; Platt, Randall Jeffrey; Barrasa, M Inmaculada; Ma, Qi; Elmes, Russell R; Rosenfeld, Michael G; Lodish, Harvey F

    2017-09-19

    An effect of thyroid hormone (TH) on erythropoiesis has been known for more than a century but the molecular mechanism(s) by which TH affects red cell formation is still elusive. Here we demonstrate an essential role of TH during terminal human erythroid cell differentiation; specific depletion of TH from the culture medium completely blocked terminal erythroid differentiation and enucleation. Treatment with TRβ agonists stimulated premature erythroblast differentiation in vivo and alleviated anemic symptoms in a chronic anemia mouse model by regulating erythroid gene expression. To identify factors that cooperate with TRβ during human erythroid terminal differentiation, we conducted RNA-seq in human reticulocytes and identified nuclear receptor coactivator 4 (NCOA4) as a critical regulator of terminal differentiation. Furthermore, Ncoa4(-/-) mice are anemic in perinatal periods and fail to respond to TH by enhanced erythropoiesis. Genome-wide analysis suggests that TH promotes NCOA4 recruitment to chromatin regions that are in proximity to Pol II and are highly associated with transcripts abundant during terminal differentiation. Collectively, our results reveal the molecular mechanism by which TH functions during red blood cell formation, results that are potentially useful to treat certain anemias.

  8. Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma.

    Science.gov (United States)

    Clarke, Loren E; Warf, M B; Flake, Darl D; Hartman, Anne-Renee; Tahan, Steven; Shea, Christopher R; Gerami, Pedram; Messina, Jane; Florell, Scott R; Wenstrup, Richard J; Rushton, Kristen; Roundy, Kirstin M; Rock, Colleen; Roa, Benjamin; Kolquist, Kathryn A; Gutin, Alexander; Billings, Steven; Leachman, Sancy

    2015-04-01

    Histopathologic examination is sometimes inadequate for accurate and reproducible diagnosis of certain melanocytic neoplasms. As a result, more sophisticated and objective methods have been sought. The goal of this study was to identify a gene expression signature that reliably differentiated benign and malignant melanocytic lesions and evaluate its potential clinical applicability. Herein, we describe the development of a gene expression signature and its clinical validation using multiple independent cohorts of melanocytic lesions representing a broad spectrum of histopathologic subtypes. Using quantitative reverse-transcription polymerase chain reaction (PCR) on a selected set of 23 differentially expressed genes, and by applying a threshold value and weighting algorithm, we developed a gene expression signature that produced a score that differentiated benign nevi from malignant melanomas. The gene expression signature classified melanocytic lesions as benign or malignant with a sensitivity of 89% and a specificity of 93% in a training cohort of 464 samples. The signature was validated in an independent clinical cohort of 437 samples, with a sensitivity of 90% and specificity of 91%. The performance, objectivity, reliability and minimal tissue requirements of this test suggest that it could have clinical application as an adjunct to histopathology in the diagnosis of melanocytic neoplasms. © 2015 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.

  9. Heterologous Liposarcomatous Differentiation in Malignant Phyllodes Tumor is Histologically Similar but Immunohistochemically and Molecularly Distinct from Well-differentiated Liposarcoma of Soft Tissue.

    Science.gov (United States)

    Inyang, Alero; Thomas, Dafydd G; Jorns, Julie

    2016-05-01

    Malignant phyllodes tumor (PT) infrequently displays heterologous differentiation, and when present is most often liposarcomatous. We identified five cases of malignant PT with regions identical to well-differentiated liposarcoma (WDLS) of soft tissue and evaluated them for MDM2 and CDK4 gene expression and amplification using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. Despite indistinguishable morphology all cases of malignant PT with WDLS-like liposarcomatous differentiation were negative for MDM2 and CDK4 IHC and FISH, supporting different underlying pathogenesis. © 2016 Wiley Periodicals, Inc.

  10. Virtual touch tissue quantifications in the differential diagnosis of benign and malignant thyroid nodules

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Seung Mi; Cho, Seong Whi [Dept. of Radiology, Kangwon National University Hospital, Chuncheon (Korea, Republic of)

    2016-06-15

    The aim of this study was to evaluate the diagnostic utility of the virtual touch tissue quantification (VTQ) technology for differentiating between benign and malignant thyroid nodules. 198 nodules (168 benign and 30 malignant nodules) identified in 164 patients with available VTQ velocity data and fine-needle aspiration cytology or post-surgical pathological results were included. The VTQ velocities of nodules and adjacent thyroid tissue were examined. Malignant nodules had a significantly higher VTQ velocity (3.06 ± 1.04 m/s, range: 1.90-6.46 m/s) than that of benign nodules (2.40 ± 0.85 m/s, range: 0.69-8.09 m/s) (p = 0.002). The VTQ velocity ratio between malignant nodules and adjacent thyroid tissue (1.39 ± 0.43, range: 0.89-2.65) was also statistically higher than that of benign nodules (1.15 ± 0.44, range: 0.26-3.47) (p = 0.008). The area under the receiver operating characteristic curve for the VTQ velocity was 0.72 with a cutoff point of 2.37 m/s and that of the VTQ velocity ratio was 0.68 with a cutoff point of 1.26. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the VTQ velocity were 86.7%, 50.6%, 23.9%, 95.5%, and 56.1%, respectively and 60.0%, 72.0%, 27.7%, 91.0%, and 70.2%, respectively for the VTQ velocity ratio. VTQ may be helpful in differentiating malignant and benign thyroid nodules with high negative predictive value.

  11. A Network Model to Describe the Terminal Differentiation of B Cells.

    Directory of Open Access Journals (Sweden)

    Akram Méndez

    2016-01-01

    Full Text Available Terminal differentiation of B cells is an essential process for the humoral immune response in vertebrates and is achieved by the concerted action of several transcription factors in response to antigen recognition and extracellular signals provided by T-helper cells. While there is a wealth of experimental data regarding the molecular and cellular signals involved in this process, there is no general consensus regarding the structure and dynamical properties of the underlying regulatory network controlling this process. We developed a dynamical model of the regulatory network controlling terminal differentiation of B cells. The structure of the network was inferred from experimental data available in the literature, and its dynamical behavior was analyzed by modeling the network both as a discrete and a continuous dynamical systems. The steady states of these models are consistent with the patterns of activation reported for the Naive, GC, Mem, and PC cell types. Moreover, the models are able to describe the patterns of differentiation from the precursor Naive to any of the GC, Mem, or PC cell types in response to a specific set of extracellular signals. We simulated all possible single loss- and gain-of-function mutants, corroborating the importance of Pax5, Bcl6, Bach2, Irf4, and Blimp1 as key regulators of B cell differentiation process. The model is able to represent the directional nature of terminal B cell differentiation and qualitatively describes key differentiation events from a precursor cell to terminally differentiated B cells.

  12. Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study

    DEFF Research Database (Denmark)

    Achiam, M P; Andersen, L P H; Klein, M

    2010-01-01

    Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium...

  13. Genetically Engineered Multilineage-Differentiating Stress-Enduring Cells as Cellular Vehicles against Malignant Gliomas

    Directory of Open Access Journals (Sweden)

    Tomohiro Yamasaki

    2017-09-01

    Full Text Available Malignant glioma, the most common malignant brain tumor in adults, is difficult to treat due to its aggressive invasive nature. Enzyme/prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSVtk/ganciclovir (GCV system is an efficient strategy for treating malignant gliomas. In the present study, we evaluated treatment with multilineage-differentiating stress-enduring (Muse cells, which are endogenous non-tumorigenic pluripotent-like stem cells that are easily collectable from the bone marrow as SSEA-3+ cells, as carriers of the HSVtk gene. Human Muse cells showed potent migratory activity toward glioma cells both in vitro and in vivo. HSVtk gene-transduced Muse cells (Muse-tk cells at a cell number of only 1/32 that of U87 human glioma cells completely eradicated U87 gliomas in nude mouse brains, showing a robust in vivo bystander effect. Pre-existing intracranial U87 gliomas in nude mouse brains injected intratumorally with Muse-tk cells followed by intraperitoneal GCV administration were significantly reduced in size within 2 weeks, and 4 of 10 treated mice survived over 200 days. These findings suggest that intratumoral Muse-tk cell injection followed by systemic GCV administration is safe and effective and that allogeneic Muse-tk cell-medicated suicide gene therapy for malignant glioma is clinically feasible.

  14. Utility Serum Marker HE4 for the Differential Diagnosis Between Endometriosis and Adnexal Malignancy.

    Science.gov (United States)

    Zapardiel, Ignacio; Gorostidi, Mikel; Ravaggi, Antonella; Allende, Maria T; Silveira, Margarida; Abehsera, Daniel; Macuks, Ronalds

    2016-01-01

    The aim of the study was to assess the utility of serum human epididymal secretory protein E4 (HE4) biomarker in the differential diagnosis of endometriosis and adnexal malignancies. Multicentric prospective observational study between January 2010 and December 2011 in 4 European centers (Italy, Portugal, Latvia, and Spain) was carried out. We collected 981 healthy patients diagnosed with adnexal patology and selected 65 patients diagnosed with endometriosis and analyzed their serum markers CA125, HE4, and Risk of Ovarian Malignancy Algorithm (ROMA) index. We also analyzed all cases of malignant histology and divided them according to CA125 levels (negative, ≤35 U/mL; intermediate, >35-150 U/mL; and highly positive, >150 U/mL). HE4 was positive only in 1.5% of cases, CA125 in 64.6%, and ROMA index in 14.1%. In the subgroup intermediate CA125 values, positive HE4 is very specific (91.2%) correctly classifying patients with benign disease, but with lower sensibility (66.1%); however, ROMA index showed a high sensibility (89.3%), with a false-positive rate of 42.8%. HE4 can be a very useful biomarker to exclude malignant disease in patients with endometriosis.

  15. How to differentiate benign from malignant myometrial tumours using MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Thomassin-Naggara, Isabelle [Hopital Tenon, Assistance Publique-Hopitaux de Paris and Universite Pierre et Marie Curie, Department of Radiology, Paris (France); Hopital Tenon, Service de Radiologie, Paris (France); Dechoux, Sophie; Morel, Audrey; Carette, Marie-France; Bazot, Marc [Hopital Tenon, Assistance Publique-Hopitaux de Paris and Universite Pierre et Marie Curie, Department of Radiology, Paris (France); Bonneau, Claire; Rouzier, Roman; Darai, Emile [Hopital Tenon, Assistance Publique-Hopitaux de Paris and Universite Pierre et Marie Curie, Department of Gynecology-Obstetrics, Paris (France)

    2013-08-15

    To retrospectively evaluate the ability of magnetic resonance imaging (MRI) to differentiate malignant from benign myometrial tumours. Fifty-one women underwent MRI before surgery for evaluation of a solitary myometrial tumour. At histopathology, there were 25 uncertain or malignant mesenchymal tumours and 26 benign leiomyomas. Conventional morphological MRI criteria were recorded in addition to b{sub 1,000} signal intensity and apparent diffusion coefficient (ADC). Odds ratios (OR) were calculated for each criterion. A multivariate analysis was performed to construct an interpretation model. The significant criteria for prediction of malignancy were high b{sub 1,000} signal intensity (OR = +{infinity}), intermediate T2-weighted signal intensity (OR = +{infinity}), mean ADC (OR = 25.1), patient age (OR = 20.1), intra-tumoral haemorrhage (OR = 21.35), endometrial thickening (OR = 11), T2-weighted signal heterogeneity (OR = 10.2), menopausal status (OR = 9.7), heterogeneous enhancement (OR = 8) and non-myometrial origin on MRI (OR = 4.9). In the recursive partitioning model, using b{sub 1,000} signal intensity, T2 signal intensity, mean ADC, and patient age, the model correctly classified benign and malignant tumours in 47 of the 51 cases (92.4 %). We have developed an interpretation model usable in routine practice for myometrial tumours discovered at MRI including T2 signal, b{sub 1,000} signal and ADC measurement. (orig.)

  16. Differentiation of benign and malignant ulcers of the stomach on computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Im Jeong; Kim, Suk; Lee, Jun Woo; Jeong, Yeon Joo; Choo, Ki Seok; Lee, Suk Hong; Kim, Gwang Ha; Kim, Tae Oh; Jo, Hong Jae [Pusan National University College of Medicine, Busan (Korea, Republic of)

    2006-10-15

    We wanted to determine the multidetector computed tomography (MDCT) findings for differentiating benign ulcers from malignant ones. 18 clinicopathologically proven benign ulcers that had been detected by both endoscopy and MDCT were the focus of this study. 26 ulcerative advanced gastric cancers and 26 early gastric cancers with ulceration, all of which had been surgically proven, were selected as a control group. Five of the 26 early gastric cancers that were confined to the mucosa and that were not detected on CT were excluded in this study. The following CT findings were reviewed by two radiologists; ulcer size, the degree of enhancement and the thickness of inner enhancing layer in the ulcer base, the total thickness and the enhancing inner layer thickness in the largest part of the thickened ulcer mound, the presence of ulcer that projected beyond the healthy lumen, and the presence of perigastric fat infiltration and perigastric lymphadenopathy. An indiscernible thin-walled ulcer base (less than 1.5 mm) and suboptimal enhancement of the ulcer base for the discrimination of benign gastric ulcers from the malignant gastric ulcers showed sensitivities of 100% (18/18) and 78% (14/18), respectively, with specificities of 98% (46/47) and 92% (43/47), respectively. Ulcer projection was more significantly present in benign ulcer (13/18, 72%) than in the malignant gastric ulcers (7/47, 15%). The enhancing inner layer thickness in the ulcer mound was significantly greater in the AGC (mean; 7.4 mm) than in the benign gastric ulcers (mean, 2.2 mm). There were insignificant differences for ulcer size, total thickness of the ulcer mound, the perigastric fat infiltration and perigastric lymphadenopathy between the benign and malignant gastric ulcers. MDCT is an additional helpful diagnostic tool when benign gastric ulcers are histologically difficult to distinguish from malignant gastric ones.

  17. The value of sonographic gallbladder wall patterns in differentiating malignant from benign ascites

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young Rae; Park, Hae Won; Lee, Young Uk; Oh, Won Ja [Koryo General Hospital, Seoul (Korea, Republic of)

    1991-09-15

    This investigation evaluates whether the appearance and thickness of the gallbladder (GB) wall can be clinically useful to determine the etiology of ascites by ultrasonography. Another purpose of this study is to verify the existence of statistically significant relationship between GB wall patterns and serum albumin level. Findings on ultrasonogram were reviewed retrospectively in 90 patients with ascites. The statistical analysis of the results reveals no correlation between hypoalbuminemia and GB wall patterns (P>0.05). There was a significant difference in GB wall patterns between benign (group 1 and 2) and malignant (group 3 and 4) conditions (P>0.05). The carcinoma, with the exception of hepatocellular the gallbladder wall was significantly thicker in the cirrhosis brougs than in the malignant group. Twenty-seven patients (87%) in group 1 had thickened GB walls, whereas 16 patients (76%) in group 3 showed normal single layered GB walls. This difference was statistically significant (P>0.05). However no statistically significant difference was found between liver cirrhosis (group 1) and liver cirrhosis associated with hepatocellular carcinoma (group 4) (P>0.05). Also, with the except of hepatocellular carcinoma (group 3) there also was no significant difference found between benign noncirrhotic pathology (group 2) and malignancy. These results suggests that there is a distant sonographic appearance of the GB wall according to different ascitis etiologies. This can pathology be seen when comparing patients with liver carrhosis and malignancy other than hepatocellular carcinoma. However sonographic findings of the GB wall patterns in ascites lacks diagnostic value in differentiating benign from malignant disease causing ascites.

  18. EGF-receptor tyrosine kinase inhibition induces keratinocyte growth arrest and terminal differentiation.

    Science.gov (United States)

    Peus, D; Hamacher, L; Pittelkow, M R

    1997-12-01

    Epidermal keratinocyte growth and differentiation are regulated by specific families of growth factors and receptors. Peptide growth factors of the epidermal growth factor family stimulate proliferation of clonal density human keratinocytes and suppress markers of terminal differentiation in confluent cultures of human keratinocytes. We present evidence that selected inhibitors of activation of the type I human epidermal growth factor receptor (EGFR or HER-1), namely, neutralizing monoclonal antibody to HER-1/EGFR and the specific tyrosine kinase inhibitor PD 153035, potently inhibit proliferation of human keratinocytes in autonomously replicating subconfluent cultures. Coupled to growth arrest is the suppression of HER-1 tyrosine autophosphorylation in inhibitor-treated human keratinocytes. Proliferation and tyrosine autophosphorylation are initially reversible following removal of the inhibitor and restimulation of cells with epidermal growth factor. Sustained inactivation of HER-1 in autonomously replicating cultures of human keratinocytes induces expression of keratin 1 and keratin 10 genes, early markers of terminal differentiation. Reversal of growth inhibition by epidermal growth factor suppresses keratin 1 and keratin 10 expression. These results demonstrate that human keratinocyte terminal differentiation as well as proliferation are mediated by HER-1. Co-expression of autocrine epidermal growth factor-related ligands as well as HER-1 by human keratinocyte may function as part of the signal transduction network in epidermis to regulate cell number, replication rate, and terminal differentiation.

  19. Terminal Bacteroid Differentiation Is Associated With Variable Morphological Changes in Legume Species Belonging to the Inverted Repeat-Lacking Clade

    National Research Council Canada - National Science Library

    Montiel, Jesús; Szűcs, Attila; Boboescu, Iulian Z; Gherman, Vasile D; Kondorosi, Éva; Kereszt, Attila

    2016-01-01

    .... As bacteroids in other IRLC legumes, such as Cicer arietinum and Glycyrrhiza lepidota, were reported not to display features of terminal differentiation, we investigated the fate of bacteroids...

  20. Value of Glut-1 and Koc markers in the differential diagnosis of reactive mesothelial hyperplasia, malignant mesothelioma and pulmonary adenocarcinoma.

    Science.gov (United States)

    Üçer, Özlem; Dağli, Adile Ferda; Kiliçarslan, Ahmet; Artaş, Gökhan

    2013-01-01

    Malignant mesothelioma (MM) is a primary malignant tumor developing from mesothelial cells lining the serosal surfaces and particularly the pleura, and has a very poor prognosis. It may display a variety of histological patterns and has a wide spectrum of cytomorphological characteristics, causing problems in its differential diagnosis from lung adenocarcinomas and sometimes from benign mesothelial proliferations. Immunohistochemical examination is the most useful method for this distinction. In our study, we aimed to determine the value of glucose transporter isoform-1 (GLUT-1) and K homology domain-containing protein (KOC) markers in the differential diagnosis of reactive mesothelial hyperplasia, malignant mesothelioma and lung adenocarcinoma. Our study included 30 samples of malignant mesothelioma, 30 samples of pulmonary adenocarcinoma and 30 samples of reactive mesothelial hyperplasia selected from the archives of the Fırat University Hospital's Pathology Department Laboratory. The samples were applied GLUT-1 and KOC markers by immunohistochemistry and the place of these markers in the differential diagnosis was examined. GLUT-1 was found positive in 80% of malignant mesothelioma cases, 83.3% of adenocarcinoma cases and 6.6% of reactive mesothelial hyperplasia cases. KOC was positive in 83.3% of malignant mesothelioma cases, 76.6% of adenocarcinoma cases and 46.6% of reactive mesothelial hyperplasia cases. There was no statistically significant difference between malignant mesothelioma and lung adenocarcinoma cases in terms of the diffuseness and intensity of staining with GLUT-1, whereas a significant difference was established when these groups were compared with reactive mesothelial hyperplasia cases. However, the KOC staining diffuseness and intensity results were similar to those obtained with GLUT-1. In conclusion, GLUT-1 and KOC markers do not differentiate malignant mesotheliomas from pulmonary adenocarcinomas but can be useful in differentiating

  1. Artificial neural network to aid differentiation of malignant and benign breast masses by ultrasound imaging

    Science.gov (United States)

    Song, Jae H.; Venkatesh, Santosh S.; Conant, Emily F.; Cary, Ted W.; Arger, Peter H.; Sehgal, Chandra M.

    2005-04-01

    The goal of this study is to evaluate an Artificial Neural Network (ANN) for differentiating benign and malignant breast masses on ultrasound scans. The ANN was designed with three layers (input, hidden and output layer), where a sigmoidal (hyperbolic tangent) response function is used as an activation function at each unit. Data from 54 patients with biopsy-proven malignant (N=20) and benign (N=34) masses were used to evaluate the diagnostic performance of the ANN. Of the seven quantitative features extracted from ultrasound images, only four showed statistically significant difference between the two categories. These features were margin sharpness, margin echogenicity, angular continuity, and age of patients. The diagnostic performance was evaluated by round-robin substitution to negate bias due to small sample size. All the input features were standardized to zero-mean and unit-variance to prevent non-uniform learning, which can generate unwanted error. The outputs of the network were analyzed by Receiver Operating Characteristics (ROC). The resulting area under the ROC curve Az was 0.856 +/- 0.058 with 95% confidence limit from 0.734 to 0.936, providing 76.5% specificity at 95% sensitivity. The performance of the ANN was comparable to the performance by logistic regression analysis reported by our group earlier. These results suggest that an ANN when combined with sonography can effectively classify malignant and benign breast lesions.

  2. [The pathological/MR tomographic correlation and differential diagnosis of malignant kidney tumors].

    Science.gov (United States)

    Kreft, B; Flacke, S; Conrad, R; Pauleit, D; Bachmann, R; Wardelmann, E; Albers, P; Schild, H

    1999-08-01

    Evaluation of malignancy criteria in MRT of kidney tumors in correlation with the histopathological findings. 41 patients with suspected malignant kidney tumors were examined using a T1 SE sequence (TR/TE 300/10 ms) before and after i.v. administration of 0.1 mmol/kg Gd-DTPA and a T2 SE sequence (TR/TE 5500/150 ms). The results were correlated with the pathological findings. 38 malignant tumors were found: 29 renal cell carcinomas (RCC), 13 with solid growth, 11 with tubulopapillary growth, and three with mixed growth forms, one cystic RCC, and one chromophobic RCC, in addition, 6 urothelial carcinomas and three other malignomas. Typical MRT criteria for RCC were an inhomogeneity of the tumor with regions of slightly increased signal intensity on the T1-weighted image (59%) and regions with reduced signal intensity on the T2-weighted image (96%) as compared with renal parenchyma; these were due to histomorphological hemorrhage and hemosiderin deposits, respectively. A further criterion for RCC was a hypointense pseudocapsule in the T2 TSE sequence in 79% of the cases. The low-signal nature of RCC in the T2-weighted image correlates with hemorrhage and hemosiderin deposits. The detection of a pseudocapsule is useful in the differential diagnosis of solid tumors in the kidney.

  3. Use of shear wave elastography to differentiate benign and malignant breast lesions.

    Science.gov (United States)

    Çebi Olgun, Deniz; Korkmazer, Bora; Kılıç, Fahrettin; Dikici, Atilla Süleyman; Velidedeoğlu, Mehmet; Aydoğan, Fatih; Kantarcı, Fatih; Yılmaz, Mehmet Halit

    2014-01-01

    We aimed to determine the correlations between the elasticity values of solid breast masses and histopathological findings to define cutoff elasticity values differentiating malignant from benign lesions. A total of 115 solid breast lesions of 109 consecutive patients were evaluated prospectively using shear wave elastography (SWE). Two orthogonal elastographic images of each lesion were obtained. Minimum, mean, and maximum elasticity values were calculated in regions of interest placed over the stiffest areas on the two images; we also calculated mass/fat elasticity ratios. Correlation of elastographic measurements with histopathological results were studied. Eighty-three benign and thirty-two malignant lesions were histopathologically diagnosed. The minimum, mean, and maximum elasticity values, and the mass/fat elasticity ratios of malignant lesions, were significantly higher than those of benign lesions. The cutoff value was 45.7 kPa for mean elasticity (sensitivity, 96%; specificity, 95%), 54.3 kPa for maximum elasticity (sensitivity, 95%; specificity, 94%), 37.1 kPa for minimum elasticity (sensitivity, 96%; specificity, 95%), and 4.6 for the mass/fat elasticity ratio (sensitivity, 97%; specificity, 95%). SWE yields additional valuable quantitative data to ultrasonographic examination on solid breast lesions. SWE may serve as a complementary tool for diagnosis of breast lesions. Long-term clinical studies are required to accurately select lesions requiring biopsy.

  4. Performance of shear wave elastography for differentiation of benign and malignant solid breast masses.

    Directory of Open Access Journals (Sweden)

    Guiling Li

    Full Text Available OBJECTIVES: To perform a meta-analysis assessing the ability of shear wave elastography (SWE to identify malignant breast masses. METHODS: PubMed, the Cochrane Library, and the ISI Web of Knowledge were searched for studies evaluating the accuracy of SWE for identifying malignant breast masses. The diagnostic accuracy of SWE was evaluated according to sensitivity, specificity, and hierarchical summary receiver operating characteristic (HSROC curves. An analysis was also performed according to the SWE mode used: supersonic shear imaging (SSI and the acoustic radiation force impulse (ARFI technique. The clinical utility of SWE for identifying malignant breast masses was evaluated using analysis of Fagan plot. RESULTS: A total of 9 studies, including 1888 women and 2000 breast masses, were analyzed. Summary sensitivities and specificities were 0.91 (95% confidence interval [CI], 0.88-0.94 and 0.82 (95% CI, 0.75-0.87 by SSI and 0.89 (95% CI, 0.81-0.94 and 0.91 (95% CI, 0.84-0.95 by ARFI, respectively. The HSROCs for SSI and ARFI were 0.92 (95% CI, 0.90-0.94 and 0.96 (95% CI, 0.93-0.97, respectively. SSI and ARFI were both very informative, with probabilities of 83% and 91%, respectively, for correctly differentiating between benign and malignant breast masses following a "positive" measurement (over the threshold value and probabilities of disease as low as 10% and 11%, respectively, following a "negative" measurement (below the threshold value when the pre-test probability was 50%. CONCLUSIONS: SWE could be used as a good identification tool for the classification of breast masses.

  5. The impact of share wave elastography in differentiation of hepatic hemangioma from malignant liver tumors in pediatric population.

    Science.gov (United States)

    Özmen, Evrim; Adaletli, Ibrahim; Kayadibi, Yasemin; Emre, Şenol; Kiliç, Fahrettin; Dervişoğlu, Sergülen; Kuruğoğlu, Sebuh; Şenyüz, Osman Faruk

    2014-09-01

    In children it is crucial to differentiate malignant liver tumors from the most common benign tumor, hepatic hemangiomas since the treatment strategies are quite different. We aimed to evaluate the efficiency of shear wave elastography (SWE) technique in differentiation of malignant hepatic tumors and hepatic hemangiomas. Twenty patients with hepatic tumor were included in our study. Two radiologists performed SWE for 13 patients with malignant hepatic tumors including hepatoblastoma (n=7), hepatocellular carcinoma (n=3), metastasis (n=2), embryonal sarcoma (n=1) and 7 patients with hepatic hemangioma. All of our patients were between the age of 1 and 192 months (mean age: 56.88 months). Receiver operating characteristic analysis was achieved to evaluate the diagnostic accuracy of SWE and to determine the optimal cut-off value in differentiation hepatic hemangioma from malignant hepatic tumors. The mean SWE values (in kPa) for the first observer were 46.94 (13.8-145) and 22.38 (6.6-49.6) and those for the second observer were 57.91 (11-237) and 23.87 (6.4-57.5), respectively for malignant hepatic tumors and hepatic hemangiomas. The SWE values of malignant hepatic tumors were significantly higher than those of hepatic hemangioma (p=0.02). The inter-observer agreement was almost perfect (0.81). The area under the receiver operating characteristic curve of SWE for differentiating the hepatic hemangioma from malignant hepatic tumors was 0.77 with a sensitivity of 72.7% and a specificity of 66.7% at a cutoff value of 23.62 with 95% confidence interval. Shear wave elastography can be helpful in differentiation of malignant hepatic tumors and hepatic hemangioma. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Precancerous stem cells have the potential for both benign and malignant differentiation.

    Directory of Open Access Journals (Sweden)

    Li Chen

    Full Text Available Cancer stem cells (CSCs have been identified in hematopoietic and solid tumors. However, their precursors-namely, precancerous stem cells (pCSCs -have not been characterized. Here we experimentally define the pCSCs that have the potential for both benign and malignant differentiation, depending on environmental cues. While clonal pCSCs can develop into various types of tissue cells in immunocompetent mice without developing into cancer, they often develop, however, into leukemic or solid cancers composed of various types of cancer cells in immunodeficient mice. The progress of the pCSCs to cancers is associated with the up-regulation of c-kit and Sca-1, as well as with lineage markers. Mechanistically, the pCSCs are regulated by the PIWI/AGO family gene called piwil2. Our results provide clear evidence that a single clone of pCSCs has the potential for both benign and malignant differentiation, depending on the environmental cues. We anticipate pCSCs to be a novel target for the early detection, prevention, and therapy of cancers.

  7. Overlapping DNA methylation dynamics in mouse intestinal cell differentiation and early stages of malignant progression.

    Directory of Open Access Journals (Sweden)

    Marta Forn

    Full Text Available Mouse models of intestinal crypt cell differentiation and tumorigenesis have been used to characterize the molecular mechanisms underlying both processes. DNA methylation is a key epigenetic mark and plays an important role in cell identity and differentiation programs and cancer. To get insights into the dynamics of cell differentiation and malignant transformation we have compared the DNA methylation profiles along the mouse small intestine crypt and early stages of tumorigenesis. Genome-scale analysis of DNA methylation together with microarray gene expression have been applied to compare intestinal crypt stem cells (EphB2high, differentiated cells (EphB2negative, ApcMin/+ adenomas and the corresponding non-tumor adjacent tissue, together with small and large intestine samples and the colon cancer cell line CT26. Compared with late stages, small intestine crypt differentiation and early stages of tumorigenesis display few and relatively small changes in DNA methylation. Hypermethylated loci are largely shared by the two processes and affect the proximities of promoter and enhancer regions, with enrichment in genes associated with the intestinal stem cell signature and the PRC2 complex. The hypermethylation is progressive, with minute levels in differentiated cells, as compared with intestinal stem cells, and reaching full methylation in advanced stages. Hypomethylation shows different signatures in differentiation and cancer and is already present in the non-tumor tissue adjacent to the adenomas in ApcMin/+ mice, but at lower levels than advanced cancers. This study provides a reference framework to decipher the mechanisms driving mouse intestinal tumorigenesis and also the human counterpart.

  8. The differentiation between malignant and non-malignant breast tissues using elastic and inelastic scattering of synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, Elaine A., E-mail: e.ryan@usyd.edu.a [Discipline of Medical Radiation Science, Faculty of Health Sciences, University of Sydney, NSW (Australia); Farquharson, Michael J. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario (Canada)

    2010-07-21

    The aim of this work was to investigate the differences in composition between malignant and non-malignant breast tissue. 38 invasive ductal carcinomas and 45 non-malignant breast tissues were measured, each being mounted in cylindrical sample holders of volume 25 mm{sup 2}. The experiments were performed at the European Synchrotron Radiation Facility (ESRF) at Grenoble, France. A monochromatic beam of 10 keV was used, focussed to a 0.5 mmx0.5 mm rectangular area on the sample. Elastic and inelastic scattered photons were collected at an angle of 120{sup o}. A novel technique was used to find the mean atomic numbers of the tissues (Z-bar). A CT scanner that has been calibrated with an ED phantom was used to find the Z-bar of 10 gels. These were composed of a gelatine base, with low concentrations of copper added to increase the Z-bar values by an incremental amount. These were then used to calibrate the scattering measurement system. The area of the elastic and inelastic scatter peaks were found using peak fitting software and the ratio of these two areas was obtained. The data was shown to be non-parametric, and was therefore analysed using a Mann-Whitney test. Using this analysis the difference between non-malignant and malignant tissues was found to be extremely significant, with a 2-tailed p-value of <0.0001. The absolute Z-bar values were also analysed.

  9. The differentiation between malignant and non-malignant breast tissues using elastic and inelastic scattering of synchrotron radiation

    Science.gov (United States)

    Ryan, Elaine A.; Farquharson, Michael J.

    2010-07-01

    The aim of this work was to investigate the differences in composition between malignant and non-malignant breast tissue. 38 invasive ductal carcinomas and 45 non-malignant breast tissues were measured, each being mounted in cylindrical sample holders of volume 25 mm 2. The experiments were performed at the European Synchrotron Radiation Facility (ESRF) at Grenoble, France. A monochromatic beam of 10 keV was used, focussed to a 0.5 mm×0.5 mm rectangular area on the sample. Elastic and inelastic scattered photons were collected at an angle of 120°. A novel technique was used to find the mean atomic numbers of the tissues ( Z¯). A CT scanner that has been calibrated with an ED phantom was used to find the Z¯ of 10 gels. These were composed of a gelatine base, with low concentrations of copper added to increase the Z¯ values by an incremental amount. These were then used to calibrate the scattering measurement system. The area of the elastic and inelastic scatter peaks were found using peak fitting software and the ratio of these two areas was obtained. The data was shown to be non-parametric, and was therefore analysed using a Mann-Whitney test. Using this analysis the difference between non-malignant and malignant tissues was found to be extremely significant, with a 2-tailed p-value of <0.0001. The absolute Z¯ values were also analysed.

  10. Differentiation of odontoblasts is negatively regulated by MEPE via its C-terminal fragment.

    Science.gov (United States)

    Wang, Hanguo; Kawashima, Nobuyuki; Iwata, Takanori; Xu, Jing; Takahashi, Satomi; Sugiyama, Toshihiro; Suda, Hideaki

    2010-07-30

    Matrix extracellular phosphoglycoprotein (MEPE) is an extracellular matrix protein that is mainly expressed in mineralizing tissues, including the dental pulp. The purposes of this study were to clarify the localization of MEPE in the tooth germ and to investigate the roles of MEPE in the differentiation of odontoblasts. The immunohistochemical staining in the tooth germ of the upper first molars of male Wistar rats (postnatal day 3) revealed that MEPE was mainly localized in odontoblasts during dentinogenesis. Stable MEPE-overexpressing and MEPE-knockdown cell lines, which were established in odontoblast-lineage cells (OLCs), showed lower and higher differentiation capabilities, respectively. Eukaryotic proteins of the N-terminal fragment of MEPE produced in HEK cells had no effect on the differentiation of OLCs, whereas the C-terminal fragment containing an RGD sequence inhibited their differentiation. These results indicated that the C-terminal fragment of MEPE containing an RGD sequence, cleaved in odontoblasts, appeared to be the active form of MEPE, which may play important roles in dentinogenesis and pulpal homeostasis by keeping the odontoblasts in immature condition. Copyright 2010 Elsevier Inc. All rights reserved.

  11. The impact of share wave elastography in differentiation of hepatic hemangioma from malignant liver tumors in pediatric population

    Energy Technology Data Exchange (ETDEWEB)

    Özmen, Evrim, E-mail: evrimkilicdr@gmail.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Adaletli, İbrahim, E-mail: iadaletli@yahoo.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Kayadibi, Yasemin, E-mail: ysmnkurdoglu@gmail.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Emre, Şenol, E-mail: senolemre@hotmail.com [Department of Pediatric Surgery, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Kılıç, Fahrettin, E-mail: fahrettinkilic@hotmail.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Dervişoğlu, Sergülen, E-mail: selozmen@gmail.com [Department of Pathology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Kuruğoğlu, Sebuh, E-mail: sebuhk@yahoo.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Şenyüz, Osman Faruk, E-mail: ofsenyuz@gmail.com [Department of Pediatric Surgery, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey)

    2014-09-15

    Highlights: • We evaluated the impact of share wave elastography technique in differentiation hepatic hemangiomas from malignant liver tumors in pediatric population. • Share wave technique can increase the diagnostic capability of conventional ultrasonography in the differential diagnosis of liver tumors in children. • Share wave elastography is a potential adjunctive diagnostic technique for pediatric liver tumors. - Abstract: Objective: In children it is crucial to differentiate malignant liver tumors from the most common benign tumor, hepatic hemangiomas since the treatment strategies are quite different. We aimed to evaluate the efficiency of shear wave elastography (SWE) technique in differentiation of malignant hepatic tumors and hepatic hemangiomas. Methods: Twenty patients with hepatic tumor were included in our study. Two radiologists performed SWE for 13 patients with malignant hepatic tumors including hepatoblastoma (n = 7), hepatocellular carcinoma (n = 3), metastasis (n = 2), embryonal sarcoma (n = 1) and 7 patients with hepatic hemangioma. All of our patients were between the age of 1 and 192 months (mean age: 56.88 months). Receiver operating characteristic analysis was achieved to evaluate the diagnostic accuracy of SWE and to determine the optimal cut-off value in differentiation hepatic hemangioma from malignant hepatic tumors. Results: The mean SWE values (in kPa) for the first observer were 46.94 (13.8–145) and 22.38 (6.6–49.6) and those for the second observer were 57.91 (11–237) and 23.87 (6.4–57.5), respectively for malignant hepatic tumors and hepatic hemangiomas. The SWE values of malignant hepatic tumors were significantly higher than those of hepatic hemangioma (p = 0.02). The inter-observer agreement was almost perfect (0.81). The area under the receiver operating characteristic curve of SWE for differentiating the hepatic hemangioma from malignant hepatic tumors was 0.77 with a sensitivity of 72.7% and a specificity of 66

  12. Homeodomain-interacting protein kinase 2 plays an important role in normal terminal erythroid differentiation.

    Science.gov (United States)

    Hattangadi, Shilpa M; Burke, Karly A; Lodish, Harvey F

    2010-06-10

    Gene-targeting experiments report that the homeodomain-interacting protein kinases 1 and 2, Hipk1 and Hipk2, are essential but redundant in hematopoietic development because Hipk1/Hipk2 double-deficient animals exhibit severe defects in hematopoiesis and vasculogenesis, whereas the single knockouts do not. These serine-threonine kinases phosphorylate and consequently modify the functions of several important hematopoietic transcription factors and cofactors. Here we show that Hipk2 knockdown alone plays a significant role in terminal fetal liver erythroid differentiation. Hipk1 and Hipk2 are highly induced during primary mouse fetal liver erythropoiesis. Specific knockdown of Hipk2 inhibits terminal erythroid cell proliferation (explained in part by impaired cell-cycle progression as well as increased apoptosis) and terminal enucleation as well as the accumulation of hemoglobin. Hipk2 knockdown also reduces the transcription of many genes involved in proliferation and apoptosis as well as important, erythroid-specific genes involved in hemoglobin biosynthesis, such as alpha-globin and mitoferrin 1, demonstrating that Hipk2 plays an important role in some but not all aspects of normal terminal erythroid differentiation.

  13. Surface-enhanced Raman spectroscopy for differentiation between benign and malignant thyroid tissues

    Science.gov (United States)

    Li, Zuanfang; Li, Chao; Lin, Duo; Huang, Zufang; Pan, Jianji; Chen, Guannan; Lin, Juqiang; Liu, Nenrong; Yu, Yun; Feng, Shangyuan; Chen, Rong

    2014-04-01

    The aim of this study was to evaluate the potential of applying silver nano-particle based surface-enhanced Raman scattering (SERS) to discriminate different types of human thyroid tissues. SERS measurements were performed on three groups of tissue samples including thyroid cancers (n = 32), nodular goiters (n = 20) and normal thyroid tissues (n = 25). Tentative assignments of the measured tissue SERS spectra suggest interesting cancer specific biomolecular differences. The principal component analysis (PCA) and linear discriminate analysis (LDA) together with the leave-one-out, cross-validated technique yielded diagnostic sensitivities of 92%, 75% and 87.5%; and specificities of 82.6%, 89.4% and 84.4%, respectively, for differentiation among normal, nodular and malignant thyroid tissue samples. This work demonstrates that tissue SERS spectroscopy associated with multivariate analysis diagnostic algorithms has great potential for detection of thyroid cancer at the molecular level.

  14. Cancer Stem Cells of Differentiated B-Cell Malignancies: Models and Consequences

    Directory of Open Access Journals (Sweden)

    Jean-Jacques Fournie

    2011-03-01

    Full Text Available The concept of cancer stem cells has revolutionized our current vision of cancer development and was validated in solid tumors and cancers of the primitive hematopoietic compartment. Proof of the principle is still lacking, however, in malignancies of differentiated B-cells. We review here the current literature, which nevertheless suggests hierarchical organizations of the tumor clone for mostly incurable B-cell cancers such as multiple myeloma, lymphomas and B-chronic lymphocytic leukemia. We propose two models accounting for cancer stem cells in these contexts: a “top-to-bottom” clonal hierarchy from memory B-cells and a “bottom-to-top” model of clonal reprogramming. Selection pressure on the growing tumor can drive such reprogramming and increase its genetic diversity.

  15. A function for Rac1 in the terminal differentiation and pigmentation of hair

    DEFF Research Database (Denmark)

    Behrendt, Kristina; Klatte, Jennifer; Pofahl, Ruth

    2012-01-01

    . Rescue mice showed a grey, dull hair coat, whereas that of wild-type and L61Rac1-transgenic mice was black and shiny. Hair analysis in rescue mice revealed altered structures of the hair shaft and the cuticle and disturbed organization of medulla cells and pigment distribution. Disorganization of medulla...... functions for Rac1 in the formation of hair structure and pigmentation and thereby identifies, for the first time, a role for Rac1 in terminal differentiation....

  16. ATF-2 immunoreactivity in post-mitotic and terminally differentiated human odontoblasts.

    Science.gov (United States)

    Keklikoglu, Nurullah; Akinci, Sevtap

    2015-09-01

    Activating transcription factor 2 (ATF-2/CRE-BP1; cAMP-responsive element binding protein 1) is a member of nuclear transcription factor activator protein-1 (AP-1) family. AP-1 regulates cellular processes including growth, proliferation, differentiation and apoptosis. However, biological relationship of cellular process to each member of the AP-1 family is not clear yet. The objective of the present study was to compare the ATF-2 immunoreactivity in the post-mitotic and terminally differentiated odontoblasts and in the pulpal fibroblasts which can be divided by mitosis when required. Fibroblasts at various stages of differentiation co-exist in the human dental pulp. ATF-2 was investigated immunohistochemically in 20 permanent human teeth. According to the findings obtained, the mean percentage of ATF-2 positive cells was 68.5 ± 19.2% in the odontoblasts and 22.8 ± 13.7% in the pulpal fibroblasts. The comparison of ATF-2 positivity revealed a statistically significant difference between odontoblasts and pulpal fibroblasts. These findings have suggested that ATF-2 is more associated with cell survival rather than cell proliferation, and revealed much of effectiveness in maintaining terminal differentiation than the various differentiation stages of the cells.

  17. Accuracy of FNAC and CT in the differentiation of benign and malignant parotid tumours in a case series.

    Science.gov (United States)

    Gavín-Clavero, Marina A; Usón-Bouthelier, Tomás; Jariod-Ferrer, Úrsula M; Fernández-Larrañaga, Arancha; Pantilie, Bianca; Lobera-Molina, Fernando; Simón-Sanz, M Victoria; Nadal Cristóbal, Bartolomé

    2017-08-24

    Parotid tumours, in addition to the wide variety of types, are histologically complex. Differentiating between benign and malignant tumours in preoperative diagnosis is important in deciding the type of surgery required. Fine needle aspiration cytology (FNAC) is a simple, quick, low-cost, low-invasive and well-tolerated tool used in the preoperative diagnosis of these tumours. we calculated the sensitivity, specificity, predictive positive value (PPV) and negative predictive value (NPV) of FNAC and computed tomography (CT) in the differentiation of benign and malignant parotid tumours operated between 2010 to 2014 in the oral and maxillofacial surgery department of the University Hospital Miguel Servet. The sensitivity of FNAC is 50%, while the specificity is high, at 98.7%. FNAC offers high reliability in the diagnosis of malignant tumours, despite its low sensitivity. However, when the diagnosis is indeterminate or benign, other than pleomorphic adenoma or Whartin tumour, the reliability to exclude malignancy decreases. The low sensitivity of FNAC to differentiate malignant from benign parotid tumours, means that we cannot rule out other diagnostic tests, clinical symptoms and especially the intraoperative vision of each surgeon. Especially when the diagnosis is indeterminate. Nevertheless, it is a technique used in a systematised way and helps in pre-surgical decision-making. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  18. Differential expression of two fibroblast growth factor-receptor genes is associated with malignant progression in human astrocytomas

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, F.; Saya, H.; Bruner, J.M.; Morrison, R.S. (Univ. of Texas M.D. Anderson Cancer Center, Houston, TX (United States))

    1994-01-18

    Malignant astrocytomas, which are highly invasive, vascular neoplasms, compose the majority of nervous system tumors in humans. Elevated expression of fibroblast growth factors (FGFs) in astrocytomas has implicated the FGF family of mitogens in the initiation and progression of astrocyte-derived tumors. In this study, the authors demonstrated that human astrocytomas undergo parallel changes in FGF-receptor (FGFR) expression during their progression from a benign to a malignant phenotype. FGFR type 2 (BEK) expression was abundant in normal white matter and in all low-grade astrocytomas but was not seen in malignant astrocytomas. Conversely, FGFR type 1 (FLG) expression was absent or barely detectable in normal white matter but was significantly elevated in malignant astrocytomas. Malignant astrocytomas also expressed an alternatively spliced form of FGFR-1 (FGFR-1[beta]) containing two immunoglobulin-like disulfide loops, whereas normal human adult and fetal brains expressed a receptor form (FGFR-1[alpha]) containing three immunoglobulin-like disulfide loops. Intermediate grades of astrocytic tumors exhibited a gradual loss of FGFR-2 and a shift in expression from FGFR-1[alpha] to FGFR-2 and a shift in expression from FGFR-1[alpha] to FGFR-1[beta] as they progressed from benign to malignant phenotype. These results suggest that differential expression and alternative splicing of FGFRs may be critical in the malignant progression of astrocytic tumors.

  19. Pilot study: Raman spectroscopy in differentiating premalignant and malignant oral lesions from normal mucosa and benign lesions in humans.

    Science.gov (United States)

    Guze, Kevin; Pawluk, Hanna C; Short, Michael; Zeng, Haishan; Lorch, Jochen; Norris, Charles; Sonis, Stephen

    2015-04-01

    Current practice for differentiating tissue lesions are based on histopathological criteria. This process is subject to error. The purpose of this study was to test whether an alternative, tissue-based molecular signatures Raman spectra could be used to differentiate premalignant and malignant lesions from normal mucosa or benign lesions. Eighteen treatment naive subjects with histologically diagnosed oral disease were studied by comparing the Raman spectra of lesions with contralateral healthy sites. Principle component and multivariate analysis were used to predict which of the tissue groups the average spectrum of each lesion or normal tissue belonged. The average spectra were clearly different between premalignant and malignant lesions and those derived from normal, benign tissues. Premalignant and malignant lesions could be predicted with 100% sensitivity and 77% specificity. Raman spectroscopy (RS) offers the potential to provide point of care diagnosis of oral disease using a noninvasive, convenient, and relatively inexpensive technology. © 2014 Wiley Periodicals, Inc.

  20. Tumor Proteins D52 and D54 Have Opposite Effects on the Terminal Differentiation of Chondrocytes

    Directory of Open Access Journals (Sweden)

    Chihiro Ito

    2017-01-01

    Full Text Available The tumor protein D (TPD family consists of four members, TPD52, TPD53, TPD54, and TPD55. The physiological roles of these genes in normal tissues, including epidermal and mesenchymal tissues, have rarely been reported. Herein, we examined the expression of TPD52 and TPD54 genes in cartilage in vivo and in vitro and investigated their involvement in the proliferation and differentiation of chondrocytes in vitro. TPD52 and TPD54 were uniformly expressed in articular cartilage and trabecular bone and were scarcely expressed in the epiphyseal growth plate. In MC3T3E-1 cells, the expressions of TPD52 and TPD54 were increased in a differentiation-dependent manner. In contrast, their expressions were decreased in ATDC5 cells. In ATDC5 cells, overexpression of TPD52 decreased alkaline phosphatase (ALPase activity, while knock-down of TPD52 showed little effect. In contrast, overexpression of TPD54 enhanced ALPase activity, Ca2+ deposition, and the expressions of type X collagen and ALPase genes, while knock-down of TPD54 reduced them. The results revealed that TPD52 inhibits and that TPD54 promotes the terminal differentiation of a chondrocyte cell line. As such, we report for the first time the important roles of TPD52 and TPD54, which work oppositely, in the terminal differentiation of chondrocytes during endochondral ossification.

  1. Comparison of magnetic resonance elastography and diffusion-weighted imaging for differentiating benign and malignant liver lesions

    Energy Technology Data Exchange (ETDEWEB)

    Hennedige, Tiffany P.; Hallinan, James Thomas Patrick Decourcy; Teo, Lynette Li San [National University Hospital, National University Health System, Department of Diagnostic Imaging, Singapore (Singapore); Leung, Fiona P. [National University Hospital, National University Health System, Department of Diagnostic Imaging, Singapore (Singapore); South West Radiology, Liverpool, NSW (Australia); Iyer, Sridhar; Chang, Stephen; Madhavan, Krishna Kumar [National University Health System, Department of Surgery, Singapore (Singapore); Wang, Gang [National University Hospital, National University Health System, Department of Diagnostic Imaging, Singapore (Singapore); University of Calgary, Alberta (Canada); Wee, Aileen [National University Hospital, National University Health System, Department of Pathology, Singapore (Singapore); Venkatesh, Sudhakar K. [Mayo Clinic, Department of Radiology, Rochester, MN (United States)

    2016-02-15

    Comparison of magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) for differentiating malignant and benign focal liver lesions (FLLs). Seventy-nine subjects with 124 FLLs (44 benign and 80 malignant) underwent both MRE and DWI. MRE was performed with a modified gradient-echo sequence and DWI with a free breathing technique (b = 0.500). Apparent diffusion coefficient (ADC) maps and stiffness maps were generated. FLL mean stiffness and ADC values were obtained by placing regions of interest over the FLLs on stiffness and ADC maps. The accuracy of MRE and DWI for differentiation of benign and malignant FLL was compared using receiver operating curve (ROC) analysis. There was a significant negative correlation between stiffness and ADC (r = -0.54, p < 0.0001) of FLLs. Malignant FLLs had significantly higher mean stiffness (7.9kPa vs. 3.1kPa, p < 0.001) and lower mean ADC (129 vs. 200 x 10{sup -3}mm{sup 2}/s, p < 0.001) than benign FLLs. The sensitivity/specificity/positive predictive value/negative predictive value for differentiating malignant from benign FLLs with MRE (cut-off, >4.54kPa) and DWI (cut-off, <151 x 10{sup -3}mm{sup 2}/s) were 96.3/95.5/97.5/93.3 % (p < 0.001) and 85/81.8/88.3/75 % (p < 0.001), respectively. ROC analysis showed significantly higher accuracy for MRE than DWI (0.986 vs. 0.82, p = 0.0016). MRE is significantly more accurate than DWI for differentiating benign and malignant FLLs. (orig.)

  2. Usefulness of acoustic radiation force impulse elastography in the differential diagnosis of benign and malignant solid pancreatic lesions

    Directory of Open Access Journals (Sweden)

    Min Kyoung Park

    2014-01-01

    Conclusion:

    ARFI elastography can determine the relative stiffness between a lesion and the background pancreatic parenchyma using VTI and VTQ, which is helpful in the differentiation between benign and malignant solid pancreatic lesions.

  3. Free breathing DCE-MRI with motion correction and its values for benign and malignant liver tumor differentiation

    Directory of Open Access Journals (Sweden)

    Xiaolin Zheng

    2015-09-01

    Conclusion: Dynamic contrast-enhanced MRI combined with tracer kinetic model and non-rigid registration was a feasible method for diagnosing of liver lesions under free breezing mode. In our approach, the contrast agent transfer rate Ktrans was a good biomarker to differentiate benign and malignant tumors of liver.

  4. FDG-PET/CT and FLT-PET/CT for differentiating between lipid-poor benign and malignant adrenal tumours

    Energy Technology Data Exchange (ETDEWEB)

    Nakajo, Masatoyo; Jinguji, Megumi; Fukukura, Yoshihiko; Nakabeppu, Yoshiaki; Nakamura, Fumihiko; Yoshiura, Takashi [Kagoshima University, Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Kajiya, Yoriko; Tani, Atushi; Nakajo, Masayuki [Nanpuh Hospital, Department of Radiology, Kagoshima (Japan); Arimura, Hiroshi; Nishio, Yoshihiko [Kagoshima University, Department of Diabetes and Endocrine Medicine, Graduate School of Medical and Dental Sciences, Kagoshima (Japan)

    2015-12-15

    To compare F-18-fluorodeoxyglucose (FDG) and F-18-fluorothymidine (FLT) PET/CT examinations for differentiating between benign and malignant adrenal tumours. Thirty lipid-poor benign and 11 malignant tumours of 40 patients were included. FDG- and FLT-based indices including visual score, maximum standardized uptake value (SUVmax) and FDG adrenal lesion/liver SUVmax (A/L SUVmax) or FLT adrenal lesion/back muscle SUVmax (A/B SUVmax) ratio were compared between benign and malignant tumours using the Mann-Whitney's U or Wilcoxon signed-rank test, and their diagnostic performances were evaluated by means of the area under the curve (AUC) values derived from the receiver operating characteristic analysis. All indices were significantly higher in malignant than benign tumours on both images (p < 0.05 each). On FDG-PET/CT, the sensitivity, specificity, and accuracy were 91 %, 63 % and 71 % for visual score, 91 %, 67 % and 73 % for SUVmax, and 100 %, 70 % and 78 % for A/L SUVmax ratio, respectively. On FLT-PET/CT, they were 100 %, 97 % and 98 % for visual score, SUVmax and A/B SUVmax ratio, respectively. All FLT indices were significantly higher than those of FDG in AUC (p < 0.05 each). FLT-PET/CT may be superior to FDG-PET/CT in differentiating lipid-poor benign from malignant adrenal tumours because of higher specificity and accuracy. (orig.)

  5. Frequency analysis of multispectral photoacoustic images for differentiating malignant region from normal region in excised human prostate

    Science.gov (United States)

    Sinha, Saugata; Rao, Navalgund A.; Valluru, Keerthi S.; Chinni, Bhargava K.; Dogra, Vikram S.; Helguera, Maria

    2014-03-01

    Frequency domain analysis of the photoacoustic (PA) radio frequency signals can potentially be used as a tool for characterizing microstructure of absorbers in tissue. This study investigates the feasibility of analyzing the spectrum of multiwavelength PA signals generated by excised human prostate tissue samples to differentiate between malignant and normal prostate regions. Photoacoustic imaging at five different wavelengths, corresponding to peak absorption coefficients of deoxyhemoglobin, whole blood, oxyhemoglobin, water and lipid in the near infrared (NIR) (700 nm - 1000 nm) region, was performed on freshly excised prostate specimens taken from patients undergoing prostatectomy for biopsy confirmed prostate cancer. The PA images were co-registered with the histopathology images of the prostate specimens to determine the region of interest (ROI) corresponding to malignant and normal tissue. The calibrated power spectrum of each PA signal from a selected ROI was fit to a linear model to extract the corresponding slope, midband fit and intercept parameters. The mean value of each parameter corresponding to malignant and adjacent normal prostate ROI was calculated for each of the five wavelengths. The results obtained for 9 different human prostate specimens, show that the mean values of midband fit and intercept are significantly different between malignant and normal regions. In addition, the average midband fit and intercept values show a decreasing trend with increasing wavelength. These preliminary results suggest that frequency analysis of multispectral PA signals can be used to differentiate malignant region from the adjacent normal region in human prostate tissue.

  6. Usefulness of acoustic radiation force impulse elastography in the differential diagnosis of benign and malignant solid pancreatic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Park, Min Kyoung; Jo, Jeong Hyun; Kwon, Hee Jin; Cho, Jin Han; Oh, Jong Young; Noh, Myung Hwan; Nam, Kyung Jin [Dong-A University College of Medicine, Busan (Korea, Republic of)

    2014-03-15

    The aim of this study was to evaluate the tissue stiffness of solid pancreatic lesions by using acoustic radiation force impulse (ARFI) elastography to differentiate benign from malignant pancreatic lesions. ARFI elastography was performed in 26 patients who had 27 focal solid pancreatic lesions, including 8 benign lesions (mass-forming pancreatitis, 5; autoimmune pancreatitis, 3) and 19 malignant lesions (pancreatic adenocarcinoma, 16; metastasis from colorectal cancer, 2; malignant neuroendocrine tumor, 1). On the elastographic images of virtual touch tissue imaging (VTI), the echogenicity of the mass was categorized on a 5-grade scale. On the elastographic image of virtual touch tissue quantification (VTQ), the shear wave velocities (SWVs) of the lesion and surrounding parenchyma were measured. On the VTI images, the mean echogenicity score of the malignant lesions (3.7±1.0) was higher than that of the benign lesions (3.1±0.4; P=0.023). On the VTQ images, there were no statistical differences in the mean SWV between the benign (2.4±1.1 m/sec) and malignant (3.3±1.0 m/sec) lesions (P=0.101). However, the mean SWV difference values between the lesion and background parenchyma of the malignant lesions (1.5±0.8 m/sec) were higher than those of the benign lesions (0.4±0.3 m/sec; P=0.011). ARFI elastography can determine the relative stiffness between a lesion and the background pancreatic parenchyma using VTI and VTQ, which is helpful in the differentiation between benign and malignant solid pancreatic lesions.

  7. Conditional deletion of Tgfbr2 in hypertrophic chondrocytes delays terminal chondrocyte differentiation.

    Science.gov (United States)

    Sueyoshi, Tatsuya; Yamamoto, Koji; Akiyama, Haruhiko

    2012-07-01

    Transforming growth factor β (Tgfb) signaling plays an important role in endochondral ossification. Previous studies of mice in which the Tgfb type II receptor gene (Tgfbr2) was deleted in the limb bud mesenchymal cells or differentiated chondrocytes showed defects in the development of the long bones or the axial skeleton, respectively. Here, we generated mouse embryos in which the Tgfbr2 gene was ablated in hypertrophic chondrocytes. These mice exhibited delays in both the hypertrophic conversion of proliferating chondrocytes and the subsequent terminal chondrocyte differentiation. The expression domains of Col10a1, Matrix metalloproteinase 13, and Osteopontin were small, and the expression of Vascular endothelial growth factor and Platelet endothelial cell adhesion molecule was downregulated. The calcification of the bone collar in the mutant mice was markedly delayed and the periosteum was thin, possibly because of the downregulation of Indian hedgehog expression. We conclude that Tgfb signaling in hypertrophic chondrocytes positively regulates terminal chondrocyte differentiation, angiogenesis in calcified cartilage, and osteogenesis in the bone collar, at least partly through Indian hedgehog signaling in vivo. Copyright © 2012 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  8. Differentiation between benign and malignant colon tumors using fast dynamic gadolinium-enhanced MR colonography; a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Achiam, M.P., E-mail: achiam1@dadlnet.d [Department of Diagnostic Radiology, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Andersen, L.P.H.; Klein, M. [Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Logager, V.; Chabanova, E.; Thomsen, H.S. [Department of Diagnostic Radiology, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark); Rosenberg, J. [Department of Surgical Gastroenterology D, Copenhagen University Hospital Herlev, Herlev Ringvej, DK-2730 Herlev (Denmark); Department of Diagnostic Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3C, DK-2200 Copenhagen (Denmark)

    2010-06-15

    Background: Colorectal cancer will present itself as a bowel obstruction in 16-23% of all cases. However, not all obstructing tumors are malignant and the differentiation between a benign and a malignant tumor can be difficult. The purpose of our study was to determine whether fast dynamic gadolinium-enhanced MR imaging combined with MR colonography could be used to differentiate a benign from a malignant obstructing colon tumor. Methods: Patients with benign colon tumor stenosis, based on diverticulitis, were asked to participate in the study. The same number of patients with verified colorectal cancer was included. Both groups had to be scheduled for surgery to be included. Two blinded observers analyzed the tumors on MR by placing a region of interest in the tumor and a series of parameters were evaluated, e.g. wash-in, wash-out and time-to-peak. Results: 14 patients were included. The wash-in and wash-out rates were significantly different between the benign and malignant tumors, and a clear distinction between benign and malignant disease was therefore possible by looking only at the MR data. Furthermore, MR colography evaluating the rest of the colon past the stenosis was possible with all patients. Conclusion: The results showed the feasibility of using fast dynamic gadolinium-enhanced MR imaging to differentiate between benign and malignant colonic tumors. With a high intra-class correlation and significant differences found on independent segments of the tumor, the method appears to be reproducible. Furthermore, the potential is big in performing a full preoperative colon evaluation even in patients with obstructing cancer. Trial number: (NCT00114829).

  9. SHP2 regulates chondrocyte terminal differentiation, growth plate architecture and skeletal cell fates.

    Directory of Open Access Journals (Sweden)

    Margot E Bowen

    Full Text Available Loss of PTPN11/SHP2 in mice or in human metachondromatosis (MC patients causes benign cartilage tumors on the bone surface (exostoses and within bones (enchondromas. To elucidate the mechanisms underlying cartilage tumor formation, we investigated the role of SHP2 in the specification, maturation and organization of chondrocytes. Firstly, we studied chondrocyte maturation by performing RNA-seq on primary chondrocyte pellet cultures. We found that SHP2 depletion, or inhibition of the ERK1/2 pathway, delays the terminal differentiation of chondrocytes from the early-hypertrophic to the late-hypertrophic stage. Secondly, we studied chondrocyte maturation and organization in mice with a mosaic postnatal inactivation of Ptpn11 in chondrocytes. We found that the vertebral growth plates of these mice have expanded domains of early-hypertrophic chondrocytes that have not yet terminally differentiated, and their enchondroma-like lesions arise from chondrocytes displaced from the growth plate due to a disruption in the organization of maturation and ossification zones. Furthermore, we observed that lesions from human MC patients also display disorganized chondrocyte maturation zones. Next, we found that inactivation of Ptpn11 in Fsp1-Cre-expressing fibroblasts induces exostosis-like outgrowths, suggesting that loss of SHP2 in cells on the bone surface and at bone-ligament attachment sites induces ectopic chondrogenesis. Finally, we performed lineage tracing to show that exostoses and enchondromas in mice likely contain mixtures of wild-type and SHP2-deficient chondrocytes. Together, these data indicate that in patients with MC, who are heterozygous for inherited PTPN11 loss-of-function mutations, second-hit mutations in PTPN11 can induce enchondromas by disrupting the organization and delaying the terminal differentiation of growth plate chondrocytes, and can induce exostoses by causing ectopic chondrogenesis of cells on the bone surface. Furthermore, the

  10. Vorinostat induces apoptosis and differentiation in myeloid malignancies: genetic and molecular mechanisms.

    Directory of Open Access Journals (Sweden)

    Gabriela Silva

    Full Text Available BACKGROUND: Aberrant epigenetic patterns are central in the pathogenesis of haematopoietic diseases such as myelodysplastic syndromes (MDS and acute myeloid leukaemia (AML. Vorinostat is a HDACi which has produced responses in these disorders. The purpose of this study was to address the functional effects of vorinostat in leukemic cell lines and primary AML and MDS myeloid cells and to dissect the genetic and molecular mechanisms by which it exerts its action. METHODOLOGY/PRINCIPAL FINDINGS: Functional assays showed vorinostat promoted cell cycle arrest, inhibited growth, and induced apoptosis and differentiation of K562, HL60 and THP-1 and of CD33(+ cells from AML and MDS patients. To explore the genetic mechanism for these effects, we quantified gene expression modulation by vorinostat in these cells. Vorinostat increased expression of genes down-regulated in MDS and/or AML (cFOS, COX2, IER3, p15, RAI3 and suppressed expression of genes over-expressed in these malignancies (AXL, c-MYC, Cyclin D1 and modulated cell cycle and apoptosis genes in a manner which would favor cell cycle arrest, differentiation, and apoptosis of neoplastic cells, consistent with the functional assays. Reporter assays showed transcriptional effect of vorinostat on some of these genes was mediated by proximal promoter elements in GC-rich regions. Vorinostat-modulated expression of some genes was potentiated by mithramycin A, a compound that interferes with SP1 binding to GC-rich DNA sequences, and siRNA-mediated SP1 reduction. ChIP assays revealed vorinostat inhibited DNA binding of SP1 to the proximal promoter regions of these genes. These results suggest vorinostat transcriptional action in some genes is regulated by proximal promoter GC-rich DNA sequences and by SP1. CONCLUSION: This study sheds light on the effects of vorinostat in AML and MDS and supports the implementation of clinical trials to explore the use of vorinostat in the treatment of these diseases.

  11. A simple and robust classification tree for differentiation between benign and malignant lesions in MR-mammography

    Energy Technology Data Exchange (ETDEWEB)

    Baltzer, Pascal A.T. [Medical University Vienna, Department of Radiology, Vienna (Austria); Dietzel, Matthias [University hospital Erlangen, Department of Neuroradiology, Erlangen (Germany); Kaiser, Werner A. [University Hospital Jena, Institute of Diagnostic and Interventional Radiology 1, Jena (Germany)

    2013-08-15

    In the face of multiple available diagnostic criteria in MR-mammography (MRM), a practical algorithm for lesion classification is needed. Such an algorithm should be as simple as possible and include only important independent lesion features to differentiate benign from malignant lesions. This investigation aimed to develop a simple classification tree for differential diagnosis in MRM. A total of 1,084 lesions in standardised MRM with subsequent histological verification (648 malignant, 436 benign) were investigated. Seventeen lesion criteria were assessed by 2 readers in consensus. Classification analysis was performed using the chi-squared automatic interaction detection (CHAID) method. Results include the probability for malignancy for every descriptor combination in the classification tree. A classification tree incorporating 5 lesion descriptors with a depth of 3 ramifications (1, root sign; 2, delayed enhancement pattern; 3, border, internal enhancement and oedema) was calculated. Of all 1,084 lesions, 262 (40.4 %) and 106 (24.3 %) could be classified as malignant and benign with an accuracy above 95 %, respectively. Overall diagnostic accuracy was 88.4 %. The classification algorithm reduced the number of categorical descriptors from 17 to 5 (29.4 %), resulting in a high classification accuracy. More than one third of all lesions could be classified with accuracy above 95 %. (orig.)

  12. A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies.

    Science.gov (United States)

    Drusco, Alessandra; Bottoni, Arianna; Laganà, Alessandro; Acunzo, Mario; Fassan, Matteo; Cascione, Luciano; Antenucci, Anna; Kumchala, Prasanthi; Vicentini, Caterina; Gardiman, Marina P; Alder, Hansjuerg; Carosi, Mariantonia A; Ammirati, Mario; Gherardi, Stefano; Luscrì, Marilena; Carapella, Carmine; Zanesi, Nicola; Croce, Carlo M

    2015-08-28

    Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application.The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies.CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization.Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies.This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications.

  13. Role of polyamines in hypertrophy and terminal differentiation of osteoarthritic chondrocytes.

    Science.gov (United States)

    Facchini, A; Borzì, R M; Olivotto, E; Platano, D; Pagani, S; Cetrullo, S; Flamigni, F

    2012-02-01

    Polyamines are naturally occurring, positively charged polycations which are able to control several cellular processes in different cell types, by interacting with negatively charged compounds and structures within the living cell. Functional genomics in rodents targeting key biosynthetic or catabolic enzymes have revealed a series of phenotypic changes, many of them related to human diseases. Several pieces of evidence from the literature point at a role of polyamines in promoting chondrocyte differentiation, a process which is physiological in growth plate maturation or fracture healing, but has pathological consequences in articular chondrocytes, programmed to keep a maturational arrested state. Inappropriate differentiation of articular chondrocytes results in osteoarthritis. Thus, we have studied the effects of exogenously added spermine or spermidine in chondrocyte maturation recapitulated in 3D cultures, to tease out the effects on gene and protein expression of key chondrogenesis regulatory transcription factors, markers and effectors, as well as their posttranscriptional regulation. The results indicate that both polyamines are able to increase the rate and the extent of chondrogenesis, with enhanced collagen 2 deposition and remodeling with downstream generation of collagen 2 bioactive peptides. These were able to promote nuclear localization of RUNX-2, the pivotal transcription factor in chondrocyte hypertrophy and osteoblast generation. Indeed, samples stimulated with polyamines showed an enhanced mineralization, along with increased caspase activity, indicating increased chondrocyte terminal differentiation. In conclusion these results indicate that the polyamine pathway can represent a potential target to control and correct chondrocyte inappropriate maturation in osteoarthritis.

  14. Hepatocyte growth factor is a mouse fetal Leydig cell terminal differentiation factor.

    Science.gov (United States)

    Ricci, Giulia; Guglielmo, Maria Cristina; Caruso, Maria; Ferranti, Francesca; Canipari, Rita; Galdieri, Michela; Catizone, Angela

    2012-06-01

    The hepatocyte growth factor (HGF) is a pleiotropic cytokine and a well-known regulator of mouse embryonic organogenesis. In previous papers, we have shown the expression pattern of HGF and its receptor, C-MET, during the different stages of testis prenatal development. We demonstrated that C-MET is expressed in fetal Leydig cells (FLCs) and that HGF stimulates testosterone secretion in organ culture of late fetal testes. In the present study, we analyzed the proliferation rate, apoptotic index, and differentiation of FLCs in testicular organ culture of 17.5 days postcoitum (17.5 dpc) embryos to clarify the physiological role of HGF in late testis organogenesis. Based on our data, we conclude the following: 1) HGF acts as an antiapoptotic factor that is able to reduce the number of apoptotic FLCs and testicular caspase-3 active fragment; 2) HGF does not affect FLC proliferation; 3) HGF significantly increases expression of insulin-like 3 (INSL3), a marker of Leydig cell terminal differentiation, without affecting 3beta-hydroxysteroid dehydrogenase (3betaHSD) expression; 4) HGF significantly decreases the expression of nestin, a marker of Leydig cell progenitors; and 5) HGF significantly increases the number of fully developed FLCs. Taken together, these observations demonstrate that HGF is able to act in vitro as a survival and differentiation factor in FLC population.

  15. Necrotic cervical nodes: Usefulness of diffusion-weighted MR imaging in the differentiation of suppurative lymphadenitis from malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Hiroki, E-mail: hkato@gifu-u.ac.jp [Department of Radiology, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Kanematsu, Masayuki, E-mail: masa_gif@yahoo.co.jp [Department of Radiology, Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); High-level Imaging Diagnosis Center, Gifu University Hospital, Gifu (Japan); Kato, Zenichiro, E-mail: zenkato@mac.com [Department of Pediatrics, Gifu University School of Medicine, Gifu (Japan); Teramoto, Takahide, E-mail: t-tera@gifu-u.ac.jp [Department of Pediatrics, Gifu University School of Medicine, Gifu (Japan); Mizuta, Keisuke, E-mail: kmizuta@gifu-u.ac.jp [Department of Otolaryngology, Gifu University School of Medicine, Gifu (Japan); Aoki, Mitsuhiro, E-mail: aoki@gifu-u.ac.jp [Department of Otolaryngology, Gifu University School of Medicine, Gifu (Japan); Makita, Hiroki, E-mail: makitah@gifu-u.ac.jp [Department of Oral and Maxillofacial Sciences, Gifu University School of Medicine, Gifu (Japan); Kato, Keizo, E-mail: keizo@gifu-u.ac.jp [Department of Oral and Maxillofacial Sciences, Gifu University School of Medicine, Gifu (Japan)

    2013-01-15

    Purpose: The purpose of this study was to assess the efficacy of diffusion-weighted (DW) MR imaging for the differentiation between suppurative lymphadenitis and malignancy in necrotic cervical lymph nodes. Materials and methods: Fifteen patients with suppurative lymphadenitis, 40 with squamous cell carcinoma (SCC), eight with lymphoma, and six with thyroid cancer were accompanied by necrotic cervical nodes. All 69 patients underwent 1.5-T MR imaging including DW and 58 underwent gadolinium-enhanced MR imaging. Necrotic area-to-spinal cord signal intensity ratios (SIR) on T1-, T2- and DW images and apparent diffusion coefficients (ADCs) [10{sup −3} mm{sup 2}/s] were correlated with the pathologies. Results: Nineteen necrotic cervical nodes with suppurative lymphadenitis, 67 with SCC, 10 with lymphoma, and 12 with thyroid cancer were identified. SIR on DW images was higher in suppurative lymphadenitis (2.50 ± 1.21) than in malignancies (1.29 ± 0.67) (p < .01), and ADC value was lower in suppurative lymphadenitis (0.89 ± 0.21) than in malignancies (1.46 ± 0.46) (p < .01). SIR on T1-weighted images was higher in thyroid cancer (1.95 ± 0.53) than in suppurative lymphadenitis (0.87 ± 0.17), SCC (0.92 ± 0.13), and lymphoma (0.95 ± 0.09) (p < .01). No significant difference in SIR on T2-weighted images was found between suppurative lymphadenitis (1.46 ± 0.50) and malignancies (1.61 ± 0.56). Conclusion: DW imaging with ADC measurements may play a supplementary role in the differentiation of necrotic cervical nodes between suppurative lymphadenitis and malignancy.

  16. Comparison of shear-wave and strain ultrasound elastography in the differentiation of benign and malignant breast lesions.

    Science.gov (United States)

    Chang, Jung Min; Won, Jae-Kyung; Lee, Kyoung-Bun; Park, In Ae; Yi, Ann; Moon, Woo Kyung

    2013-08-01

    The purpose of this article is to compare the diagnostic performances of shearwave and strain elastography for the differentiation of benign and malignant breast lesions. B-mode ultrasound and shear-wave and strain elastography were performed in 150 breast lesions; 71 were malignant. BI-RADS final assessment, elasticity values in kilopascals, and elasticity scores on a 5-point scale were assessed before biopsy. The results were compared using the area under the receiver operating characteristic curve (AUC). The AUC for shear-wave elastography was similar to that of strain elastography (0.928 vs 0.943). The combined use of B-mode ultrasound and either elastography technique improved diagnostic performance in the differentiation of benign and malignant breast lesions compared with the use of B-mode ultrasound alone (B-mode alone, AUC = 0.851; B-mode plus shear-wave elastography, AUC = 0.964; B-mode plus strain elastography, AUC = 0.965; p < 0.001). With the best cutoff points of 80 kPa on shear-wave elastography and a score between 3 and 4 on strain elastography, the sensitivity was higher in shear-wave elastography, and specificity was higher in strain elastography (95.8% vs 81.7%, p = 0.002; 93.7% vs 84.8%, p = 0.016). In cases of infiltrating ductal carcinoma, mean elasticity scores were lower in grade 3 than in grade 1 and 2 cancers (p = 0.017) with strain elastography causing false-negative findings. The diagnostic performance of shear-wave and strain elastography was similar. Either elastography technique can improve overall diagnostic performance in the differentiation of benign and malignant lesions when combined with B-mode ultrasound. However, the sensitivity and specificity of shear-wave and strain elastography were different according to lesion histologic profile, tumor grade, and breast thickness.

  17. Study of Nitrogen terminated doped zigzag GNR FET exhibiting negative differential resistance

    Science.gov (United States)

    Gupta, Santosh Kumar; Jaiswal, Girija Nandan

    2015-10-01

    This paper presents the study of Gallium and Aluminum doped Nitrogen terminated zigzag Graphene Nano Ribbon (GNR) FET with high-k dielectric. The GNR FET structure has been designed and simulated using Quantumwise Atomistix Toolkit software package. The presented GNR FET with n-type (Nitrogen doped) electrodes and p-type (Gallium or Aluminum doped) scattering region are simulated and analyzed using Density Functional Theory combined with NEGF formalism and Device Density of States (DDOS). The device shows a negative differential resistance phenomenon which can be controlled by the gate of the zigzag GNR FET. It is found that doping of Gallium and Aluminum in scattering region provides higher drain current, higher ION/IOFF and IP/IV ratios as compared to that of Boron doped zigzag GNR FET. The potential applications of the device are in logical, high frequency, and memory devices.

  18. Phorbol ester-induced terminal differentiation is inhibited in human U-937 monoblastic cells expressing a v-myc oncogene

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, L.G.; Ivhed, I.; Gidlund, M.; Pettersson, U.; Vennstroem, B.; Nilsson, K.

    1988-04-01

    Induction of differentiation of the human monoblastic cell line U-937 in vitro by several physiologic and nonphysiologic inducers is accompanied by a rapid decrease in expression of MYC, the endogenous human myc protooncogene. To investigate whether this reduction is a prerequisite for terminal differentiation. The authors introduced a constitutively expressed v-myc gene into U-937 cells. The results show that constitutive expression of an avian v-myc oncogene does not interfere with phorbol 12-myristate 13-acetate-induced differentiation of U-937 cells early after stimulation. However, after 24 hr the differentiation process is reversed, as judged by a full recovery of the proliferative capacity and reexpression of the immature phenotype, within the next 2-4 days. They conclude that the terminal stage of macrophage differentiation is inhibited in U-937 cells constitutively expressing a v-myc oncogene.

  19. Apparent diffusion coefficient measurements in the differentiation between benign and malignant neck masses

    Directory of Open Access Journals (Sweden)

    Faten Salem

    2014-06-01

    Conclusion: ADC value calculation are promising noninvasive imaging approach that can be used in distinguishing between benign and malignant neck masses. Benign lesions have higher mean ADC values than malignant lesions, the cutoff value was 1.25 × 10-3 mm2/s while 0.8 × 10-3 mm2/s in thyroid lesions.

  20. {sup 18}F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Kenji; Shiga, Tohru; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo, Hokkaido (Japan); Terasaka, Shunsuke; Kobayashi, Hiroyuki; Yamaguchi, Shigeru; Houkin, Kiyohiro [Graduate School of Medicine, Hokkaido University, Department of Neurosurgery, Sapporo (Japan); Hattori, Naoya [Graduate School of Medicine, Hokkaido University, Department of Molecular Imaging, Sapporo (Japan); Magota, Keiichi [Hokkaido University Hospital, Department of Radiology, Sapporo (Japan); Tanaka, Shinya [Graduate School of Medicine, Hokkaido University, Department of Cancer Pathology, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan)

    2012-05-15

    Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that {sup 18}F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas. This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and {sup 18}F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated. Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p {<=} 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 {+-} 0.60, range 1.71-3.81) than in non-GBM patients (1.22 {+-} 0.06, range 1.09-1.29, p {<=} 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also

  1. Constitutive β-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality

    Energy Technology Data Exchange (ETDEWEB)

    Bao, Quanwei; Chen, Sixu; Qin, Hao [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China); Feng, Jianquan [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A& M Health Science Center, Dallas, TX 75246 (United States); Liu, Huayu; Liu, Daocheng; Li, Ang; Shen, Yue; Zhong, Xiaozheng; Li, Junfeng [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China); Zong, Zhaowen, E-mail: zongzhaowen@sina.cn [State Key Laboratory of Trauma, Burn and Combined injury, Department of Trauma Surgery, Daping Hospital, Third Military Medical University, ChongQing 400042 (China)

    2017-01-01

    Accumulating evidence suggests that Wnt/β-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of β-catenin (CA-β-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-β-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-β-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-β-catenin mice. Then the effect of CA-β-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-β-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-β-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-β-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-β-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-β-catenin mice. In summary, osteoblastic CA-β-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength. - Highlights: • Wnt/β-catenin signaling plays a central role in controlling bone mass. • CA-β-catenin has side effects on the bone

  2. Differentiating benign from malignant solid breast masses: value of shear wave elastography according to lesion stiffness combined with greyscale ultrasound according to BI-RADS classification

    National Research Council Canada - National Science Library

    Evans, A; Whelehan, P; Thomson, K; Brauer, K; Jordan, L; Purdie, C; McLean, D; Baker, L; Vinnicombe, S; Thompson, A

    2012-01-01

    The aim of this study was to assess the performance of shear wave elastography combined with BI-RADS classification of greyscale ultrasound images for benign/malignant differentiation in a large group of patients...

  3. The differentiation of malignant and benign musculoskeletal tumors by F-18 FDG PET/CT studies-determination of maxSUV by analysis of ROC curve

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Eun Jung; Cho, Ihn Ho; Chun, Kyung Ah; Won, Kyu Chang; Lee, Hyung Woo; Choi, Jun Heok; Shin, Duk Seop [Yeungnam University College of Medicine, Daegu (Korea, Republic of)

    2007-12-15

    We evaluated the standard uptake value (SUV) of F-18 FDG at PET/CT for differentiation of benign from malignant tumor in primary musculoskeletal tumors. Forty-six tumors (11 benign and 12 malignant soft tissue tumors, 9 benign and 14 malignant bone tumors) were examined with F-18 FDG PET/CT (Discovery ST, GE) prior to tissue diagnosis. The maxSUV(maximum value of SUV) were calculated and compared between benign and malignant lesions. The lesion analysis was based on the transverse whole body image. The maxSUV with cutoff of 4.1 was used in distinguishing benign from malignant soft tissue tumor and 3.05 was used in bone tumor by ROC curve. There was a statistically significant difference in maxSUV between benign (n = 11; maxSUV 3.4 {+-} 3.2) and malignant (n = 12; maxSUV 14.8 {+-} 12.2) lesion in soft tissue tumor ({rho} = 0.001). Between benign bone tumor (n = 9; maxSUV 5.4 {+-} 4.0) and malignant bone tumor (n = 14; maxSUV 7.3 {+-} 3.2), there was not a significant difference in maxSUV. The sensitivity and specificity for differentiating malignant from benign soft tissue tumor was 83% and 91%, respectively. There were four false positive malignant bone tumor cases to include fibrous dysplasia, Langerhans-cell histiocytosis (n = 2) and osteoid osteoma. Also, one false positive case of malignant soft tissue tumor was nodular fasciitis. The maxSUV was useful for differentiation of benign from malignant lesion in primary soft tissue tumors. In bone tumor, the low maxSUV correlated well with benign lesions but high maxSUV did not always mean malignancy.

  4. Sono-elastography for differentiating benign and malignant cervical lymph nodes: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Mahsa Ghajarzadeh

    2014-01-01

    Full Text Available We did this systematic review to determine diagnostic accuracy of sono-elastography in evaluating cervical lymph nodes (LNs. A highly sensitive search for sono-elastography and LNs was performed in MEDLINE, Cochrane Library, ACP Journal Club, EMBASE, Health Technology assessment, and ISI web of knowledge for studies published prior to December 2012. SPSS version 18 (SPSS Inc., Chicago, IL, USA used for descriptive analysis and meta-disk version 1.4 applied for meta-analysis. Forest plots for pooled estimates and summery of receiver operating characteristic plots for different cut-offs were produced. The literature and manual search yielded 69 articles, of which 10 were eligible to include. A total of 578 individuals with a total number of 936 cervical LNs was evaluated (502 malignant and 434 benign. The summary sensitivity of the scoring and strain ratio (SR measurements for the differentiation of benign and malignant LNs were 0.76 (95% CI: 0.71-0.8 and 0.83 (95% CI: 0.78-0.87. The summary specificities were 0.8 (95% confidence interval [CI]: 0.75-0.84 and 0.84 (95% CI: 0.79-0.88, respectively. Area under the curve for scoring system was 0.86 (standard error [SE] = 0.03 and 0.95 (SE = 0.02 for SR measurement. Sono-elastograohy has high accuracy in differentiating benign and malignant cervical LNs.

  5. Diffusion-weighted MR imaging for differentiating borderline from malignant epithelial tumours of the ovary: pathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Shu Hui; Qiang, Jin Wei; Ma, Feng Hua; Cai, Song Qi; Li, Hai Ming [Fudan University, Department of Radiology, Jinshan Hospital, Shanghai (China); Zhang, Guo Fu [Fudan University, Department of Radiology, Obstetrics and Gynecology Hospital, Shanghai (China); Wang, Li [Fudan University, Department of Pathology, Jinshan Hospital, Shanghai (China)

    2014-09-15

    To investigate diffusion-weighted (DW) magnetic resonance (MR) imaging for differentiating borderline from malignant epithelial tumours of the ovary. This retrospective study included 60 borderline epithelial ovarian tumours (BEOTs) in 48 patients and 65 malignant epithelial ovarian tumours (MEOTs) in 54 patients. DW imaging as well as conventional MR imaging was performed. Signal intensity on DW imaging was assessed and apparent diffusion coefficient (ADC) value was measured. The results were correlated with histopathology and cell density. The majority of MEOTs showed high signal intensity on DW imaging, whereas most BEOTs showed low or moderate signal intensity (P = 0.000). The mean ADC value of the solid components in BEOTs (1.562 ± 0.346 x 10{sup -3} mm{sup 2}/s) was significantly higher than in MEOTs (0.841 ± 0.209 x 10{sup -3} mm{sup 2}/s). A threshold value of 1.039 x 10{sup -3} mm{sup 2}/s permitted the distinction with a sensitivity of 97.0 %, a specificity of 92.2 % and an accuracy of 96.4 %. There was an inverse correlation between ADC value and cell density (r = -0.609; P = 0.0000) which was significantly lower in BEOTs than in MEOTs. DW imaging is useful for differentiating borderline from malignant epithelial tumours of the ovary. (orig.)

  6. Diagnostic Value of ARFI (Acoustic Radiation Force Impulse) in Differentiating Benign From Malignant Breast Lesions.

    Science.gov (United States)

    Magalhães, Mafalda; Belo-Oliveira, Pedro; Casalta-Lopes, João; Costa, Yessica; Gonçalo, Manuela; Gomes, Paula; Caseiro-Alves, Filipe

    2017-01-01

    The aim of this study was to correlate acoustic radiation force impulse (ARFI) imaging velocities with the pathology results and to evaluate the ability of ARFI in distinguishing benign from malignant breast lesions. B-mode ultrasonography (US) and ARFI were performed in patients with previously diagnosed and selected breast lesions for biopsy. Shear wave velocity (SWV) was measured inside lesions and in the surrounding parenchyma (m/s). SWV measurements as well as lesion-to-parenchyma ratio (LPR) were compared between benign and malignant lesions, and receiver operating characteristic (ROC) curves were plotted. Two blinded readers independently classified the lesions as benign or malignant in two separate reading sessions, one using B-mode US alone and the other using a combined set of B-mode US and ARFI. Eighty-one patients with a total of 92 breast lesions were included (57 benign and 35 malignant nodules). SWV inside lesions were significantly higher for malignant neoplasms compared to benign (medians of 9.1 m/s vs 3.5 m/s; P elasticity measurements, adding valuable complementary information to B-mode ultrasound, that can potentially help in breast lesion characterization and assisting the decision for biopsy recommendations. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  7. Malignant phyllodes tumor with heterologous differentiation: Clinicopathological spectrum of nine cases in a tertiary care institute in Eastern India

    Directory of Open Access Journals (Sweden)

    Mamita Nayak

    2017-01-01

    Full Text Available Phyllodes tumors are uncommon fibroepithelial neoplasms of breast. Heterologous sarcomatous differentiation of malignant phyllodes tumor (MPT is a rare phenomenon as shown in the literature. Herein we report a series of nine cases from a tertiary care centre in Eastern India. Patients demographic data and clinical details were obtained from the medical records. Histopathology and immunohistochemical studies were analysed and diagnosed accordingly. Out of 38 cases of PT, 13 were found to be MPT, of which 9 cases showed heterologous differentiation in the form of angiosarcoma, fibrosarcoma, undifferentiated sarcoma, extensive squamous differentiation and with lipomatous metaplasia. Proper diagnosis and subtyping of the sarcomatous component is essential for deciding the correct treatment modality and prognostication of the disease. However there is no clear cut treatment protocol is available because of paucity of data.

  8. Cytological features of well-differentiated tumors of uncertain malignant potential: Indeterminate cytology and WDT-UMP.

    Science.gov (United States)

    Nishigami, Keiko; Liu, Zhiyan; Taniguchi, Emiko; Koike, Eisuke; Ozaki, Takashi; Mori, Ichiro; Kakudo, Kennichi

    2012-01-01

    The purpose of this study was to clarify the cytopathological features of well-differentiated tumors of uncertain malignant potential (WDT-UMP), a possible borderline lesion of thyroid follicular cell tumor. We analysed the cytopathological findings of fine needle aspiration (FNA) smears from 6 cases histologically diagnosed as WDT-UMP. WDT-UMP, benign and malignant lesions were compared retrospectively and morphologically. No (0%) nuclear pseudoinclusions were found in adenomatous goiter (AG), follicular adenoma (FTA) and WDT-UMP. Nuclear pseudoinclusions were increased in number in papillary thyroid carcinoma (PTC) with indeterminate cytology (0.8%) and PTC with malignant cytology (1.2%). The incidence of nuclear grooves increased gradually from AG/FTA (0%), WDT-UMP (4.5%), PTC with indeterminate cytology (6.2%) and PTC with malignant cytology (6.5%). The nuclear area of WDT-UMP, an average of 40.0 µm(2), was between that for benign AG/FTA and PTC with malignant cytology. The maximum/minimum axis of WDT-UMP (0.934) lied between that of AG/FTA and PTC. The degree of the nuclear circularity of WDT-UMP was less than that for PTC. WDT-UMP belong to indeterminate category between PTC and follicular adenoma morphologically, and this is one of the major reasons why some of PTC can be found in the indeterminate category. Questionable PTC-N including questionable nucler inclusions (artifact vacuole) may be seen in WDT-UMP, but absolute or definite nuclear inclusions with sharp border are not found in our 6 cases. Therefore this group of thyroid tumors (EnFVPTC and WDT-UMP) may be found in indeterminate category more often, because of intermediate nuclear morphology and incomplete nuclear vacuoles.

  9. Value of diffusion-weighted MR imaging in the differentiation between benign and malignant cervical lymph nodes

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    Holzapfel, Konstantin [Department of Radiology, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, D-81675 Munich (Germany)], E-mail: holzapfel@roe.med.tum.de; Duetsch, Sabrina; Fauser, Claudius [Department of Otorhinolaryngology, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, D-81675 Munich (Germany); Eiber, Matthias; Rummeny, Ernst J.; Gaa, Jochen [Department of Radiology, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, D-81675 Munich (Germany)

    2009-12-15

    Purpose: To evaluate echo-planar diffusion-weighted MR imaging (DWI) in the differentiation between benign and malignant cervical lymph nodes. Materials and methods: 35 consecutive patients with 55 enlarged (>10 mm) cervical lymph nodes underwent MR imaging at 1.5-T. DWI was performed using a single-shot echo-planar (SSEPI) MR imaging sequence with b values (b: diffusion factor) of 0, 500 and 1000 s/mm{sup 2}. Apparent diffusion coefficient (ADC) maps were reconstructed for all patients and ADC values were calculated for each lymph node. Imaging results were correlated with histopathologic findings after neck dissection or surgical biopsy, findings in PET/CT or imaging follow-up. Mann-Whitney test was used for statistical analysis and a receiver operating characteristic (ROC) curve analysis was performed. Results: Cervical lymph node enlargement was secondary to metastases from squamous cell carcinomas [n = 25], non-Hodgkin's lymphoma [n = 6], reactive lymphadenitis [n = 20], cat scratch lymphadenitis [n = 2] and sarcoidosis [n = 2]. The mean ADC values (x10{sup -3} mm{sup 2}/s) were 0.78 {+-} 0.09 for metastatic lymph nodes, 0.64 {+-} 0.09 for lymphomatous nodes and 1.24 {+-} 0.16 for benign cervical lymph nodes. ADC values of malignant lymph nodes were significantly lower than ADC values of benign lymph nodes. 94.3% of lesions were correctly classified as benign or malignant using a threshold ADC value of 1.02 x 10{sup -3} mm{sup 2}/s. Conclusion: According to our first experience, DWI using a SSEPI sequence allows reliable differentiation between benign and malignant cervical lymph nodes.

  10. Semi-quantitative and qualitative assessment of breast ultrasound elastography in differentiating between malignant and benign lesions.

    Science.gov (United States)

    Alhabshi, Sharifah Majedah Idrus; Rahmat, Kartini; Abdul Halim, Nurazidawati; Aziz, Suraya; Radhika, Sridharan; Gan, Gek Choo; Vijayananthan, Anushya; Westerhout, Caroline Judy; Mohd-Shah, Mohammad Nazri; Jaszle, Saladina; Harlina Mohd Latar, Nani; Muhammad, Rohaizak

    2013-04-01

    The purpose of this study was to evaluate the diagnostic value of qualitative and semi-quantitative assessment of ultrasound elastography in differentiating between benign and malignant breast lesions. This prospective study was conducted in two tertiary medical centers. Consecutive B-mode ultrasound and real-time elastographic images were obtained for 67 malignant and 101 benign breast lesions in 168 women. Four experienced radiologists analyzed B-mode ultrasound alone and B-mode ultrasound combined with elastography independently. Conventional ultrasound findings were classified according to the American College of Radiology Breast Imaging Reporting and Data System classification. The elastographic assessment was based on qualitative and semi-quantitative parameters (i.e., strain pattern, width ratio, strain ratio). The sensitivity and specificity of combined elastography and conventional ultrasound were significantly higher than that of conventional ultrasound alone. The sensitivity, specificity, positive predictive value and negative predictive value was 97%, 61.4%, 62.5% and 96.8%, respectively, for conventional ultrasound and 100%, 93%, 99% and 90%, respectively, for combined technique. The semi-quantitative assessment with strain ratio and width ratio in elastography were the most useful parameters in differentiating between benign and malignant breast lesions. Cut-off point values for width ratio of more than 1.1 and strain ratio of more than 5.6 showed a high predictive value of malignancy with specificities of 84% and 76%, respectively (p technique also had the best results in detecting carcinoma and could reduce the need of unnecessary biopsy for benign lesions with indeterminate or equivocal features. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  11. Can early malignant melanoma be differentiated from atypical melanocytic nevus by in vivo techniques?: Part II. Automatic machine vision classification.

    Science.gov (United States)

    Gutkowicz-Krusin, D; Elbaum, M; Szwaykowski, P; Kopf, A W

    1997-02-01

    Differentiation between early (Breslow thickness less than 1 mm) malignant melanoma (MM) and atypical melanocytic nevus (AMN) remains a challenge even to trained clinicians. The purpose of this study is to determine the feasibility of reliable discrimination between early MM and AMN with noninvasive, objective, automatic machine vision techniques. A data base of 104 digitized dermoscopic color transparencies of melanocytic lesions was used to develop and test our computer-based algorithms for classification of such lesions as malignant (MM) or benign (AMN). Histopathologic diagnoses (30 MM and 74 AMN) were used as the "gold standard" for training and testing the algorithms. A fully automatic, objective technique for differentiating between early MM and AMN from their dermoscopic digital images was developed. The multiparameter linear classifier was trained to provide 100% sensitivity for MM. In the blind test, this technique did not miss a single MM and its specificity was comparable to that of skilled dermatologists. Reliable differentiation between early MM and AMN with high sensitivity is possible using machine vision techniques to analyze digitized dermoscopic lesion images.

  12. Efficiency of diffusion weighted magnetic resonance in differentiation between benign and malignant endometrial lesions

    Directory of Open Access Journals (Sweden)

    Ahmed Elsammak

    2017-09-01

    Full Text Available Objectives: To assess the role of DW-MRI and ADC values in distinguishing benign from malignant endometrial disorders. Patients and methods: Pelvic ultrasound, conventional MRI, DW-MRI and histopathologic examinations were done for 42 female patients with abnormal vaginal bleeding. Mean ADC values of endometrial lesions were calculated and compared. Results: Endometrial malignancies showed significant low ADC values (0.82 + 1.09 × 10−3 mm2/s compared to benign lesions (1.44 + 0.15 × 10−3 mm2/s (p: 0.000. Using 1.19 × 10−3 mm2/s as cut-off value for distinguishing malignant from benign lesions achieved 88.9% sensitivity and 100% specificity. Conclusion: DW-MRI is useful in distinguishing malignant from benign endometrial lesions and tumor staging as well. Keywords: Pelvic DWI-MRI, Endometrial lesions, ADC value

  13. Differentiation of benign and malignant skeletal lesions with quantitative diffusion weighted MRI at 3 T

    Energy Technology Data Exchange (ETDEWEB)

    Ahlawat, Shivani, E-mail: sahlawa1@jhmi.edu [The Russell H. Morgan Department of Radiology & Radiological Science, The Johns Hopkins University School of Medicine, 601 North Wolfe Street, Baltimore MD 21287 (United States); Khandheria, Paras, E-mail: pkhandh1@jhmi.edu [The Russell H. Morgan Department of Radiology & Radiological Science, The Johns Hopkins University School of Medicine, 601 North Wolfe Street, Baltimore MD 21287 (United States); Subhawong, Ty K., E-mail: TSubhawong@med.miami.edu [Department of Radiology (R-109), University of Miami Leonard M. Miller Miami, FL 33101 (United States); Fayad, Laura M., E-mail: lfayad1@jhmi.edu [The Russell H. Morgan Department of Radiology & Radiological Science, The Johns Hopkins University School of Medicine, 601 North Wolfe Street, Baltimore MD 21287 (United States)

    2015-06-15

    Highlights: • DWI may have predictive value for the characterization of bone lesions. • Benign lesions have higher minimum, and mean ADC values than malignancies. • Minimum ADC has the highest accuracy in discerning benign from malignant lesion. • Minimum ADC of 0.9 × 10. • All ADC measurements were made with high inter-observer concordance. - Abstract: Objectives: To investigate the accuracy of quantitative diffusion-weighted imaging with apparent diffusion coefficient (ADC) mapping for characterizing bone lesions as benign or malignant. Methods: At 3 T, 31 subjects with intramedullary lesions imaged by DWI (b-values 50, 400, 800 s/mm{sup 2}) were included. ADC values (minimum, mean, maximum) were recorded by three observers independently. Interobserver variability and differences between ADC values in benign and malignant lesions were assessed (unpaired t-test, receiver operating characteristic (ROC) analysis). Results: Of 31 lesions, 18 were benign (osteoblastic (n = 1), chondroid (n = 6), cysts (n = 4), hemangiomatosis (n = 1), fibrous (n = 3), eosinophilic granuloma (n = 1), giant cell tumor (n = 1), osteomyelitis (n = 1)) and 13 were malignant (primary (n = 5), metastases (n = 8)). Overall, there were higher minimum (1.27 × 10{sup −3} mm{sup 2}/s vs 0.68 × 10{sup −3} mm{sup 2}/s, p < 0.001), mean (1.68 × 10{sup −3} mm{sup 2}/s vs 1.13 × 10{sup −3} mm{sup 2}/s, p < 0.001), and maximum (2.09 × 10{sup −3} mm{sup 2}/s vs 1. 7 × 10{sup −3} mm{sup 2}/s, p = 0.03). ADC values in benign lesions compared with those in malignancies. ROC analysis revealed areas under the curve for minimum, mean, and maximum ADC values of 0.91, 0.85, and 0.71, respectively. ADC measurements were made with high inter-observer concordance (ρ = 0.83–0.96). Conclusion: Quantitative ADC maps may have predictive value for the characterization of bone lesions. Benign lesions generally have higher minimum, mean, and maximum ADC values than malignancies, with the

  14. Ultrasound-based differentiation of malignant and benign thyroid Nodules: An extreme learning machine approach.

    Science.gov (United States)

    Xia, Jianfu; Chen, Huiling; Li, Qiang; Zhou, Minda; Chen, Limin; Cai, Zhennao; Fang, Yang; Zhou, Hong

    2017-08-01

    It is important to be able to accurately distinguish between benign and malignant thyroid nodules in order to make appropriate clinical decisions. The purpose of this study was to improve the effectiveness and efficiency for discriminating the malignant from benign thyroid cancers based on the Ultrasonography (US) features. There were 114 benign nodules in 106 patients (82 women and 24 men) and 89 malignant nodules in 81 patients (69 women and 12 men) included in this study. The potential of extreme learning machine (ELM) has been explored for the first time to discriminate malignant and benign thyroid nodules based on the sonographic features in ultrasound images. The influence of two key parameters (the number of hidden neurons and type of activation function) on the performance of ELM was investigated. The relationship between feature subsets obtained by the feature selection method and the classification performance of ELM was also examined. A real-life dataset was used to evaluate the effectiveness of the proposed method in terms of classification accuracy, sensitivity, specificity, and area under the ROC (receiver operating characteristic) curve (AUC). The results demonstrate that there are significant differences between the malignant and benign thyroid nodules (p-value<0.01), the most discriminative features are echogenicity, calcification, margin, composition and shape. Compared with other methods, the proposed method not only has achieved very promising classification accuracy via 10-fold cross-validation (CV) scheme, but also greatly reduced the computational cost compared to other counterparts. The proposed ELM-based approach achieves 87.72% ACC, 0.8672 AUC, 78.89% sensitivity, and 94.55% specificity. Based on the empirical analysis, the proposed ELM-based approach for thyroid cancer detection has promising potential in clinical use, and it can be of assistance as an optional tool for the clinicians. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Wavelet-packet-based texture analysis for differentiation between benign and malignant liver tumours in ultrasound images

    Science.gov (United States)

    Yoshida, Hiroyuki; Casalino, David D.; Keserci, Bilgin; Coskun, Abdulhakim; Ozturk, Omer; Savranlar, Ahmet

    2003-11-01

    The purpose of this study was to apply a novel method of multiscale echo texture analysis for distinguishing benign (hemangiomas) from malignant (hepatocellular carcinomas (HCCs) and metastases) focal liver lesions in B-mode ultrasound images. In this method, regions of interest (ROIs) extracted from within the lesions were decomposed into subimages by wavelet packets. Multiscale texture features that quantify homogeneity of the echogenicity were calculated from these subimages and were combined by an artificial neural network (ANN). A subset of the multiscale features was selected that yielded the highest performance in the classification of lesions measured by the area under the receiver operating characteristic curve (Az). In an analysis of 193 ROIs consisting of 50 hemangiomas, 87 hepatocellular carcinomas and 56 metastases, the multiscale features yielded a high Az value of 0.92 in distinguishing benign from malignant lesions, 0.93 in distinguishing hemangiomas from HCCs and 0.94 in distinguishing hemangiomas from metastases. Our new multiscale texture analysis method can effectively differentiate malignant from benign lesions, and thus has the potential to increase the accuracy of diagnosis of focal liver lesions in ultrasound images.

  16. Importance of P53, Ki-67 expression in the differential diagnosis of benign/malignant phyllodes tumors of the breast

    Directory of Open Access Journals (Sweden)

    Ulku Kucuk

    2013-01-01

    Full Text Available Background: Conventionally growth pattern, stromal overgrowth, stromal cellularity and stromal mitotic activity are the main parameters in the grading of phyllodes tumors (PTs. Recent studies revealed that both p53 and Ki-67 expressions are correlated with grade of PTs of the breast. Expression of hormone receptors and overexpression/amplification of HER2 has been studied in PTs to discover the roles of these markers as new treatment modalities. Materials and Method: We studied 26 PT cases. Seventeen benign and nine malignant PTs were re-evaluated as regards stromal cellularity mitotic activity, p53/Ki-67 expression rates and the relation between these parameters. Estrogen receptor and progesterone receptor (ER, PR positivity were determined by counting nuclear staining in five high-power fields. Also, the presence of any HER2 staining and staining patterns were documanted. Results: Stromal cellularity, mitotic rate, p53 and Ki-67 expression rates were all correlated with benign and malignant histologic subgroups (P = 0.000-0.001. Ki-67 and p53 expressions were statistically significantly correlated with histologic subgroups, stromal cellularity and mitotic rate (P < 0.005. ER and PR expressions in the epithelial component were not statistically significant between the two groups. HER2 showed different staining patterns in the epithelial component, and there was no staining in the stromal component. Conclusion: Ki-67 and p53 expression rates were statistically significantly correlated with grade of mammary PTs; therefore, they can be used in the determination of tumor grade, especially for the differential diagnosis of benign and malignant tumors. Malignant and benign tumors did not differ significantly in terms of hormone receptor and HER2 expression. HER2 expression showed different patterns in the epithelial component of the PTs.

  17. Photoacoustic imaging for differential diagnosis of benign polyps versus malignant polyps of the gallbladder: A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Chae, Hee Dong; Lee, Jae Young; Han, Joon Koo [Dept. of Radiology and Institute of Radiation Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul (Korea, Republic of); Jang, Jin Young; Kang, Mee Joo [Div. of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul (Korea, Republic of); Chang, Jin Ho; Kang, Jeeun [Sogang University, Seoul (Korea, Republic of)

    2017-09-15

    To investigate the feasibility of ex vivo multispectral photoacoustic (PA) imaging in differentiating cholesterol versus neoplastic polyps, and benign versus malignant polyps, of the gallbladder. A total of 38 surgically confirmed gallbladder polyps (24 cholesterol polyps, 4 adenomas, and 10 adenocarcinomas) from 38 patients were prospectively included in this study. The surgical specimens were set on a gel pad immersed in a saline-filled container. The PA intensities of polyps were then measured, using two separate wavelength intervals (421–647 nm and 692–917 nm). Mann-Whitney U test was performed for the comparison of normalized PA intensities between the cholesterol and neoplastic polyps, and between the benign and malignant polyps. Kruskal-Wallis test was conducted for the comparison of normalized PA intensities among the cholesterol polyps, adenomas, and adenocarcinomas. A significant difference was observed in the normalized PA intensities between the cholesterol and neoplastic polyps at 459 nm (median, 1.00 vs. 0.73; p = 0.032). Comparing the benign and malignant polyps, there were significant differences in the normalized PA intensities at 765 nm (median, 0.67 vs. 0.78; p = 0.013), 787 nm (median, 0.65 vs. 0.77; p = 0.034), and 853 nm (median, 0.59 vs. 0.85; p = 0.028). The comparison of the normalized PA intensities among cholesterol polyps, adenomas, and adenocarcinomas demonstrated marginally significant differences at 765 nm (median, 0.67 vs. 0.66 vs. 0.78, respectively; p = 0.049). These preliminary results indicate that benign versus malignant gallbladder polyps might exhibit different spectral patterns on multispectral PA imaging.

  18. Assessment of dynamic contrast-enhanced magnetic resonance imaging in the differentiation of malignant from benign orbital masses

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Ying [Department of Radiology, Shanghai Ninth People' s Hospital, Affiliated to JiaoTong University School of Medicine, Shanghai 200011 (China); Kuai, Xin-Ping [Department of Radiology, Changshu Second People' s Hospital, Jiangsu Province 215500 (China); Department of Radiology, Changzheng Hospital, Affiliated to Second Military Medical University, Shanghai 200003 (China); Chen, Xiao-Song [Comprehensive Breast Health Center, Ruijin Hospital Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai 20025 (China); Tao, Xiao-Feng, E-mail: cjr.taoxiaofeng@vip.163.com [Department of Radiology, Shanghai Ninth People' s Hospital, Affiliated to JiaoTong University School of Medicine, Shanghai 200011 (China)

    2013-09-15

    Objective: Dynamic contrast enhanced MR imaging (DCE-MRI) allows imaging of the physiology of the microcirculation. The purpose of this study was to determine the diagnostic efficacy of time intensity curve (TIC) and DCE parameters for characterization of orbital masses. Methods: Fifty-nine patients with untreated orbital lesions underwent DCE-MRI before surgery. For each lesion, peak height (PH), maximum enhancement ratio (ER{sub max}), time of peak enhancement (T{sub peak}) and maximum rise slope (Slope{sub max}) were plotted and calculated. Receiver operator characteristics (ROC) analysis was conducted to assess the appropriate cut-off value. Results: All 26 lesions that demonstrated persistent pattern (type-I) TICs were benign. Most of the masses with the washout pattern (type-III) TIC were malignant (10/14), including lymphoma (n = 6) and melanoma (n = 4). The Slope{sub max} of benign lesions was statistically lower than malignant ones, while the ER{sub max} and T{sub peak} values of benign lesions were significantly higher. No statistical difference was found in PH (P = 0.121). The AUC for ER{sub max}, T{sub peak} and Slope{sub max} in differentiating benign orbital lesions from malignant ones were 0.683, 0.837 and 0.738, respectively. In the three DCE parameters, Slope{sub max} cut-off value of 1.10 provided the highest sensitivity of 93.8%; however, the corresponding specificity was low (58.1%). The ER{sub max} cut-off value of 1.37 and T{sub peak} cut-off value of 35.14 respectively offered the best diagnostic performances. Conclusion: DCE-MRI, especially the qualitative TIC pattern and quantitative value of Slope{sub max}, ER{sub max} and T{sub peak}, could be a complementary investigation in distinguishing malignant orbital tumor from benign ones.

  19. Pattern classification of ShearWave™ Elastography images for differential diagnosis between benign and malignant solid breast masses.

    Science.gov (United States)

    Tozaki, Mitsuhiro; Fukuma, Eisuke

    2011-12-01

    ShearWave™ Elastography (SWE) provides a quantitative measurement of tissue stiffness and may improve characterization of breast masses. However, the significance of Young's modulus measurements and appropriate SWE evaluation criteria has not been established yet. To assess the usefulness of the pattern classification and Young's modulus measurements in the differential diagnosis between benign and malignant solid breast masses. Ninety-six patients (age range 18-84 years, mean 54 years) with 100 solid breast masses who underwent tissue sampling after a US examination were analyzed. We tried to create a visual pattern classification based on the SWE images. After classifying the visual patterns, the Young's modulus of the lesions was measured in every case. It was possible to classify the images into four patterns by the visual evaluation: no findings (coded blue homogeneously; Pattern 1), vertical stripe pattern artifacts (Pattern 2), a localized colored area at the margin of the lesion (Pattern 3), and heterogeneously colored areas in the interior of the lesion (Pattern 4). There were 17 Pattern 1 lesions, 14 Pattern 2 lesions, 20 Pattern 3 lesions, and 49 Pattern 4 lesions. When Patterns 1 and 2 were assumed to be benign, and Patterns 3 and 4 were assumed to be malignant, the sensitivity and specificity were 91.3% (63/69) and 80.6% (25/31), respectively. The mean Young's modulus measurements of the benign and the malignant lesions were 42 kPa and 146 kPa, respectively (P modulus of the benign lesions (50 kPa) was lower than the smallest Young's modulus of malignant lesions (61 kPa). The visual pattern classification and adding Young's modulus measurements may improve characterization of solid breast masses.

  20. [A case of spermatic granuloma difficult to differentiate from malignant tumor].

    Science.gov (United States)

    Wada, Naoki; Kato, Yuji; Iwata, Tatsuya; Numata, Atsushi; Yamaguchi, Satoshi; Hashimoto, Hiroshi; Yachiku, Sunao

    2002-09-01

    A 33-year-old man visited our hospital with complaint of painless left intrascrotal mass. A hard and rough induration in contact with the left testis was palpable. The laboratory data including beta-human churionic gonadotropin, alpha fetoprotein and lactate dehydrogenase were normal. Ultrasound sonography showed a large hypoechoic lesion at the left epididymis. Surgical exploration of this lesion indicated a malignant tumor of the epididymis or spermatic cord, and left high orchiectomy was performed. A milk-white nodule 6 cm in diameter was found in the resected specimen. Pathological diagnosis was spermatic granuloma. Fourteen cases of spermatic granuloma have been reported in the last twenty years in Japan. All of them were relatively small nodules and epididymectomy was performed for most of them. We selected radical orchiectomy because of a large nodule with suspicion of malignant lesion.

  1. CT diagnosis and differentiation of benign and malignant varieties of solitary fibrous tumor of the pleura

    Science.gov (United States)

    You, Xiaofang; Sun, Xiwen; Yang, Chunyan; Fang, Yong

    2017-01-01

    Abstract To investigate computed tomography (CT) characteristics of benign and malignant solitary fibrous tumors of the pleura (SFTPs). Preoperative CTs for 60 SFTP cases (49 benign and 11 malignant) with subsequently confirmed diagnoses were retrospectively analyzed. Tumor morphologies included mounded or mushroom umbrella-shape (19 cases, 31.7%), quasi-circular or oval-shape (30 cases, 50%), and growth resembling a casting mould (12 cases, 20%). Maximum tumor diameters were 1.1 to 18.9 cm (average: 6.4 ± 4.8 cm). Fifty-seven cases had clear boundaries, and 3 had partially coarse boundaries. Twenty-seven cases showed homogeneous density; 33, “geographic”-patterned inhomogeneous density; 6, calcifications; 12, intratumor blood vessels; and 3, thick nourishing peritumoral blood vessels. Pleural thickening (regular and irregular) was found adjacent to tumors in 4, compression of adjacent ribs with absorption and cortical sclerosis in 2, and location adjacent to ribs with bony destruction in 1. Four cases had a small amount of lung tissue enfolded along the boundary, 2 had multiple peritumoral pulmonary bullae, and 9 had small ipsilateral pleural effusions. Compared with benign and malignant SFTPs were larger (P < .001), had inhomogeneous density, and were more commonly associated with intratumor blood vessels and pleural effusions (P < .01). CT revealed characteristic patterns in SFTPs, including casting mould-like growth, rich blood supply, and “geographic”-patterned enhancement. In addition, larger tumor size, inhomogeneous intensities, abundant intratumor blood vessels, and pleural effusions were more common with malignancy. Lastly, multislice CT angiography can reveal feeding arteries and help guide surgical management. PMID:29245313

  2. The human Bosniak model applied to a cat with renal cystadenoma. A classification to differentiate benign and malignant cystic renal masses via computed tomography and ultrasound.

    Science.gov (United States)

    Baloi, P; Del Chicca, F; Ruetten, M; Gerber, B

    2015-01-01

    A 13-year-old domestic shorthair cat was presented with weight loss and azotemia. Abdominal ultrasound revealed a large cystic space- occupying lesion with multiple septae in the left kidney. A core needle biopsy yielded a renal cystadenoma originating from the epithelial cells. This report describes the clinical, ultrasonographic and computed tomographic features and the growth progression of a renal cystadenoma. We describe the first attempt to apply the human Bosniak classification to a cat with renal cystic neoplasia to differentiate between benign and malignant lesions. Cystadenoma should be a differential diagnosis in cases of renal cystic space-occupying lesions. Other differentials, imaging features to differentiate benign and malignant lesions and the risk of malignant transformation will be discussed.

  3. Magnetic Resonance Imaging in the Assessment of Cystic Pancreatic Lesions: Differentiation of Benign and Malignant Lesion Status

    Energy Technology Data Exchange (ETDEWEB)

    Haenninen, E. Lopez; Pech, M.; Ricke, J.; Denecke, T.; Amthauer, H.; Lehmkuhl, L.; Boehmig, M.; Roettgen, R.; Pinkernelle, J.; Felix, R.; Langrehr, J. [Charite Medical Univ. Center, Campus Virchow Clinic, Berlin (Germany). Depts. of Radiology, Visceral and Transplant Surgery, Gastroenterology and Hepatology

    2006-03-15

    Purpose: To characterize cystic pancreatic lesions and tumors with magnetic resonance imaging (MRI), and to assess the value of morphological criteria in differentiating pseudocysts versus cystic tumors and benign versus malignant cystic tumors. Material and Methods: Twenty-three patients with cystic pancreatic tumors or lesions underwent plain and contrast-material-enhanced MRI, including magnetic resonance cholangiopancreatography (MRCP). The MR findings were characterized and analyzed by two readers, and the role of various imaging criteria and combinations thereof for final lesion assignment were assessed. Final diagnoses were obtained from the results of open surgery (n = 19) and/or biopsy (n = 4). Results: Final diagnoses included cystic tumors (n = 11) and pseudocysts (n = 12). The lesions were located in the head (56%) and body or tail (44%). Lesion diameters ranged from 7 to 50 mm. Various lesion contrast enhancement patterns were observed for both benign and malignant lesions. Serous cystadenomas were located in the head, they were lobulated, and had wall diameters >2 mm; with the combination of these characteristics all patients with serous cystadenoma could be identified, whereas in no other patient was this constellation observed. Conclusion: MRI facilitated the diagnosis of serous cystadenomas, although no definite morphologic criterion for the differentiation between pseudocysts and mucinous cystadenomas was identified. In consideration of the substantial therapeutic consequences, either diagnostics in unclear cystic pancreatic lesions should comprise cyst fluid analysis if necessary, or eligible patients should be referred for surgical resection.

  4. Shape-induced terminal differentiation of human epidermal stem cells requires p38 and is regulated by histone acetylation.

    Directory of Open Access Journals (Sweden)

    John T Connelly

    Full Text Available Engineered model substrates are powerful tools for examining interactions between stem cells and their microenvironment. Using this approach, we have previously shown that restricted cell adhesion promotes terminal differentiation of human epidermal stem cells via activation of serum response factor (SRF and transcription of AP-1 genes. Here we investigate the roles of p38 MAPK and histone acetylation. Inhibition of p38 activity impaired SRF transcriptional activity and shape-induced terminal differentiation of human keratinocytes. In addition, inhibiting p38 reduced histone H3 acetylation at the promoters of SRF target genes, FOS and JUNB. Although histone acetylation correlated with SRF transcriptional activity and target gene expression, treatment with the histone de-acetylase inhibitor, trichostatin A (TSA blocked terminal differentiation on micro-patterned substrates and in suspension. TSA treatment simultaneously maintained expression of LRIG1, TP63, and ITGB1. Therefore, global histone de-acetylation represses stem cell maintenance genes independent of SRF. Our studies establish a novel role for extrinsic physical cues in the regulation of chromatin remodeling, transcription, and differentiation of human epidermal stem cells.

  5. Dynamic Contrast Magnetic Resonance Imaging (DCE-MRI) and Diffusion Weighted MR Imaging (DWI) for Differentiation between Benign and Malignant Salivary Gland Tumors

    OpenAIRE

    Assili S; Fathi Kazerooni A; Aghaghazvini L; Saligheh Rad. H.R.; Pirayesh Islamian J.

    2015-01-01

    Background: Salivary gland tumors form nearly 3% of head and neck tumors. Due to their large histological variety and vicinity to facial nerves, pre-operative diagnosis and differentiation of benign and malignant parotid tumors are a major challenge for radiologists. Objective: The majority of these tumors are benign; however, sometimes they tend to transform into a malignant form. Functional MRI techniques, namely dynamic contrast enhanced (DCE-) MRI and diffusion-weighted ...

  6. Is the necrosis/wall ADC ratio useful for the differentiation of benign and malignant breast lesions?

    Science.gov (United States)

    Durur-Subasi, Irmak; Durur-Karakaya, Afak; Karaman, Adem; Seker, Mehmet; Demirci, Elif; Alper, Fatih

    2017-05-01

    To determine whether the necrosis/wall apparent diffusion coefficient (ADC) ratio is useful for the malignant-benign differentiation of necrotic breast lesions. Breast MRI was performed using a 3-T system. In this retrospective study, calculation of the necrosis/wall ADC ratio was based on ADC values measured from the necrosis and from the wall of malignant and benign breast lesions by diffusion-weighted imaging (DWI). By synchronizing post-contrast T1 weighted images, the separate parts of wall and necrosis were maintained. All the diagnoses were pathologically confirmed. Statistical analyses were conducted using an independent sample t-test and receiver operating characteristic analysis. The intraclass and interclass correlations were evaluated. A total of 66 female patients were enrolled, 38 of whom had necrotic breast carcinomas and 28 of whom had breast abscesses. The ADC values were obtained from both the wall and necrosis. The mean necrosis/wall ADC ratio (± standard deviation) was 1.61 ± 0.51 in carcinomas, and it was 0.65 ± 0.33 in abscesses. The area under the curve values for necrosis ADC, wall ADC and the necrosis/wall ADC ratio were 0.680, 0.068 and 0.942, respectively. A wall/necrosis ADC ratio cut-off value of 1.18 demonstrated a sensitivity of 97%, specificity of 93%, a positive-predictive value of 95%, a negative-predictive value of 96% and an accuracy of 95% in determining the malignant nature of necrotic breast lesions. There was a good intra- and interclass reliability for the ADC values of both necrosis and wall. The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating breast carcinomas from abscesses using DWI. Advances in knowledge: ADC values of the necrosis obtained by DWI are valuable for malignant-benign differentiation in necrotic breast lesions. The necrosis/wall ADC ratio appears to be a reliable and promising tool in the breast imaging field.

  7. miR-130A as a diagnostic marker to differentiate malignant mesothelioma from lung adenocarcinoma in pleural effusion cytology.

    Science.gov (United States)

    Cappellesso, Rocco; Galasso, Marco; Nicolè, Lorenzo; Dabrilli, Paolo; Volinia, Stefano; Fassina, Ambrogio

    2017-08-01

    Malignant pleural mesothelioma is a rare tumor with a dismal prognosis, usually presenting with recurrent effusions. However, the majority of malignant pleural effusions are due to lung adenocarcinoma (AdC). The distinction between these tumors has considerable therapeutic and medicolegal implications and can be very challenging both histologically and cytologically. Appropriate immunohistochemistry (IHC) is required to support the diagnosis. MicroRNA (miRNA) expression analysis could be a viable diagnostic tool for distinguishing between these tumors. The purpose of the current study was to assess the reliability of miRNAs as diagnostic markers to differentiate epithelioid malignant mesothelioma (MM) from lung AdC. Bioinformatic analysis of publicly searchable data sets regarding miRNA expression profiling was performed to select the most significant differentially expressed miRNAs. These were analyzed by quantitative polymerase chain reaction on histologic (41 MM cases and 40 lung AdC cases) and cytological (26 MM cases and 27 lung AdC cases) specimens and the diagnostic performances were assessed. miR-130a, miR-193a, miR-675, miR-141, miR-205, and miR-375 were found to be the best distinguishing markers. Of these, only miR-130a was significantly overexpressed in MM compared with lung AdC (P =.029 in histologic and P =.014 in cytological samples). miR-130a demonstrated a sensitivity of 77%, a specificity of 67%, a positive predictive value of 69%, a negative predictive value of 75%, and an accuracy of 72% in identifying MM. The diagnostic performances of miR-130a expression analysis and IHC appear to be similar. miR-130a quantification could be used reliably as second-level diagnostic tool to differentiate MM from lung AdC in pleural effusion cytology, mainly in those cases with ambiguous or negative IHC. Further validation is needed. Cancer Cytopathol 2017;125:635-43. © 2017 American Cancer Society. © 2017 American Cancer Society.

  8. AKT1-mediated Lamin A/C degradation is required for nuclear degradation and normal epidermal terminal differentiation

    OpenAIRE

    Naeem, A S; Zhu, Y.; Di, W L; Marmiroli, S.; O Shaughnessy, R. F. L.

    2015-01-01

    Nuclear degradation is a key stage in keratinocyte terminal differentiation and the formation of the cornified envelope that comprises the majority of epidermal barrier function. Parakeratosis, the retention of nuclear material in the cornified layer of the epidermis, is a common histological observation in many skin diseases, notably in atopic dermatitis and psoriasis. Keratinocyte nuclear degradation is not well characterised, and it is unclear whether the retained nuclei contribute to the ...

  9. C/ebpα controls osteoclast terminal differentiation, activation, function, and postnatal bone homeostasis through direct regulation of Nfatc1.

    Science.gov (United States)

    Chen, Wei; Zhu, Guochun; Tang, Jun; Zhou, Hou-De; Li, Yi-Ping

    2017-10-30

    Osteoclast lineage commitment and differentiation have been studied extensively, although the mechanism by which transcription factor(s) control osteoclast terminal differentiation, activation and function remains unclear. CCAAT/enhancer-binding protein α (C/ebpα) has been reported to be a key regulator of osteoclast cell lineage commitment, yet C/ebpα's roles in osteoclast terminal differentiation, activation and function and bone homeostasis, under physiological or pathological conditions, have not been studied because newborn C/ebpα null mice die within several hours after birth. Furthermore, the function of C/ebpα in osteoclast terminal differentiation, activation and function are largely unknown. Herein, we generated and analyzed an osteoclast-specific C/ebpα conditional knockout (CKO) mouse model via Ctsk-Cre mice and found that C/ebpα-deficient mice exhibited a severe osteopetrosis phenotype due to impaired osteoclast terminal differentiation, activation and function, including mildly reduced osteoclast number, impaired osteoclast polarization, actin formation, and bone resorption, which demonstrated the novel function of C/ebpα in cell function and terminal differentiation. Interestingly, C/ebpα deficiency did not affect bone formation or monocyte/macrophage development. Our results further demonstrated that C/ebpα deficiency suppressed the expression of osteoclast functional genes, e.g. encoding Cathepsin K (Ctsk), Atp6i (Tcirg1) and osteoclast regulator genes, e.g. encoding c-fos (Fos), and nuclear factor of activated T-cells 1 (Nfatc1), while having no effect on Pu.1 (Spi1) expression. Promoter activity mapping and ChIP assay defined the critical cis-regulatory element (CCRE) in the promoter region of Nfatc1, and also showed that the CCREs were directly associated with C/ebpα, which enhanced the promoter's activity. The deficiency of C/ebpα in osteoclasts completely blocked ovariectomy-induced bone loss, indicating C/ebpα is a promising new

  10. Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions

    Science.gov (United States)

    Yan, Jun; Zhuo, Shuangmu; Chen, Gang; Wu, Xiufeng; Zhou, Dong; Xie, Shusen; Jiang, Jiahao; Ying, Mingang; Jia, Fan; Chen, Jianxin; Zhou, Jian

    2012-02-01

    Recently, the miniaturized multiphoton microscopy (MPM) and multiphoton probe allow the clinical use of multiphoton endoscopy for diagnosing cancer via ``optical biopsy''. The purpose of this study was to establish MPM optical diagnostic features for liver cancer and evaluate the sensitivity, specificity, and accuracy of MPM optical diagnosis. Firstly, we performed a pilot study to establish the MPM diagnostic features by investigating 60 surgical specimens, and found that high-resolution MPM images clearly demonstrated apparent differences between benign and malignant liver lesions in terms of their tissue architecture and cell morphology. Cancer cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, were identified by MPM images, which were comparable to hematoxylin-eosin staining images. Secondly, we performed a blinded study to evaluate the sensitivity, specificity, and accuracy of MPM optical diagnosis by investigating another 164 specimens, and found that the sensitivity, specificity, and accuracy of MPM diagnosis was 96.32%, 96.43%, and 96.34%, respectively. In conclusion, it is feasible to use MPM to diagnose liver cancer and differentiate benign and malignant liver lesions. This preclinical study provides the groundwork for further using multiphoton endoscopy to perform real-time noninvasive ``optical biopsy'' for liver lesions in the near future.

  11. Multidetector CT Findings and Differential Diagnoses of Malignant Pleural Mesothelioma and Metastatic Pleural Diseases in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoon Kyung [Department of Radiology, Gachon University Gil Medical Center, Incheon 21565 (Korea, Republic of); Kim, Jeung Sook [Department of Radiology, Dongguk University Ilsan Hospital, Goyang 10326 (Korea, Republic of); Lee, Kyung Won [Department of Radiology, Seoul National University Bundang Hospital, Seongnam 13620 (Korea, Republic of); Yi, Chin A [Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351 (Korea, Republic of); Koo, Jin Mo [Department of Radiology, Seoul National University College of Medicine, Seoul 03080 (Korea, Republic of); Jung, Soon-Hee [Department of Pathology, Yonsei University Wonju College of Medicine, Wonju 26426 (Korea, Republic of)

    2016-11-01

    To compare the multidetector CT (MDCT) features of malignant pleural mesothelioma (MPM) and metastatic pleural disease (MPD). The authors reviewed the MDCT images of 167 patients, 103 patients with MPM and 64 patients with MPD. All 167 cases were pathologically confirmed by sonography-guided needle biopsy of pleura, thoracoscopic pleural biopsy, or open thoracotomy. CT features were evaluated with respect to pleural effusion, pleural thickening, invasion of other organs, lung abnormality, lymphadenopathy, mediastinal shifting, thoracic volume decrease, asbestosis, and the presence of pleural plaque. Pleural thickening was the most common CT finding in MPM (96.1%) and MPD (93.8%). Circumferential pleural thickening (31.1% vs. 10.9%, odds ratio [OR] 3.670), thickening of fissural pleura (83.5% vs. 67.2%, OR 2.471), thickening of diaphragmatic pleura (90.3% vs. 73.4%, OR 3.364), pleural mass (38.8% vs. 23.4%, OR 2.074), pericardial involvement (56.3% vs. 20.3%, OR 5.056), and pleural plaque (66.0% vs. 21.9%, OR 6.939) were more frequently seen in MPM than in MPD. On the other hand, nodular pleural thickening (59.2% vs. 76.6%, OR 0.445), hilar lymph node metastasis (5.8% vs. 20.3%, OR 0.243), mediastinal lymph node metastasis (10.7% vs. 37.5%, OR 0.199), and hematogenous lung metastasis (9.7% vs. 29.2%, OR 0.261) were less frequent in MPM than in MPD. When we analyzed MPD from extrathoracic malignancy (EMPD) separately and compared them to MPM, circumferential pleural thickening, thickening of interlobar fissure, pericardial involvement and presence of pleural plaque were significant findings indicating MPM than EMPD. MPM had significantly lower occurrence of hematogenous lung metastasis, as compared with EMPD. Awareness of frequent and infrequent CT findings could aid in distinguishing MPM from MPD.

  12. Multidetector CT findings and differential diagnoses of malignant pleural mesothelioma and metastatic pleural diseases in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoon Kyung [Dept. of Radiology, Gachon University Gil Medical Center, Incheon (Korea, Republic of); Kim, Jeung Sook [Dept. of Radiology, Dongguk University Ilsan Hospital, Goyang (Korea, Republic of); Lee, Kyung Won [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Yi, Chin A [Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Koo, Jin Mo [Dept. of Radiology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Soon Hee [Dept. of Pathology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)

    2016-07-15

    To compare the multidetector CT (MDCT) features of malignant pleural mesothelioma (MPM) and metastatic pleural disease (MPD). The authors reviewed the MDCT images of 167 patients, 103 patients with MPM and 64 patients with MPD. All 167 cases were pathologically confirmed by sonography-guided needle biopsy of pleura, thoracoscopic pleural biopsy, or open thoracotomy. CT features were evaluated with respect to pleural effusion, pleural thickening, invasion of other organs, lung abnormality, lymphadenopathy, mediastinal shifting, thoracic volume decrease, asbestosis, and the presence of pleural plaque. Pleural thickening was the most common CT finding in MPM (96.1%) and MPD (93.8%). Circumferential pleural thickening (31.1% vs. 10.9%, odds ratio [OR] 3.670), thickening of fissural pleura (83.5% vs. 67.2%, OR 2.471), thickening of diaphragmatic pleura (90.3% vs. 73.4%, OR 3.364), pleural mass (38.8% vs. 23.4%, OR 2.074), pericardial involvement (56.3% vs. 20.3%, OR 5.056), and pleural plaque (66.0% vs. 21.9%, OR 6.939) were more frequently seen in MPM than in MPD. On the other hand, nodular pleural thickening (59.2% vs. 76.6%, OR 0.445), hilar lymph node metastasis (5.8% vs. 20.3%, OR 0.243), mediastinal lymph node metastasis (10.7% vs. 37.5%, OR 0.199), and hematogenous lung metastasis (9.7% vs. 29.2%, OR 0.261) were less frequent in MPM than in MPD. When we analyzed MPD from extrathoracic malignancy (EMPD) separately and compared them to MPM, circumferential pleural thickening, thickening of interlobar fissure, pericardial involvement and presence of pleural plaque were significant findings indicating MPM than EMPD. MPM had significantly lower occurrence of hematogenous lung metastasis, as compared with EMPD. Awareness of frequent and infrequent CT findings could aid in distinguishing MPM from MPD.

  13. Terminal Bacteroid Differentiation Is Associated With Variable Morphological Changes in Legume Species Belonging to the Inverted Repeat-Lacking Clade.

    Science.gov (United States)

    Montiel, Jesús; Szűcs, Attila; Boboescu, Iulian Z; Gherman, Vasile D; Kondorosi, Éva; Kereszt, Attila

    2016-03-01

    Medicago and closely related legume species from the inverted repeat-lacking clade (IRLC) impose terminal differentiation onto their bacterial endosymbionts, manifested in genome endoreduplication, cell enlargement, and loss of cell-division capacity. Nodule-specific cysteine-rich (NCR) secreted host peptides are plant effectors of this process. As bacteroids in other IRLC legumes, such as Cicer arietinum and Glycyrrhiza lepidota, were reported not to display features of terminal differentiation, we investigated the fate of bacteroids in species from these genera as well as in four other species representing distinct genera of the phylogenetic tree for this clade. Bacteroids in all tested legumes proved to be larger in size and DNA content than cultured cells; however, the degree of cell elongation was rather variable in the different species. In addition, the reproductive ability of the bacteroids isolated from these legumes was remarkably reduced. In all IRLC species with available sequence data, the existence of NCR genes was found. These results indicate that IRLC legumes provoke terminal differentiation of their endosymbionts with different morphotypes, probably with the help of NCR peptides.

  14. Chromatin condensation in terminally differentiating mouse erythroblasts does not involve special architectural proteins but depends on histone deacetylation

    Energy Technology Data Exchange (ETDEWEB)

    Popova, Evgenya Y.; Krauss, Sharon Wald; Short, Sarah A.; Lee, Gloria; Villalobos, Jonathan; Etzell, Joan; Koury, Mark J.; Ney, Paul A.; Chasis, Joel Anne; Grigoryev, Sergei A.

    2008-08-21

    Terminal erythroid differentiation in vertebrates is characterized by progressive heterochromatin formation, chromatin condensation and, in mammals, culminates in nuclear extrusion. To date, although mechanisms regulating avian erythroid chromatin condensation have been identified, little is known regarding this process during mammalian erythropoiesis. To elucidate the molecular basis for mammalian erythroblast chromatin condensation, we used Friend virus-infected murine spleen erythroblasts that undergo terminal differentiation in vitro. Chromatin isolated from early and late stage erythroblasts had similar levels of linker and core histones, only a slight difference in nucleosome repeats, and no significant accumulation of known developmentally-regulated architectural chromatin proteins. However, histone H3(K9) dimethylation markedly increased while histone H4(K12) acetylation dramatically decreased and became segregated from the histone methylation as chromatin condensed. One histone deacetylase, HDAC5, was significantly upregulated during the terminal stages of Friend virus-infected erythroblast differentiation. Treatment with histone deacetylase inhibitor, trichostatin A, blocked both chromatin condensation and nuclear extrusion. Based on our data, we propose a model for a unique mechanism in which extensive histone deacetylation at pericentromeric heterochromatin mediates heterochromatin condensation in vertebrate erythroblasts that would otherwise be mediated by developmentally-regulated architectural proteins in nucleated blood cells.

  15. Combined 3 Tesla MRI Biomarkers Improve the Differentiation between Benign vs Malignant Single Ring Enhancing Brain Masses.

    Directory of Open Access Journals (Sweden)

    Simone Salice

    Full Text Available To evaluate whether the combination of imaging biomarkers obtained by means of different 3 Tesla (3T Magnetic Resonance Imaging (MRI advanced techniques can improve the diagnostic accuracy in the differentiation between benign and malignant single ring-enhancing brain masses.14 patients presenting at conventional 3T MRI single brain mass with similar appearance as regard ring enhancement, presence of peri-lesional edema and absence of hemorrhage signs were included in the study. All lesions were histologically proven: 5 pyogenic abscesses, 6 glioblastomas, and 3 metastases. MRI was performed at 3 Tesla and included Diffusion Weighted Imaging (DWI, Dynamic Susceptibility Contrast -Perfusion Weighted Imaging (DSC-PWI, Magnetic Resonance Spectroscopy (MRS, and Diffusion Tensor Imaging (DTI. Imaging biomarkers derived by those advanced techniques [Cerebral Blood Flow (CBF, relative Cerebral Blood Volume (rCBV, relative Main Transit Time (rMTT, Choline (Cho, Creatine (Cr, Succinate, N-Acetyl Aspartate (NAA, Lactate (Lac, Lipids, relative Apparent Diffusion Coefficient (rADC, and Fractional Anisotropy (FA] were detected by two experienced neuroradiologists in joint session in 4 areas: Internal Cavity (IC, Ring Enhancement (RE, Peri-Lesional edema (PL, and Contralateral Normal Appearing White Matter (CNAWM. Significant differences between benign (n = 5 and malignant (n = 9 ring enhancing lesions were tested with Mann-Withney U test. The diagnostic accuracy of MRI biomarkers taken alone and MRI biomarkers ratios were tested with Receiver Operating Characteristic (ROC analysis with an Area Under the Curve (AUC ≥ 0.9 indicating a very good diagnostic accuracy of the variable.Five MRI biomarker ratios achieved excellent accuracy: IC-rADC/PL-NAA (AUC = 1, IC-rADC/IC-FA (AUC = 0.978, RE-rCBV/RE-FA (AUC = 0.933, IC-rADC/RE-FA (AUC = 0.911, and IC-rADC/PL-FA (AUC = 0.911. Only IC-rADC achieved a very good diagnostic accuracy (AUC = 0.909 among MRI biomarkers

  16. [Clinical value estimation of the Doppler indicies: PI, RI and PSV, TAMXV and MEDV in early differentiation of the ovarian tumors malignancy].

    Science.gov (United States)

    Szpurek, Dariusz; Moszyński, Rafał; Englert-Golon, Monika; Pawlak, Michał; Sajdak, Stefan

    2006-08-01

    THE OBJECTIVES: The aim of this study was to evaluate the clinical value of blood flow indicies for differentiating between benign and malignant ovarian tumours. Realisation of the aim was based on the analysis of examinations' results of 686 ovarian tumors. For each recorded blood flow wave the followind parameters of examined tumor vessels were analysed: pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV), time-averaged maximum velocity (TAMXV) and maximum and diastolic velocity (MEDV). Apart from conditional probabilities we also presented assessing areas under the ROC curves, which introducted information over practical usefulness of each test. Vascular perfusion was observed in 100% of malignant tumors and 92% of non-malignant tumors. In group of patients with malignant tumors PI and RI were significantly lower; and PSV, TAMXV and MEDV were higher than in group with non-malignant tumors. (p<0.05) Transvaginal ultrasonography with the Doppler technique is valuable diagnostic method in preoperative differentiation of tumor malignancies. The best predictive value in analysed group was observed for PI (AUROC=o.87) and MEDV (AUROC=0.86). Similar correlation was observed for premenopausal patients. In group of postmenopausal patients the best predictive value was for RI (AUROC=0.90) and MEDV (AUROC=0.88).

  17. Non-invasive quantification of tumour heterogeneity in water diffusivity to differentiate malignant from benign tissues of urinary bladder: a phase I study.

    Science.gov (United States)

    Nguyen, Huyen T; Shah, Zarine K; Mortazavi, Amir; Pohar, Kamal S; Wei, Lai; Jia, Guang; Zynger, Debra L; Knopp, Michael V

    2017-05-01

    To quantify the heterogeneity of the tumour apparent diffusion coefficient (ADC) using voxel-based analysis to differentiate malignancy from benign wall thickening of the urinary bladder. Nineteen patients with histopathological findings of their cystectomy specimen were included. A data set of voxel-based ADC values was acquired for each patient's lesion. Histogram analysis was performed on each data set to calculate uniformity (U) and entropy (E). The k-means clustering of the voxel-wised ADC data set was implemented to measure mean intra-cluster distance (MICD) and largest inter-cluster distance (LICD). Subsequently, U, E, MICD, and LICD for malignant tumours were compared with those for benign lesions using a two-sample t-test. Eleven patients had pathological confirmation of malignancy and eight with benign wall thickening. Histogram analysis showed that malignant tumours had a significantly higher degree of ADC heterogeneity with lower U (P = 0.016) and higher E (P = 0.005) than benign lesions. In agreement with these findings, k-means clustering of voxel-wise ADC indicated that bladder malignancy presented with significantly higher MICD (P bladder cancer. • Heterogeneity is an intrinsic characteristic of tumoral tissue. • Non-invasive quantification of tumour heterogeneity can provide adjunctive information to improve cancer diagnosis accuracy. • Histogram analysis and k-means clustering can quantify tumour diffusion heterogeneity. • The quantification helps differentiate malignant from benign urinary bladder tissue.

  18. Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest

    Directory of Open Access Journals (Sweden)

    Helena Carén

    2015-11-01

    Full Text Available Glioblastoma (GBM is an aggressive brain tumor whose growth is driven by stem cell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM stem cells (GSCs and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany differentiation remain poorly defined. It is also unclear whether cell-cycle arrest is terminal. Here we find only a subset of GSC cultures exhibit astrocyte differentiation in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they remain vulnerable to cell-cycle re-entry and fail to appropriately reconfigure DNA methylation patterns. Chromatin accessibility mapping identified loci that failed to alter in response to BMP and these were enriched in SOX transcription factor-binding motifs. SOX transcription factors, therefore, may limit differentiation commitment. A similar propensity for cell-cycle re-entry and de-differentiation was observed in GSC-derived oligodendrocyte-like cells. These findings highlight significant obstacles to BMP-induced differentiation as therapy for GBM.

  19. Differential DNA methylation profile of key genes in malignant prostate epithelial cells transformed by inorganic arsenic or cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Pelch, Katherine E.; Tokar, Erik J. [National Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Merrick, B. Alex [Molecular Toxicology and Informatics Group, Biomolecular Screening Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Morrisville, NC 27560 (United States); Waalkes, Michael P., E-mail: waalkes@niehs.nih.gov [National Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States)

    2015-08-01

    Previous work shows altered methylation patterns in inorganic arsenic (iAs)- or cadmium (Cd)-transformed epithelial cells. Here, the methylation status near the transcriptional start site was assessed in the normal human prostate epithelial cell line (RWPE-1) that was malignantly transformed by 10 μM Cd for 11 weeks (CTPE) or 5 μM iAs for 29 weeks (CAsE-PE), at which time cells showed multiple markers of acquired cancer phenotype. Next generation sequencing of the transcriptome of CAsE-PE cells identified multiple dysregulated genes. Of the most highly dysregulated genes, five genes that can be relevant to the carcinogenic process (S100P, HYAL1, NTM, NES, ALDH1A1) were chosen for an in-depth analysis of the DNA methylation profile. DNA was isolated, bisulfite converted, and combined bisulfite restriction analysis was used to identify differentially methylated CpG sites, which was confirmed with bisulfite sequencing. Four of the five genes showed differential methylation in transformants relative to control cells that was inversely related to altered gene expression. Increased expression of HYAL1 (> 25-fold) and S100P (> 40-fold) in transformants was correlated with hypomethylation near the transcriptional start site. Decreased expression of NES (> 15-fold) and NTM (> 1000-fold) in transformants was correlated with hypermethylation near the transcriptional start site. ALDH1A1 expression was differentially expressed in transformed cells but was not differentially methylated relative to control. In conclusion, altered gene expression observed in Cd and iAs transformed cells may result from altered DNA methylation status. - Highlights: • Cd and iAs are known human carcinogens, yet neither appears directly mutagenic. • Prior data suggest epigenetic modification plays a role in Cd or iAs induced cancer. • Altered methylation of four misregulated genes was found in Cd or iAs transformants. • The resulting altered gene expression may be relevant to cellular

  20. Disseminated Histoplasmosis: A Challenging Differential Diagnostic Consideration for Suspected Malignant Lesions in the Digestive Tract

    Directory of Open Access Journals (Sweden)

    Bernhard Doleschal

    2016-11-01

    Full Text Available Histoplasmosis is well characterized as an endemic fungal disease restricted to certain areas of the USA. In Middle Europe, most patients present with acute pulmonary symptoms after travelling to endemic areas. Here, we want to illustrate the case of a 67-year-old man who presented with persistent oral ulcers, hoarseness, dysphagia, diarrhea, and weight loss to our Department of Otorhinolaryngology in December 2014. He was a retired construction worker and had a history of soil-disruptive activities in Africa and Middle and South America during employment. A positron emission tomography-computed tomography scan revealed prominent hypermetabolic lesions in the cecum and the lung, pointing towards a malignant disease. Surprisingly, histological examination of colonic and oral biopsies revealed abundant intracellular fungal elements, highly suspicious of Histoplasma capsulatum. Diagnosis was finally confirmed by panfungal polymerase chain reaction. Upon treatment with liposomal amphotericin followed by itraconazole, the severely ill patient showed an impressive clinical response. This case describes a disseminated manifestation of H. capsulatum years after the first exposure in an otherwise immunocompetent patient descending from a nonendemic area.

  1. 18F-FDG PET/CT to differentiate malignant necrotic lymph node from benign cystic lesions in the neck

    DEFF Research Database (Denmark)

    Mobarak-Abadi, Peymaneh; Johansen, Allan; Godballe, Christian

    2017-01-01

    OBJECTIVE: Patients presenting with cystic lesions in the neck without obvious signs of malignancy constitute a diagnostic challenge since fine needle aspiration is often insufficient and a diagnosis may not be reached until surgical resection/biopsy is performed. The differential diagnosis...... of a cystic cervical mass comprises a variety of benign conditions, but malignancy must be ruled out. We examined the diagnostic performance of fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET/CT to identify malignancy. METHODS: We retrospectively included consecutive patients referred from the Department...... of ENT Head and Neck Surgery for (18)F-FDG PET/CT-scans because of a solitary neck cyst. Scan results were compared to histopathology and follow-up. RESULTS: The study comprised 58 patients. Twenty patients (34%) were diagnosed with cancer during follow-up. PET/CT suggested malignancy in 34 patients (19...

  2. Acoustic radiation force impulse imaging (ARFI) for differentiation of benign and malignant thyroid nodules--A meta-analysis.

    Science.gov (United States)

    Zhan, Jia; Jin, Jia-Mei; Diao, Xue-Hong; Chen, Yue

    2015-11-01

    Work-up of thyroid nodules remains challenging. Acoustic radiation force impulse imaging (ARFI)-generated shear wave elastography, which can measure quantitatively tissue stiffness (virtual touch tissue quantification) is used as a complement to conventional sonography for improving the diagnosis of thyroid nodules. This meta-analysis was performed to expand on a previous meta-analysis to assess the diagnostic power of ARFI in differentiating benign and malignant thyroid nodules. The MEDLINE, PubMed, SpringerLink databases up to December 31, 2014, were searched. The pooled sensitivity, specificity, and summary receiver operating characteristic curve were obtained from individual studies with a random effects model. Sixteen studies that included a total of 2436 nodules in 2147 patients for ARFI studies were analyzed. The overall mean sensitivity and specificity of ARFI for differentiation of thyroid nodules were 0.80 (95% confidence interval [CI], 0.73-0.87) and 0.85 (95% CI, 0.80-0.90), respectively. A significant heterogeneity was found for both sensitivity and specificity of the different studies (P<0.001). The area under the curve for the ARFI was 0.91. ARFI has high sensitivity and specificity for identification of thyroid. This technique might be useful to select patients with thyroid nodules for surgery. Copyright © 2015. Published by Elsevier Ireland Ltd.

  3. MR Imaging Findings of Ovarian Cystadenofibroma: Clues for Making the Differential Diagnosis from Ovarian Malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Jae Young [The Catholic University of Korea, Seoul (Korea, Republic of)

    2006-09-15

    Ovarian cystadenofibromas are uncommon epithelial ovarian tumors in which fibrous stroma is the dominant component of the neoplasm, in addition to the epithelial lining of the cystic tumor. These tumors are classified, according to the epithelial cell types, into the serous, endometrioid, mucinous, clear cell and mixed categories. Outwater et al. have reported that ovarian cystadenofibromas were multilocular cystic masses with a solid component and they had a specific MR signal intensity for the solid portion, which consisted of fibrous tissue that had very low signal intensity on the T2-weighted sequences. Takeuchi et al. reported that small or tiny cystic locules within the solid component are the characteristic findings of cystadenofibroma, corresponding to a black sponge-like appearance on T2-weignted image. Cho et al. found that about half of ovarian cystadenofibromas are purely cystic and the other half are complex cystic masses with one or more solid components on CT or MR imaging. The imaging findings of purely cystic ovarian cystadenofibromas were identical to those of ovarian cystadenomas on CT or MR imaging. Upon reviewing of the pathology of these tumors, they had small foci of fibrous stromas that were detected only on microscopic examination. The cystadenofibromas with a complex cystic nature demonstrated variable amounts of solid components in the cystic tumor on the CT or MR imaging. Familiarity with the above mentioned MR imaging features of ovarian cystadenofibromas may allow a specific diagnosis and help distinguish this benign tumor from malignant tumors, and this can be a big help during surgical planning to avoid inappropriate management or excessive surgical intervention.

  4. Human epididymis protein 4 immunostaining of malignant ascites differentiates cancer of Müllerian origin from gastrointestinal cancer.

    Science.gov (United States)

    Stiekema, Anna; Van de Vijver, Koen K; Boot, Henk; Broeks, Annegien; Korse, Catharina M; van Driel, Willemien J; Kenter, Gemma G; Lok, Christianne A R

    2017-03-01

    An accurate diagnosis of cancer of Müllerian origin is required before the initiation of treatment. An overlap in clinical presentation and cytological, histological, or imaging studies with other nongynecological tumors does occur. Therefore, immunocytochemistry markers are used to determine tumor origin. Human epididymis protein 4 (HE4) is overexpressed in tissue of epithelial ovarian cancer (EOC). It has shown to be a sensitive and specific serum marker for EOC and to be of value for the differentiation between EOC and ovarian metastases of gastrointestinal origin. The objective of the current study was to evaluate HE4 immunocytochemistry in malignant ascites for differentiation between cancer of Müllerian origin, including EOC, and adenocarcinomas of the gastrointestinal tract. Cytological specimens of 115 different adenocarcinomas (45 EOCs, 46 cases of gastric cancer, and 24 cases of colorectal cancer) were stained for HE4, paired box 8 (PAX8), and other specific markers. 91% of the ascites samples from patients with EOC stained for both HE4 and PAX8. The 4 samples without HE4 staining were a clear cell carcinoma, a low-grade serous adenocarcinoma, an undifferentiated adenocarcinoma, and a neuroendocrine carcinoma. All high-grade serous adenocarcinomas (n = 37, 100%) stained with HE4, compared with 94% that stained positively for PAX8. In cases of gastric or colorectal cancer, 25% and 21% of cases, respectively, stained positive for HE4. No PAX8 staining was observed in colorectal or gastric adenocarcinomas. HE4 staining in ascites is feasible and appears to have a high sensitivity for high-grade serous ovarian cancer. HE4 is a useful addition to the current panel of immunocytochemistry markers for the diagnosis of EOC and for differentiation with gastrointestinal adenocarcinomas. Cancer Cytopathol 2017;125:197-204. © 2016 American Cancer Society. © 2017 American Cancer Society.

  5. Adult sertoli cells are not terminally differentiated in the Djungarian hamster: effect of FSH on proliferation and junction protein organization.

    Science.gov (United States)

    Tarulli, Gerard A; Stanton, Peter G; Lerchl, Alexander; Meachem, Sarah J

    2006-05-01

    Sertoli cell number is considered to be stable and unmodifiable by hormones after puberty in mammals, although recent data using the seasonal breeding adult Djungarian hamster (Phodopus sungorus) model challenged this assertion by demonstrating a decrease in Sertoli cell number after gonadotropin depletion and a return to control levels following 7 days of FSH replacement. The present study aimed to determine whether adult Sertoli cells are terminally differentiated using known characteristics of cellular differentiation, including proliferation, junction protein localization, and expression of particular maturational markers, in the Djungarian hamster model. Adult long-day (LD) photoperiod (16L:8D) hamsters were exposed to short-day (SD) photoperiod (8L:16D) for 11 wk to suppress gonadotropins and then received exogenous FSH for up to 10 days. Sertoli cell proliferation was assessed by immunofluorescence by the colocalization of GATA4 and proliferating cell nuclear antigen and quantified by stereology. Markers of Sertoli cell maturation (immature, cytokeratin 18 [KRT18]; mature, GATA1) and junction proteins (actin, espin, claudin 11 [CLDN11], and tight junction protein 1 [TJP1, also known as ZO-1]) also were localized using confocal immunofluorescence. In response to FSH treatment, proliferation was upregulated within 2 days compared with SD controls (90% vs. 0.2%, P < 0.001) and declined gradually thereafter. In LD hamsters, junction proteins colocalized at the basal aspect of Sertoli cells, consistent with inter-Sertoli cell junctions, and were disordered within the Sertoli cell cytoplasm in SD animals. Exogenous FSH treatment promptly restored localization of these junction markers to the LD phenotype. Protein markers of maturity remain consistent with those of adult Sertoli cells. It is concluded that adult Sertoli cells are not terminally differentiated in the Djungarian hamster and that FSH plays an important role in governing the differentiation process. It

  6. Cytotoxicity and terminal differentiation of human oral keratinocyte by indium ions from a silver-palladium-gold-indium dental alloy.

    Science.gov (United States)

    Lee, Jung-Hwan; Seo, Sang-Hee; Lee, Sang-Bae; Om, Ji-Yeon; Kim, Kwang-Mahn; Kim, Kyoung-Nam

    2015-02-01

    Dental alloys containing indium (In) have been used in dental restoration for two decades; however, no study has investigated the biological effects of In ions, which may be released in the oral cavity, on human oral keratinocytes. The objective of the present study was to investigate the biological effects of In ions on human oral keratinocyte after confirming their release from a silver-palladium-gold-indium (Ag-Pd-Au-In) dental alloy. As a corrosion assay, a static immersion tests were performed by detecting the released ions in the corrosion solution from the Ag-Pd-Au-In dental alloy using inductively coupled plasma atomic emission spectroscopy. The cytotoxicity and biological effects of In ions were then studied with In compounds in three human oral keratinocyte cell lines: immortalized human oral keratinocyte (IHOK), HSC-2, and SCC-15. Higher concentrations of In and Cu ions were detected in Ag-Pd-Au-In (P<0.05) than in Ag-Pd-Au, and AgCl deposition occurred on the surface of Ag-Pd-Au-In after a 7-day corrosion test due to its low corrosion resistance. At high concentrations, In ions induced cytotoxicity; however, at low concentrations (∼0.8In(3+)mM), terminal differentiation was observed in human oral keratinocytes. Intracellular ROS was revealed to be a key component of In-induced terminal differentiation. In ions were released from dental alloys containing In, and high concentrations of In ions resulted in cytotoxicity, whereas low concentrations induced the terminal differentiation of human oral keratinocytes via increased intracellular ROS. Therefore, dental alloys containing In must be biologically evaluated for their safe use. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  7. A New Isolated Mediastinal Lymph Node or Small Pulmonary Nodule Arising during Breast Cancer Surveillance Following Curative Surgery: Clinical Factors That Differentiate Malignant from Benign Lesions.

    Science.gov (United States)

    Kim, Tae-Yong; Lee, Kyung-Hun; Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Han, Wonshik; Kim, Kyubo; Chie, Eui Kyu; Park, In-Ae; Kim, Young Tae; Noh, Dong-Young; Ha, Sung Whan; Bang, Yung-Jue

    2014-07-01

    A newly isolated mediastinal lymph node (LN) or a small pulmonary nodule, which appears during breast cancer surveillance, may pose a diagnostic dilemma with regard to malignancy. We conducted this study to determine which clinical factors were useful for the differentiation of malignant lesions from benign lesions under these circumstances. We enrolled breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule that arose during surveillance, and whose lesions were pathologically confirmed. Tissue diagnosis was made by mediastinoscopy, video-assisted thoracic surgery or thoracotomy. A total of 43 patients were enrolled (mediastinal LN, 13 patients; pulmonary nodule, 30 patients). Eighteen patients (41.9%) were pathologically confirmed to have a benign lesion (benign group), and 25 patients (58.1%) were confirmed to have malignant lesion (malignant group). Between the two groups, the initial tumor size (p=0.096) and N stage (p=0.749) were similar. Hormone receptor negativity was more prevalent in the malignant group (59.1% vs. 40.9%, p=0.048). The mean lesion size was larger in the malignant group than in the benign group (20.8 mm vs. 14.4 mm, p=0.024). Metastatic lesions had a significantly higher value of maximal standardized uptake (mSUV) than that of benign lesions (6.4 vs. 3.4, p=0.021). Hormone receptor status, lesion size, and mSUV on positron emission tomography are helpful in the differentiation of malignant lesions from benign lesions in breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule during surveillance.

  8. [Application of support vector machine-recursive feature elimination algorithm in Raman spectroscopy for differential diagnosis of benign and malignant breast diseases].

    Science.gov (United States)

    Zhang, Haipeng; Fu, Tong; Zhang, Zhiru; Fan, Zhimin; Zheng, Chao; Han, Bing

    2014-08-01

    To explore the value of application of support vector machine-recursive feature elimination (SVM-RFE) method in Raman spectroscopy for differential diagnosis of benign and malignant breast diseases. Fresh breast tissue samples of 168 patients (all female; ages 22-75) were obtained by routine surgical resection from May 2011 to May 2012 at the Department of Breast Surgery, the First Hospital of Jilin University. Among them, there were 51 normal tissues, 66 benign and 51 malignant breast lesions. All the specimens were assessed by Raman spectroscopy, and the SVM-RFE algorithm was used to process the data and build the mathematical model. Mahalanobis distance and spectral residuals were used as discriminating criteria to evaluate this data-processing method. 1 800 Raman spectra were acquired from the fresh samples of human breast tissues. Based on spectral profiles, the presence of 1 078, 1 267, 1 301, 1 437, 1 653, and 1 743 cm(-1) peaks were identified in the normal tissues; and 1 281, 1 341, 1 381, 1 417, 1 465, 1 530, and 1 637 cm(-1) peaks were found in the benign and malignant tissues. The main characteristic peaks differentiating benign and malignant lesions were 1 340 and 1 480 cm(-1). The accuracy of SVM-RFE in discriminating normal and malignant lesions was 100.0%, while that in the assessment of benign lesions was 93.0%. There are distinct differences among the Raman spectra of normal, benign and malignant breast tissues, and SVM-RFE method can be used to build differentiation model of breast lesions.

  9. Differential Utilization of Dietary Fatty Acids in Benign and Malignant Cells of the Prostate.

    Directory of Open Access Journals (Sweden)

    Andrea Dueregger

    Full Text Available Tumor cells adapt via metabolic reprogramming to meet elevated energy demands due to continuous proliferation, for example by switching to alternative energy sources. Nutrients such as glucose, fatty acids, ketone bodies and amino acids may be utilized as preferred substrates to fulfill increased energy requirements. In this study we investigated the metabolic characteristics of benign and cancer cells of the prostate with respect to their utilization of medium chain (MCTs and long chain triglycerides (LCTs under standard and glucose-starved culture conditions by assessing cell viability, glycolytic activity, mitochondrial respiration, the expression of genes encoding key metabolic enzymes as well as mitochondrial mass and mtDNA content. We report that BE prostate cells (RWPE-1 have a higher competence to utilize fatty acids as energy source than PCa cells (LNCaP, ABL, PC3 as shown not only by increased cell viability upon fatty acid supplementation but also by an increased ß-oxidation of fatty acids, although the base-line respiration was 2-fold higher in prostate cancer cells. Moreover, BE RWPE-1 cells were found to compensate for glucose starvation in the presence of fatty acids. Of notice, these findings were confirmed in vivo by showing that PCa tissue has a lower capacity in oxidizing fatty acids than benign prostate. Collectively, these metabolic differences between benign and prostate cancer cells and especially their differential utilization of fatty acids could be exploited to establish novel diagnostic and therapeutic strategies.

  10. Differential Utilization and Localization of ErbB Receptor Tyrosine Kinases in Skin Compared to Normal and Malignant Keratinocytes

    Directory of Open Access Journals (Sweden)

    Stefan W. Stoll

    2001-01-01

    Full Text Available Induction of heparin-binding epidermal growth factorlike growth factor (HB-EGF mRNA in mouse skin organ culture was blocked by two pan-ErbB receptor tyrosine kinase (RTK inhibitors but not by genetic ablation of ErbB1, suggesting involvement of multiple ErbB species in skin physiology. Human skin, cultured normal keratinocytes, and A431 skin carcinoma cells expressed ErbB1, ErbB2, and ErbB3, but not ErbB4. Skin and A431 cells expressed more ErbB3 than did keratinocytes. Despite strong expression of ErbB2 and ErbB3, heregulin was inactive in stimulating tyrosine phosphorylation in A431 cells. In contrast, it was highly active in MDA-MB-453 breast carcinoma cells. ErbB2 displayed punctate cytoplasmic staining in A431 and keratinocytes, compared to strong cell surface staining in MDA-MB-453. In skin, ErbB2 was cytoplasmic in basal keratinocytes, assuming a cell surface pattern in the upper suprabasal layers. In contrast, ErbB1 retained a cell surface distribution in all epidermal layers. Keratinocyte proliferation in culture was found to be ErbB1-RTK-dependent, using a selective inhibitor. These results suggest that in skin keratinocytes, ErbB2 transduces ligand-dependent differentiation signals, whereas ErbB1 transduces ligand-dependent proliferation/survival signals. Intracellular sequestration of ErbB2 may contribute to the malignant phenotype of A431 cells, by allowing them to respond to ErbB1dependent growth/survival signals, while evading ErbB2-dependent differentiation signals.

  11. Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP.

    OpenAIRE

    Bang, Y J; Pirnia, F; Fang, W G; Kang, W K; Sartor, O; Whitesell, L; Ha, M J; Tsokos, M.; Sheahan, M D; Nguyen, P.

    1994-01-01

    Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analog...

  12. Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and NeuroD2.

    Science.gov (United States)

    Micheli, Laura; Ceccarelli, Manuela; Gioia, Roberta; D'Andrea, Giorgio; Farioli-Vecchioli, Stefano; Costanzi, Marco; Saraulli, Daniele; Cestari, Vincenzo; Tirone, Felice

    2017-01-01

    Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As a model we used the Tis21 knockout mouse, whose dentate gyrus neurons, as demonstrated by us and others, have an intrinsic defect of terminal differentiation. We first tested the effect of two proliferative as well as differentiative neurogenic stimuli, one pharmacological (fluoxetine), the other cognitive (the Morris water maze (MWM) training). Both effectively enhanced the number of new dentate gyrus neurons produced, and fluoxetine also reduced the S-phase length of Tis21 knockout dentate gyrus progenitor cells and increased the rate of differentiation of control cells, but neither factor enhanced the defective rate of differentiation. In contrast, the defect of terminal differentiation was fully rescued by in vivo infection of proliferating dentate gyrus progenitor cells with retroviruses either silencing Id3, an inhibitor of neural differentiation, or expressing NeuroD2, a proneural gene expressed in terminally differentiated dentate gyrus neurons. This is the first demonstration that NeuroD2 or the silencing of Id3 can activate the differentiation of dentate gyrus neurons, complementing a defect of differentiation. It also highlights how the rate of differentiation of dentate gyrus neurons is regulated genetically at several levels and that a neurogenic stimulus for amplification of neural stem/progenitor cells may not be sufficient in itself to modify this rate.

  13. Hematopoiesis at the onset of metamorphosis: terminal differentiation and dissociation of the Drosophila lymph gland.

    Science.gov (United States)

    Grigorian, Melina; Mandal, Lolitika; Hartenstein, Volker

    2011-08-01

    The Drosophila melanogaster hematopoietic organ, called lymph gland, proliferates and differentiates throughout the larval period. The lymph gland of the late larva is comprised of a large primary lobe and several smaller secondary lobes. Differentiation into two types of hemocytes, plasmatocytes and crystal cells, is confined to the outer layer (cortical zone) of the primary lobe; the center of the primary lobe (medullary zone), as well as the secondary lobes, contain only proliferating prohemocytes. A small cluster of cells located at the posterior tip of the primary lobe serves as a signaling center (PSC) that inhibits precocious differentiation of the medullary zone. The larval lymph gland is stabilized by layers of extracellular matrix (basement membranes) that surround individual hemocytes, groups of hemocytes, as well as the lymph gland as a whole. In this paper, we investigated the events shaping the lymph gland in the early pupa. The lymph gland dissociates and hemocytes disperse during the first 12 h after puparium formation (APF), leaving behind empty husks of basement membrane. Prior to lymph gland dissociation, cells of the medullary zone differentiate, expressing the early differentiation marker Peroxidasin (Pxn), as well as, in part, the late differentiation marker P1. Cells of the PSC spread throughout the pupal lymph gland prior to their dispersal. Cells of the secondary lobes undergo a rapid phase of proliferation that lasts until 8 h APF, followed by expression of Pxn and dispersal. These hemocytes do not express P1, indicating that they disperse prior to full maturation.

  14. Glycogen Synthase Kinase-3β Inhibition Links Mitochondrial Dysfunction, Extracellular Matrix Remodelling and Terminal Differentiation in Chondrocytes.

    Science.gov (United States)

    Guidotti, S; Minguzzi, M; Platano, D; Santi, S; Trisolino, G; Filardo, G; Mariani, E; Borzì, R M

    2017-09-21

    Following inflammatory stimuli, GSK3 inhibition functions as a hub with pleiotropic effects leading to cartilage degradation. However, little is known about the effects triggered by its direct inhibition as well as the effects on mitochondrial pathology, that contributes to osteoarthritis pathogenesis. To this aim we assessed the molecular mechanisms triggered by GSK3β inactivating stimuli on 3-D (micromass) cultures of human articular chondrocytes. Stimuli were delivered either at micromass seeding (long term) or after maturation (short term) to explore "late" effects on terminal differentiation or "early" mitochondrial effects, respectively. GSK3β inhibition significantly enhanced mitochondrial oxidative stress and damage and endochondral ossification based on increased nuclear translocation of Runx-2 and β-catenin, calcium deposition, cell death and enhanced remodelling of the extracellular matrix as demonstrated by the increased collagenolytic activity of supernatants, despite unmodified (MMP-1) or even reduced (MMP-13) collagenase gene/protein expression. Molecular dissection of the underlying mechanisms showed that GSK3β inhibition achieved with pharmacological/silencing strategies impacted on the control of collagenolytic activity, via both decreased inhibition (reduced TIMP-3) and increased activation (increased MMP-10 and MMP-14). To conclude, the inhibition of GSK3β enhances terminal differentiation via concerted effects on ECM and therefore its activity represents a tool to keep articular cartilage homeostasis.

  15. Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination.

    Directory of Open Access Journals (Sweden)

    Samantha F Kornfeld

    Full Text Available Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as

  16. Establishment of a new OSCC cell line derived from OLK and identification of malignant transformation-related proteins by differential proteomics approach.

    Science.gov (United States)

    Dong, Yan; Zhao, Qun; Ma, Xiaoyan; Ma, Guowu; Liu, Caiyun; Chen, Zhuwen; Yu, Liyuan; Liu, Xuefeng; Zhang, Yanguang; Shao, Shujuan; Xiao, Jing; Li, Jia; Zhang, Weimin; Fu, Ming; Dong, Lijia; Yang, Xiandong; Guo, Xu; Xue, Liyan; Fang, Fei; Zhan, Qimin; Zhang, Lihua

    2015-08-03

    Oral squamous cell carcinoma (OSCC) is usually preceded by the oral premalignant lesions, mainly oral leukoplakia (OLK) after repeated insults of carcinogens, tobacco. B(a)P and DMBA are key carcinogens in tobacco smoke. In the present study, for the first time we established the cancerous cell line OSCC-BD induced by B(a)P/DMBA mixture and transformed from dysplastic oral leukoplakia cell line DOK. Cell morphology, proliferation ability, migration ability, colony formation, and tumorigenicity were studied and confirmed the malignant characteristics of OSCC-BD cells. We further identified the differential proteins between DOK and OSCC-BD cells by stable isotope dimethyl labeling based quantitative proteomic method, which showed 18 proteins up-regulated and 16 proteins down-regulated with RSD < 8%. Differential proteins are mainly related to cell cycle, cell proliferation, DNA replication, RNA splicing and apoptosis. Abberant binding function, catalysis activity and transportor activity of differential proteins might contribute to the malignant transformation of OLK. Of the 34 identified differential proteins with RSD < 8%, 13 novel cancer-related proteins were reported in the present study. This study might provide a new insight into the mechanism of OLK malignant transformation and the potent biomarkers for early diagnosis, meanwhile further facilitate the application of the quantification proteomics to carcinogenesis research.

  17. Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation.

    Science.gov (United States)

    Hu, Wenqian; Yuan, Bingbing; Flygare, Johan; Lodish, Harvey F

    2011-12-15

    Long noncoding RNAs (lncRNAs) are differentially expressed under both normal and pathological conditions, implying that they may play important biological functions. Here we examined the expression of lncRNAs during erythropoiesis and identified an erythroid-specific lncRNA with anti-apoptotic activity. Inhibition of this lncRNA blocks erythroid differentiation and promotes apoptosis. Conversely, ectopic expression of this lncRNA can inhibit apoptosis in mouse erythroid cells. This lncRNA represses expression of Pycard, a proapoptotic gene, explaining in part the inhibition of programmed cell death. These findings reveal a novel layer of regulation of cell differentiation and apoptosis by a lncRNA. © 2011 by Cold Spring Harbor Laboratory Press

  18. Molecular imaging with (99m)Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison.

    Science.gov (United States)

    Giovanella, L; Campenni, A; Treglia, G; Verburg, F A; Trimboli, P; Ceriani, L; Bongiovanni, M

    2016-06-01

    To compare mutation analysis of cytology specimens and (99m)Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm. Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and (99m)Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of (99m)Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method. In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. (99m)Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative (99m)Tc-MIBI scan reliably excluded malignancy. In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of (99m)Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material.

  19. Fluorescence cytology with 5-aminolevulinic acid in EUS-guided FNA as a method for differentiating between malignant and benign lesions (with video).

    Science.gov (United States)

    Ikeura, Tsukasa; Takaoka, Makoto; Uchida, Kazushige; Shimatani, Masaaki; Miyoshi, Hideaki; Kato, Kota; Ohe, Chisato; Uemura, Yoshiko; Kaibori, Masaki; Kwon, A-Hon; Okazaki, Kazuichi

    2015-01-01

    EUS-guided FNA (EUS-FNA) has been increasingly performed to obtain specimens for the pathological evaluation of patients with GI and pancreaticobiliary masses as well as lymphadenopathies of unknown origin. Photodynamic diagnosis by using 5-aminolebulinic acid (ALA) has been reported to be useful for enabling the visual differentiation between malignant and normal tissue in various cancers. To evaluate the diagnostic accuracy of fluorescence cytology with ALA in EUS-FNA. A prospective study. A single center. A total of 28 consecutive patients who underwent EUS-FNA for the pathological diagnosis of a pancreaticobiliary mass lesion or intra-abdominal lymphadenopathy of unknown origin. Patients were orally administered ALA 3 to 6 hours before EUS-FNA. The sample was obtained via EUS-FNA for fluorescence cytology and conventional cytology. A single gastroenterologist performed the fluorescence cytology by using fluorescence microscopy after the procedure, independently of the conventional cytology by pathologists. The accuracy of fluorescence cytology with ALA in the differentiation between benign and malignant lesions by comparing the results of fluorescence cytology with the final diagnosis. Of the 28 patients included in the study, 22 were considered as having malignant lesions and 6 patients as having benign lesions. Fluorescence cytology could correctly discriminate between benign and malignant lesions in all patients. Therefore, both the sensitivity and specificity of fluorescence cytology were 100% in our study. Fluorescence cytology was performed by only 1 gastroenterologist with a small number of patients. Fluorescence cytology with ALA in EUS-FNA may be an effective and simple method for differentiating between benign and malignant lesions. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  20. Molecular imaging with {sup 99m}Tc-MIBI and molecular testing for mutations in differentiating benign from malignant follicular neoplasm: a prospective comparison

    Energy Technology Data Exchange (ETDEWEB)

    Giovanella, L.; Treglia, G.; Ceriani, L. [Oncology Institute of Southern Switzerland, Department of Nuclear Medicine and Thyroid Centre, Bellinzona (Switzerland); Campenni, A. [Policlinico Universitario, Istituto di Medicina Nucleare, Messina (Italy); Verburg, F.A. [RWTH University Hospital Aachen, Department of Nuclear Medicine, Aachen (Germany); Trimboli, P. [Oncology Institute of Southern Switzerland, Department of Nuclear Medicine and Thyroid Centre, Bellinzona (Switzerland); Ospedale Israelitico, Sezione di Endocrinologia e Diabetologia, Roma (Italy); Bongiovanni, M. [Centre Hopitalier Universitaire Vaudouise, Institut de Pathologie, Lausanne (Switzerland)

    2016-06-15

    To compare mutation analysis of cytology specimens and {sup 99m}Tc-MIBI thyroid scintigraphy for differentiating benign from malignant thyroid nodules in patients with a cytological reading of follicular neoplasm. Patients ≥18 years of age with a solitary hypofunctioning thyroid nodule (≥10 mm), normal thyrotropin and calcitonin levels, and a cytological diagnosis of follicular neoplasm were prospectively enrolled. Mutation analysis and {sup 99m}Tc-MIBI scintigraphy were performed and patients were subsequently operated on to confirm or exclude a malignant lesion. Mutations for KRAS, HRAS and NRAS and for BRAF and translocations of PAX8/PPARγ, RET/PTC1 and RET/PTC3 were investigated. Static thyroid scintigraphic images were acquired 10 and 60 min after intravenous injection of 200 MBq of {sup 99m}Tc-MIBI and visually assessed. Additionally, the MIBI washout index was calculated using a semiquantitative method. In our series, 26 % of nodules with a follicular pattern on cytology were malignant with a prevalence of follicular carcinomas. {sup 99m}Tc-MIBI scintigraphy was found to be significantly more accurate (positive likelihood ratio 4.56 for visual assessment and 12.35 for semiquantitative assessment) than mutation analysis (positive likelihood ratio 1.74). A negative {sup 99m}Tc-MIBI scan reliably excluded malignancy. In patients with a thyroid nodule cytologically diagnosed as a follicular proliferation, semiquantitative analysis of {sup 99m}Tc-MIBI scintigraphy should be the preferred method for differentiating benign from malignant nodules. It is superior to molecular testing for the presence of differentiated thyroid cancer-associated mutations in fine-needle aspiration cytology sample material. (orig.)

  1. Comparison of 3D and 2D shear-wave elastography for differentiating benign and malignant breast masses: focus on the diagnostic performance.

    Science.gov (United States)

    Choi, H Y; Sohn, Y-M; Seo, M

    2017-10-01

    To evaluate the diagnostic performance of three-dimensional (3D) image shear-wave elastography (SWE) for differentiating benign from malignant breast masses compared to two-dimensional (2D) SWE and B-mode ultrasound (US). This study consisted of 205 breast lesions from 199 patients who underwent B-mode US and SWE before biopsy from January 2014 to March 2016. Quantitative elasticity values (maximum and mean elasticity, Emax and Emean) obtained from 2D and 3D SWE (axial, sagittal, and coronal images) were reviewed retrospectively, in addition to the histopathological findings including immunohistochemistry profiles (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer) in cases of malignancy. Histopathological findings were regarded as the reference standard. The diagnostic performance of each data set was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC) analysis to compare sensitivity and specificity. Among 205 lesions, 105 (51.22%) were malignant and 100 (48.78%) were benign. Compared to benign masses, malignant masses had higher values of Emax and Emean on both 2D and 3D SWE, the differences of which were statistically significant (psuperior diagnostic performance compared to 3D coronal images. Addition of 3D SWE images to B-mode US improved the diagnostic performance for distinguishing benign from malignant masses. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  2. Tumour exosomes display different differential mechanical and complement activation properties dependent on malignant state: implications in endothelial leakiness

    DEFF Research Database (Denmark)

    Whitehead, Bradley Joseph; Wu, Linping; Hvam, Michael Lykke

    2015-01-01

    Background : Exosomes have been implicated in tumour progression and metastatic spread. Little is known of the effect of mechanical and innate immune interactions of malignant cell-derived exosomes on endothelial integrity, which may relate to increased extravasation of circulating tumour cells a......-malignant cell line exosomes, which may explain the observed increased endothelial monolayer disruption and transendothelial transport of these vesicles....

  3. Differentiating benign from malignant solid breast masses: value of shear wave elastography according to lesion stiffness combined with greyscale ultrasound according to BI-RADS classification

    OpenAIRE

    Evans, A; Whelehan, P; Thomson, K; Brauer, K; Jordan, L; Purdie, C; McLean, D; Baker, L; Vinnicombe, S; Thompson, A.

    2012-01-01

    Background: The aim of this study was to assess the performance of shear wave elastography combined with BI-RADS classification of greyscale ultrasound images for benign/malignant differentiation in a large group of patients. Methods: One hundred and seventy-five consecutive patients with solid breast masses on routine ultrasonography undergoing percutaneous biopsy had the greyscale findings classified according to the American College of Radiology BI-RADS. The mean elasticity values from fou...

  4. Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells

    Directory of Open Access Journals (Sweden)

    Gersende Caron

    2015-11-01

    Full Text Available Molecular mechanisms underlying terminal differentiation of B cells into plasma cells are major determinants of adaptive immunity but remain only partially understood. Here we present the transcriptional and epigenomic landscapes of cell subsets arising from activation of human naive B cells and differentiation into plasmablasts. Cell proliferation of activated B cells was linked to a slight decrease in DNA methylation levels, but followed by a committal step in which an S phase-synchronized differentiation switch was associated with an extensive DNA demethylation and local acquisition of 5-hydroxymethylcytosine at enhancers and genes related to plasma cell identity. Downregulation of both TGF-β1/SMAD3 signaling and p53 pathway supported this final step, allowing the emergence of a CD23-negative subpopulation in transition from B cells to plasma cells. Remarkably, hydroxymethylation of PRDM1, a gene essential for plasma cell fate, was coupled to progression in S phase, revealing an intricate connection among cell cycle, DNA (hydroxymethylation, and cell fate determination.

  5. Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure

    Energy Technology Data Exchange (ETDEWEB)

    Gennaro, G. de; Longobardi, F.; Stallone, G.; Trizio, L.; Tutino, M. [University of Bari Aldo Moro, Department of Chemistry, Bari (Italy); Dragonieri, S. [University of Bari Aldo Moro, Department of Pulmonology, Bari (Italy); Musti, M. [University of Bari Aldo Moro, Department of Occupational Medicine, Bari (Italy)

    2010-12-15

    Malignant pleural mesothelioma (MPM) is an aggressive tumour whose main aetiology is the long-term exposure to asbestos fibres. The diagnostic procedure of MPM is difficult and often requires invasive approaches; therefore, it is clinically important to find accurate markers for MPM by new noninvasive methods that may facilitate the diagnostic process and identify patients at an earlier stage. In the present study, the exhaled breath of 13 patients with histology-established diagnosis of MPM, 13 subjects with long-term certified professional exposure to asbestos (EXP) and 13 healthy subjects without exposure to asbestos (healthy controls, HC) were analysed. An analytical procedure to determine volatile organic compounds by sampling of air on a bed of solid sorbent and thermal desorption GC-MS analysis was developed in order to identify the compounds capable of discriminating among the three groups. The application of univariate (ANOVA) and multivariate statistical treatments (PCA, DFA and CP-ANN) showed that cyclopentane and cyclohexane were the dominant variables able to discriminate among the three groups. In particular, it was found that cyclohexane is the only compound able to differentiate the MPM group from the other two; therefore, it can be a possible marker of MPM. Cyclopentane is the dominant compound in the discrimination between EXP and the other groups (MPM and HC); then, it can be considered a good indicator for long-term asbestos exposure. This result suggests the need to perform frequent and thorough investigations on people exposed to asbestos in order to constantly monitor their state of health or possibly to study the evolution of disease over time. (orig.)

  6. Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure.

    Science.gov (United States)

    de Gennaro, G; Dragonieri, S; Longobardi, F; Musti, M; Stallone, G; Trizio, L; Tutino, M

    2010-12-01

    Malignant pleural mesothelioma (MPM) is an aggressive tumour whose main aetiology is the long-term exposure to asbestos fibres. The diagnostic procedure of MPM is difficult and often requires invasive approaches; therefore, it is clinically important to find accurate markers for MPM by new noninvasive methods that may facilitate the diagnostic process and identify patients at an earlier stage. In the present study, the exhaled breath of 13 patients with histology-established diagnosis of MPM, 13 subjects with long-term certified professional exposure to asbestos (EXP) and 13 healthy subjects without exposure to asbestos (healthy controls, HC) were analysed. An analytical procedure to determine volatile organic compounds by sampling of air on a bed of solid sorbent and thermal desorption GC-MS analysis was developed in order to identify the compounds capable of discriminating among the three groups. The application of univariate (ANOVA) and multivariate statistical treatments (PCA, DFA and CP-ANN) showed that cyclopentane and cyclohexane were the dominant variables able to discriminate among the three groups. In particular, it was found that cyclohexane is the only compound able to differentiate the MPM group from the other two; therefore, it can be a possible marker of MPM. Cyclopentane is the dominant compound in the discrimination between EXP and the other groups (MPM and HC); then, it can be considered a good indicator for long-term asbestos exposure. This result suggests the need to perform frequent and thorough investigations on people exposed to asbestos in order to constantly monitor their state of health or possibly to study the evolution of disease over time.

  7. Measurement and calculation of the differential reflectance spectrum of hydrogen-terminated silicon surfaces having different crystal orientations.

    Science.gov (United States)

    Inagaki, K; Okada, N; Noda, T; Endo, K; Hirose, K

    2007-09-12

    The differential reflectance spectrum between the (001) and the (111) hydrogen-terminated Si surfaces without native oxidation is investigated. Careful measurements using developed apparatus and an ultra-clean process are performed. The measured spectrum is compared with the reported one (Chongsawangvirod and Irene 1991 J. Electrochem. Soc. 138 1748-52), and is shown to be roughly identical even though a native oxidation effect exists. The theoretical calculation based on density-functional theory (DFT) and local density approximation (LDA) is also performed. The peak positions in the calculated and the measured spectra are in good accordance with each other, while the magnitudes of the peaks are in relatively worse agreement. Although the inclusion of advanced approximations would provide more accurate results, a qualitative reproduction is achieved in this study as well. It is concluded that the origin of the spectrum is mainly in the deformation of the bulk states induced by surface perturbation.

  8. N-cadherin induces partial differentiation of cholinergic presynaptic terminals in heterologous cultures of brainstem neurons and CHO cells

    Directory of Open Access Journals (Sweden)

    Richard J Flannery

    2012-12-01

    Full Text Available N-cadherin is a calcium-sensitive cell adhesion molecule commonly expressed at synaptic junctions and contributes to formation and maturation of synaptic contacts. This study used heterologous cell cultures of brainstem cholinergic neurons and transfected Chinese Hamster Ovary (CHO cells to examine whether N-cadherin is sufficient to induce differentiation of cholinergic presynaptic terminals. Brainstem nuclei isolated from transgenic mice expressing EGFP under the control of choline acetyltransferase transcriptional regulatory elements (ChATBACEGFP were cultured as tissue explants for five days and cocultured with transfected CHO cells for an additional two days. Immunostaining for synaptic vesicle proteins SV2 and synapsin I revealed a ~3-fold increase in the area of SV2 immunolabeling over N-cadherin expressing CHO cells, and this effect was enhanced by coexpression of p120-catenin. Synapsin I immunolabeling per axon length was also increased on N-cadherin expressing CHO cells but required coexpression of p120-catenin. To determine whether N-cadherin induces formation of neurotransmitter release sites, whole-cell voltage-clamp recordings of CHO cells expressing alpha-3 and beta-4 nicotinic acetylcholine receptor (nAChR subunits in contact with cholinergic axons were used to monitor excitatory postsynaptic potentials (EPSPs and miniature EPSPs (mEPSPs. EPSPs and mEPSPs were not detected in both, control and in N-cadherin expressing CHO cells in the absence or presence of tetrodotoxin. These results indicate that expression of N-cadherin in non-neuronal cells is sufficient to initiate differentiation of presynaptic cholinergic terminals by inducing accumulation of synaptic vesicles; however, development of readily detectable mature cholinergic release sites and/or clustering of postsynaptic nAChR may require expression of additional synaptogenic proteins.

  9. Differential pre- and postsynaptic effects of desipramine on cardiac sympathetic nerve terminals in RHF.

    Science.gov (United States)

    Liang, Chang-Seng; Himura, Yoshihiro; Kashiki, Michihiro; Stevens, Suzanne Y

    2002-11-01

    Right heart failure (RHF) is characterized by chamber-specific reductions of myocardial norepinephrine (NE) reuptake, beta-receptor density, and profiles of cardiac sympathetic nerve ending neurotransmitters. To study the functional linkage between NE uptake and the pre- and postsynaptic changes, we administered desipramine (225 mg/day), a NE uptake inhibitor, to dogs with RHF produced by tricuspid avulsion and progressive pulmonary constriction or sham-operated dogs for 6 wk. Animals receiving no desipramine were studied as controls. We measured myocardial NE uptake activity using [(3)H]NE, beta-receptor density by [(125)I]iodocyanopindolol, inotropic responses to dobutamine, and noradrenergic terminal neurotransmitter profiles by glyoxylic acid-induced histofluorescence for catecholamines, and immunocytochemical staining for tyrosine hydroxylase and neuropeptide Y. Desipramine decreased myocardial NE uptake activity and had no effect on the resting hemodynamics in both RHF and sham animals but decreased myocardial beta-adrenoceptor density and beta-adrenergic inotropic responses in both ventricles of the RHF animals. However, desipramine treatment prevented the reduction of sympathetic neurotransmitter profiles in the failing heart. Our results indicate that NE uptake inhibition facilitates the reduction of myocardial beta-adrenoceptor density and beta-adrenergic subsensitivity in RHF, probably by increasing interstitial NE concentrations, but protects the cardiac noradrenergic nerve endings from damage, probably via blockade of NE-derived neurotoxic metabolites into the nerve endings.

  10. Inhibition of the terminal differentiation of odontoblasts and their transdifferentiation into osteoblasts in Runx2 transgenic mice.

    Science.gov (United States)

    Miyazaki, Toshihiro; Kanatani, Naoko; Rokutanda, Satoshi; Yoshida, Carolina; Toyosawa, Satoru; Nakamura, Reiko; Takada, Shinji; Komori, Toshihisa

    2008-09-01

    Runx2 is an essential transcription factor for bone and tooth development whose function in odontoblast differentiation remains to be clarified. To pursue this issue, we examined tooth development in Runx2 transgenic mice under the control of Col1a1 promoter (Tg(Col1a1-Runx2) mice). Endogenous Runx2 protein was detected in the nuclei of preodontoblasts, immature odontoblasts, mesenchymal cells in the dental sac, and osteoblasts, while transgene expression was detected in odontoblasts and osteoblasts. Odontoblasts in Tg(Col1a1-Runx2) mice lost their columnar shape and dentin was deposited around the odontoblasts, which were cuboid or flat in shape. The dentin in Tg(Col1a1-Runx2) mice was thin and possessed lacunae that contained odontoblasts and bone canaliculi-like structures, while predentin and dentinal tubules were absent. We examined the expression of dentin matrix protein genes, Col1a1 and dentin sialophosphoprotein (DSPP), by in situ hybridization, and dentin matrix proteins, osteocalcin, osteopontin, and dentin matrix protein 1 (DMP1) as well as an intermediate filament, nestin, by immunohistochemistry to characterize odontoblasts in Tg(Col1a1-Runx2) mice. Results showed Col1a1 expression was down-regulated, DSPP expression was lost, and nestin expression was severely decreased in the odontoblasts of Tg(Col1a1-Runx2) mice. Further, the expressions of osteocalcin, osteopontin, and DMP1 were up-regulated in odontoblasts, although the up-regulation of osteocalcin expression was transient. These findings indicate that Runx2 inhibits the terminal differentiation of odontoblasts, and that Runx2 induces transdifferentiation of odontoblasts into osteoblasts forming a bone structure. Thus, Runx2 expression has to be down-regulated during odontoblast differentiation to acquire full odontoblast differentiation for dentinogenesis.

  11. Comparison of muscle-to-nodule and parenchyma-to-nodule strain ratios in the differentiation of benign and malignant thyroid nodules: Which one should we use?

    Energy Technology Data Exchange (ETDEWEB)

    Aydin, Ramazan, E-mail: raydin1984@hotmail.com [Department of Radiology, Samsun Education and Research Hospital, Samsun (Turkey); Elmali, Muzaffer, E-mail: muzafel@yahoo.com.tr [Department of Radiology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey); Polat, Ahmet Veysel, E-mail: veyselp@hotmail.com [Department of Radiology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey); Danaci, Murat, E-mail: danacim55@yahoo.com [Department of Radiology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey); Akpolat, Ilkser, E-mail: ilkserakpolat@yahoo.com [Department of Pathology, Ondokuz Mayis University, Faculty of Medicine, Samsun (Turkey)

    2014-03-15

    Objective: The aim of this study is to investigate the diagnostic accuracy of muscle-to-nodule strain ratio (MNSR) in the differentiation of benign and malignant thyroid nodules and to see if there was a difference between MNSR and parenchyma-to-nodule strain ratios (PNSR) in diagnosis. Methods: A total of 106 consecutive patients (88 women and 18 men; age range 19–79 years) with thyroid nodules were prospectively examined using ultrasound and sonoelastography before the fine-needle aspiration biopsy. The mean MNSR and PNSR were calculated for each nodule and the elasticity score was determined according to four-point scoring system. Results: According to the four-point scoring system, 44 of the 83 benign nodules had a score of one or two while 22 of the 23 malignant nodules had a score of three or four (p < 0.001). Using ROC analysis, the best cutoff point for MNSR 1.85 and for PNSR 3.14 was calculated. The sensitivity and specificity for the MNSR were 95.6%, 92.8%, respectively; for the PNSR were 95.6%, 93.4%, respectively, when the best cutoff points were used (p < 0.001). The κ value for the PNSR and MNSR methods was 0.87, which indicated an almost perfect agreement (p < 0.001). Conclusions: Sonoelastography has a high diagnostic accuracy in the differentiation of benign and malignant thyroid nodules. There was no significant difference between MNSR and PNSR in the differentiation of benign and malignant thyroid nodules. Therefore, we think that MNSR could safely be used in situations where PNSR could not be used.

  12. Involvement of the Notch Pathway in Terminal Astrocytic Differentiation: Role of PKA

    Directory of Open Access Journals (Sweden)

    Carla Angulo-Rojo

    2013-11-01

    Full Text Available The Notch pathway is a highly conserved signaling system essential for modulating neurogenesis and promoting astrogenesis. Similarly, the cAMP signaling cascade can promote astrocytic commitment in several cell culture models, such as the C6 glioma cell line. These cells have the capacity to differentiate into oligodendrocytes or astrocytes, characteristics that allow their use as a glial progenitor model. In this context, we explore here the plausible involvement of cAMP in Notch-dependent signal transactions. The exposure of C6 cells to a non-hydrolysable cAMP analogue resulted in a sustained augmentation of Notch activity, as detected by nuclear translocation of its intracellular domain portion (NICD and transcriptional activity. The cAMP effect is mediated through the activation of the γ-secretase complex, responsible for Notch cleavage and is sensitive to inhibitors of the cAMP-dependent protein kinase, PKA. As expected, Notch cleavage and nuclear translocation resulted in the up-regulation of the mRNA levels of one of its target genes, the transcription factor Hair and enhancer of split 5. Moreover, the glutamate uptake activity, as well as the expression of astrocytic markers such as glial fibrillary acidic protein, S100β protein and GLAST was also enhanced in cAMP-exposed cells. Our results clearly suggest that during the process of C6 astrocytic differentiation, cAMP activates the PKA/γ-secretase/NICD/RBPJK pathway and Notch1 expression, leading to transcriptional activation of the genes responsible for glial progenitor cell fate decision.

  13. The value of energy spectral CT in the differential diagnosis between benign and malignant soft tissue masses of the musculoskeletal system

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Xin [Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong (China); Shao, Xiaodong [Department of Radiology, Qingdao Municipal Hospital, Qingdao, Shandong (China); Chen, Haisong, E-mail: chsEJR@163.com [Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong (China)

    2015-06-15

    Highlights: • Different types of tissues have different types of spectral curves. • We find that spectral curve is useful in the differential diagnosis of benign and malignant tumor of the musculoskeletal system. • Arc shaped curve is a specific sign for tumors containing abundant fat. - Abstract: Objective: To explore the value of energy spectral CT in the differential diagnosis between benign and malignant tumor of the musculoskeletal system. Methods: Energy spectral CT scan was performed on 100 patients with soft tissue mass caused by musculoskeletal tumors found by MRI. Solid areas with homogenous density were chosen as region of interests (ROI), avoiding necrosis, hemorrhage and calcification region. Select the optimal keV on single energy images, and then the keV–CT curve was automatically generated. All 100 cases of tumors proved by histological examination were divided into four groups, 38 cases were in benign group, 10 cases in borderline group, 49 cases in malignant group, and 3 cases of lipoma (that were analyzed separately since its curve was arc shaped, significantly different from other curves). The formula used to calculate the slope of spectral curve was as follows: slope = (Hu40 keV − Hu80 keV)/40. As the slope was steep within the range of 40–80 keV based on preliminary observations, 40 keV and 80 keV were used as the reference points to calculate the slope value of the energy spectral curve. Kruskal–Wallis rank sum test was applied for statistical analysis, and P < 0.05 was considered to indicate a statistically significant difference. Results: The spectral curve of benign group was gradually falling type with a mean slope of 0.75 ± 0.30, that of malignant group was sharply falling type with a mean slope of 1.64 ± 1.00, and that of borderline group was a falling type between the above two groups with a mean slope of 1.34 ± 0.45. The differences of slopes between benign and malignant group, benign and borderline group were of

  14. Differentiation of Malignant and Benign Incidental Breast Lesions Detected by Chest Multidetector-Row Computed Tomography: Added Value of Quantitative Enhancement Analysis.

    Directory of Open Access Journals (Sweden)

    Yu-Pang Lin

    Full Text Available To retrospectively determine the association between breast lesion morphology and malignancy and to determine the optimal value of lesion enhancement (HU, Hounsfield units to improve the diagnostic accuracy of breast cancer in patients with incidental breast lesions (IBLs. A total of 97 patients with 102 IBLs detected from July 2009 to December 2012 were enrolled in this study. Two radiologists analyzed CT images for the presence of malignancy based on the morphology of the lesions alone and in combination with an enhancement value (HU analysis. There were 36 malignant and 66 benign IBLs. When the morphology and enhancement values were combined, the sensitivity, specificity, and accuracy were 92%, 97%, and 95%, respectively, for reader 1 and 89%, 94%, and 92%, respectively, for reader 2. The addition of HU values led to correct changes in the diagnosis; specifically, the accuracy of the diagnosis of reader 1 and reader 2 improved by 6.9% and 11.8%, respectively. The addition of the enhancement value (HU to the CT morphology improved the diagnostic accuracy in the differentiation of malignant from benign IBLs by using the region of interest (ROI to measure the HU within the most suspicious part of the lesion.

  15. Differentiation of Malignant and Benign Incidental Breast Lesions Detected by Chest Multidetector-Row Computed Tomography: Added Value of Quantitative Enhancement Analysis.

    Science.gov (United States)

    Lin, Yu-Pang; Hsu, Hsian-He; Ko, Kai-Hsiung; Chu, Chi-Ming; Chou, Yu-Ching; Chang, Wei-Chou; Chang, Tsun-Hou

    2016-01-01

    To retrospectively determine the association between breast lesion morphology and malignancy and to determine the optimal value of lesion enhancement (HU, Hounsfield units) to improve the diagnostic accuracy of breast cancer in patients with incidental breast lesions (IBLs). A total of 97 patients with 102 IBLs detected from July 2009 to December 2012 were enrolled in this study. Two radiologists analyzed CT images for the presence of malignancy based on the morphology of the lesions alone and in combination with an enhancement value (HU) analysis. There were 36 malignant and 66 benign IBLs. When the morphology and enhancement values were combined, the sensitivity, specificity, and accuracy were 92%, 97%, and 95%, respectively, for reader 1 and 89%, 94%, and 92%, respectively, for reader 2. The addition of HU values led to correct changes in the diagnosis; specifically, the accuracy of the diagnosis of reader 1 and reader 2 improved by 6.9% and 11.8%, respectively. The addition of the enhancement value (HU) to the CT morphology improved the diagnostic accuracy in the differentiation of malignant from benign IBLs by using the region of interest (ROI) to measure the HU within the most suspicious part of the lesion.

  16. WNT4 acts downstream of BMP2 to mediate the regulation of ATRA signaling on RUNX1 expression: Implications for terminal differentiation of antler chondrocytes.

    Science.gov (United States)

    Zhang, Hong-Liang; Yang, Zhan-Qing; Duan, Cui-Cui; Geng, Shuang; Wang, Kai; Yu, Hai-Fan; Yue, Zhan-Peng; Guo, Bin

    2017-04-24

    Although ATRA is involved in regulating the proliferation and differentiation of chondrocytes, its underlying mechanism remains unknown. Here we showed that ATRA could stimulate the proliferation of antler chondrocytes and expression of COL X and MMP13 which were two well-known markers for hypertrophic chondrocytes. Silencing of CRABP2 prevented the induction of ATRA on chondrocyte terminal differentiation, while overexpression of CRABP2 exhibited the opposite effects. CYP26A1 and CYP26B1 weakened the sensitivity of antler chondrocytes to ATRA. Further analysis evidenced that ATRA might induce chondrocyte terminal differentiation and modulate the expression of BMP2, WNT4, and RUNX1 through RARα/RXRα. Knockdown of BMP2 enhanced the induction of ATRA on the expression of COL X and MMP13, whereas overexpression of BMP2 abrogated this effectiveness. WNT4 might mediate the effects of ATRA and BMP2 on chondrocyte terminal differentiation. Dysregulation of BMP2 impaired the regulation of ATRA on WNT4 expression. Administration of ATRA to antler chondrocytes transfected with RUNX1 siRNA failed to induce the differentiation. Conversely, rRUNX1 strengthened the stimulation of ATRA on the expression of COL X and MMP13. Simultaneously, RUNX1 was a downstream effector of BMP2 and WNT4 in chondrocyte terminal differentiation. Moreover, WNT4 might play an important role in the crosstalk between BMP2 and RUNX1. Attenuation of BMP2 or WNT4 enhanced the interaction between ATRA and RUNX1, while constitutive expression of BMP2 or WNT4 reversed the regulation of ATRA on RUNX1. Collectively, WNT4 may act downstream of BMP2 to mediate the effects of ATRA on the terminal differentiation of antler chondrocytes through targeting RUNX1. © 2017 Wiley Periodicals, Inc.

  17. Tumour exosomes display differential mechanical and complement activation properties dependent on malignant state: implications in endothelial leakiness

    Directory of Open Access Journals (Sweden)

    Bradley Whitehead

    2015-12-01

    Full Text Available Background: Exosomes have been implicated in tumour progression and metastatic spread. Little is known of the effect of mechanical and innate immune interactions of malignant cell-derived exosomes on endothelial integrity, which may relate to increased extravasation of circulating tumour cells and, therefore, increased metastatic spread. Methods: Exosomes isolated from non-malignant immortalized HCV-29 and isogenic malignant non-metastatic T24 and malignant metastatic FL3 bladder cells were characterized by nanoparticle tracking analysis and quantitative nanomechanical mapping atomic force microscopy (QNM AFM to determine size and nanomechanical properties. Effect of HCV-29, T24 and FL3 exosomes on human umbilical vein endothelial cell (HUVEC monolayer integrity was determined by transendothelial electrical resistance (TEER measurements and transport was determined by flow cytometry. Complement activation studies in human serum of malignant and non-malignant cell-derived exosomes were performed. Results: FL3, T24 and HCV-29 cells produced exosomes at similar concentration per cell (6.64, 6.61 and 6.46×104 exosomes per cell for FL3, T24 and HCV-29 cells, respectively and of similar size (120.2 nm for FL3, 127.6 nm for T24 and 117.9 nm for HCV-29, respectively. T24 and FL3 cell-derived exosomes exhibited a markedly reduced stiffness, 95 MPa and 280 MPa, respectively, compared with 1,527 MPa with non-malignant HCV-29 cell-derived exosomes determined by QNM AFM. FL3 and T24 exosomes induced endothelial disruption as measured by a decrease in TEER in HUVEC monolayers, whereas no effect was observed for HCV-29 derived exosomes. FL3 and T24 exosomes traffic more readily (11.6 and 21.4% of applied exosomes, respectively across HUVEC monolayers than HCV-29 derived exosomes (7.2% of applied exosomes. Malignant cell-derived exosomes activated complement through calcium-sensitive pathways in a concentration-dependent manner. Conclusions: Malignant

  18. Angular distribution of cross-sectioned cell boundaries at the distal terminal web in differentiating preameloblasts, inner enamel secretory ameloblasts and outer enamel secretory ameloblasts.

    Science.gov (United States)

    Yuan, Xiaohong; Nishikawa, Sumio

    2014-02-01

    The cross-sectioned profiles of differentiating preameloblasts, inner enamel secretory ameloblasts and outer enamel secretory ameloblasts at the distal terminal web were quantitatively compared. First, the angles of each line constituting the sectioned cell polygons were measured, and the patterns of angular distribution histograms were compared. Second, all groups of line angles from one differentiating preameloblast population, two inner enamel secretory ameloblast and one outer enamel secretory ameloblast populations at the distal terminal web were compared statistically by the χ(2)-test using the multiple comparison method. The results showed that cell shapes between differentiating preameloblasts and inner enamel secretory ameloblasts were similar, but that those between differentiating preameloblasts and outer enamel secretory ameloblasts and between inner enamel secretory ameloblasts and outer enamel secretory ameloblasts were significantly different. Third, F-actin fluorescence microscopy in the distal terminal web was performed and was consistent with the angular distribution. These results suggest that cell shapes of inner enamel secretory ameloblasts and differentiating preameloblasts at the distal terminal web are specialized for sideways cell movement during decussating tooth enamel formation.

  19. Dynamic Contrast Magnetic Resonance Imaging (DCE-MRI) and Diffusion Weighted MR Imaging (DWI) for Differentiation between Benign and Malignant Salivary Gland Tumors.

    Science.gov (United States)

    Assili, S; Fathi Kazerooni, A; Aghaghazvini, L; Saligheh Rad, H R; Pirayesh Islamian, J

    2015-12-01

    Salivary gland tumors form nearly 3% of head and neck tumors. Due to their large histological variety and vicinity to facial nerves, pre-operative diagnosis and differentiation of benign and malignant parotid tumors are a major challenge for radiologists. The majority of these tumors are benign; however, sometimes they tend to transform into a malignant form. Functional MRI techniques, namely dynamic contrast enhanced (DCE-) MRI and diffusion-weighted MRI (DWI) can indicate the characteristics of tumor tissue. DCE-MRI analysis is based on the parameters of time intensity curve (TIC) before and after contrast agent injection. This method has the potential to identify the angiogenesis of tumors. DWI analysis is performed according to diffusion of water molecules in a tissue for determination of the cellularity of tumors. According to the literature, these methods cannot be used individually to differentiate benign from malignant salivary gland tumors. An effective approach could be to combine the aforementioned methods to increase the accuracy of discrimination between different tumor types. The main objective of this study is to explore the application of DCE-MRI and DWI for assessment of salivary gland tumor types.

  20. Dynamic Contrast Magnetic Resonance Imaging (DCE-MRI and Diffusion Weighted MR Imaging (DWI for Differentiation between Benign and Malignant Salivary Gland Tumors

    Directory of Open Access Journals (Sweden)

    Assili S

    2012-12-01

    Full Text Available Background: Salivary gland tumors form nearly 3% of head and neck tumors. Due to their large histological variety and vicinity to facial nerves, pre-operative diagnosis and differentiation of benign and malignant parotid tumors are a major challenge for radiologists. Objective: The majority of these tumors are benign; however, sometimes they tend to transform into a malignant form. Functional MRI techniques, namely dynamic contrast enhanced (DCE- MRI and diffusion-weighted MRI (DWI can indicate the characteristics of tumor tissue. Methods: DCE-MRI analysis is based on the parameters of time intensity curve (TIC before and after contrast agent injection. This method has the potential to identify the angiogenesis of tumors. DWI analysis is performed according to diffusion of water molecules in a tissue for determination of the cellularity of tumors. Conclusion: According to the literature, these methods cannot be used individually to differentiate benign from malignant salivary gland tumors. An effective approach could be to combine the aforementioned methods to increase the accuracy of discrimination between different tumor types. The main objective of this study is to explore the application of DCE-MRI and DWI for assessment of salivary gland tumor types.

  1. Differential Findings of Tc 99m Sestamibi Dual Phase Parathyroid Scintigraphy Between Benign and Malignant Parathyroid Lesions in Patients with Primary Hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Miju; Choi, Joon Young; Chung, Jae Hoon; Lee, Ji Young; Cho, Sook Kyung; Yoo, Jang; Park, Soo Bin; Lee, Kyung Han; Kim, Byung Tae [Sungkyunkwan, Univ. School of Medicine, Seoul (Korea, Republic of)

    2011-12-15

    This study aimed to investigate the differential findings in clinical and biochemical features, and Tc 99m sestamibi (MIBI) dual phase parathyroid lesions in patients with primary hyperparathyroidism. Subjects were 102 parathyroid lesions from 91 patients with primary hyperparathyroidism. Scintigraphic findings included radioactivity grade, uptake pattern, uptake contour lesion size on early and delayed images, and degree of washout. Clinical and biochemical features were also evaluated. Histopathology confirmed the final diagnosis for all the patients. Final diagnoses were 94 benign parathyroid lesions and 8 parathyroid carcinomas. The patients with parathyroid carcinoma were significantly older (p=0.002) and had significantly higher serum parathyroid hormone concentrations than those with benign parathyroid lesions (p<0.001). All malignant parathyroid lesions showed intense radioactivity similar to or greater than the submandibular gland activity on delayed images (p=0.007), and little radioactivity difference between early and delayed images (p=0.012). The cancer incidence for parathyroid lesions with both intense radioactivity and no washout was 17.0% (8/47). When parathyroid lesions with all of the above mentioned findings were regarded as malignant, the cancer incidence significantly increased from 17.0% to 33.3% (8/24, p<0.001). For Tc 99m MIBI dual phase parathyroid scintigraphy, uptake grade on delayed images and washout were significantly useful diagnostic criteria for differentiating benign from malignant parathyroid lesions, along with age and parathyroid hormone serum concentration.

  2. Proline isomerase Pin1 represses terminal differentiation and myocyte enhancer factor 2C function in skeletal muscle cells.

    Science.gov (United States)

    Magli, Alessandro; Angelelli, Cecilia; Ganassi, Massimo; Baruffaldi, Fiorenza; Matafora, Vittoria; Battini, Renata; Bachi, Angela; Messina, Graziella; Rustighi, Alessandra; Del Sal, Giannino; Ferrari, Stefano; Molinari, Susanna

    2010-11-05

    Reversible proline-directed phosphorylation at Ser/Thr-Pro motifs has an essential role in myogenesis, a multistep process strictly regulated by several signaling pathways that impinge on two families of myogenic effectors, the basic helix-loop-helix myogenic transcription factors and the MEF2 (myocyte enhancer factor 2) proteins. The question of how these signals are deciphered by the myogenic effectors remains largely unaddressed. In this study, we show that the peptidyl-prolyl isomerase Pin1, which catalyzes the isomerization of phosphorylated Ser/Thr-Pro peptide bonds to induce conformational changes of its target proteins, acts as an inhibitor of muscle differentiation because its knockdown in myoblasts promotes myotube formation. With the aim of clarifying the mechanism of Pin1 function in skeletal myogenesis, we investigated whether MEF2C, a critical regulator of the myogenic program that is the end point of several signaling pathways, might serve as a/the target for the inhibitory effects of Pin1 on muscle differentiation. We show that Pin1 interacts selectively with phosphorylated MEF2C in skeletal muscle cells, both in vitro and in vivo. The interaction with Pin1 requires two novel critical phospho-Ser/Thr-Pro motifs in MEF2C, Ser(98) and Ser(110), which are phosphorylated in vivo. Overexpression of Pin1 decreases MEF2C stability and activity and its ability to cooperate with MyoD to activate myogenic conversion. Collectively, these findings reveal a novel role for Pin1 as a regulator of muscle terminal differentiation and suggest that Pin1-mediated repression of MEF2C function could contribute to this function.

  3. On a fractional order calculus model in diffusion weighted breast imaging to differentiate between malignant and benign breast lesions detected on X-ray screening mammography.

    Science.gov (United States)

    Bickelhaupt, Sebastian; Steudle, Franziska; Paech, Daniel; Mlynarska, Anna; Kuder, Tristan Anselm; Lederer, Wolfgang; Daniel, Heidi; Freitag, Martin; Delorme, Stefan; Schlemmer, Heinz-Peter; Laun, Frederik Bernd

    2017-01-01

    To evaluate a fractional order calculus (FROC) model in diffusion weighted imaging to differentiate between malignant and benign breast lesions in breast cancer screening work-up using recently introduced parameters (βFROC, DFROC and μFROC). This retrospective analysis within a prospective IRB-approved study included 51 participants (mean 58.4 years) after written informed consent. All patients had suspicious screening mammograms and indication for biopsy. Prior to biopsy, full diagnostic contrast-enhanced MRI examination was acquired including diffusion-weighted-imaging (DWI, b = 0,100,750,1500 s/mm2). Conventional apparent diffusion coefficient Dapp and FROC parameters (βFROC, DFROC and μFROC) as suggested further indicators of diffusivity components were measured in benign and malignant lesions. Receiver operating characteristics (ROC) were calculated to evaluate the diagnostic performance of the parameters. 29/51 patients histopathologically revealed malignant lesions. The analysis revealed an AUC for Dapp of 0.89 (95% CI 0.80-0.98). For FROC derived parameters, AUC was 0.75 (0.60-0.89) for DFROC, 0.59 (0.43-0.75) for βFROC and 0.59 (0.42-0.77) for μFROC. Comparison of the AUC curves revealed a significantly higher AUC of Dapp compared to the FROC parameters DFROC (p = 0.009), βFROC (p = 0.003) and μFROC (p = 0.001). In contrast to recent description in brain tumors, the apparent diffusion coefficient Dapp showed a significantly higher AUC than the recently proposed FROC parameters βFROC, DFROC and μFROC for differentiating between malignant and benign breast lesions. This might be related to the intrinsic high heterogeneity within breast tissue or to the lower maximal b-value used in our study.

  4. On a fractional order calculus model in diffusion weighted breast imaging to differentiate between malignant and benign breast lesions detected on X-ray screening mammography.

    Directory of Open Access Journals (Sweden)

    Sebastian Bickelhaupt

    Full Text Available To evaluate a fractional order calculus (FROC model in diffusion weighted imaging to differentiate between malignant and benign breast lesions in breast cancer screening work-up using recently introduced parameters (βFROC, DFROC and μFROC.This retrospective analysis within a prospective IRB-approved study included 51 participants (mean 58.4 years after written informed consent. All patients had suspicious screening mammograms and indication for biopsy. Prior to biopsy, full diagnostic contrast-enhanced MRI examination was acquired including diffusion-weighted-imaging (DWI, b = 0,100,750,1500 s/mm2. Conventional apparent diffusion coefficient Dapp and FROC parameters (βFROC, DFROC and μFROC as suggested further indicators of diffusivity components were measured in benign and malignant lesions. Receiver operating characteristics (ROC were calculated to evaluate the diagnostic performance of the parameters.29/51 patients histopathologically revealed malignant lesions. The analysis revealed an AUC for Dapp of 0.89 (95% CI 0.80-0.98. For FROC derived parameters, AUC was 0.75 (0.60-0.89 for DFROC, 0.59 (0.43-0.75 for βFROC and 0.59 (0.42-0.77 for μFROC. Comparison of the AUC curves revealed a significantly higher AUC of Dapp compared to the FROC parameters DFROC (p = 0.009, βFROC (p = 0.003 and μFROC (p = 0.001.In contrast to recent description in brain tumors, the apparent diffusion coefficient Dapp showed a significantly higher AUC than the recently proposed FROC parameters βFROC, DFROC and μFROC for differentiating between malignant and benign breast lesions. This might be related to the intrinsic high heterogeneity within breast tissue or to the lower maximal b-value used in our study.

  5. Differentiation between malignant and benign pathologic fractures with F-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography

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    Shin, D.S.; Shon, O.J.; Byun, S.J. [Yeungnam University, Department of Orthopedic Surgery College of Medicine, Daegu (Korea); Choi, J.H. [Yeungnam University, Department of Surgical Pathology, College of Medicine, Daegu (Korea); Chun, K.A.; Cho, I.H. [Yeungnam University, Department of Nuclear Medicine, College of Medicine, Daegu (Korea)

    2008-05-15

    To evaluate the efficacy of F-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET/CT) in differentiating malignant from benign pathologic fractures. F-18 FDG PET/CT was performed on 34 patients with pathologic fractures between May 2004 and June 2007. Fractures were located in tubular bones (26), in the pelvis (six), in the spine (one) and in a rib (one). The FDG uptake pattern at the fracture site was described, whether FDG uptake occurred in the marrow or cortex and soft tissue. Maximum standardized uptake values (SUVmax, the largest value at the region of interest) were measured at the fracture site, including cortical bone, bone marrow and soft tissue. As a reference standard, biopsy was used for 12 patients and clinical follow-up for 22 patients. Sensitivity, specificity and diagnostic accuracy of PET/CT were calculated. There were 19 malignant and 15 benign fractures. In the malignant fractures, PET/CT demonstrated high (mean SUVmax 12.0, range 4.3 to 45.7) F-18 FDG uptake in bone marrow in most cases (17 of 19). In benign fractures, there was low FDG uptake (mean SUVmax 2.9, range 0.6 to 5.5) within cortical bone or adjacent soft tissue around the fracture, rarely in the marrow. There were significant differences in the pattern of intramedullary FDG uptake (P < 0.001) and in the mean SUVmax (P < 0.01) between malignant and benign fractures. The sensitivity, specificity and diagnostic accuracy of F-18 FDG PET/CT were 89.5%, 86.7% and 88.2%, respectively, with a cut-off SUVmax set at 4.7. The time interval between fracture and PET/CT did not significantly influence FDG uptake at the fracture site. F-18 FDG PET/CT reliably differentiated between malignant and benign fractures based on the SUVmax and based on medullary uptake, which was characteristic for malignant fractures. (orig.)

  6. VEGF-C Is a Thyroid Marker of Malignancy Superior to VEGF-A in the Differential Diagnostics of Thyroid Lesions.

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    Kosma Woliński

    Full Text Available Thyroid nodular goiter is one of the most common medical conditions affecting even over a half of adult population. The risk of malignancy is rather small but noticeable-estimated by numerous studies to be about 3-10%. The definite differentiation between benign and malignant ones is a vital issue in endocrine practice. The aim of the current study was to assess the expression of vascular endothelial growth factor A (VEGF-A and VEGF-C on the mRNA level in FNAB washouts in case of benign and malignant thyroid nodules and to evaluate the diagnostic value of these markers of malignancy.Patients undergoing fine-needle aspiration biopsy (FNAB in our department between January 2013 and May 2014 were included. In case of all patients who gave the written consent, after ultrasonography (US and fine-needle aspiration biopsy (FNAB performed as routine medical procedure the needle was flushed with RNA Later solution, the washouts were frozen in -80 Celsius degrees. Expression of VEGF-A and VEGF-C and GADPH (reference gene was assessed in washouts on the mRNA level using the real-time PCR technique. Probes of patients who underwent subsequent thyroidectomy and were diagnosed with differentiated thyroid cancer (DTC; proved by post-surgical histopathology were analyzed. Similar number of patients with benign cytology were randomly selected to be a control group.Thirty one DTCs and 28 benign thyroid lesions were analyzed. Expression of VEGF-A was insignificantly higher in patients with DTCs (p = 0.13. Expression of VEGF-C was significantly higher in patients with DTC. The relative expression of VEGF-C (in comparison with GAPDH was 0.0049 for DTCs and 0.00070 for benign lesions, medians - 0.0036 and 0.000024 respectively (p<0.0001.Measurement of expression VEGF-C on the mRNA level in washouts from FNAB is more useful than more commonly investigated VEGF-A. Measurement of VEGF-C in FNAB washouts do not allow for fully reliable differentiation of benign and

  7. Differentiating malignant from benign breast tumors on acoustic radiation force impulse imaging using fuzzy-based neural networks with principle component analysis

    Science.gov (United States)

    Liu, Hsiao-Chuan; Chou, Yi-Hong; Tiu, Chui-Mei; Hsieh, Chi-Wen; Liu, Brent; Shung, K. Kirk

    2017-03-01

    Many modalities have been developed as screening tools for breast cancer. A new screening method called acoustic radiation force impulse (ARFI) imaging was created for distinguishing breast lesions based on localized tissue displacement. This displacement was quantitated by virtual touch tissue imaging (VTI). However, VTIs sometimes express reverse results to intensity information in clinical observation. In the study, a fuzzy-based neural network with principle component analysis (PCA) was proposed to differentiate texture patterns of malignant breast from benign tumors. Eighty VTIs were randomly retrospected. Thirty four patients were determined as BI-RADS category 2 or 3, and the rest of them were determined as BI-RADS category 4 or 5 by two leading radiologists. Morphological method and Boolean algebra were performed as the image preprocessing to acquire region of interests (ROIs) on VTIs. Twenty four quantitative parameters deriving from first-order statistics (FOS), fractal dimension and gray level co-occurrence matrix (GLCM) were utilized to analyze the texture pattern of breast tumors on VTIs. PCA was employed to reduce the dimension of features. Fuzzy-based neural network as a classifier to differentiate malignant from benign breast tumors. Independent samples test was used to examine the significance of the difference between benign and malignant breast tumors. The area Az under the receiver operator characteristic (ROC) curve, sensitivity, specificity and accuracy were calculated to evaluate the performance of the system. Most all of texture parameters present significant difference between malignant and benign tumors with p-value of less than 0.05 except the average of fractal dimension. For all features classified by fuzzy-based neural network, the sensitivity, specificity, accuracy and Az were 95.7%, 97.1%, 95% and 0.964, respectively. However, the sensitivity, specificity, accuracy and Az can be increased to 100%, 97.1%, 98.8% and 0.985, respectively

  8. The utility of PAX8 and IMP3 immunohistochemical stains in the differential diagnosis of benign, premalignant, and malignant endocervical glandular lesions.

    Science.gov (United States)

    Danialan, Richard; Assaad, Margaret; Burghardt, Jason; Newcomb, Pamela; Cartun, Richard W; Mandavilli, Srinivas

    2013-08-01

    Glandular lesions of the endocervix can be diagnostically challenging and occasionally the differential diagnosis includes endocervical adenocarcinoma in situ (EC AIS) and well-differentiated endocervical adenocarcinoma (ECA). PAX8 and IMP3 are two markers which have not been well studied in the endocervix. Our aim was to evaluate their immunohistochemical (IHC) expression in benign and malignant endocervical glandular lesions as well as to compare them to the traditionally used panel (Ki-67, p16, CEA). We searched our surgical pathology files for a cohort of benign endocervical glandular lesions as well as premalignant and malignant groups including EC AIS and ECA. An IHC panel consisting of PAX8, IMP3, Ki-67, p16, and CEA was performed on all cases. Immunoreactivity was scored on a degree of positivity (S0=no immunoreactivity, S1=up to 10% cells, S2=between 10 and 50% cells, S3=>50% cells) and intensity (Int0 - absent, Int1 - mild/faint, Int2 - moderate, Int3 - strong). PAX8 showed diffuse positivity (S3) with at least a moderate intensity of staining (Int2) in the benign group. PAX8 was focal (S1) in ECA and faint (Int1), compared to EC AIS, which was moderate (S2) and faint (Int1). IMP3 expression was focal in the benign group (S1), moderate (S2) in EC AIS and moderate-to-diffuse (S2-3) in ECA. IMP3 intensity was faint (Int1) in benign lesions, moderate (Int2) in EC AIS, and strong (Int3) in ECA. Significant Ki-67, p16, and CEA expression was noted in the premalignant/malignant cohort. PAX8 and IMP3 can be helpful in the differential diagnosis of benign vs. malignant endocervical glandular lesions. Our study, however, shows that there is some degree of overlap of staining in both the benign and malignant group. As such, PAX8 and IMP3 should always be interpreted with caution and in combination with the histomorphology. Published by Elsevier Inc.

  9. Diffusion weighted imaging for differentiating benign from malignant orbital tumors: Diagnostic performance of the apparent diffusion coefficient based on region of interest selection method

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    Xu, Xiao Quan; Hu, Hao Hu; Su, Guo Yi; Liu, Hu; Shi, Hai Bin; Wu, Fei Yun [First Affiliated Hospital of Nanjing Medical University, Nanjing (China)

    2016-09-15

    To evaluate the differences in the apparent diffusion coefficient (ADC) measurements based on three different region of interest (ROI) selection methods, and compare their diagnostic performance in differentiating benign from malignant orbital tumors. Diffusion-weighted imaging data of sixty-four patients with orbital tumors (33 benign and 31 malignant) were retrospectively analyzed. Two readers independently measured the ADC values using three different ROIs selection methods including whole-tumor (WT), single-slice (SS), and reader-defined small sample (RDSS). The differences of ADC values (ADC-ROI{sub WT}, ADC-ROI{sub SS}, and ADC-ROI{sub RDSS}) between benign and malignant group were compared using unpaired t test. Receiver operating characteristic curve was used to determine and compare their diagnostic ability. The ADC measurement time was compared using ANOVA analysis and the measurement reproducibility was assessed using Bland-Altman method and intra-class correlation coefficient (ICC). Malignant group showed significantly lower ADC-ROI{sub WT}, ADC-ROI{sub SS}, and ADC-ROI{sub RDSS} than benign group (all p < 0.05). The areas under the curve showed no significant difference when using ADC-ROI{sub WT}, ADC-ROI{sub SS}, and ADC-ROI{sub RDSS} as differentiating index, respectively (all p > 0.05). The ROI{sub SS} and ROI{sub RDSS} required comparable measurement time (p > 0.05), while significantly shorter than ROI{sub WT} (p < 0.05). The ROI{sub SS} showed the best reproducibility (mean difference ± limits of agreement between two readers were 0.022 [-0.080–0.123] × 10{sup -3} mm{sup 2}/s; ICC, 0.997) among three ROI method. Apparent diffusion coefficient values based on the three different ROI selection methods can help to differentiate benign from malignant orbital tumors. The results of measurement time, reproducibility and diagnostic ability suggest that the ROI{sub SS} method are potentially useful for clinical practice.

  10. Real-time quantitative PCR of telomerase mRNA is useful for the differentiation of benign and malignant pancreatic disorders.

    Science.gov (United States)

    Büchler, P; Conejo-Garcia, J R; Lehmann, G; Müller, M; Emrich, T; Reber, H A; Büchler, M W; Friess, H

    2001-05-01

    The presence of telomerase activity has been proposed as a specific and sensitive marker for malignant tissue, and positivity rates of up to 95% have been reported in pancreatic cancer. In the present study telomerase activity analysis was reevaluated in 29 pancreatic cancer tissues compared with 36 chronic pancreatitis tissues and 21 normal controls, and a study was made of whether malignant and benign pancreatic disorders can be better differentiated using a novel technique real-time quantitative PCR analysis-analyzing telomerase mRNA expression. Telomerase activity was present in 35% (10 of 29) of pancreatic cancer samples, 3% (one of 36) of chronic pancreatitis samples, and none of the normal pancreatic tissue samples in the TRAP assay. Real-time quantitative PCR analysis revealed the presence of telomerase mRNA expression in 50% (10 of 20) of normal, 86% (31 of 36) of chronic pancreatitis, and 90% (26 of 29) of pancreatic cancer samples. However, quantification of the expression data revealed that the relative increase above normal was 5.5 (range, 3.5-8.6) for chronic pancreatitis and 23.9 (range, 18.6-30.7) for pancreatic cancer samples (p data indicate that detection of telomerase activity using the TRAP assay has limitations in differentiating benign and malignant pancreatic disorders. However, telomerase mRNA analysis by real-time quantitative PCR analysis allows a highly sensitive detection and differentiation of pancreatic cancer from normal pancreas and chronic pancreatitis and thereby may serve as a new reliable, easy, and effective diagnostic tool for cancer diagnosis.

  11. Surface-enhanced Raman spectroscopy of saliva proteins for the noninvasive differentiation of benign and malignant breast tumors

    Science.gov (United States)

    Feng, Shangyuan; Huang, Shaohua; Lin, Duo; Chen, Guannan; Xu, Yuanji; Li, Yongzeng; Huang, Zufang; Pan, Jianji; Chen, Rong; Zeng, Haishan

    2015-01-01

    The capability of saliva protein analysis, based on membrane protein purification and surface-enhanced Raman spectroscopy (SERS), for detecting benign and malignant breast tumors is presented in this paper. A total of 97 SERS spectra from purified saliva proteins were acquired from samples obtained from three groups: 33 healthy subjects; 33 patients with benign breast tumors; and 31 patients with malignant breast tumors. Subtle but discernible changes in the mean SERS spectra of the three groups were observed. Tentative assignments of the saliva protein SERS spectra demonstrated that benign and malignant breast tumors led to several specific biomolecular changes of the saliva proteins. Multiclass partial least squares–discriminant analysis was utilized to analyze and classify the saliva protein SERS spectra from healthy subjects, benign breast tumor patients, and malignant breast tumor patients, yielding diagnostic sensitivities of 75.75%, 72.73%, and 74.19%, as well as specificities of 93.75%, 81.25%, and 86.36%, respectively. The results from this exploratory work demonstrate that saliva protein SERS analysis combined with partial least squares–discriminant analysis diagnostic algorithms has great potential for the noninvasive and label-free detection of breast cancer. PMID:25609959

  12. 99mTc-MIBI Scintigraphy to differentiate malignancies from benign lesions detected on Planar bone scans

    Directory of Open Access Journals (Sweden)

    Aniqa Jabeen

    2016-03-01

    99mTc-MIBI scintigraphy provides its usefulness by distinguishing malignant from benign lesions along with correct identification of metastatic lesions. NPV points toward its ability to correctly diagnose the normal (benign cases. However biopsy still remains the gold standard and a definitive diagnostic modality.

  13. Fbxw7-associated drug resistance is reversed by induction of terminal differentiation in murine intestinal organoid culture

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    Federica Lorenzi

    2016-01-01

    Full Text Available Colorectal cancer (CRC is one of the top three cancer-related causes of death worldwide. FBXW7 is a known tumor-suppressor gene, commonly mutated in CRC and in a variety of other epithelial tumors. Low expression of FBXW7 is also associated with poor prognosis. Loss of FBXW7 sensitizes cancer cells to certain drugs, while making them more resistant to other types of chemotherapies. However, is not fully understood how epithelial cells within normal gut and primary tumors respond to potential cancer therapeutics. We have studied genetically engineered mice in which the fbxw7 gene is conditionally knocked-out in the intestine (fbxw7ΔG. To further investigate the mechanism of Fbxw7-action, we grew intestinal crypts from floxed-fbxw7 (fbxw7fl/fl and fbxw7ΔG mice, in a Matrigel-based organoid (mini-gut culture. The fbxw7ΔG organoids exhibited rapid budding events in the crypt region. Furthermore, to test organoids for drug response, we exposed day 3 intestinal organoids from fbxw7fl/fl and fbxw7ΔG mice, to various concentrations of 5-fluorouracil (5-FU for 72 hours. 5-FU triggers phenotypic differences in organoids including changing shape, survival, resistance, and death. 5-FU however, rescues the drug-resistance phenotype of fbxw7ΔG through the induction of terminal differentiation. Our results support the hypothesis that a differentiating therapy successfully targets FBXW7-mutated CRC cells.

  14. Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma

    OpenAIRE

    Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

    2017-01-01

    A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quan...

  15. Abrupt onset of mutations in a developmentally regulated gene during terminal differentiation of post-mitotic photoreceptor neurons in mice.

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    Ivette M Sandoval

    Full Text Available For sensitive detection of rare gene repair events in terminally differentiated photoreceptors, we generated a knockin mouse model by replacing one mouse rhodopsin allele with a form of the human rhodopsin gene that causes a severe, early-onset form of retinitis pigmentosa. The human gene contains a premature stop codon at position 344 (Q344X, cDNA encoding the enhanced green fluorescent protein (EGFP at its 3' end, and a modified 5' untranslated region to reduce translation rate so that the mutant protein does not induce retinal degeneration. Mutations that eliminate the stop codon express a human rhodopsin-EGFP fusion protein (hRho-GFP, which can be readily detected by fluorescence microscopy. Spontaneous mutations were observed at a frequency of about one per retina; in every case, they gave rise to single fluorescent rod cells, indicating that each mutation occurred during or after the last mitotic division. Additionally, the number of fluorescent rods did not increase with age, suggesting that the rhodopsin gene in mature rod cells is less sensitive to mutation than it is in developing rods. Thus, there is a brief developmental window, coinciding with the transcriptional activation of the rhodopsin locus, in which somatic mutations of the rhodopsin gene abruptly begin to appear.

  16. Differentiating benign from malignant solid breast masses: value of shear wave elastography according to lesion stiffness combined with greyscale ultrasound according to BI-RADS classification.

    Science.gov (United States)

    Evans, A; Whelehan, P; Thomson, K; Brauer, K; Jordan, L; Purdie, C; McLean, D; Baker, L; Vinnicombe, S; Thompson, A

    2012-07-10

    The aim of this study was to assess the performance of shear wave elastography combined with BI-RADS classification of greyscale ultrasound images for benign/malignant differentiation in a large group of patients. One hundred and seventy-five consecutive patients with solid breast masses on routine ultrasonography undergoing percutaneous biopsy had the greyscale findings classified according to the American College of Radiology BI-RADS. The mean elasticity values from four shear wave images were obtained. For mean elasticity vs greyscale BI-RADS, the performance results against histology were sensitivity: 95% vs 95%, specificity: 77% vs 69%, Positive Predictive Value (PPV): 88% vs 84%, Negative Predictive Value (NPV): 90% vs 91%, and accuracy: 89% vs 86% (all P>0.05). The results for the combination (positive result from either modality counted as malignant) were sensitivity 100%, specificity 61%, PPV 82%, NPV 100%, and accuracy 86%. The combination of BI-RADS greyscale and shear wave elastography yielded superior sensitivity to BI-RADS alone (P=0.03) or shear wave alone (P=0.03). The NPV was superior in combination compared with either alone (BI-RADS P=0.01 and shear wave P=0.02). Together, BI-RADS assessment of greyscale ultrasound images and shear wave ultrasound elastography are extremely sensitive for detection of malignancy.

  17. MR spectroscopy of intracranial tuberculomas: A singlet peak at 3.8 ppm as potential marker to differentiate them from malignant tumors

    Science.gov (United States)

    Alfaro, David; Martinot, Carlos; Fayed, Nicolas; Gaskill-Shipley, Mary

    2015-01-01

    Purpose The diagnosis of intracranial tuberculomas is often challenging. Our purpose is to describe the most common metabolic patterns of tuberculomas by MR spectroscopy (MRS) with emphasis on potential specific markers. Methods Single-voxel MRS short echo time was performed in 13 cases of tuberculomas proven by histology and/or response to anti-mycobacterial therapy. For comparison MRS was also performed in 19 biopsy-proven malignant tumors (13 high-grade gliomas and six metastasis). Presence of metabolic peaks was assessed visually and categorical variables between groups were compared using chi-square. Metabolite ratios were compared using Mann-Whitney test and diagnostic accuracy of the metabolite ratios was compared using receiver-operating characteristic (ROC) curves analysis. Results Spectroscopic peaks representing lipids and glutamate/glutamine (Glx) as well as a peak at ∼3.8 ppm were well defined in 77% (10/13), 77% (10/13) and 69% (nine of 13) of tuberculomas, respectively. Lipid and Glx peaks were also present in most of the malignant lesions, 79% (15/19) and 74% (14/19) respectively. However, a peak at ∼3.8 ppm was present in only 10% (two of 19) of the tumor cases (p < 0.001). Higher Cho/Cr and mI/Cr ratios helped discriminate malignant lesions with an area under the ROC curve of 0.86 (SE: 0.078, p < 0.002, CI: 0.7–1) and 0.8 (SE: 0.1, p < 0.009, CI: 0.6–1), respectively. Threshold values between 1.7–1.9 for Cho/Cr and 0.8–0.9 for mI/Cr provided high specificity (91% for both metabolites) and adequate sensitivity (75% and 80%, respectively) for discrimination of malignant lesions. Conclusion A singlet peak at ∼3.8 ppm is present in the majority of tuberculomas and absent in most malignant tumors, potentially a marker to differentiate these lesions. The assignment of the peak is difficult from our analysis; however, guanidinoacetate (Gua) is a possibility. Higher Cho/Cr and mI/Cr ratios should favor malignant lesions

  18. Validation of the diagnostic utility of salivary interleukin 8 in the differentiation of potentially malignant oral lesions and oral squamous cell carcinoma in a region with high endemicity.

    Science.gov (United States)

    Rajkumar, K; Nandhini, G; Ramya, R; Rajashree, P; Kumar, A Ramesh; Anandan, S Nirmala

    2014-09-01

    To evaluate the clinical utility of salivary interleukin 8 (IL-8) in the differential diagnosis of potentially malignant lesions (PMLs) and oral squamous cell carcinoma (OSCC) in a region with high oral cancer prevalence. Saliva and blood samples were collected from 100 participants in each group (OSCC, PMLs, and healthy controls). Serum and salivary IL-8 levels were measured by enzyme-linked immunosorbent assay. The data were subjected to appropriate statistical analysis. A significant increase in levels of serum and salivary IL-8 was found in OSCC compared with PMLs and healthy controls. Receiver operating characteristic curve analysis found salivary IL-8 to have superior sensitivity in detecting OSCC. A significant increase in IL-8 levels based on the histologic grading of OSCC was also observed. This study confirms that salivary IL-8 can be a potent marker that can be used as a tool in the differential diagnosis of PMLs and OSCC. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Utility of FDG-PETCT and magnetic resonance spectroscopy in differentiating between cerebral lymphoma and non-malignant CNS lesions in HIV-infected patients

    Energy Technology Data Exchange (ETDEWEB)

    Westwood, Thomas D., E-mail: tdwestwood@googlemail.com [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Hogan, Celia, E-mail: celiahogan@hotmail.com [Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Pennine Acute Hospitals NHS Trust (United Kingdom); Julyan, Peter J., E-mail: Peter.Julyan@christie.nhs.uk [Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Coutts, Glyn, E-mail: Glyn.Coutts@christie.nhs.uk [Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Bonington, Suzie, E-mail: suzi.bonington@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Carrington, Bernadette, E-mail: Bernadette.Carrington@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Taylor, Ben, E-mail: Ben.taylor@christie.nhs.uk [Department of Radiology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester (United Kingdom); Khoo, Saye, E-mail: S.H.Khoo@liverpool.ac.uk [Department of Infectious Diseases and Tropical Medicine, Royal Liverpool Hospital, Liverpool (United Kingdom); Bonington, Alec, E-mail: Alec.Bonington@pat.nhs.uk [Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Pennine Acute Hospitals NHS Trust (United Kingdom)

    2013-08-15

    Background and purpose: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. Methods: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. Results: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. Conclusion: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort.

  20. Malignant pleural mesothelioma with heterologous osteoblastic differentiation: case report of the characteristic CT and bone scan findings

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Young Jun; Kim, Joung Sook; Kim, Ji Young; Choi, Soo Jeon; Choi, Sang Bong [Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of)

    2008-06-15

    Malignant pleural mesothelioma is an uncommon neoplasm which is accompanied extremely rarely by osteoblastic heterologous elements. The CT manifestations of this tumor have been reported in several references. And, to our knowledge, only one case report provides a description of the bone scan findings. Here, we report the case of a rapidly progressing malignant pleural mesothelioma with heterologous osteoblastic elements. A CT scan reveals diffuse irregular pleural thickening and very coarse nodular calcifications along the right pleura and major fissure. A bone scan revealed an area of extensive increased radioactivity consistent with the pleural calcifications on the CT scan in the right hemithorax. A follow-up CT scan performed 40 days later suggests the presence of rapidly progressing nodular coarse calcifications.

  1. Serum Carbohydrate Antigen 19-9 in Differential Diagnosis of Benign and Malignant Pancreatic Cystic Neoplasms: A Meta-Analysis.

    Science.gov (United States)

    Cao, Shaobo; Hu, Ya; Gao, Xiang; Liao, Quan; Zhao, Yupei

    2016-01-01

    Using serum carbohydrate antigen 19-9 (CA 19-9) in discriminating between benign and malignant pancreatic disease remains controversial. We aim to evaluate the diagnostic value of serum CA 19-9 in predicting malignant pancreatic cystic lesions. Eligible studies were identified through searching MEDLINE and EMBASE prior to March 2016. Studies were assessed for quality using the Quality Assessment for Studies of Diagnostic Accuracy, 2nd version (QUADAS-2). Pooled sensitivity and specificity with 95% confidence interval (CI) were calculated using random-effects models. Summary receiver operator characteristic (SROC) curves and the area under curve (AUC) were performed. A total of thirteen studies including 1437 patients were enrolled in this meta-analysis. The pooled sensitivity and specificity were 0.47(95% CI: 0.35-0.59), and 0.88(95% CI: 0.86-0.91), respectively, and the AUC was 0.87(95% CI, 0.84-0.90). Meta-regression analysis showed that sample size, region and reference standards were not the main sources of heterogeneity. Serum CA 19-9 has satisfying pooled specificity while poor pooled sensitivity for discriminating benign from malignant PCNs. It deserves to be widely used as complementary to other clinical diagnostic methods.

  2. Evaluation of significance of AgNOR counts in differentiating benign from malignant lesions in the breast.

    Science.gov (United States)

    Dube, M K; Govil, A

    1995-01-01

    Nucleolar organizer regions (NORs) have been identified by means of an argyrophilic technique (AgNOR) in routinely processed formalin-fixed paraffin sections of breast lesions. 85 cases of different breast lesions were examined. The AgNOR counts were, normal breast 1.2 (1.0-1.5) Fibroadenoma 1.74 (1.6-2.7), purely cystic disease 1.6 (1.5-1.82) adenosis 2.1 (1.7-2.8), Epitheliosis 2.4 (1.9-3.2) gynaecomastia 3.7 (3.6-4.7), Noninvasive caccinoma 2.8 (2.6-4.4) invasive carcimomas 3.89 (2.7-9.9) i.e. mean AgNOR counts between benign and malignant lesions. Also gynaecomastia, a benign condition had a high mean AgNOR count. There was no significant difference in the mean AgNOR count of various types of invasive breast caninoma. Higher the histological grade, higher was the AgNOR count. To conclude, AgNOR technique does not enable a clear distinction between benign & malignant lesions. But, it could be used with other prognostic indices to predict the behaviour of breast malignancy.

  3. How to differentiate benign versus malignant cardiac and paracardiac 18F FDG uptake at oncologic PET/CT.

    Science.gov (United States)

    Maurer, Alan H; Burshteyn, Mark; Adler, Lee P; Steiner, Robert M

    2011-01-01

    Patients undergoing 2-[fluorine 18]fluoro-2-deoxy-d-glucose (FDG) whole-body oncologic positron emission tomography (PET)/computed tomography (CT) are studied while fasting. Cardiac FDG uptake in fasted patients has been widely reported as variable. It is important to understand the normal patterns of cardiac FDG activity that can be seen in oncologic FDG PET/CT studies. These include focal and regional patterns of increased FDG myocardial activity. Focal activity can be observed in papillary muscles, the atria, the base, and the distal anteroapical region of the left ventricle. Regional increased cardiac FDG activity may be diffuse or localized in the posterolateral wall or the base of the left ventricle. Abnormal patterns of cardiac FDG activity not related to malignancy include those associated with lipomatous hypertrophy of the interatrial septum, epicardial and pericardial fat, increased atrial activity associated with atrial fibrillation or a prominent crista terminalis, cardiac sarcoidosis, endocarditis, myocarditis, and pericarditis. Knowledge of these patterns of cardiac FDG activity is important to be able to recognize malignant disease involving the paracardiac spaces, myocardium, and pericardium. With a better understanding of the range of normal and abnormal patterns of cardiac FDG activity, important benign and malignant diseases involving the heart and pericardium can be recognized and diagnosed.

  4. Can computed tomography and magnetic resonance imaging differentiate between malignant pathology and osteomyelitis in the central skull base?

    Science.gov (United States)

    Lesser, F D; Derbyshire, S G; Lewis-Jones, H

    2015-09-01

    Central skull base osteomyelitis is clinically difficult to distinguish from malignancy. The computed tomography and magnetic resonance imaging scans of six patients with central skull base osteomyelitis were compared with scans from patients with a range of skull base conditions. Computed tomography scans of central skull base osteomyelitis show much less bony destruction relative to the magnetic resonance imaging changes, whereas malignancy cases were associated with similar bony destruction on computed tomography and magnetic resonance imaging. In magnetic resonance imaging scans, it was possible to confirm previous findings of clival hypointensity on T1-weighted images relative to normal fatty marrow. In addition, there were signs of pre- and para-clival soft tissue infiltration, with the obliteration of normal fat planes and frank soft tissue masses in all six central skull base osteomyelitis patients. Signal intensity on T2-weighted images of the clivus was high in five central skull base osteomyelitis patients. With intravenous contrast, fascial plane anatomy appeared restored in central skull base osteomyelitis cases, almost in keeping with that of non-involved areas. This was not a feature in any of the malignant conditions.

  5. Terminal differentiation of cardiac and skeletal myocytes induces permissivity to AAV transduction by relieving inhibition imposed by DNA damage response proteins.

    Science.gov (United States)

    Lovric, Jasmina; Mano, Miguel; Zentilin, Lorena; Eulalio, Ana; Zacchigna, Serena; Giacca, Mauro

    2012-11-01

    Gene therapy vectors based on the adeno-associated virus (AAV) are extremely efficient for gene transfer into post-mitotic cells of heart, muscle, brain, and retina. The reason for their exquisite tropism for these cells has long remained elusive. Here, we show that upon terminal differentiation, cardiac and skeletal myocytes downregulate proteins of the DNA damage response (DDR) and that this markedly induces permissivity to AAV transduction. We observed that expression of members of the MRN complex (Mre11, Rad50, Nbs1), which bind the incoming AAV genomes, faded in cardiomyocytes at ~2 weeks after birth, as well as upon myoblast differentiation in vitro; in both cases, withdrawal of the cells from the cell cycle coincided with increased AAV permissivity. Treatment of proliferating cells with short-interfering RNAs (siRNAs) against the MRN proteins, or with microRNA-24, which is normally upregulated upon terminal differentiation and negatively controls the Nbs1 levels, significantly increased permissivity to AAV transduction. Consistently, delivery of these small RNAs to the juvenile liver concomitant with AAV markedly improved in vivo hepatocyte transduction. Collectively, these findings support the conclusion that cellular DDR proteins inhibit AAV transduction and that terminal cell differentiation relieves this restriction.

  6. Microtubule-associated protein tau (Mapt) is expressed in terminally differentiated odontoblasts and severely down-regulated in morphologically disturbed odontoblasts of Runx2 transgenic mice.

    Science.gov (United States)

    Miyazaki, Toshihiro; Baba, Tomomi T; Mori, Masako; Moriishi, Takeshi; Komori, Toshihisa

    2015-08-01

    Runx2 is an essential transcription factor for osteoblast and odontoblast differentiation and the terminal differentiation of chondrocytes. We have previously shown that the terminal differentiation of odontoblasts is inhibited in Runx2 transgenic {Tg(Col1a1-Runx2)} mice under the control of the 2.3-kb Col1a1 promoter, which directs the transgene expression to osteoblasts and odontoblasts. Odontoblasts show severe reductions in Dspp and nestin expression and lose their characteristic polarized morphology, including a long process extending to dentin, in Tg(Col1a1-Runx2) mice. We study the molecular mechanism of odontoblast morphogenesis by comparing gene expression in the molars of wild-type and Tg(Col1a1-Runx2) mice, focusing on cytoskeleton-related genes. Using microarray, we found that the gene expression of microtubule-associated protein tau (Mapt), a neuronal phosphoprotein with important roles in neuronal biology and microtubule dynamics and assembly, was high in wild-type molars but severely reduced in Tg(Col1a1-Runx2) molars. Immunohistochemical analysis revealed that Mapt was specifically expressed in terminally differentiated odontoblasts including their processes in wild-type molars but its expression was barely detectable in Tg(Col1a1-Runx2) molars. Double-staining of Mapt and Runx2 showed their reciprocal expression in odontoblasts. Mapt and tubulin co-localized in odontoblasts in wild-type molars. Immunoelectron microscopic analysis demonstrated Mapt lying around α-tubulin-positive filamentous structures in odontoblast processes. Thus, Mapt is a useful marker for terminally differentiated odontoblasts and might play an important role in odontoblast morphogenesis.

  7. F-18 FDG PET differentiation of benign from malignant chondroid neoplasms: a systematic review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Subhawong, Ty K.; Winn, Aaron [University of Miami Miller School of Medicine/Jackson Memorial Hospital, Department of Radiology, Miami, FL (United States); Shemesh, Shai S.; Pretell-Mazzini, Juan [University of Miami Miller School of Medicine, Department of Orthopaedics, Miami, FL (United States)

    2017-09-15

    Discriminating among benign chondroid tumors, low-grade chondrosarcomas, and grade 2/3 chondrosarcomas is frequently difficult with standard imaging modalities. We systematically reviewed the literature to determine the performance of PET-CT in making this distinction. A systematic review was performed identifying 811 PubMed- and Embase-indexed articles containing combinations of ''chondrosarcoma,'' ''enchondroma,'' ''chondroid,'' ''cartilage'' and ''PET/CT,'' ''PET,'' ''positron.'' Eight articles including 166 lesions were included. Age, gender, tumor size, histologic grade, and SUVmax values were extracted for individual lesions when possible and otherwise recorded as aggregated data. Comparisons in SUVmax among benign, low-grade, and intermediate-/high-grade chondroid neoplasms were made. Individual SUVs were available for 101 lesions; 65 additional lesions were reported as aggregated data. There were 101 malignant and 65 benign tumors. Benign tumors were seen more frequently in females (p = 0.04, Fischer's exact test), but malignancy was not associated with age or lesion size. SUVmax was lower for benign (1.6 ± 0.7) than malignant tumors (4.4 ± 2.5) (p < 0.0001, t-test). SUVmax was lower for grade 0/1 (2.0 ± 0.7) than grade 2/3 (6.0 ± 3.2) (p < 0.0001, t-test). Increasing SUVmax correlated with higher grade chondroid tumors (Spearman's rank, ρ = 0.78). SUVmax ≥4.4 was 99% specific for grade 2/3 chondrosarcoma. SUVmax correlates with histologic grade in intraosseous chondroid neoplasms; very low SUVmax supports a diagnosis of benign tumor, while elevated SUVmax is suggestive of higher grade chondrosarcoma. (orig.)

  8. Identification of Pro-Differentiation p53 Target Genes and Evaluation of Expression in Normal and Malignant Mammary Gland

    Science.gov (United States)

    2009-04-01

    treatment, nestin transcript level was up- regulated from T24 hours to T48 hours, then decreased from T72 to T96 hours again. In IMECs cells , the effect of...RA treatment on nestin mRNA level was not so dramatic as in MCF-10A cells , but it could up- regulated nestin transcript at T24 hours, and from T48 to...code) Abstract Tumor stem cell theory implies that causative lesions underlying human malignancies occur and are harbored in multi-potent

  9. VEGF-C Is a Thyroid Marker of Malignancy Superior to VEGF-A in the Differential Diagnostics of Thyroid Lesions.

    Science.gov (United States)

    Woliński, Kosma; Stangierski, Adam; Szczepanek-Parulska, Ewelina; Gurgul, Edyta; Budny, Bartłomiej; Wrotkowska, Elzbieta; Biczysko, Maciej; Ruchala, Marek

    2016-01-01

    Thyroid nodular goiter is one of the most common medical conditions affecting even over a half of adult population. The risk of malignancy is rather small but noticeable-estimated by numerous studies to be about 3-10%. The definite differentiation between benign and malignant ones is a vital issue in endocrine practice. The aim of the current study was to assess the expression of vascular endothelial growth factor A (VEGF-A) and VEGF-C on the mRNA level in FNAB washouts in case of benign and malignant thyroid nodules and to evaluate the diagnostic value of these markers of malignancy. Patients undergoing fine-needle aspiration biopsy (FNAB) in our department between January 2013 and May 2014 were included. In case of all patients who gave the written consent, after ultrasonography (US) and fine-needle aspiration biopsy (FNAB) performed as routine medical procedure the needle was flushed with RNA Later solution, the washouts were frozen in -80 Celsius degrees. Expression of VEGF-A and VEGF-C and GADPH (reference gene) was assessed in washouts on the mRNA level using the real-time PCR technique. Probes of patients who underwent subsequent thyroidectomy and were diagnosed with differentiated thyroid cancer (DTC; proved by post-surgical histopathology) were analyzed. Similar number of patients with benign cytology were randomly selected to be a control group. Thirty one DTCs and 28 benign thyroid lesions were analyzed. Expression of VEGF-A was insignificantly higher in patients with DTCs (p = 0.13). Expression of VEGF-C was significantly higher in patients with DTC. The relative expression of VEGF-C (in comparison with GAPDH) was 0.0049 for DTCs and 0.00070 for benign lesions, medians - 0.0036 and 0.000024 respectively (pthyroid nodules and should be interpreted carefully. Further studies on larger groups are indicated. However, measurement of VEGF-C on mRNA level can bring important information without exposing patient for additional risk and invasive procedures.

  10. Dynamic {sup 11}C-methionine PET analysis has an additional value for differentiating malignant tumors from granulomas: an experimental study using small animal PET

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Songji; Zhao, Yan [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo (Japan); Hokkaido University, Department of Tracer Kinetics and Bioanalysis, Graduate School of Medicine, Sapporo (Japan); Kuge, Yuji; Hatano, Toshiyuki [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Yi, Min; Kohanawa, Masashi [Hokkaido University, Department of Advanced Medicine, Graduate School of Medicine, Sapporo (Japan); Magota, Keiichi; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo (Japan); Nishijima, Ken-ichi [Hokkaido University, Department of Molecular Imaging, Graduate School of Medicine, Sapporo (Japan)

    2011-10-15

    We evaluated whether the dynamic profile of L-{sup 11}C-methionine ({sup 11}C-MET) may have an additional value in differentiating malignant tumors from granulomas in experimental rat models by small animal positron emission tomography (PET). Rhodococcus aurantiacus and allogenic rat C6 glioma cells were inoculated, respectively, into the right and left calf muscles to generate a rat model bearing both granulomas and tumors (n = 6). Ten days after the inoculations, dynamic {sup 11}C-MET PET was performed by small animal PET up to 120 min after injection of {sup 11}C-MET. The next day, after overnight fasting, the rats were injected with {sup 18}F-2-deoxy-2-fluoro-D-glucose ({sup 18}F-FDG), and dynamic {sup 18}F-FDG PET was performed up to 180 min. The time-activity curves, static images, and mean standardized uptake value (SUV) in the lesions were calculated. {sup 11}C-MET uptake in the granuloma showed a slow exponential clearance after an initial distribution, while the uptake in the tumor gradually increased with time. The dynamic pattern of {sup 11}C-MET uptake in the granuloma was significantly different from that in the tumor (p < 0.001). In the static analysis of {sup 11}C-MET, visual assessment and SUV analysis could not differentiate the tumor from the granuloma in all cases, although the mean SUV in the granuloma (1.48 {+-} 0.09) was significantly lower than that in the tumor (1.72 {+-} 0.18, p < 0.01). The dynamic patterns, static images, and mean SUVs of {sup 18}F-FDG in the granuloma were similar to those in the tumor (p = NS). Dynamic {sup 11}C-MET PET has an additional value for differentiating malignant tumors from granulomatous lesions, which deserves further elucidation in clinical settings. (orig.)

  11. Synthesis of novel vitamin K derivatives with alkylated phenyl groups introduced at the ω-terminal side chain and evaluation of their neural differentiation activities.

    Science.gov (United States)

    Sakane, Rie; Kimura, Kimito; Hirota, Yoshihisa; Ishizawa, Michiyasu; Takagi, Yuta; Wada, Akimori; Kuwahara, Shigefumi; Makishima, Makoto; Suhara, Yoshitomo

    2017-11-01

    Vitamin K is an essential cofactor of γ-glutamylcarboxylase as related to blood coagulation and bone formation. Menaquinone-4, one of the vitamin K homologues, is biosynthesized in the body and has various biological activities such as being a ligand for steroid and xenobiotic receptors, protection of neuronal cells from oxidative stress, and so on. From this background, we focused on the role of menaquinone in the differentiation activity of progenitor cells into neuronal cells and we synthesized novel vitamin K derivatives with modification of the ω-terminal side chain. We report here new vitamin K analogues, which introduced an alkylated phenyl group at the ω-terminal side chain. These compounds exhibited potent differentiation activity as compared to control. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

    Science.gov (United States)

    Kobari, Ladan; Yates, Frank; Oudrhiri, Noufissa; Francina, Alain; Kiger, Laurent; Mazurier, Christelle; Rouzbeh, Shaghayegh; El-Nemer, Wassim; Hebert, Nicolas; Giarratana, Marie-Catherine; François, Sabine; Chapel, Alain; Lapillonne, Hélène; Luton, Dominique; Bennaceur-Griscelli, Annelise; Douay, Luc

    2012-01-01

    Background Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors. Design and Methods We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation. Results We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice. Conclusions These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment. PMID:22733021

  13. Pulmonary MRI at 3T: Non-enhanced pulmonary magnetic resonance Imaging Characterization Quotients for differentiation of infectious and malignant lesions.

    Science.gov (United States)

    Nagel, Sebastian Niko; Kim, Damon; Penzkofer, Tobias; Steffen, Ingo G; Wyschkon, Sebastian; Hamm, Bernd; Schwartz, Stefan; Elgeti, Thomas

    2017-04-01

    To investigate 3T pulmonary magnetic resonance imaging (MRI) for characterization of solid pulmonary lesions in immunocompromised patients and to differentiate infectious from malignant lesions. Thirty-eight pulmonary lesions in 29 patients were evaluated. Seventeen patients were immunocompromised (11 infections and 6 lymphomas) and 12 served as controls (4 bacterial pneumonias, 8 solid tumors). Ten of the 15 infections were acute. Signal intensities (SI) were measured in the lesion, chest wall muscle, and subcutaneous fat. Scaled SIs as Non-enhanced Imaging Characterization Quotients ((SI Lesion -SI Muscle )/(SI Fat -SI Muscle )*100) were calculated from the T2-weighted images using the mean SI (T2-NICQ mean ) or the 90th percentile of SI (T2-NICQ 90th ) of the lesion. Simple quotients were calculated by dividing the SI of the lesion by the SI of chest wall muscle (e.g. T1-Q mean : SI Lesion /SI Muscle ). Infectious pulmonary lesions showed a higher T2-NICQ mean (40.1 [14.6-56.0] vs. 20.9 [2.4-30.1], p24h prior to MRI (81.8 [71.8-97.6] vs. 41.4 [26.6-51.1], p<0.01). Using Youden's index (YI), the optimal cutoff to differentiate infectious from malignant lesions was 43.1 for T2-NICQ mean (YI=0.42, 0.47 sensitivity, 0.95 specificity) and 55.5 for T2-NICQ 90th (YI=0.61, 0.71 sensitivity, 0.91 specificity). Combining T2-NICQ 90th and T1-Q mean increased diagnostic performance (YI=0.72, 0.77 sensitivity, 0.95 specificity). Considering each quotient alone, T2-NICQ 90th showed the best diagnostic performance and could allow differentiation of acute infectious from malignant pulmonary lesions with high specificity. Combining T2-NICQ 90th with T1-Q mean increased overall performance, especially regarding sensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Circulating forms of immunoreactive parathyroid hormone-related protein for identifying patients with humoral hypercalcemia of malignancy. A comparative study with C-terminal (109-141)- and N-terminal (1-86)-region-specific PTHrP radioassay

    Energy Technology Data Exchange (ETDEWEB)

    Suehiro, Mitsuko; Murakami, Minoru; Fukuchi, Minoru (Hyogo Coll. of Medicine, Nishinomiya (Japan))

    1994-11-01

    We evaluated the circulating forms of immunoreactive parathyroid hormone-related protein(PTHrP) in 115 healthy subjects and 122 patients with malignant diseases by using radioassay systems (RAS) specific for the C-terminal (109-141) fragment of PTHrP (C-RAS) and for the N-terminal(1-86) (N-RAS). PTHrP levels in healthy controls ranged from 1.5 to 38.2 (mean: 24.5) pmol/L with the C-RAS and from 0.9 to 2.5 (mean: 1.7) pmol/L with the N-RAS. The ratio of circulating N-terminal fragment (N) to C-terminal fragment (C) of PTHrP was calculated to be about 1 : 14.4 in the healthy subjects. Of the 122 patients with malignant diseases, 40 (32.8%) had circulating PTHrP levels undetectable with the N-RAS, but only 11 (9.0%) patients had levels undetectable with the C-RAS. Of the former 122 patients, 41 (33.6%) had high PTHrP as determined with the C-RAS, and 10 (8.2%) had high PTHrP as determined with the N-RAS. The former of these included only 8 (19.5%) humoral hypercalcemia malignancy(HHM) patients, while the latter included 8 (80.0%) HHM patients. The circulating N to C ratio was about 1 : 70.7 in the HHM patients. The N and C obtained with the different RASs showed a close correlation (r=0.86). The values also showed a close correlation with serum Ca; r=0.75 for C-RAS and r=0.81 for N-RAS. In addition, the correlation between the PTHrP reading obtained with the different RASs and serum Cr were: r=0.42 with C-RAS and r=0.26 with N-RAS. The circulating form of immunoreactive PTHrP fragments is therefore comprised mainly of PTHrP (109-141). In contrast, circulating concentrations of the PTHrP (1-86) fragment are very low, but detection of the PTHrP (1-86) fragment with the N-RAS is a more useful indicator of HHM with fewer false positive results and is less likely to be influenced by renal function than the detection of the PHPrP (109-141) fragment with C-RAS. (author).

  15. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  16. SSH-EPI diffusion-weighted MR imaging of the spine with low b values: is it useful in differentiating malignant metastatic tumor infiltration from benign fracture edema?

    Science.gov (United States)

    Oztekin, Ozgur; Ozan, Ebru; Hilal Adibelli, Zehra; Unal, Gökhan; Abali, Yusuf

    2009-07-01

    Conventional MR sequences are sometimes not helpful in differentiating benign from pathologic fractures. Our aim was to evaluate the usefulness of single-shot echo-planar imaging sequences (diffusion-weighted imaging (DWI)/SSH-EPI) with low b value in differentiating malignant metastatic tumor infiltration of vertebral bone marrow from benign vertebral fracture edema. A total of 47 patients, 20 with benign fractures and 27 with tumor infiltration, were included in this prospective study. Diffusion-weighted MR images were obtained by single-shot echo-planar imaging technique with diffusion gradient (b = 300 s/mm2; TR/TE, 1,400/100), using a 1.5 T MR scanner. T1- and T2-weighted images and short inversion time inversion-recovery images were available for all 64 lesions. The lesions on DWI/SSH-EPI were categorized as having hypo-, iso-, or hyperintense signal intensity relative to normal vertebrae by two experienced radiologists. We evaluated signal intensity patterns on DWI/SSH-EPI in 64 lesions, which showed low signal intensity on T1-weighted images in both benign fractures and metastasis. With the exception of sclerotic metastases in two patients, malignant metastatic tumor infiltration was hyperintense with respect to normal bone marrow on diffusion-weighted images; all but four benign vertebral fractures were isointense with respect to normal bone marrow. Single-shot echo-planar imaging sequences (DWI/SSH-EPI) with low b value provided excellent distinction between metastatic tumor infiltration and benign vertebral fracture edema. Hyperintense signal intensity on DWI/SSH-EPI was highly specific for the diagnosis of metastatic tumor infiltration of the spine.

  17. [Primary Pituitary Malignant Lymphoma that was Difficult to Differentiate from Nonfunctioning Pituitary Adenoma:A Case Report].

    Science.gov (United States)

    Murakami, Yuta; Sato, Taku; Jinguji, Shinya; Kishida, Yugo; Watanabe, Tadashi; Suzuki, Osamu; Ikeda, Kazuhiko; Homma, Miyuki; Midorikawa, Sanae; Saito, Kiyoshi

    2016-09-01

    We report a rare case of primary pituitary lymphoma in a 75-year-old immunocompetent woman. The patient was blind in the right eye and presented with visual disturbance in the left eye that started 2 months previously. She also exhibited right third and fifth cranial nerve palsy. Magnetic resonance imaging(MRI)revealed an intrasellar mass lesion with right cavernous sinus invasion and suprasellar extension with compression of the optic chiasm. The mass lesion was isointense on both T1WI and T2WI, and showed less enhancement than a normal pituitary gland on gadolinium-enhanced T1WI. We therefore suspected the tumor to be a nonfunctioning pituitary adenoma. The patient underwent endoscopic endonasal transsphenoidal surgery. The tumor was firm and grayish, and had an ill-defined border along the normal pituitary gland. Histological examination revealed a malignant CD5-positive diffuse large B-cell lymphoma. After surgery, the patient received both chemotherapy and radiotherapy. Although the visual acuity of the right eye did not improved, other symptoms improved. At the 34-month follow-up, no recurrence was detected on serial MRI. Patients with primary pituitary lymphoma often exhibit ophthalmoplegia and/or panhypopituitarism more frequently than expected from radiological findings. In cases of pituitary tumors with atypical symptoms, a biopsy and general physical examination should be performed immediately to determine the diagnosis and perform adjuvant therapy even when the tumor is assumed as nonfunctioning pituitary adenoma from the image findings.

  18. Non-invasive optical estimate of tissue composition to differentiate malignant from benign breast lesions: A pilot study

    Science.gov (United States)

    Taroni, Paola; Paganoni, Anna Maria; Ieva, Francesca; Pifferi, Antonio; Quarto, Giovanna; Abbate, Francesca; Cassano, Enrico; Cubeddu, Rinaldo

    2017-01-01

    Several techniques are being investigated as a complement to screening mammography, to reduce its false-positive rate, but results are still insufficient to draw conclusions. This initial study explores time domain diffuse optical imaging as an adjunct method to classify non-invasively malignant vs benign breast lesions. We estimated differences in tissue composition (oxy- and deoxyhemoglobin, lipid, water, collagen) and absorption properties between lesion and average healthy tissue in the same breast applying a perturbative approach to optical images collected at 7 red-near infrared wavelengths (635-1060 nm) from subjects bearing breast lesions. The Discrete AdaBoost procedure, a machine-learning algorithm, was then exploited to classify lesions based on optically derived information (either tissue composition or absorption) and risk factors obtained from patient’s anamnesis (age, body mass index, familiarity, parity, use of oral contraceptives, and use of Tamoxifen). Collagen content, in particular, turned out to be the most important parameter for discrimination. Based on the initial results of this study the proposed method deserves further investigation.

  19. Differential functions of C- and N-terminal hepatitis B x protein in liver cells treated with doxorubicin in normoxic or hypoxic condition.

    Directory of Open Access Journals (Sweden)

    Davor Kin-Fan Chau

    Full Text Available Hepatitis viral B x protein (HBx, a hepatocarcinogen, is frequently mutated. Hypoxia influences the growth of HCC and also the sensitivity of tumor cells to treatments. We aimed to test the role of HBx and acute hypoxia in the efficacy of chemotherapy. In this study, we established 4 Chang liver cell lines with the full-length HBx (HBx, the first 50 amino acids of N-terminal HBx (HBx/50, the last 104 amino acids of C-terminal HBx (HBx/51 and empty vector (CL, respectively. MTT and TNUEL assays were used to assess cell viability and apoptosis respectively. Western blot was used to determine the expression of relevant proteins. Results showed that among 4 cell lines, doxorubicin was most effective in decreasing the viability and enhancing apoptosis in HBx/51 cells, while HBx/50 cells were most resistant to the treatment. Cells in hypoxia were more susceptible to doxorubicin than cells in normoxia. Hypoxia facilitated the Bid cleavage especially in HBx/51 cells via phosphorylating p38 MAPK. p38 MAPK inhibitor significantly reduced the tBid level and increased cell viability. In conclusion, N-terminal HBx and C-terminal HBx function differentially in their ability to regulate cell growth, with the former being promotive but the latter being inhibitory. The acute hypoxia may overcome the HBx-induced resistance and facilitate the chemotherapy.

  20. Diagnostic performance of MR imaging findings and quantitative values in the differentiation of seromucinous borderline tumour from endometriosis-related malignant ovarian tumour

    Energy Technology Data Exchange (ETDEWEB)

    Kurata, Yasuhisa; Kido, Aki; Moribata, Yusaku; Kameyama, Kyoko; Himoto, Yuki; Togashi, Kaori [Kyoto University Graduate School of Medicine, Department of Diagnostic Imaging and Nuclear Medicine, 54 Kawahara-cho, Shogoin, Sakyoku, Kyoto (Japan); Minamiguchi, Sachiko [Kyoto University Graduate School of Medicine, Department of Diagnostic Pathology, 54 Kawahara-cho, Shogoin, Sakyoku, Kyoto (Japan); Konishi, Ikuo [Kyoto University Graduate School of Medicine, Department of Gynecology and Obstetrics, 54 Kawahara-cho, Shogoin, Sakyoku, Kyoto (Japan)

    2017-04-15

    To evaluate the diagnostic performance of quantitative values and MRI findings for differentiating seromucinous borderline tumours (SMBTs) from endometriosis-related malignant ovarian tumours (MT). This retrospective study examined 19 lesions from SMBT and 84 lesions from MT. The following quantitative values were evaluated using receiver-operating characteristic analysis: overall and solid portion sizes, fluid signal intensity (SI), degree of contrast-enhancement, and mean and minimum apparent diffusion coefficient (ADC) values of the solid portion. Two radiologists independently evaluated four MRI findings characteristic of SMBT, fluid SI on the T1-weighted image and SI of the solid portion on diffusion-weighted image. The diagnostic values of these findings and interobserver agreement were assessed. For diagnosing SMBT, the mean ADC value of the solid portion showed the greatest area under the curve (0.860) (cut-off value: 1.31 x 10{sup -3} mm{sup 2}/s, sensitivity: 1.00, specificity: 0.61). The T2-weighted image (T2WI) high SI solid portion was the most useful finding, with high specificity and interobserver agreement (sensitivity, 0.58; specificity, 0.95-0.96, kappa = 0.96), followed by T2WI low SI core (sensitivity, 0.48-0.63; specificity, 0.98, kappa = 0.68). Mean ADC values of the solid portion, T2WI high SI solid portion, and T2WI low SI core were useful for differentiating SMBT from MT. (orig.)

  1. Calcium Electroporation: Evidence for Differential Effects in Normal and Malignant Cell Lines, Evaluated in a 3D Spheroid Model.

    Science.gov (United States)

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha; Gehl, Julie; Rols, Marie-Pierre

    2015-01-01

    Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill efficacy-and normal cell sensitivity. Using a 3D spheroid cell culture model we have tested the effect of calcium electroporation and electrochemotherapy using bleomycin on three different human cancer cell lines: a colorectal adenocarcinoma (HT29), a bladder transitional cell carcinoma (SW780), and a breast adenocarcinoma (MDA-MB231), as well as on primary normal human dermal fibroblasts (HDF-n). The results showed a clear reduction in spheroid size in all three cancer cell spheroids three days after treatment with respectively calcium electroporation (pspheroids was neither affected after calcium electroporation nor electrochemotherapy using bleomycin, indicating that calcium electroporation, like electrochemotherapy, will have limited adverse effects on the surrounding normal tissue when treating with calcium electroporation. The intracellular ATP level, which has previously been shown to be depleted after calcium electroporation, was measured in the spheroids after treatment. The results showed a dramatic decrease in the intracellular ATP level (pspheroid types-malignant as well as normal. In conclusion, calcium electroporation seems to be more effective in inducing cell death in cancer cell spheroids than in a normal fibroblast spheroid, even though intracellular ATP level is depleted in all spheroid types after treatment. These results may indicate an important therapeutic window for this therapy; although further studies are needed in vivo and in patients to investigate the effect of calcium electroporation on surrounding normal tissue when treating tumors.

  2. The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells

    Directory of Open Access Journals (Sweden)

    Halsey Christina

    2012-08-01

    Full Text Available Abstract Background Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL where GATA1FL mutations are an essential driver for disease pathogenesis. Methods Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation. Results We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI. Conclusions These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL.

  3. A spin-Seebeck diode with a negative differential spin-Seebeck effect in a hydrogen-terminated zigzag silicene nanoribbon heterojunction.

    Science.gov (United States)

    Fu, Hua-Hua; Gu, Lei; Wu, Dan-Dan

    2016-05-14

    The spin-Seebeck effect (SSE), the central topic of spin caloritronics, provides a new direction for future low power consumption technology. To realize device applications of SSE, a spin-Seebeck diode (SSD) with a negative differential SSE is very desirable. To this end, we constructed a spin caloritronics device that was composed of a ferromagnetic double-single-hydrogen-terminated zigzag silicene nanoribbon (ZSiNR-H2-H) and an antiferromagnetic double-double-hydrogen-terminated zigzag silicene nanoribbon (ZSiNR-H2-H2). By using ab initio calculations combined with nonequilibrium Green's function technique, we found that thermally driven spin current through the heterojunction featured the SSD effect and negative differential SSE. The former originates from the asymmetrical thermal-driven conducting electrons and holes, and the latter ascribes to the thermal spin compensation effect. Their physical mechanisms are much different from the previous ones mainly relying on the spin-wave excitations in the interface between metals and magnetic insulators, supporting our study that puts forward a new route to realize the SSD with a negative differential SSE.

  4. Comparison and Combination of Strain and Shear Wave Elastography of Breast Masses for Differentiation of Benign and Malignant Lesions by Quantitative Assessment: Preliminary Study.

    Science.gov (United States)

    Seo, Mirinae; Ahn, Hye Shin; Park, Sung Hee; Lee, Jong Beum; Choi, Byung Ihn; Sohn, Yu-Mee; Shin, So Youn

    2018-01-01

    To compare the diagnostic performance of strain and shear wave elastography of breast masses for quantitative assessment in differentiating benign and malignant lesions and to evaluate the diagnostic accuracy of combined strain and shear wave elastography. Between January and February 2016, 37 women with 45 breast masses underwent both strain and shear wave ultrasound (US) elastographic examinations. The American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) final assessment on B-mode US imaging was assessed. We calculated strain ratios for strain elastography and the mean elasticity value and elasticity ratio of the lesion to fat for shear wave elastography. Diagnostic performances were compared by using the area under the receiver operating characteristic curve (AUC). The 37 women had a mean age of 47.4 years (range, 20-79 years). Of the 45 lesions, 20 were malignant, and 25 were benign. The AUCs for elasticity values on strain and shear wave elastography showed no significant differences (strain ratio, 0.929; mean elasticity, 0.898; and elasticity ratio, 0.868; P > .05). After selectively downgrading BI-RADS category 4a lesions based on strain and shear wave elastographic cutoffs, the AUCs for the combined sets of B-mode US and elastography were improved (B-mode + strain, 0.940; B-mode + shear wave; 0.964; and B-mode, 0.724; P < .001). Combined strain and shear wave elastography showed significantly higher diagnostic accuracy than each individual elastographic modality (P = .031). These preliminary results showed that strain and shear wave elastography had similar diagnostic performance. The addition of strain and shear wave elastography to B-mode US improved diagnostic performance. The combination of strain and shear wave elastography results in a higher diagnostic yield than each individual elastographic modality. © 2017 by the American Institute of Ultrasound in Medicine.

  5. The differential diagnosis of pilocytic astrocytoma with atypical features and malignant glioma: an analysis of 16 cases with emphasis on distinguishing molecular features.

    Science.gov (United States)

    Cykowski, Matthew D; Allen, Richard A; Kanaly, Angela C; Fung, Kar-Ming; Marshall, Roxanne; Perry, Arie; Stolzenberg, Ethan D; Dunn, S Terence

    2013-12-01

    Rare pilocytic astrocytomas (PA) have atypical histologic and clinicoradiologic features that raise the differential diagnosis of glioblastoma. Whether ancillary studies can supplement histopathologic examination in placing these cases accurately on the spectrum of WHO Grade I PA to higher-grade glioma is not always clear, partly because these cases are not common. Here, ten PAs with atypical clinicoradiologic and histologic features and six pediatric glioblastoma multiforme (pGBMs) were analyzed for BRAF V600E, IDH1, IDH2, and TP53 mutations. Ki-67, p53, and p16 protein expression were also examined by immunohistochemistry. BRAF-KIAA1549 fusion status was assessed in the PA subgroup. The rate of BRAF-KIAA1549 fusion was high in these PAs (5/7 tumors) including four extracerebellar examples. A single BRAF V600E mutation was identified in the fusion-negative extracerebellar PA of a very young child who succumbed to the disease. TP53 mutations were present only in malignant gliomas, including three pGBMs and one case designated as PA with anaplastic features (with consultation opinion of pGBM). IDH1 and IDH2 were wild type in all cases, consistent with earlier findings that IDH mutations are not typical in high-grade gliomas of patients ≤14 years of age. Immunohistochemical studies showed substantial overlap in Ki-67 labeling indices, an imperfect correlation between p53 labeling and TP53 mutation status, and complete p16 loss in only two pGBMs but in no PAs. These results suggest that (a) BRAF-KIAA1549 fusion may be common in PAs with atypical clinicoradiologic and histologic features, including those at extracerebellar sites, (b) BRAF V600E mutation is uncommon in extracerebellar PAs, and (c) TP53 mutation analysis remains a valuable tool in identifying childhood gliomas that will likely behave in a malignant fashion.

  6. Is radioactive iodine-{sup 131} treatment related to the occurrence of non-synchronous second primary malignancy in patients with differentiated thyroid cancer?

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Marcelo Cruzick de; Momesso, Denise P.; Vieira Neto, Leonardo; Vaisman, Mario, E-mail: dmomesso@terra.com.br [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, (Brazil). Servico de Endocrinologia; Vaisman, Fernanda; Corbo, Rossana [Instituto Nacional do Cancer (INCA), Rio de Janeiro, RJ (Brazil). Servico de Endocrinologia; Martins, Rosangela Aparecida Gomes [Hospital Universitario Clementino Fraga Filho (HUCFF), Rio de Janeiro, RJ (Brazil). Divisao de Pesquisa

    2016-02-15

    Objective: Much controversy relates to the risk of non-synchronous second primary malignancies (NSSPM) after radioactive iodine treatment (RAI-131) in differentiated thyroid cancer (DTC) patients. This study evaluated the relationship between RAI-131 and NSSPM in DTC survivors with long-term follow-up. Materials and methods: Retrospective analysis of 413 DTC cases was performed; 252 received RAI-131 and 161 were treated with thyroidectomy alone. Exclusion criteria were: prior or synchronous non-thyroidal malignancies (within the first year), familial syndromes associated to multiple neoplasms, ionizing radiation exposure or second tumors with unknown histopathology. Results: During a mean follow-up of 11.0 ± 7.5 years, 17 (4.1%) patients developed solid NSSPM. Patients with NSSPM were older than those without (p = 0.02). RAI-131 and I-131 cumulative activity were similar in patients with and without NSSPM (p = 0.18 and p = 0.78, respectively). Incidence of NSSPM was 5.2% in patients with RAI-131 treatment and 2.5% in those without RAI-131 (p = 0.18). Using multivariate analysis, RAI-131 was not significantly associated with NSSPM occurrence (p = 0.35); age was the only independent predictor (p = 0.04). Under log rank statistical analysis, after 10 years of follow-up, it was observed a tendency of lower NSSPM-free survival among patients that received RAI-131 treatment (0.96 vs. 0.87; p = 0.06), what was not affected by age at DTC diagnosis. Conclusion: In our cohort of DTC survivors, with a long-term follow-up period, RAI-131 treatment and I-131 cumulative dose were not significantly associated with NSSPM occurrence. A tendency of premature NSSPM occurrence among patients treated with RAI-131 was observed, suggesting an anticipating oncogenic effect by interaction with other risk factors. (author)

  7. Induction of calcium sensing receptor in human colon cancer cells by calcium, vitamin D and aquamin: Promotion of a more differentiated, less malignant and indolent phenotype.

    Science.gov (United States)

    Singh, Navneet; Aslam, Muhammad N; Varani, James; Chakrabarty, Subhas

    2015-07-01

    The calcium sensing receptor (CaSR) is a robust promoter of differentiation in colonic epithelial cells and functions as a tumor suppressor. Cancer cells that do not express CaSR (termed CaSR null) are highly malignant while acquisition of CaSR expression in these cells circumvents the malignant phenotype. We hypothesize that chemopreventive agents mediate their action through the induction of CaSR. Here, we compare the effectiveness of Ca(2+), vitamin D, and Aquamin (a marine algae product containing Ca(2+), magnesium and detectable levels of 72 additional minerals) on the induction of CaSR in the CBS and HCT116 human colon carcinoma cell lines and the corresponding CaSR null cells isolated from these lines. All three agonists induced CaSR mRNA and protein expression and inhibited cellular proliferation in the parental and CaSR null cells. Aquamin was found to be most potent in this regard. Induction of CaSR expression by these agonists resulted in demethylation of the CaSR gene promoter with a concurrent increase in CaSR promoter reporter activity. However, demethylation per se did not induce CaSR transcription. Induction of CaSR expression resulted in a down-regulated expression of tumor inducers and up-regulated expression of tumor suppressors. Again, Aquamin was found to be most potent in these biologic effects. This study provides a rationale for the use of a multi-mineral approach in the chemoprevention of colon cancer and suggests that induction of CaSR may be a measure of the effectiveness of chemopreventive agents. © 2013 Wiley Periodicals, Inc.

  8. Autofluorescence endoscopy with "real-time" digital image processing in differential diagnostics of selected benign and malignant lesions in the oesophagus.

    Science.gov (United States)

    Sieroń-Stołtny, Karolina; Kwiatek, Sebastian; Latos, Wojciech; Kawczyk-Krupka, Aleksandra; Cieślar, Grzegorz; Stanek, Agata; Ziaja, Damian; Bugaj, Andrzej M; Sieroń, Aleksander

    2012-03-01

    . Especially in two-modal imaging including white light endoscopy, autofluorescence imaging with digital image processing seems to be a useful modality of early diagnostics. Also in observation of papilloma changes, it facilitates differentiation between neoplastic and benign lesions and more accurate estimation of the risk of potential malignancy. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Terminal Duplex Stability and Nucleotide Identity Differentially Control siRNA Loading and Activity in RNA Interference.

    Science.gov (United States)

    Angart, Phillip A; Carlson, Rebecca J; Adu-Berchie, Kwasi; Walton, S Patrick

    2016-10-01

    Efficient short interfering RNA (siRNA)-mediated gene silencing requires selection of a sequence that is complementary to the intended target and possesses sequence and structural features that encourage favorable functional interactions with the RNA interference (RNAi) pathway proteins. In this study, we investigated how terminal sequence and structural characteristics of siRNAs contribute to siRNA strand loading and silencing activity and how these characteristics ultimately result in a functionally asymmetric duplex in cultured HeLa cells. Our results reiterate that the most important characteristic in determining siRNA activity is the 5' terminal nucleotide identity. Our findings further suggest that siRNA loading is controlled principally by the hybridization stability of the 5' terminus (Nucleotides: 1-2) of each siRNA strand, independent of the opposing terminus. Postloading, RNA-induced silencing complex (RISC)-specific activity was found to be improved by lower hybridization stability in the 5' terminus (Nucleotides: 3-4) of the loaded siRNA strand and greater hybridization stability toward the 3' terminus (Nucleotides: 17-18). Concomitantly, specific recognition of the 5' terminal nucleotide sequence by human Argonaute 2 (Ago2) improves RISC half-life. These findings indicate that careful selection of siRNA sequences can maximize both the loading and the specific activity of the intended guide strand.

  10. Correlation between pathology and MR tomography and differential diagnosis of malignant kidney tumors; Pathologisch/MR-tomographische Korrelation und Differentialdiagnose von malignen Nierentumoren

    Energy Technology Data Exchange (ETDEWEB)

    Kreft, B.; Flacke, S.; Conrad, R.; Pauleit, D.; Bachmann, R.; Schild, H. [Bonn Univ. (Germany). Radiologische Klinik; Wardelmann, E. [Bonn Univ. (Germany). Pathologisches Inst.; Albers, P. [Bonn Univ. (Germany). Urologische Klinik

    1999-08-01

    Purpose: Evaluation of malignancy criteria in MRT of kidney tumors in correlation with the histopathological findings. Materials and Methods: 41 patients with suspected malignant kidney tumors were examined using a T{sub 1} SE sequence (TR/TE 300/10 ms) before and after i.v. administration of 0.1 mmol/kg Gd-DTPA and a T{sub 2} SE sequence (TR/TE 5500/150 ms). The results were correlated with the pathological findings. Results: 38 malignant tumors were found: 29 renal cell carcinomas (RCC), 13 with solid growth, 11 with tubulopapillary growth, and three with mixed growth forms, one cystic RCC, and one chromophobic RCC, in addition, 6 urothelial carcinomas and three other malignomas. Typical MRT criteria for RCC were an inhomogeneity of the tumor with regions of slightly increased signal intensity on the T{sub 1}-weighted image (59%) and regions with reduced signal intensity on the T{sub 2}-weighted image (96%) as compared with renal parenchyma; these were due to histomorphological hemorrhage and hemosiderin deposits, respectively. A further criterion for RCC was a hypointense pseudocapsule in the T{sub 2} TSE sequence in 79% of the case. Conclusions: The low-signal nature of RCC in the T{sub 2}-weighted image correlates with hemorrhage and hemosiderin deposits. The detection of a pseudocapsule is useful in the differential diagnosis of solid tumors in the kidney. (orig.) [German] Ziel: Evaluierung von Malignitaetskriterien in der MRT bei Nierentumoren in Korrelation mit den histopathologischen Befunden. Material und Methode: Einschluss von 41 Patienten mit Verdacht auf einen malignen Nierentumor. MRT-Protokoll: T{sub 1} SE Sequenz (TR/TE 300/10 ms) vor und nach i.v. Gabe von 0,1 mmol/kg Gd-DTPA und eine T{sub 2} TSE Sequenz (TR/TE 5500/150 ms). Die Befunde wurden mit dem pathologischen Befund korreliert. Ergebnisse: Es lagen 38 maligne Tumoren vor: 29 Nierenzellkarzinome (NZK), davon 13 mit solidem, 11 mit tubulopapillaerem und drei mit gemischtem Wachstum, ein

  11. Ultrasonographic differentiation of malignant from benign breast lesions: a meta-analytic comparison of elasticity and BIRADS scoring.

    Science.gov (United States)

    Sadigh, Gelareh; Carlos, Ruth C; Neal, Colleen H; Dwamena, Ben A

    2012-05-01

    There has been controversy regarding the accuracy of breast ultrasound elastography (USE) compared to conventional B-mode Ultrasound (USB). The purpose of this study was to conduct a direct comparative effectiveness analysis of USB versus USE or their combination in differentiating breast lesions through systematically reviewing recent literature. An extensive literature search of PubMed and other medical and general purpose databases from inception through August 2011 was conducted. Published studies that reported a direct comparison of the diagnostic performance of USE, using elasticity score versus USB, using breast imaging reporting and data system (BIRADS) for characterization of focal breast lesions were included. Summary diagnostic performance measures were assessed for each of the tests and their combination using bivariate generalized linear mixed modeling. The two tests were combined as: (1) conjunctive, where the outcome of the combination of tests is positive only if both test results are positive; (2) disjunctive, where the outcome of a combination of tests is negative only if both tests are negative. Twenty nine studies provided relevant information on 5,511 breast masses (2,065 cancers, 3,446 benign lesions). Sensitivity of USB, USE, and their conjunctive and disjunctive combinations were 96% (95% credible interval (CrI), 93-98%), 79% (95% CrI, 74-83%), 73% (95% CrI, 67-78%), and 99% (95% CrI, 98-99%), respectively. Specificity of USB, USE, and their conjunctive and disjunctive combinations were 70% (95% CrI, 55-83%), 88% (95% CrI, 82-92%), 97% (95% CrI, 95-99%), and 56% (95% CrI, 43-69%), respectively. The application of USE as a single test is not superior to USB alone. However, in low risk patients it is recommended to perform an USE following a positive USB result to decrease the rate of unnecessary biopsies.

  12. [Pregnancy and malignant melanoma].

    Science.gov (United States)

    Pankova, T; Stoikov, S; Nikolova, M

    2010-01-01

    The authors review on a rare pregnancy accompanying disease--Melanoma malignum. After the definition are presented the epidemiology, etiology, pathogenesis, pathomorphology, clinical forms, diagnosis, differential diagnosis, treatment and prevention. Described are the effects of the pregnancy on this malignant disease and the impact of it during the pregnancy.

  13. p16INK4a and its regulator miR-24 link senescence and chondrocyte terminal differentiation-associated matrix remodeling in osteoarthritis.

    Science.gov (United States)

    Philipot, Didier; Guérit, David; Platano, Daniela; Chuchana, Paul; Olivotto, Eleonora; Espinoza, Francisco; Dorandeu, Anne; Pers, Yves-Marie; Piette, Jacques; Borzi, Rosa Maria; Jorgensen, Christian; Noel, Danièle; Brondello, Jean-Marc

    2014-02-27

    Recent evidence suggests that tissue accumulation of senescent p16INK4a-positive cells during the life span would be deleterious for tissue functions and could be the consequence of inherent age-associated disorders. Osteoarthritis (OA) is characterized by the accumulation of chondrocytes expressing p16INK4a and markers of the senescence-associated secretory phenotype (SASP), including the matrix remodeling metalloproteases MMP1/MMP13 and pro-inflammatory cytokines interleukin-8 (IL-8) and IL-6. Here, we evaluated the role of p16INK4a in the OA-induced SASP and its regulation by microRNAs (miRs). We used IL-1-beta-treated primary OA chondrocytes cultured in three-dimensional setting or mesenchymal stem cells differentiated into chondrocyte to follow p16INK4a expression. By transient transfection experiments and the use of knockout mice, we validate p16INK4a function in chondrocytes and its regulation by one miR identified by means of a genome-wide miR-array analysis. p16INK4a is induced upon IL-1-beta treatment and also during in vitro chondrogenesis. In the mouse model, Ink4a locus favors in vivo the proportion of terminally differentiated chondrocytes. When overexpressed in chondrocytes, p16INK4a is sufficient to induce the production of the two matrix remodeling enzymes, MMP1 and MMP13, thus linking senescence with OA pathogenesis and bone development. We identified miR-24 as a negative regulator of p16INK4a. Accordingly, p16INK4a expression increased while miR-24 level was repressed upon IL-1-beta addition, in OA cartilage and during in vitro terminal chondrogenesis. We disclosed herein a new role of the senescence marker p16INK4a and its regulation by miR-24 during OA and terminal chondrogenesis.

  14. Proliferation, cell cycle exit, and onset of terminal differentiation in cultured keratinocytes: pre-programmed pathways in control of C-Myc and Notch1 prevail over extracellular calcium signals.

    Science.gov (United States)

    Kolly, Carine; Suter, Maja M; Müller, Eliane J

    2005-05-01

    So far it was reported that a switch from low to high extracellular calcium induces growth arrest and terminal differentiation in cultured human and mouse keratinocytes. We had observed that both canine and mouse keratinocytes proliferate in high (1.8 mM, respectively, 1.2 mM) or low (0.09 and 0.06 mM) calcium-containing medium. In-depth analysis of this phenomenon revealed, as reported here, that the switch between proliferation and terminal differentiation occurred irrespective of calcium conditions when the canine and murine keratinocytes reach confluency. The "confluency switch" coincided with transcriptional upregulation of cell cycle inhibitors p21(WAF1) and p27(KIP1) as well as proteins marking onset of terminal differentiation. It was further accompanied by downregulation and nuclear clearance of c-Myc, and conversely activation of Notch1, which are shown to be critical determinants of this process. Together, this study demonstrates that even in the absence of and similar to their in vivo environment, cultured canine and mouse keratinocytes follow a pre-defined differentiation program. This program is in control of c-Myc and Notch1 and does not require complementary signals for onset of terminal differentiation except those given by cell-cell contact. Once triggered, completion of the terminal differentiation process depends on elevated extracellular calcium to stabilize intercellular junctions and components of the cornified envelope.

  15. SSH-BM-I, a tryptamine derivative, stimulates mineralization in terminal osteoblast differentiation but inhibits osteogenesis of pre-committed progenitor cells.

    Science.gov (United States)

    Mikami, Yoshikazu; Somei, Masanori; Tsuda, Hiromasa

    2011-01-01

    SSH-BM-I was synthesized from tryptamine by using a newly developed synthetic method, and it has structural similarity to bromomelatonin. Recently, it had been reported that SSH-BM-I increases osteoblasts in scales of gold fish. However, the effect of SSH-BM-I on osteoblast differentiation in mammalian cells has not yet been examined. Therefore, this study examined the effect of SSH-BM-I on osteoblast differentiation in mesenchymal progenitor-like cells and mature osteoblast-like cells. SSH-BM-I enhanced terminal osteoblast differentiation, as indicated by mineralization, which was accompanied by upregulation of the osteogenic marker genes bone sialoprotein (BSP) and osteocalcin (OC). However, in mesenchymal progenitor ROB-C26 cultures, no mineralized nodules were observed regardless of SSH-BM-I treatment, although BMP-2 was able to induce nodule formation in these cells. Furthermore, BMP-2-induced nodule formation was suppressed by SSH-BM-I treatment in ROB-C26 cultures. We further investigated the impact of the timing and duration of SSH-BM-I treatment on osteoblast differentiation. The effect of SSH-BM-I treatment on osteoblast differentiation of ROB-C26 in the presence of BMP-2 switches from negative to positive sometime between day 6 and 9, because SSH-BM-I treatment enhanced the formation of mineralized nodules when it was started on day 9, but suppressed nodule formation when it was started at day 6 or earlier. These results suggest that the stimulatory effects of SSH-BM-I on the formation of mineralized nodules depend on the degree of cell differentiation.

  16. TGF-{beta} receptors, in a Smad-independent manner, are required for terminal skeletal muscle differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Droguett, Rebeca; Cabello-Verrugio, Claudio; Santander, Cristian [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile); Brandan, Enrique, E-mail: ebrandan@bio.puc.cl [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile)

    2010-09-10

    Skeletal muscle differentiation is strongly inhibited by transforming growth factor type {beta} (TGF-{beta}), although muscle formation as well as regeneration normally occurs in an environment rich in this growth factor. In this study, we evaluated the role of intracellular regulatory Smads proteins as well as TGF-{beta}-receptors (TGF-{beta}-Rs) during skeletal muscle differentiation. We found a decrease of TGF-{beta} signaling during differentiation. This phenomenon is explained by a decline in the levels of the regulatory proteins Smad-2, -3, and -4, a decrease in the phosphorylation of Smad-2 and lost of nuclear translocation of Smad-3 and -4 in response to TGF-{beta}. No change in the levels and inhibitory function of Smad-7 was observed. In contrast, we found that TGF-{beta}-R type I (TGF-{beta}-RI) and type II (TGF-{beta}-RII) increased on the cell surface during skeletal muscle differentiation. To analyze the direct role of the serine/threonine kinase activities of TGF-{beta}-Rs, we used the specific inhibitor SB 431542 and the dominant-negative form of TGF-{beta}-RII lacking the cytoplasmic domain. The TGF-{beta}-Rs were important for successful muscle formation, determined by the induction of myogenin, creatine kinase activity, and myosin. Silencing of Smad-2/3 expression by specific siRNA treatments accelerated myogenin, myosin expression, and myotube formation; although when SB 431542 was present inhibition in myosin induction and myotube formation was observed, suggesting that these last steps of skeletal muscle differentiation require active TGF-{beta}-Rs. These results suggest that both down-regulation of Smad regulatory proteins and cell signaling through the TGF-{beta} receptors independent of Smad proteins are essential for skeletal muscle differentiation.

  17. RNase L controls terminal adipocyte differentiation, lipids storage and insulin sensitivity via CHOP10 mRNA regulation

    DEFF Research Database (Denmark)

    Fabre, Odile Martine Julie; Salehzada, T; Lambert, K

    2012-01-01

    Adipose tissue structure is altered during obesity, leading to deregulation of whole-body metabolism. Its function depends on its structure, in particular adipocytes number and differentiation stage. To better understand the mechanisms regulating adipogenesis, we have investigated the role...... RNase L in RNase L(-/-)-MEFs triggers CHOP10 mRNA instability, allowing increased lipids storage, insulin response and glucose uptake. Similarly, downregulation of CHOP10 mRNA with CHOP10 siRNA in RNase L(-/-)-MEFs improves their differentiation in adipocyte. In vivo, aged RNase L(-)/(-) mice present...

  18. Pleural malignancies.

    Science.gov (United States)

    Friedberg, Joseph S; Cengel, Keith A

    2010-07-01

    Pleural malignancies, primary or metastatic, portend a grim prognosis. In addition to the serious oncologic implications of a pleural malignancy, these tumors can be highly symptomatic. A malignant pleural effusion can cause dyspnea, secondary to lung compression, or even tension physiology from a hydrothorax under pressure. The need to palliate these effusions is a seemingly straightforward clinical scenario, but with nuances that can result in disastrous complications for the patient if not attended to appropriately. Solid pleural malignancies can cause great pain from chest wall invasion or can cause a myriad of morbid symptoms because of the invasion of thoracic structures, such as the heart, lungs, or esophagus. This article reviews pleural malignancies, the purely palliative treatments, and the treatments that are performed with definitive (curative) intent. Copyright 2010 Elsevier Inc. All rights reserved.

  19. Epidermal cell proliferation and terminal differentiation in skin organ culture after topical exposure to sodium dodecyl sulphate

    NARCIS (Netherlands)

    Sandt, J.J.M. van de; Bos, T.A.; Rutten, A.A.J.J.L.

    1995-01-01

    Epidermal cell proliferation and differentiation were investigated in vitro after exposure to the anionic surfactant sodium dodecyl sulfate (SDS). Human skin organ cultures were exposed topically to various concentrations of SDS for 22 h, after which the irritant was removed. Cell proliferation was

  20. WNT6 promotes the migration and differentiation of human dental pulp cells partly through c-Jun N-terminal kinase signaling pathway.

    Science.gov (United States)

    Li, Ruimin; Wang, Chenglin; Tong, Juan; Su, Yingying; Lin, Yunfeng; Zhou, Xuedong; Ye, Ling

    2014-07-01

    During the dental pulp repair process, human dental pulp cells (HDPCs) migrate to injury sites where they may differentiate into odontoblastlike cells. WNT6 plays a role in dental development and can activate a noncanonical pathway including the c-Jun N-terminal kinase (JNK) pathway. The mechanism of WNT6 in dental pulp repair is still unknown. The purpose of this study was to explore the potential role of the WNT6/JNK signaling pathway in the promotion of cell migration and the differentiation of HDPCs. The third passage of HDPCs were cultured in vitro and treated with WNT6 conditioned medium with or without the pretreatment of JNK inhibitor SP600125. The activation of JNK was detected by Western blot, the expression of c-Jun was quantified by reverse-transcription polymerase chain reaction, the migration of HDPCs was determined by wound healing and transwell migration assays, and the differentiation of HDPCs was investigated using alkaline phosphatase staining and alizarin red staining. The expression of odontogenesis-related genes such as Runt-related transcription factor 2, dentin sialophosphoprotein, and dentin matrix protein 1 was quantified. WNT6 activates the JNK pathway in HDPCs and enhances cell migration, mineralization nodule formation, and alkaline phosphatase activation. WNT6 also increases the expression of Runt-related transcription factor 2, dentin sialophosphoprotein, and dentin matrix protein messenger RNA in HDPCs. Blockage of the JNK pathway in HDPCs decreases but does not completely abolish the cell migration and differentiation capacity induced by WNT6. WNT6 activates the JNK signaling pathway in HDPCs, leading to migration and differentiation. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  1. Characterisation of cell cycle arrest and terminal differentiation in a maximally proliferative human epithelial tissue: Lessons from the human hair follicle matrix.

    Science.gov (United States)

    Purba, Talveen S; Brunken, Lars; Peake, Michael; Shahmalak, Asim; Chaves, Asuncion; Poblet, Enrique; Ceballos, Laura; Gandarillas, Alberto; Paus, Ralf

    2017-09-01

    Human hair follicle (HF) growth and hair shaft formation require terminal differentiation-associated cell cycle arrest of highly proliferative matrix keratinocytes. However, the regulation of this complex event remains unknown. CIP/KIP family member proteins (p21(CIP1), p27(KIP1) and p57(KIP2)) regulate cell cycle progression/arrest, endoreplication, differentiation and apoptosis. Since they have not yet been adequately characterized in the human HF, we asked whether and where CIP/KIP proteins localise in the human hair matrix and pre-cortex in relation to cell cycle activity and HF-specific epithelial cell differentiation that is marked by keratin 85 (K85) protein expression. K85 expression coincided with loss or reduction in cell cycle activity markers, including in situ DNA synthesis (EdU incorporation), Ki-67, phospho-histone H3 and cyclins A and B1, affirming a post-mitotic state of pre-cortical HF keratinocytes. Expression of CIP/KIP proteins was found abundantly within the proliferative hair matrix, concomitant with a role in cell cycle checkpoint control. p21(CIP1), p27(KIP1) and cyclin E persisted within post-mitotic keratinocytes of the pre-cortex, whereas p57(KIP2) protein decreased but became nuclear. These data imply a supportive role for CIP/KIP proteins in maintaining proliferative arrest, differentiation and anti-apoptotic pathways, promoting continuous hair bulb growth and hair shaft formation in anagen VI. Moreover, post-mitotic hair matrix regions contained cells with enlarged nuclei, and DNA in situ hybridisation showed cells that were >2N in the pre-cortex. This suggests that CIP/KIP proteins might counterbalance cyclin E to control further rounds of DNA replication in a cell population that has a propensity to become tetraploid. These data shed new light on the in situ-biography of human hair matrix keratinocytes on their path of active cell cycling, arrest and terminal differentiation, and showcase the human HF as an excellent, clinically

  2. Genome-wide mapping of Sox6 binding sites in skeletal muscle reveals both direct and indirect regulation of muscle terminal differentiation by Sox6

    Directory of Open Access Journals (Sweden)

    An Chung-Il

    2011-10-01

    Full Text Available Abstract Background Sox6 is a multi-faceted transcription factor involved in the terminal differentiation of many different cell types in vertebrates. It has been suggested that in mice as well as in zebrafish Sox6 plays a role in the terminal differentiation of skeletal muscle by suppressing transcription of slow fiber specific genes. In order to understand how Sox6 coordinately regulates the transcription of multiple fiber type specific genes during muscle development, we have performed ChIP-seq analyses to identify Sox6 target genes in mouse fetal myotubes and generated muscle-specific Sox6 knockout (KO mice to determine the Sox6 null muscle phenotype in adult mice. Results We have identified 1,066 Sox6 binding sites using mouse fetal myotubes. The Sox6 binding sites were found to be associated with slow fiber-specific, cardiac, and embryonic isoform genes that are expressed in the sarcomere as well as transcription factor genes known to play roles in muscle development. The concurrently performed RNA polymerase II (Pol II ChIP-seq analysis revealed that 84% of the Sox6 peak-associated genes exhibited little to no binding of Pol II, suggesting that the majority of the Sox6 target genes are transcriptionally inactive. These results indicate that Sox6 directly regulates terminal differentiation of muscle by affecting the expression of sarcomere protein genes as well as indirectly through influencing the expression of transcription factors relevant to muscle development. Gene expression profiling of Sox6 KO skeletal and cardiac muscle revealed a significant increase in the expression of the genes associated with Sox6 binding. In the absence of the Sox6 gene, there was dramatic upregulation of slow fiber-specific, cardiac, and embryonic isoform gene expression in Sox6 KO skeletal muscle and fetal isoform gene expression in Sox6 KO cardiac muscle, thus confirming the role Sox6 plays as a transcriptional suppressor in muscle development

  3. BET N-terminal bromodomain inhibition selectively blocks Th17 cell differentiation and ameliorates colitis in mice.

    Science.gov (United States)

    Cheung, Kalung; Lu, Geming; Sharma, Rajal; Vincek, Adam; Zhang, Ruihua; Plotnikov, Alexander N; Zhang, Fan; Zhang, Qiang; Ju, Ying; Hu, Yuan; Zhao, Li; Han, Xinye; Meslamani, Jamel; Xu, Feihong; Jaganathan, Anbalagan; Shen, Tong; Zhu, Hongfa; Rusinova, Elena; Zeng, Lei; Zhou, Jiachi; Yang, Jianjun; Peng, Liang; Ohlmeyer, Michael; Walsh, Martin J; Zhang, David Y; Xiong, Huabao; Zhou, Ming-Ming

    2017-03-14

    T-helper 17 (Th17) cells have important functions in adaptor immunity and have also been implicated in inflammatory disorders. The bromodomain and extraterminal domain (BET) family proteins regulate gene transcription during lineage-specific differentiation of naïve CD4(+) T cells to produce mature T-helper cells. Inhibition of acetyl-lysine binding of the BET proteins by pan-BET bromodomain (BrD) inhibitors, such as JQ1, broadly affects differentiation of Th17, Th1, and Th2 cells that have distinct immune functions, thus limiting their therapeutic potential. Whether these BET proteins represent viable new epigenetic drug targets for inflammatory disorders has remained an unanswered question. In this study, we report that selective inhibition of the first bromodomain of BET proteins with our newly designed small molecule MS402 inhibits primarily Th17 cell differentiation with a little or almost no effect on Th1 or Th2 and Treg cells. MS402 preferentially renders Brd4 binding to Th17 signature gene loci over those of housekeeping genes and reduces Brd4 recruitment of p-TEFb to phosphorylate and activate RNA polymerase II for transcription elongation. We further show that MS402 prevents and ameliorates T-cell transfer-induced colitis in mice by blocking Th17 cell overdevelopment. Thus, selective pharmacological modulation of individual bromodomains likely represents a strategy for treatment of inflammatory bowel diseases.

  4. Leukoplakia: A short review on malignant potential

    Directory of Open Access Journals (Sweden)

    K. M. K. Masthan

    2015-01-01

    Full Text Available Oral leukoplakia is one of the most common potentially malignant disorders. Right diagnosis of potentially malignant disorders may help to prevent these lesions from malignant transformation. Proper understanding, recognizing, identification and differentiating these lesions from normal mucosa are necessary for proper treatment.

  5. Differential effects of combined Ad5- delta 24RGD and radiation therapy in in vitro versus in vivo models of malignant glioma.

    Science.gov (United States)

    Lamfers, Martine L M; Idema, Sander; Bosscher, Lisette; Heukelom, Stan; Moeniralm, Sharif; van der Meulen-Muileman, Ida H; Overmeer, Renée M; van der Valk, Paul; van Beusechem, Victor W; Gerritsen, Winald R; Vandertop, W Peter; Dirven, Clemens M F

    2007-12-15

    The integrin-targeted conditionally replicating adenovirus Ad5-delta 24RGD has been shown to possess strong oncolytic activity in experimental tumors and is currently being developed toward phase I clinical evaluation for ovarian cancer and malignant glioma. Previously, we reported that combination therapy of Ad5-delta 24RGD with irradiation led to synergistic antitumor activity in s.c. glioma xenografts. In the current study, the underlying mechanism of action to this synergy was studied and the effects of combined therapy were assessed in an orthotopic glioma model. Sequencing studies in U-87 monolayers showed that delivery of irradiation before Ad5-delta 24RGD infection led to a greater oncolytic effect than simultaneous delivery or infection before irradiation. This effect was not due to enhanced virus production or release. Experiments using a luciferase-encoding vector revealed a small increase in transgene expression in irradiated cells. In tumor spheroids, combination therapy was more effective than Ad5-delta 24RGD or irradiation alone. Staining of spheroid sections showed improved penetration of virus to the core of irradiated spheroids. Mice bearing intracranial tumors received a combination of Ad5-delta 24RGD with 1 x 5 Gy total body irradiation or with 2 x 6 Gy whole brain irradiation. In contrast to the in vitro data and reported results in s.c. tumors, addition of radiotherapy did not significantly enhance the antitumor effect of Ad5-delta 24RGD. Combined treatment with Ad5-delta 24RGD and irradiation shows enhanced antitumor activity in vitro and in s.c. tumors, but not in an orthotopic glioma model. These differential results underscore the significance of the selected tumor model in assessing the effects of combination therapies with oncolytic adenoviruses.

  6. Growth-differentiation factor-15, endoglin and N-terminal pro-brain natriuretic peptide induction in athletes participating in an ultramarathon foot race.

    Science.gov (United States)

    Tchou, Isabelle; Margeli, Alexandra; Tsironi, Maria; Skenderi, Katerina; Barnet, Marc; Kanaka-Gantenbein, Christina; Papassotiriou, Ioannis; Beris, Photis

    2009-09-01

    We investigated the actions of growth-differentiation factor (GDF)-15, endoglin and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in 15 male athletes who participated in the ultradistance foot race of the 246 km 'Sparthathlon'. Measurements were performed before (phase I), at the end of the race (phase II) and 48 h post-race (phase III). GDF-15 and endoglin serum concentrations were determined with enzyme-linked immunosorbent assay and NT-pro-BNP plasma levels by electrochemiluminescence. GDF-15 levels were increased from phase I (563.9 +/- 57.1 pg ml(-1)) to phase II (2311.1 +/- 462.3 pg ml(-1)) and decreased at phase III (862.0 +/- 158.0 pg ml(-1)) (p foot race consisting of continuous, prolonged and brisk exercise.

  7. Mesothelioma - malignant

    Science.gov (United States)

    ... 2016:chap 82. National Cancer Institute. PDQ malignant mesothelioma treatment. Updated August 5, 2015. www.cancer.gov/types/mesothelioma/hp/mesothelioma-treatment-pdq#section/29 . Accessed July 8, 2016. National ...

  8. Carboxyl-terminal receptor domains control the differential dephosphorylation of somatostatin receptors by protein phosphatase 1 isoforms.

    Directory of Open Access Journals (Sweden)

    Andreas Lehmann

    Full Text Available We have recently identified protein phosphatase 1β (PP1β as G protein-coupled receptor (GPCR phosphatase for the sst2 somatostatin receptor using siRNA knockdown screening. By contrast, for the sst5 somatostatin receptor we identified protein phosphatase 1γ (PP1γ as GPCR phosphatase using the same approach. We have also shown that sst2 and sst5 receptors differ substantially in the temporal dynamics of their dephosphorylation and trafficking patterns. Whereas dephosphorylation and recycling of the sst2 receptor requires extended time periods of ∼30 min, dephosphorylation and recycling of the sst5 receptor is completed in less than 10 min. Here, we examined which receptor domains determine the selection of phosphatases for receptor dephosphorylation. We found that generation of tail-swap mutants between sst2 and sst5 was required and sufficient to reverse the patterns of dephosphorylation and trafficking of these two receptors. In fact, siRNA knockdown confirmed that the sst5 receptor carrying the sst2 tail is predominantly dephosphorylated by PP1β, whereas the sst2 receptor carrying the sst5 tail is predominantly dephosphorylated by PP1γ. Thus, the GPCR phosphatase responsible for dephosphorylation of individual somatostatin receptor subtypes is primarily determined by their different carboxyl-terminal receptor domains. This phosphatase specificity has in turn profound consequences for the dephosphorylation dynamics and trafficking patterns of GPCRs.

  9. A novel Atoh1 "self-terminating" mouse model reveals the necessity of proper Atoh1 level and duration for hair cell differentiation and viability.

    Science.gov (United States)

    Pan, Ning; Jahan, Israt; Kersigo, Jennifer; Duncan, Jeremy S; Kopecky, Benjamin; Fritzsch, Bernd

    2012-01-01

    Atonal homolog1 (Atoh1) is a bHLH transcription factor essential for inner ear hair cell differentiation. Targeted expression of Atoh1 at various stages in development can result in hair cell differentiation in the ear. However, the level and duration of Atoh1 expression required for proper hair cell differentiation and maintenance remain unknown. We generated an Atoh1 conditional knockout (CKO) mouse line using Tg(Atoh1-cre), in which the cre expression is driven by an Atoh1 enhancer element that is regulated by Atoh1 protein to "self-terminate" its expression. The mutant mice show transient, limited expression of Atoh1 in all hair cells in the ear. In the organ of Corti, reduction and delayed deletion of Atoh1 result in progressive loss of almost all the inner hair cells and the majority of the outer hair cells within three weeks after birth. The remaining cells express hair cell marker Myo7a and attract nerve fibers, but do not differentiate normal stereocilia bundles. Some Myo7a-positive cells persist in the cochlea into adult stages in the position of outer hair cells, flanked by a single row of pillar cells and two to three rows of disorganized Deiters cells. Gene expression analyses of Atoh1, Barhl1 and Pou4f3, genes required for survival and maturation of hair cells, reveal earlier and higher expression levels in the inner compared to the outer hair cells. Our data show that Atoh1 is crucial for hair cell mechanotransduction development, viability, and maintenance and also suggest that Atoh1 expression level and duration may play a role in inner vs. outer hair cell development. These genetically engineered Atoh1 CKO mice provide a novel model for establishing critical conditions needed to regenerate viable and functional hair cells with Atoh1 therapy.

  10. A novel Atoh1 "self-terminating" mouse model reveals the necessity of proper Atoh1 level and duration for hair cell differentiation and viability.

    Directory of Open Access Journals (Sweden)

    Ning Pan

    Full Text Available Atonal homolog1 (Atoh1 is a bHLH transcription factor essential for inner ear hair cell differentiation. Targeted expression of Atoh1 at various stages in development can result in hair cell differentiation in the ear. However, the level and duration of Atoh1 expression required for proper hair cell differentiation and maintenance remain unknown. We generated an Atoh1 conditional knockout (CKO mouse line using Tg(Atoh1-cre, in which the cre expression is driven by an Atoh1 enhancer element that is regulated by Atoh1 protein to "self-terminate" its expression. The mutant mice show transient, limited expression of Atoh1 in all hair cells in the ear. In the organ of Corti, reduction and delayed deletion of Atoh1 result in progressive loss of almost all the inner hair cells and the majority of the outer hair cells within three weeks after birth. The remaining cells express hair cell marker Myo7a and attract nerve fibers, but do not differentiate normal stereocilia bundles. Some Myo7a-positive cells persist in the cochlea into adult stages in the position of outer hair cells, flanked by a single row of pillar cells and two to three rows of disorganized Deiters cells. Gene expression analyses of Atoh1, Barhl1 and Pou4f3, genes required for survival and maturation of hair cells, reveal earlier and higher expression levels in the inner compared to the outer hair cells. Our data show that Atoh1 is crucial for hair cell mechanotransduction development, viability, and maintenance and also suggest that Atoh1 expression level and duration may play a role in inner vs. outer hair cell development. These genetically engineered Atoh1 CKO mice provide a novel model for establishing critical conditions needed to regenerate viable and functional hair cells with Atoh1 therapy.

  11. Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide, Troponin-T, and Growth-Differentiation Factor 15 in Adult Congenital Heart Disease.

    Science.gov (United States)

    Baggen, Vivan J M; van den Bosch, Annemien E; Eindhoven, Jannet A; Schut, Anne-Rose W; Cuypers, Judith A A E; Witsenburg, Maarten; de Waart, Monique; van Schaik, Ron H N; Zijlstra, Felix; Boersma, Eric; Roos-Hesselink, Jolien W

    2017-01-17

    The number of patients with adult congenital heart disease (ACHD) is rapidly increasing. To optimize patient management, there is a great need to accurately identify high-risk patients. Still, no biomarker has been firmly established as a clinically useful prognostic tool in this group. We studied the association of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitive troponin-T, and growth-differentiation factor 15 with cardiovascular events in ACHD. Clinically stable patients with ACHD who routinely visited the outpatient clinic between April 2011 and April 2013 underwent clinical assessment, electrocardiography, echocardiography, and biomarker measurement (NT-proBNP, high-sensitive troponin-T, and growth-differentiation factor 15) at the time of study inclusion. Patients were prospectively followed for the occurrence of cardiovascular events (death, heart failure, hospitalization, arrhythmia, thromboembolic events, and reintervention). Survival curves were derived by the Kaplan-Meier method, and Cox regression was performed to investigate the relation between biomarkers and events with adjustment for multiple clinical and echocardiographic variables. In total, 595 patients were included (median age, 33 years; interquartile range, 25-41 years; 58% male; 90% New York Heart Association class I). Patients were followed during a median of 42 (interquartile range, 37-46) months. Of the 3 evaluated biomarkers, NT-proBNP in the upper quartile (>33.3 pmol/L) was most strongly associated with cardiovascular events (n=165, adjusted hazard ratio, 9.05 [3.24-25.3], P14 pmol/L), elevated high-sensitive troponin-T (>14 ng/L), and elevated growth-differentiation factor 15 (>1109 ng/L) identified those patients at highest risk of cardiovascular events (log-rank PT, and growth-differentiation factor 15 identify patients at highest risk of cardiovascular events. These biomarkers therefore may play an important role in the monitoring and management of patients with

  12. The insulator protein BEAF-32 is required for Hippo pathway activity in the terminal differentiation of neuronal subtypes.

    Science.gov (United States)

    Jukam, David; Viets, Kayla; Anderson, Caitlin; Zhou, Cyrus; DeFord, Peter; Yan, Jenny; Cao, Jinshuai; Johnston, Robert J

    2016-07-01

    The Hippo pathway is crucial for not only normal growth and apoptosis but also cell fate specification during development. What controls Hippo pathway activity during cell fate specification is incompletely understood. In this article, we identify the insulator protein BEAF-32 as a regulator of Hippo pathway activity in Drosophila photoreceptor differentiation. Though morphologically uniform, the fly eye is composed of two subtypes of R8 photoreceptor neurons defined by expression of light-detecting Rhodopsin proteins. In one R8 subtype, active Hippo signaling induces Rhodopsin 6 (Rh6) and represses Rhodopsin 5 (Rh5), whereas in the other subtype, inactive Hippo signaling induces Rh5 and represses Rh6. The activity state of the Hippo pathway in R8 cells is determined by the expression of warts, a core pathway kinase, which interacts with the growth regulator melted in a double-negative feedback loop. We show that BEAF-32 is required for expression of warts and repression of melted Furthermore, BEAF-32 plays a second role downstream of Warts to induce Rh6 and prevent Rh5 fate. BEAF-32 is dispensable for Warts feedback, indicating that BEAF-32 differentially regulates warts and Rhodopsins. Loss of BEAF-32 does not noticeably impair the functions of the Hippo pathway in eye growth regulation. Our study identifies a context-specific regulator of Hippo pathway activity in post-mitotic neuronal fate, and reveals a developmentally specific role for a broadly expressed insulator protein. © 2016. Published by The Company of Biologists Ltd.

  13. The block of adipocyte differentiation by a C-terminally truncated, but not by full-length, simian virus 40 large tumor antigen is dependent on an intact retinoblastoma susceptibility protein family binding domain.

    Science.gov (United States)

    Higgins, C; Chatterjee, S; Cherington, V

    1996-02-01

    Simian virus 40 (SV40) can promote cell transformation and suppress differentiation. It does this partly by targeting tumor suppressors such as p53 and members of the retinoblastoma susceptibility protein (Rb) family. This work concentrates on mechanisms by which SV40 large tumor antigen (SVLT) suppresses adipocyte differentiation. We created cell lines derived from murine 3T3-L1 preadipocytes expressing different versions of SV40 early-region sequences. SVLT-expressing cells failed to exhibit adipocyte morphology, to induce glycerophosphate dehydrogenase activity, and to induce differentiation-dependent mRNA for adipocyte P2. SVLT alone was sufficient, in the absence of SV40 small tumor antigen, to inhibit differentiation. A truncated SVLT containing only the N-terminal 121 amino acids (SVLT1-121) blocked differentiation, thus mapping at least one differentiation blocking function to the N-terminal region. K1 (Glu-107-->Lys) point mutants of SVLT, which are unable to bind to the Rb protein family or induce neoplastic transformation, are defective for blocking differentiation in the case of SVLT1-121 but retain the ability to block differentiation in the case of full-length SVLT. This finding demonstrates that Rb family proteins are important in regulating adipocyte differentiation but that other functions of full-length SVLT can block adipocyte differentiation independently of RB family binding and transformation.

  14. Malignant Catatonia

    Directory of Open Access Journals (Sweden)

    Ayca Ozkul

    2010-12-01

    Full Text Available Catatonia is a syndrome characterized by mutism, immobility, negativism, stereotypy, mannerisms, echophenomena, perseveration and passive obedience. The underlying causes can be psychiatric or may be associated with general medical status or neurological diseases. Additionally catatonia has two subtypes as malignant and nonmalignant catatonia. Main symptoms of malignant catatonia are hyperthermia and autonomic symptoms such as tachycardia, tachypnea and hyperhidrosis. It is important to make the diagnosis as early as possible for an appropriate medical treatment. Clinicians should be aware of the fatal outcome of the disease.

  15. CD8αα expression marks terminally differentiated human CD8+ T cells expanded in chronic viral infection

    Directory of Open Access Journals (Sweden)

    Lucy Jane Walker

    2013-08-01

    Full Text Available The T cell co-receptor CD8αβ enhances T cell sensitivity to antigen, however studies indicate CD8αα has the converse effect and acts as a co-repressor. Using a combination of Thymic Leukaemia antigen (TL tetramer, which directly binds CD8αα, anti-CD161 and anti-Vα7.2 antibodies we have been able for the first time to clearly define CD8αα expression on human CD8 T cells subsets. In healthy controls CD8αα is most highly expressed by CD161 bright (CD161++ mucosal associated invariant T (MAIT cells, with CD8αα expression highly restricted to the TCR Vα7.2+ cells of this subset. We also identified CD8αα-expressing populations within the CD161 mid (CD161+ and negative (CD161- non-MAIT CD8 T cell subsets and show TL-tetramer binding to correlate with expression of CD8β at low levels in the context of maintained CD8α expression (CD8α+CD8βlow. In addition, we found CD161-CD8α+CD8βlow populations to be significantly expanded in the peripheral blood of HIV-1 and hepatitis B (mean of 47% and 40% of CD161- T cells respectively infected individuals. Such CD8αα expressing T cells are an effector-memory population (CD45RA-, CCR7-, CD62L- that express markers of activation and maturation (HLA-DR+, CD28-, CD27-, CD57+ and are functionally distinct, expressing greater levels of TNF-α and IFN-γ on stimulation and perforin at rest than their CD8α+CD8βhigh counterparts. Antigen-specific T cells in HLA-B*4201+HIV-1 infected patients are found within both the CD161-CD8α+CD8βhigh and CD161-CD8α+CD8βlow populations. Overall we have clearly defined CD8αα expressing human T cell subsets using the TL-tetramer, and have demonstrated CD161-CD8α+CD8βlow populations, highly expanded in disease settings, to co-express CD8αβ and CD8αα. Co-expression of CD8αα on CD8αβ T cells may impact on their overall function in-vivo and contribute to the distinctive phenotype of highly differentiated populations in HBV and HIV-1 infection.

  16. Perfusion pattern and time of vascularisation with CEUS increase accuracy in differentiating between benign and malignant tumours in 216 musculoskeletal soft tissue masses

    Energy Technology Data Exchange (ETDEWEB)

    De Marchi, Armanda, E-mail: armanda.demarchi@tiscali.it [Department of Imaging, Azienda Ospedaliera Città della Salute e della Scienza, CTO Hospital, Via Zuretti 29, 10126 Torino (Italy); Prever, Elena Brach del, E-mail: elena.brach@unito.it [Department of OrthopaedicOncology and ReconstructiveSurgery, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, CTO Hospital, Via Zuretti 29, 10126 Torino (Italy); Cavallo, Franco, E-mail: franco.cavallo@unito.it [Department of Public health and Paediatrics, University of Turin, Via Santena 5-bis, 10126 Torino (Italy); Pozza, Simona, E-mail: simona.pozza@tin.it [Department of Imaging, Azienda Ospedaliera Città della Salute e della Scienza, CTO Hospital, Via Zuretti 29, 10126 Torino (Italy); Linari, Alessandra, E-mail: linaralessandra@libero.it [Department of Pathology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Regina Margherita Hospital, Piazza Polonia, 10126 Torino (Italy); Lombardo, Paolo, E-mail: pao.lombardo82@gmail.com [Department of DiagnosticImaging and Radiotherapy of the University of Turin, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Via Genova 3, 10126 Torino (Italy); Comandone, Alessandro, E-mail: alessandro.comandone@gradenigo.it [Department of Oncology, Gradenigo Hospital, Corso Regina Margherita, 8/10.10153 Torino (Italy); Piana, Raimondo, E-mail: raimondo.piana@libero.it [Department of OrthopaedicOncology and ReconstructiveSurgery, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, CTO Hospital, Via Zuretti 29, 10126 Torino (Italy); Faletti, Carlo [Department of Imaging, Azienda Ospedaliera Città della Salute e della Scienza, CTO Hospital, Via Zuretti 29, 10126 Torino (Italy)

    2015-01-15

    Introduction: Musculoskeletal Soft Tissue Tumours (STT) are frequent heterogeneous lesions. Guidelines consider a mass larger than 5 cm and deep with respect to the deep fascia potentially malignant. Contrast Enhanced Ultrasound (CEUS) can detect both vascularity and tumour neoangiogenesis. We hypothesised that perfusion patterns and vascularisation time could improve the accuracy of CEUS in discriminating malignant tumours from benign lesions. Materials and methods: 216 STT were studied: 40% benign lesions, 60% malignant tumours, 56% in the lower limbs. Seven CEUS perfusion patterns and three types of vascularisation (arterial-venous uptake, absence of uptake) were applied. Accuracy was evaluated by comparing imaging with the histological diagnosis. Univariate and multivariate analysis, Chi-square test and t-test for independent variables were applied; significance was set at p < 0.05 level, 95% computed CI. Results: CEUS pattern 6 (inhomogeneous perfusion), arterial uptake and location in the lower limb were associated with high risk of malignancy. CEUS pattern has PPV 77%, rapidity of vascularisation PPV 69%; location in the limbs is the most sensitive indicator, but NPV 52%, PPV 65%. The combination of CEUS-pattern and vascularisation has 74% PPV, 60% NPV, 70% sensitivity. No correlation with size and location in relation to the deep fascia was found. Conclusion: US with CEUS qualitative analysis could be an accurate technique to identify potentially malignant STT, for which second line imaging and biopsy are indicated in Referral Centers. Intense inhomogeneous enhancement with avascular areas and rapid vascularisation time could be useful in discriminating benign from malignant SST, overall when the lower limbs are involved.

  17. Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells

    Science.gov (United States)

    Stadtfeld, Matthias; Apostolou, Effie; Ferrari, Francesco; Choi, Jiho; Walsh, Ryan M.; Chen, Taiping; Oi, Steen; Kim, Sang Yong; Bestor, Tim; Shioda, Toshi; Park, Peter J.; Hochedlinger, Konrad

    2012-01-01

    The generation of induced pluripotent stem cells (iPSCs) often results in aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster, which compromises the cells’ ability to generate entirely iPSC-derived adult mice (“all-iPSC mice”). Here, we show that reprogramming in the presence of ascorbic acid attenuates hypermethylation of Dlk1-Dio3 by enabling a chromatin configuration that interferes with binding of the de novo DNA methyltransferase Dnmt3a. This allowed us to generate all-iPSC mice from mature B cells, which have thus far failed to support the development of exclusively iPSC-derived postnatal animals. Our data demonstrate that transcription factor-mediated reprogramming can endow a defined, terminally differentiated cell type with a developmental potential equivalent to that of embryonic stem cells. More generally, these findings indicate that culture conditions during cellular reprogramming can strongly influence the epigenetic and biological properties of resultant iPSCs. PMID:22387999

  18. E2F activates late-G1 events but cannot replace E1A in inducing S phase in terminally differentiated skeletal muscle cells

    DEFF Research Database (Denmark)

    Pajalunga, D; Tognozzi, D; Tiainen, M

    1999-01-01

    that overexpression of E2F-1, E2F-2 and E2F-4, or a chimeric E2F-4 tethered to a nuclear localization signal cannot reactivate postmitotic skeletal muscle cells (myotubes). This is not due to lack of transcriptional activity, as demonstrated on both a reporter construct and a number of endogenous target genes......We have previously shown that the adenovirus E1A oncogene can reactivate the cell cycle in terminally differentiated cells. Current models imply that much or all of this E1A activity is mediated by the release of the E2F transcription factors from pocket-protein control. In contrast, we show here...... in the presence of E1A, as dominant-negative DP-1 mutants inhibit E1A-mediated cell cycle reentry. Our data show that, to reactivate myotubes, E1A must exert other functions, in addition to releasing E2F. They also establish mouse myotubes as an experimental system uniquely suited to study the most direct E2F...

  19. [Selected immunologic indicators in malignant bone tumors].

    Science.gov (United States)

    Keleová, A; Huraj, E; Jahnová, E; Janota, S; Nyulassy, S

    1990-02-01

    In patients with the malignant tumor of bone (17 osteosarcomas, 8 Ewing tumors) longterm observations were made, and namely at the beginning of the disease, after the surgical removal of the tumor, during chemotherapy and in the terminal phase of the disease. The observations concentrated on the following selected immunology parameters: active lymphocytes T, lymphocytes T, lymphocytes B, large granular lymphocytes, IgG, IgA, IgM and circulating immune complexes. In non-treated patients prior to diagnosing the disease, reduction of active lymphocytes T was found out while the total lymphocytes T remained unchanged. However, no significant differences were found out between benign and malignant tumors. The surgical removal of the tumor results in the change in imunologic indicators, the increase of active lyphocytes T, lymphocytes T and the decrease in the circulating immune complexes. The change is of temporary nature, the subsequent deterioration is caused by both the progression of the disease and chemotherapy. The values of immunoglobulins and lymphocytes B fluctuated during the whole course of the disease in physiological levels. The observation of active lymphocytes T and lymphocytes T can be used for monitoring of the immunosuppression in cytostatic treatment. The levl of IgG is differentially diagnostically used to distinguish between the tumor and inflammatory processes.

  20. Intravoxel incoherent motion diffusion-weighted magnetic resonance imaging of focal vertebral bone marrow lesions: initial experience of the differentiation of nodular hyperplastic hematopoietic bone marrow from malignant lesions

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sunghoon; Kwack, Kyu-Sung; Kim, Jae Ho [Ajou University School of Medicine, Division of Musculoskeletal Radiology, Department of Radiology, Suwon, Gyeonggi-do (Korea, Republic of); Ajou University Medical Center, Musculoskeletal Imaging Laboratory, Suwon (Korea, Republic of); Chung, Nam-Su [Ajou University School of Medicine, Department of Orthopaedic Surgery, Suwon (Korea, Republic of); Hwang, Jinwoo [Philips Healthcare, Department of Clinical Science, Seoul (Korea, Republic of); Lee, Hyun Young [Ajou University Medical Center, Regional Clinical Trial Center, Suwon (Korea, Republic of); Yonsei University College of Medicine, Department of Biostatistics, Seoul (Korea, Republic of)

    2017-05-15

    To evaluate the ability of intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) parameters to differentiate nodular hyperplastic hematopoietic bone marrow (HHBM) from malignant vertebral bone marrow lesions (VBMLs). A total of 33 patients with 58 VBMLs, including 9 nodular HHBM lesions, 39 bone metastases, and 10 myelomas, were retrospectively assessed. All diagnoses were confirmed either pathologically or via image assessment. IVIM diffusion-weighted MRI with 11 b values (from 0 to 800 s/mm{sup 2}) were obtained using a 3.0-T MR imager. The apparent diffusion coefficient (ADC), pure diffusion coefficient (D), perfusion fraction (f), and pseudodiffusion coefficient (D*) were calculated. ADC and IVIM parameters were compared using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performances of ADC, D, f, and D* in terms of VBML characterization. The diagnostic performance of morphological MR sequences was also assessed for comparison. The ADC and D values of nodular HHBM were significantly lower than those of malignant VBML (both p values < 0.001), whereas the f value was significantly higher (p < 0.001). However, there were no significant differences in D* between the two groups (p = 0.688). On ROC analysis, the area under the curve (AUC) for D was 1.000, which was significantly larger than that for ADC (AUC = 0.902). Intravoxel incoherent motion diffusion-weighted MRI can be used to differentiate between nodular HHBM and malignant VBML. The D value was significantly lower for nodular HHBM, and afforded a better diagnostic performance than the ADC, f, and D* values in terms of such differentiation. (orig.)

  1. Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue

    OpenAIRE

    Jinping He; Nan Wang; Hiromichi Tsurui; Masashi Kato; Machiko Iida; Takayoshi Kobayashi

    2016-01-01

    Skin cancer is one of the most common cancers. Melanoma accounts for less than 2% of skin cancer cases but causes a large majority of skin cancer deaths. Early detection of malignant melanoma remains the key factor in saving lives. However, the melanoma diagnosis is still clinically challenging. Here, we developed a confocal photothermal microscope for noninvasive, label-free, three-dimensional imaging of melanoma. The axial resolution of confocal photothermal microscope is ~3 times higher th...

  2. Malignant Triton Tumor (MTT) of the neck

    DEFF Research Database (Denmark)

    Sørensen, Kristine Bjørndal; Godballe, Christian; Krogdahl, Annelise

    2006-01-01

    Malignant Triton Tumor (MTT) is a rare, malignant periphere nerve sheath tumor with rhabdomyoblastic differentiation. One third of described MTT's were located at the head and neck region. One third of these are associated with neurofibromatosis type 1. MTT most often appears in the third decade...

  3. Malignant melanocytic neoplasm of pancreas with liver metastasis: Is it malignant melanoma or clear cell sarcoma?

    Science.gov (United States)

    Kodiatte, Thomas Alex; George, Sam Varghese; Chacko, Raju Titus; Ramakrishna, Banumathi

    2017-01-01

    Malignant melanocytic neoplasm, usually seen in soft tissues, is rare in a visceral location and presents as a diagnostic dilemma. We present a case of pancreatic malignant melanocytic neoplasm with liver metastasis. A 58-year-old man presented with left upper abdominal swelling and loss of appetite. Imaging revealed a large mass arising from the pancreatic tail, and this was diagnosed as malignant neoplasm with melanocytic differentiation on biopsy with the possible differentials of malignant melanoma, clear cell sarcoma (CCS), and perivascular epithelioid cell neoplasm. The patient underwent distal pancreatectomy and splenectomy for the same. Follow-up imaging 6 months later showed a metastatic liver lesion, for which he also underwent a liver resection. BRAF mutational analysis was found to be negative. Both CCS and malignant melanoma have similar morphological features and melanocytic differentiation, but each harbors a distinct genetic background. Differentiation of both has diagnostic and therapeutic implications.

  4. Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue

    Science.gov (United States)

    He, Jinping; Wang, Nan; Tsurui, Hiromichi; Kato, Masashi; Iida, Machiko; Kobayashi, Takayoshi

    2016-07-01

    Skin cancer is one of the most common cancers. Melanoma accounts for less than 2% of skin cancer cases but causes a large majority of skin cancer deaths. Early detection of malignant melanoma remains the key factor in saving lives. However, the melanoma diagnosis is still clinically challenging. Here, we developed a confocal photothermal microscope for noninvasive, label-free, three-dimensional imaging of melanoma. The axial resolution of confocal photothermal microscope is ~3 times higher than that of commonly used photothermal microscope. Three-dimensional microscopic distribution of melanin in pigmented lesions of mouse skin is obtained directly with this setup. Classic morphometric and fractal analysis of sixteen 3D images (eight for benign melanoma and eight for malignant) showed a capability of pathology of melanoma: melanin density and size become larger during the melanoma growth, and the melanin distribution also becomes more chaotic and unregulated. The results suggested new options for monitoring the melanoma growth and also for the melanoma diagnosis.

  5. BACE1 elevation is involved in amyloid plaque development in the triple transgenic model of Alzheimer's disease: differential Aβ antibody labeling of early-onset axon terminal pathology.

    Science.gov (United States)

    Cai, Yan; Zhang, Xue-Mei; Macklin, Lauren N; Cai, Huaibin; Luo, Xue-Gang; Oddo, Salvatore; Laferla, Frank M; Struble, Robert G; Rose, Gregory M; Patrylo, Peter R; Yan, Xiao-Xin

    2012-02-01

    β-amyloid precursor protein (APP) and presenilins mutations cause early-onset familial Alzheimer's disease (FAD). Some FAD-based mouse models produce amyloid plaques, others do not. β-Amyloid (Aβ) deposition can manifest as compact and diffuse plaques; it is unclear why the same Aβ molecules aggregate in different patterns. Is there a basic cellular process governing Aβ plaque pathogenesis? We showed in some FAD mouse models that compact plaque formation is associated with a progressive axonal pathology inherent with increased expression of β-secretase (BACE1), the enzyme initiating the amyloidogenic processing of APP. A monoclonal Aβ antibody, 3D6, visualized distinct axon terminal labeling before plaque onset. The present study was set to understand BACE1 and axonal changes relative to diffuse plaque development and to further characterize the novel axonal Aβ antibody immunoreactivity (IR), using triple transgenic AD (3xTg-AD) mice as experimental model. Diffuse-like plaques existed in the forebrain in aged transgenics and were regionally associated with increased BACE1 labeled swollen/sprouting axon terminals. Increased BACE1/3D6 IR at axon terminals occurred in young animals before plaque onset. These axonal elements were also co-labeled by other antibodies targeting the N-terminal and mid-region of Aβ domain and the C-terminal of APP, but not co-labeled by antibodies against the Aβ C-terminal and APP N-terminal. The results suggest that amyloidogenic axonal pathology precedes diffuse plaque formation in the 3xTg-AD mice, and that the early-onset axonal Aβ antibody IR in transgenic models of AD might relate to a cross-reactivity of putative APP β-carboxyl terminal fragments.

  6. Differentiation between focal malignant marrow-replacing lesions and benign red marrow deposition of the spine with T2*-corrected fat-signal fraction map using a three-echo volume interpolated breath-hold gradient echo Dixon sequence.

    Science.gov (United States)

    Kim, Yong Pyo; Kannengiesser, Stephan; Paek, Mun-Young; Kim, Sungjun; Chung, Tae-Sub; Yoo, Yeon Hwa; Yoon, Choon-Sik; Song, Ho-Taek; Lee, Young Han; Suh, Jin-Suck

    2014-01-01

    To assess the feasibility of T2*-corrected fat-signal fraction (FF) map by using the three-echo volume interpolated breath-hold gradient echo (VIBE) Dixon sequence to differentiate between malignant marrow-replacing lesions and benign red marrow deposition of vertebrae. We assessed 32 lesions from 32 patients who underwent magnetic resonance imaging after being referred for assessment of a known or possible vertebral marrow abnormality. The lesions were divided into 21 malignant marrow-replacing lesions and 11 benign red marrow depositions. Three sequences for the parameter measurements were obtained by using a 1.5-T MR imaging scanner as follows: three-echo VIBE Dixon sequence for FF; conventional T1-weighted imaging for the lesion-disc ratio (LDR); pre- and post-gadolinium enhanced fat-suppressed T1-weighted images for the contrast-enhancement ratio (CER). A region of interest was drawn for each lesion for parameter measurements. The areas under the curve (AUC) of the parameters and their sensitivities and specificities at the most ideal cutoff values from receiver operating characteristic curve analysis were obtained. AUC, sensitivity, and specificity were respectively compared between FF and CER. The AUCs of FF, LDR, and CER were 0.96, 0.80, and 0.72, respectively. In the comparison of diagnostic performance between the FF and CER, the FF showed a significantly larger AUC as compared to the CER (p = 0.030), although the difference of sensitivity (p = 0.157) and specificity (p = 0.157) were not significant. Fat-signal fraction measurement using T2*-corrected three-echo VIBE Dixon sequence is feasible and has a more accurate diagnostic performance, than the CER, in distinguishing benign red marrow deposition from malignant bone marrow-replacing lesions.

  7. Identification of potential hot spots in the carboxy-terminal part of the Epstein-Barr virus (EBV) BNLF-1 gene in both malignant and benign EBV-associated diseases

    DEFF Research Database (Denmark)

    Sandvej, K; Peh, S C; Andresen, B S

    1994-01-01

    In this study, we have sequenced the C-terminal part of the Epstein-Barr virus (EBV)-BNLF-1 gene encoding for the latent membrane protein-1 from tissues of EBV-positive Danish Hodgkin's disease (HD) and of Danish and Malaysian peripheral T-cell lymphomas (PTLs) and from tonsils of Danish infectious...

  8. Hematuria and urologic malignancies

    National Research Council Canada - National Science Library

    Lien, Yeong-Hau H

    2014-01-01

    ...% of total malignancies and 3.7% of malignancy-related mortality. Asymptomatic microscopic hematuria is the most common presenting sign of urologic malignancies that may lead to early diagnosis and cure of these cancers...

  9. Differential inhibition of ex-vivo tumor kinase activity by vemurafenib in BRAF(V600E and BRAF wild-type metastatic malignant melanoma.

    Directory of Open Access Journals (Sweden)

    Andliena Tahiri

    Full Text Available Treatment of metastatic malignant melanoma patients harboring BRAF(V600E has improved drastically after the discovery of the BRAF inhibitor, vemurafenib. However, drug resistance is a recurring problem, and prognoses are still very bad for patients harboring BRAF wild-type. Better markers for targeted therapy are therefore urgently needed.In this study, we assessed the individual kinase activity profiles in 26 tumor samples obtained from patients with metastatic malignant melanoma using peptide arrays with 144 kinase substrates. In addition, we studied the overall ex-vivo inhibitory effects of vemurafenib and sunitinib on kinase activity status.Overall kinase activity was significantly higher in lysates from melanoma tumors compared to normal skin tissue. Furthermore, ex-vivo incubation with both vemurafenib and sunitinib caused significant decrease in phosphorylation of kinase substrates, i.e kinase activity. While basal phosphorylation profiles were similar in BRAF wild-type and BRAF(V600E tumors, analysis with ex-vivo vemurafenib treatment identified a subset of 40 kinase substrates showing stronger inhibition in BRAF(V600E tumor lysates, distinguishing the BRAF wild-type and BRAF(V600E tumors. Interestingly, a few BRAF wild-type tumors showed inhibition profiles similar to BRAF(V600E tumors. The kinase inhibitory effect of vemurafenib was subsequently analyzed in cell lines harboring different BRAF mutational status with various vemurafenib sensitivity in-vitro.Our findings suggest that multiplex kinase substrate array analysis give valuable information about overall tumor kinase activity. Furthermore, intra-assay exposure to kinase inhibiting drugs may provide a useful tool to study mechanisms of resistance, as well as to identify predictive markers.

  10. Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-κB in immortalized and malignant oral keratinocytes

    Directory of Open Access Journals (Sweden)

    Lee Suk-Keun

    2007-09-01

    Full Text Available Abstract Background Interleukin-8 (IL-8 is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK and malignant human oral keratinocytes (HN12 cells with deferoxamine (DFO. Methods IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR analysis. Electrophoretic mobility shift assays was used to determine NF-κB binding activity. Phosphorylation and degradation of the I-κB were analyized by Western blot. Results IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1β to strongly up-regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IκB, and activation of NF-κB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione, and by pyrrolidine dithiocarbamate, an inhibitor of NF-κB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(PH oxidase. Conclusion This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions.

  11. Deleted in Malignant Brain Tumors 1 is a versatile mucin-like molecule likely to play a differential role in digestive tract cancer

    DEFF Research Database (Denmark)

    Mollenhauer, J; Herbertz, S; Helmke, B

    2001-01-01

    , a loss of DMBT1 expression also takes place in adenocarcinomas. Regarding DMBT1 as a mucin-like molecule is a new perspective that is instructive for its functions and its role in cancer. We conclude that DMBT1 is likely to play a differential role in the genesis of digestive tract carcinomas. However...... in epithelial differentiation. Squamous cell carcinomas of the esophagus show an early loss of DMBT1 expression. In contrast, adenocarcinomas of the esophagus commonly maintain higher DMBT1 expression levels. However, presumably subsequent to a transition from the lumenal secretion to a targeting to the ECM...

  12. Malignant hypercalcemia.

    Science.gov (United States)

    Basso, U; Maruzzo, M; Roma, A; Camozzi, V; Luisetto, G; Lumachi, F

    2011-01-01

    Malignancy-associated hypercalcemia (MAH) is one of the clinical emergencies in medical oncology, arising early or, more often, during the late phases of disease. Prevalence cannot be estimated accurately because previous figures of 5-30% of all cancer patients have progressively reduced thanks to the widespread use of bisphosphonates for the prevention of skeletal events. The classic distinction of humoral vs. osteolytic hypercalcemia is still relevant from an etiological point of view, but should not be considered as a rigid alternative since both mechanisms may be active in the same patients and the activation of the RANKL pathway is a common pathogenetic mechanism. Parathyroid hormone-related protein mimics the effects of PTH on the bone and kidney (tubular calcium resorption) and may represent an attractive druggable target, but additional agents (cytokines or other mediators) as well as ectopic production of 1,25(OH)₂D₃ may give an important contribution to humoral hypercalcemia. Conversely, bone invasion by cancer cells determines massive bone reabsorption due to the release of proteolytic enzymes and pro-osteolytic agents with paracrine activity on adjacent bone and stromal cells. When cancer patients develop headache, confusion, de-hydration and tremors hypercalcemia should be suspected although slow rise of calcium levels may produce more indolent symptoms. Bisphosphonates (with or without hydration and diuretics) may efficiently control MAH but only if an active treatment for the underlying cancer is promptly started. The anti-RANKL monoclonal antibody denosumab represents a novel agent able to revert the vicious cycle of bone metastases and data from phase III studies are currently showing promising activity in reverting bone resorption with manageable toxicity.

  13. Segmental neurofibromatosis and malignancy.

    Science.gov (United States)

    Dang, Julie D; Cohen, Philip R

    2010-01-01

    Segmental neurofibromatosis is an uncommon variant of neurofibromatosis type I characterized by neurofibromas and/or café-au-lait macules localized to one sector of the body. Although patients with neurofibromatosis type I have an associated increased risk of certain malignancies, malignancy has only occasionally been reported in patients with segmental neurofibromatosis. The published reports of patients with segmental neurofibromatosis who developed malignancy were reviewed and the characteristics of these patients and their cancers were summarized. Ten individuals (6 women and 4 men) with segmental neurofibromatosis and malignancy have been reported. The malignancies include malignant peripheral nerve sheath tumor (3), malignant melanoma (2), breast cancer (1), colon cancer (1), gastric cancer (1), lung cancer (1), and Hodgkin lymphoma (1). The most common malignancies in patients with segmental neurofibromatosis are derived from neural crest cells: malignant peripheral nerve sheath tumor and malignant melanoma. The incidence of malignancy in patients with segmental neurofibromatosis may approach that of patients with neurofibromatosis type I.

  14. Terminating supervision.

    Science.gov (United States)

    Levendosky, Alytia A; Hopwood, Christopher J

    2017-03-01

    The focus of this paper is on the termination of clinical supervision. Although clinical supervision is considered the backbone of most mental health training programs, it gets relatively little theoretical or empirical attention. The termination of supervision has received even less attention. In this paper, we describe an approach to terminating supervision in our treatment team, which integrates intensive assessment with a relational perspective in a clinical science training program (Levendosky & Hopwood, 2016). We describe our established conceptual framework, review empirical evidence, and provide verbatim examples from final supervision meetings on our team to elaborate the importance of conceptualizing individual differences across trainees and parallels between supervision and psychotherapy dynamics. We conclude by emphasizing the need for research on supervision in general and supervision termination in particular. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  15. Rapid staining and imaging of subnuclear features to differentiate between malignant and benign breast tissues at a point-of-care setting.

    Science.gov (United States)

    Mueller, Jenna L; Gallagher, Jennifer E; Chitalia, Rhea; Krieger, Marlee; Erkanli, Alaattin; Willett, Rebecca M; Geradts, Joseph; Ramanujam, Nimmi

    2016-07-01

    Histopathology is the clinical standard for tissue diagnosis; however, it requires tissue processing, laboratory personnel and infrastructure, and a highly trained pathologist to diagnose the tissue. Optical microscopy can provide real-time diagnosis, which could be used to inform the management of breast cancer. The goal of this work is to obtain images of tissue morphology through fluorescence microscopy and vital fluorescent stains and to develop a strategy to segment and quantify breast tissue features in order to enable automated tissue diagnosis. We combined acriflavine staining, fluorescence microscopy, and a technique called sparse component analysis to segment nuclei and nucleoli, which are collectively referred to as acriflavine positive features (APFs). A series of variables, which included the density, area fraction, diameter, and spacing of APFs, were quantified from images taken from clinical core needle breast biopsies and used to create a multivariate classification model. The model was developed using a training data set and validated using an independent testing data set. The top performing classification model included the density and area fraction of smaller APFs (those less than 7 µm in diameter, which likely correspond to stained nucleoli).When applied to the independent testing set composed of 25 biopsy panels, the model achieved a sensitivity of 82 %, a specificity of 79 %, and an overall accuracy of 80 %. These results indicate that our quantitative microscopy toolbox is a potentially viable approach for detecting the presence of malignancy in clinical core needle breast biopsies.

  16. Malignant hyperthermia

    Directory of Open Access Journals (Sweden)

    Pollock Neil

    2007-04-01

    Full Text Available Abstract Malignant hyperthermia (MH is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with

  17. Genomic analyses reveal broad impact of miR-137 on genes associated with malignant transformation and neuronal differentiation in glioblastoma cells.

    Directory of Open Access Journals (Sweden)

    Saleh Tamim

    Full Text Available miR-137 plays critical roles in the nervous system and tumor development; an increase in its expression is required for neuronal differentiation while its reduction is implicated in gliomagenesis. To evaluate the potential of miR-137 in glioblastoma therapy, we conducted genome-wide target mapping in glioblastoma cells by measuring the level of association between PABP and mRNAs in cells transfected with miR-137 mimics vs. controls via RIPSeq. Impact on mRNA levels was also measured by RNASeq. By combining the results of both experimental approaches, 1468 genes were found to be negatively impacted by miR-137--among them, 595 (40% contain miR-137 predicted sites. The most relevant targets include oncogenic proteins and key players in neurogenesis like c-KIT, YBX1, AKT2, CDC42, CDK6 and TGFβ2. Interestingly, we observed that several identified miR-137 targets are also predicted to be regulated by miR-124, miR-128 and miR-7, which are equally implicated in neuronal differentiation and gliomagenesis. We suggest that the concomitant increase of these four miRNAs in neuronal stem cells or their repression in tumor cells could produce a robust regulatory effect with major consequences to neuronal differentiation and tumorigenesis.

  18. Differential cellulolytic activity of native-form and C-terminal tagged-form cellulase derived from coptotermes formosanus and expressed in E. coli

    Science.gov (United States)

    The endogenous cellulase gene (CfEG3a) of Coptotermes formosanus, an economically important pest termite, was cloned and overexpressed in both native form (nCfEG) and C-terminal His-tagged form (tCfEG) in E.coli. Both forms of recombinant cellulases showed hydrolytic activity on cellulosic substrate...

  19. MFH Mimic in Breast: A High-Grade Malignant Phyllodes Tumor

    Directory of Open Access Journals (Sweden)

    A. L. Hemalatha

    2012-01-01

    Full Text Available Malignant phyllodes tumor is usually diagnosed by the presence of benign duct-like epithelium and malignant mesenchymal tissue. In addition to the usual fibrosarcomatous features, the mesenchymal component may show areas resembling osteogenic sarcoma, chondrosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, malignant mesenchymoma, and, very rarely, malignant fibrous histiocytoma. We present one such rare case of malignant phyllodes tumor with malignant fibrous histiocytoma-like stromal differentiation.

  20. Comparison of the diagnostic accuracy of contrast-enhanced MRI and diffusion-weighted MRI in the differentiation between uterine leiomyosarcoma / smooth muscle tumor with uncertain malignant potential and benign leiomyoma.

    Science.gov (United States)

    Lin, Gigin; Yang, Lan-Yan; Huang, Yu-Ting; Ng, Koon-Kwan; Ng, Shu-Hang; Ueng, Shir-Hwa; Chao, Angel; Yen, Tzu-Chen; Chang, Ting-Chang; Lai, Chyong-Huey

    2016-02-01

    To compare the diagnostic accuracy of contrast-enhanced (CE) magnetic resonance imaging (MRI) and diffusion-weighted MRI (DWI) in the differentiation between uterine leiomyosarcoma (LMS) / smooth muscle tumor with uncertain malignant potential (STUMP) and benign leiomyoma. A consecutive cohort of 8 LMS/STUMP and 25 benign leiomyomas underwent pelvic MRI exam at 3T. Two radiologists independently evaluated images based on CE-MRI (central nonenhancement at equilibrial phase) and DWI (hyperintensity on b = 1000 s/mm2 and hypointensity on apparent diffusion coefficients [ADC] map). The ADC values were calculated from b = 0 and 1000 s/mm2 . CE-MRI yielded a significantly superior diagnostic accuracy (0.94 vs. 0.52) and a significantly higher specificity (0.96 vs. 0.36) than DWI (P < 0.05 for both), and remained a comparably high sensitivity as DWI (0.88 vs. 1.00). A combination of DWI and ADC value <1.08 × 10(-3) mm2 /s (determined by receiver operating characteristic analysis) improved diagnostic accuracy, sensitivity, and specificity of DWI to 0.88, 0.88, and 0.88, respectively, by post-hoc analysis based on the same study cohort. For prospective differentiation between uterine LMS/STUMP and benign leiomyoma, CE-MRI can provide accurate information and is preferable to DWI. Combination of DWI and ADC values can achieve a comparable diagnostic accuracy to CE-MRI. © 2015 Wiley Periodicals, Inc.

  1. Determination of the state of operating mechanical stresses acting on surface piping with problems of differential collapses in the Venta de Carpio Terminal; Determinacion del estado de esfuerzos mecanicos actuantes en tuberias superficiales con problemas de hundimientos diferenciales en la Terminal Venta de Carpio

    Energy Technology Data Exchange (ETDEWEB)

    Neri B, Ernesto R; Garcia E, Nairoby [Instituto de Investigaciones Electricas, Cuernavaca, Morelos (Mexico)

    2004-07-01

    The Venta de Carpio Terminal is located in the Northern part of the old Texcoco Lake, State of Mexico, in highly compressible soil. In it, it is received, regulated, measured and distributed natural gas, LP gas and PEMEX Refinacion products that are supplied to distribution terminals of and consumption centers located in the central area of the country, that encompasses the states of Puebla, Tlaxcala, Mexico, Hidalgo, Queretaro and a small part of the Federal District. The construction of the Venta de Carpio station dates from 1960; since then, it has presented important regional settlements, mainly due to the water extraction of the subsoil, that have imposed deformations to the piping systems connected to the surface facilities that have been piloted in the terminal. Equally, other surface piping systems and facilities present deformations by differential settlement between their supports. [Spanish] La Terminal Venta de Carpio se ubica en la parte norte del antiguo Lago de Texcoco, Estado de Mexico, en terreno altamente compresible. En ella, se recibe, regula, mide y distribuye gas natural, gas LP y productos de Pemex Refinacion que se suministran a terminales de distribucion y centros de consumo localizados en el area central del pais, que comprende los estados de Puebla, Tlaxcala, Mexico, Hidalgo, Queretaro y una pequena parte del Distrito Federal. La construccion de la estacion Venta de Carpio data de 1960; desde entonces, se han presentado asentamientos regionales importantes debidos, principalmente a la extraccion de agua del subsuelo, que han impuesto deformaciones a los sistemas de tuberias conectados con las instalaciones superficiales que han sido piloteadas en la terminal. De igual modo, otros sistemas de tuberias e instalaciones superficiales presentan deformaciones por hundimientos diferenciales entre sus apoyos.

  2. In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography.

    Science.gov (United States)

    Boone, M A L M; Suppa, M; Dhaenens, F; Miyamoto, M; Marneffe, A; Jemec, G B E; Del Marmol, V; Nebosis, R

    2016-01-01

    One of the most challenging problems in clinical dermatology is the early detection of melanoma. Reflectance confocal microscopy (RCM) is an added tool to dermoscopy improving considerably diagnostic accuracy. However, diagnosis strongly depends on the experience of physicians. High-definition optical coherence tomography (HD-OCT) appears to offer additional structural and cellular information on melanocytic lesions complementary to that of RCM. However, the diagnostic potential of HD-OCT seems to be not high enough for ruling out the diagnosis of melanoma if based on morphology analysis. The aim of this paper is first to quantify in vivo optical properties such as light attenuation in melanocytic lesions by HD-OCT. The second objective is to determine the best critical value of these optical properties for melanoma diagnosis. The technique of semi-log plot whereby an exponential function becomes a straight line has been implemented on HD-OCT signals coming from four successive skin layers (epidermis, upper papillary dermis, deeper papillary dermis and superficial reticular dermis). This permitted the HD-OCT in vivo measurement of skin entrance signal (SES), relative attenuation factor normalized for the skin entrance signal (µ raf1) and half value layer (z 1/2). The diagnostic accuracy of HD-OCT for melanoma detection based on the optical properties, µ raf1 , SES and z 1/2 was high (95.6, 82.2 and 88.9 %, respectively). High negative predictive values could be found for these optical properties (96.7, 89.3 and 96.3 %, respectively) compared to morphologic assessment alone (89.9 %), reducing the risk of mistreating a malignant lesion to a more acceptable level (3.3 % instead of 11.1 %). HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with in vivo analysis of optical properties of tissue scatterers in melanocytic lesions. In vivo HD-OCT analysis of optical properties permits melanoma

  3. ImmunoPET of Malignant and Normal B Cells with (89)Zr- and (124)I-Labeled Obinutuzumab Antibody Fragments Reveals Differential CD20 Internalization In Vivo.

    Science.gov (United States)

    Zettlitz, Kirstin A; Tavaré, Richard; Knowles, Scott M; Steward, Kristopher K; Timmerman, John M; Wu, Anna M

    2017-09-19

    Purpose: The B-cell antigen CD20 provides a target for antibody-based positron emission tomography (immunoPET). We engineered antibody fragments targeting human CD20 and studied their potential as immunoPET tracers in transgenic mice (huCD20TM) and in a murine lymphoma model expressing human CD20.Experimental Design: Anti-CD20 cys-diabody (cDb) and cys-minibody (cMb) based on rituximab and obinutuzumab (GA101) were radioiodinated and used for immunoPET imaging of a murine lymphoma model. Pairwise comparison of obinutuzumab-based antibody fragments labeled with residualizing ((89)Zr) versus non-residualizing ((124)I) radionuclides by region of interest analysis of serial PET images was conducted both in the murine lymphoma model and in huCD20TM to assess antigen modulation in vivoResults:(124)I-GAcDb and (124)I-GAcMb produced high-contrast immunoPET images of B-cell lymphoma and outperformed the respective rituximab-based tracers. ImmunoPET imaging of huCD20TM showed specific uptake in lymphoid tissues. The use of the radiometal (89)Zr as alternative label for GAcDb and GAcMb yielded greater target-specific uptake and retention compared with (124)I-labeled tracers. Pairwise comparison of (89)Zr- and (124)I-labeled GAcDb and GAcMb allowed assessment of in vivo internalization of CD20/antibody complexes and revealed that CD20 internalization differs between malignant and endogenous B cells.Conclusions: These obinutuzumab-based PET tracers have the ability to noninvasively and quantitatively monitor CD20-expression and have revealed insights into CD20 internalization upon antibody binding in vivo Because they are based on a humanized mAb they have the potential for direct clinical translation and could improve patient selection for targeted therapy, dosimetry prior to radioimmunotherapy, and prediction of response to therapy. Clin Cancer Res; 1-11. ©2017 AACR. ©2017 American Association for Cancer Research.

  4. A novel marker for terminal Schwann cells, homocysteine-responsive ER-resident protein, as isolated by a single cell PCR-differential display.

    Science.gov (United States)

    Oda, Ryo; Yaoi, Takeshi; Okajima, Seiichiro; Kobashi, Hiroaki; Kubo, Toshikazu; Fushiki, Shinji

    2003-09-05

    Terminal Schwann cells (TSCs) that cover motor neuron terminals are known to play important roles in maintaining neuromuscular junctions, as well as in the repair process after nerve injury. However, molecular characteristics of TSCs remain unknown, because of the difficulties in analyzing them due to their paucity. We have established a method of selectively and efficiently collecting TSCs so that cDNA analysis can be done properly. The expression of 1-2% of whole mRNAs was compared between myelinating Schwann cells (MSCs) and TSCs, and it turned out that approximately one-third of the bands could be categorized as cell-type-specific bands. TSCs thus constitute a distinct entity from the viewpoint of gene expression. As one of the cDNA clones belonging to TSC-specific bands was identified homocysteine-responsive ER-resident protein (Herp), and in situ hybridization confirmed that Herp mRNA is expressed in TSCs on motor nerve terminals but not in MSCs, both in developing and adult rats. In conclusion, we have been able to identify Herp as a novel molecular marker for TSCs.

  5. p63/p51-induced Onset of Keratinocyte Differentiation via the c-Jun N-terminal Kinase Pathway Is Counteracted by Keratinocyte Growth Factor*

    OpenAIRE

    Ogawa, Eisaku; Okuyama, Ryuhei; Egawa, Teie; Nagoshi, Hirokazu; Obinata, Masuo; Tagami, Hachiro; Ikawa, Shuntaro; Aiba, Setsuya

    2008-01-01

    p63/p51, a homolog of the tumor suppressor protein p53, is chiefly expressed in epithelial tissues, including the epidermis. p63 affects cell death similar to p53, and also plays important roles in the development of epithelial tissues and the maintenance of epithelial stem cells. Because it remains unclear how p63 regulates epithelial cell differentiation, we examined the function(s) of p63 in keratinocyte differentiation through the use of a keratinocyte culture syst...

  6. Metastatic malignant phyllodes tumor involving the cerebellum.

    Science.gov (United States)

    Rowe, J Jordi; Prayson, Richard A

    2015-01-01

    Brain metastases from malignant phyllodes tumors of the breast are a rare occurrence. We report a patient with a malignant phyllodes tumor of the right breast which subsequently metastasized to the right lower lobe of the lung 1 year after initial presentation, and to the right cerebellar hemisphere 2 years after diagnosis of her breast mass. After both chemotherapy and whole brain radiotherapy the patient is tumor free at most recent follow-up, 116 months after the breast tumor diagnosis was made. The literature is briefly reviewed and the differential diagnosis of malignant spindle cell brain tumors is discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Diverse functions of IGF/insulin signaling in malignant and noncancerous prostate cells: proliferation in cancer cells and differentiation in noncancerous cells.

    Science.gov (United States)

    Heidegger, Isabel; Ofer, Philipp; Doppler, Wolfgang; Rotter, Varda; Klocker, Helmut; Massoner, Petra

    2012-10-01

    The insulin-like growth factor (IGF) pathway represents one of the most studied molecular regulatory networks in oncology. Clinical trials investigating the therapeutic value of anti-IGF1 receptor (IGF1R) therapies in cancer, including prostate cancer, are ongoing. However, the multiple functions of the IGF network in the prostate are not entirely known. To elucidate the effects of IGF and insulin (INS) on prostate cells, we stimulated prostate cancer (PC3, DU145, LNCaP, DUCaP) and noncancerous prostate cells (EP156T, RWPE-1) and observed differing responses: whereas cancer cells responded to IGF and INS exposure by way of enhanced cell proliferation and glucose consumption, basal to luminal differentiation was induced in noncancerous cells. The same diverse responses were observed when the growth factor receptors IGF1R or INSR were overexpressed. Down-regulation of IGF1R or INSR isoform A (INSRA) also inhibited only proliferation of cancer cells. The proliferative response induced by the INSR in cancer cells was mediated solely by the INSRA. Moreover we observed that the receptors of the IGF network mutually influence their expression and exert redundant functions, thus underscoring the functional molecular network formed by IGF, INS, IGF1R, and INSR. Collectively we found that both IGF1R and INSRA have oncogenic effects in prostate cancer, but the IGF network also has important physiological functions in the noncancerous prostate. These data provide new insights into the biology of the IGF network in the prostate, thereby facilitating the design and interpretation of clinical studies investigating IGF1R targeting agents.

  8. Terminal Ballistics

    CERN Document Server

    Rosenberg, Zvi

    2012-01-01

    This book covers the important issues of terminal ballistics in a comprehensive way combining experimental data, numerical simulations and analytical modeling. The first chapter reviews the experimental equipment which are used for ballistic tests and the diagnostics for material characterization under impulsive loading conditions. The second chapter covers essential features of the codes which are used for terminal ballistics such as the Euler vs. Lagrange schemes and meshing techniques, as well as the most popular material models. The third chapter, devoted to the penetration mechanics of rigid penetrators, brings the update of modeling in this field. The fourth chapter deals with plate perforation and the fifth chapter deals with the penetration mechanics of shaped charge jets and eroding long rods. The last two chapters discuss several techniques for the disruption and defeating of the main threats in armor design. Throughout the book the authors demonstrate the advantages of numerical simulations in unde...

  9. Lysophospholipid receptors are differentially expressed in rat terminal Schwann cells, as revealed by a single cell rt-PCR and in situ hybridization.

    Science.gov (United States)

    Kobashi, Hiroaki; Yaoi, Takeshi; Oda, Ryo; Okajima, Seiichiro; Fujiwara, Hiroyoshi; Kubo, Toshikazu; Fushiki, Shinji

    2006-04-22

    Terminal Schwann cells (TSCs) that cover motor neuron terminals, are known to play an important role in maintaining neuromuscular junctions, as well as in the repair process after nerve injury. However, the molecular characteristics of TSCs remain unknown, because of the difficulties in analyzing them due to their paucity. By using our previously reported method of selectively and efficiently collecting TSCs, we have analyzed the difference in expression patterns of lysophospholipid (LPL) receptor genes (LPA1, LPA2, LPA3, S1P1, S1P2, S1P3, S1P4, and S1P5) between TSCs and myelinating Schwann cells (MSCs). LPL, which includes lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), is the bioactive lipid that induces a myriad of cellular responses through specific members of G-protein coupled receptors for LPA. It turned out that LPA3 was expressed only in TSCs, whereas S1P1 was expressed in TSCs and skeletal muscle, but not in MSCs. Other types of LPL receptor genes, including LPA1, S1P2, S1P3, S1P4, were expressed in both types of Schwann cells. None of the LPL receptor gene family showed MSCs-specific expression.

  10. Small-cell Carcinomas of the Urinary Bladder and Prostate: TERT Promoter Mutation Status Differentiates Sites of Malignancy and Provides Evidence of Common Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial Carcinoma.

    Science.gov (United States)

    Priemer, David S; Wang, Mingsheng; Zhang, Shaobo; Lopez-Beltran, Antonio; Kouba, Erik; Montironi, Rodolfo; Davidson, Darrell D; MacLennan, Gregory T; Wang, Lisha; Osunkoya, Adeboye O; Deng, Youping; Emerson, Robert E; Cheng, Liang

    2017-03-31

    Small-cell carcinoma (SCC) of the urinary bladder frequently appears alongside urothelial carcinoma, suggesting common clonality. TERT promoter mutations have been recently implicated in urothelial carcinogenesis. To investigate the degree to which TERT promoter mutations are involved in SCC of the urinary bladder, the linked tumorigenesis between urothelial carcinoma and SCC of the urinary bladder, and the molecular distinctions between SCC of the urinary bladder and of the prostate. We investigated TERT promoter mutations in 53 cases of SCC of the urinary bladder and in 26 cases of SCC of the prostate using laboratory-based studies of tissue samples and clinical data. We measured the frequency of TERT promoter mutations in SCCs of the urinary bladder and prostate, and concordance of the mutation status between concurrent urinary bladder SCC and urothelial carcinoma. TERT promoter mutations were detected in 29/53 (55%) cases of urinary bladder and 0/26 (0%) cases of prostate SCC. Of 25 cases with concurrent urinary bladder SCC and non-small-cell components, all cases harbored identical TERT promoter mutation status in both phenotypes. TERT promoter mutations are found in more than half of urinary bladder SCCs. Mutation status is also identical in urothelial carcinoma and SCC components of concomitant malignancies, providing evidence of a common clonality. TERT promoter mutation status can differentiate SCC of the urinary bladder from prostate SCC, suggesting potential diagnostic use. Small-cell carcinoma of the urinary bladder shares a common clonal origin with conventional urothelial carcinoma and may arise from a heterogeneous subclone. TERT promoter mutations may have utility as a differential biomarker for determining the primary site of a genitourinary small-cell carcinoma. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  11. Malignant phyllodes breast tumor

    OpenAIRE

    Lisa R. Shah-Patel, MD

    2017-01-01

    Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  12. Malignant phyllodes breast tumor

    Directory of Open Access Journals (Sweden)

    Lisa R. Shah-Patel, MD

    2017-12-01

    Full Text Available Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  13. Malignant small round cell tumors

    Science.gov (United States)

    Rajwanshi, Arvind; Srinivas, Radhika; Upasana, Gautam

    2009-01-01

    Malignant small round cell tumors are characterised by small, round, relatively undifferentiated cells. They generally include Ewing's sarcoma, peripheral neuroectodermal tumor, rhabdomyosarcoma, synovial sarcoma, non-Hodgkin's lymphoma, retinoblastoma, neuroblastoma, hepatoblastoma, and nephroblastoma or Wilms’ tumor. Other differential diagnoses of small round cell tumors include small cell osteogenic sarcoma, undifferentiated hepatoblastoma, granulocytic sarcoma, and intraabdominal desmoplastic small round cell tumor. Differential diagnosis of small round cell tumors is particularly difficult due to their undifferentiated or primitive character. Tumors that show good differentiation are generally easy to diagnose, but when a tumor is poorly differentiated, identification of the diagnostic, morphological features is difficult and therefore, no definitive diagnosis may be possible. As seen in several study reports, fine needle aspiration cytology (FNAC) has become an important modality of diagnosis for these tumors. The technique yields adequate numbers of dissociated, viable cells, making it ideally suitable for ancillary techniques. Typically, a multimodal approach is employed and the principal ancillary techniques that have been found to be useful in classification are immunohistochemistry and immunophenotyping by flow cytometry, reverse transcriptase polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and electron microscopy. However, the recent characterization of chromosomal breakpoints and the corresponding genes involved in malignant small round cell tumors means that it is possible to use molecular genetic approaches for detection. PMID:21938141

  14. Vimentin 3, the new hope, differentiating RCC versus oncocytoma.

    Science.gov (United States)

    von Brandenstein, Melanie; Puetz, Katharina; Schlosser, Monika; Löser, Heike; Kallinowski, Joachim P; Gödde, Daniel; Buettner, Reinhard; Störkel, Stefan; Fries, Jochen W U

    2015-01-01

    Vimentin is currently used to differentiate between malignant renal carcinomas and benign oncocytomas. Recent reports showing Vimentin positive oncocytomas seriously question the validity of this present diagnostic approach. Vimentin 3 is a spliced variant and ends with a unique C-terminal ending after exon 7 which differentiates it from the full length version that has 9 exons. Therefore, the protein size is different; the full length Vimentin version has a protein size of ~57 kDa and the truncated version of ~47 kDa. We designed an antibody, called Vim3, against the unique C-terminal ending of the Vimentin 3 variant. Using immune histology, immune fluorescence, Western blot, and qRT-PCR analysis, a Vim3 overexpression was detectable exclusively in oncocytoma, making the detection of Vim3 a potential specific marker for benign kidney tumors. This antibody is the first to clearly differentiate benign oncocytoma and the mimicking eosinophilic variants of the RCCs. This differentiation between malignant and benign RCCs is essential for operative planning, follow-up therapy, and patients' survival. In the future the usage of Vimentin antibodies in routine pathology has to be applied with care. Consideration must be given to Vimentin specific binding epitopes otherwise a misdiagnosis of the patients' tumor samples may result.

  15. Vimentin 3, the New Hope, Differentiating RCC versus Oncocytoma

    Directory of Open Access Journals (Sweden)

    Melanie von Brandenstein

    2015-01-01

    Full Text Available Vimentin is currently used to differentiate between malignant renal carcinomas and benign oncocytomas. Recent reports showing Vimentin positive oncocytomas seriously question the validity of this present diagnostic approach. Vimentin 3 is a spliced variant and ends with a unique C-terminal ending after exon 7 which differentiates it from the full length version that has 9 exons. Therefore, the protein size is different; the full length Vimentin version has a protein size of ~57 kDa and the truncated version of ~47 kDa. We designed an antibody, called Vim3, against the unique C-terminal ending of the Vimentin 3 variant. Using immune histology, immune fluorescence, Western blot, and qRT-PCR analysis, a Vim3 overexpression was detectable exclusively in oncocytoma, making the detection of Vim3 a potential specific marker for benign kidney tumors. This antibody is the first to clearly differentiate benign oncocytoma and the mimicking eosinophilic variants of the RCCs. This differentiation between malignant and benign RCCs is essential for operative planning, follow-up therapy, and patients’ survival. In the future the usage of Vimentin antibodies in routine pathology has to be applied with care. Consideration must be given to Vimentin specific binding epitopes otherwise a misdiagnosis of the patients’ tumor samples may result.

  16. Side-to-side axial movements. Adding a new sign to the asymmetry of the clonic phase and asymmetric seizure termination in differentiating primary and secondarily generalised tonic-clonic seizures.

    Science.gov (United States)

    Franca, Sara; Gupta, Deepak K; Rao, Shyam; Pestana, Elia; Freitas, Joel; Loplumlert, Jakrin; Lhatoo, Samden D

    2014-03-01

    To study new semiological signs which help distinguish between primary and secondarily generalised tonic-clonic seizures (GTCS). We retrospectively studied 86 GTCS, 13 primary and 73 secondary, in 58 patients who underwent video-EEG (vEEG) evaluation in our epilepsy monitoring unit. Eleven patients had generalised epilepsy and 47 focal epilepsy. Two expert epileptologists, blinded to diagnosis, examined the vEEGs independently for the presence of five semiological signs. Asymmetry of limb movements in clonic phase, side-to-side axial movements, and asymmetric seizure termination occurred more frequently (pseizure semiology can help differentiate primary from secondary GTCS. The semiological sign of side-to-side axial movements, which has not previously been studied in this context, may add to existing literature of semiological signs and be of value for the evaluation of surgical patients in the epilepsy monitoring unit. In the out-patient setting, a clear history of these signs may help guide drug treatment choices.

  17. Hh-induced Smoothened conformational switch is mediated by differential phosphorylation at its C-terminal tail in a dose- and position-dependent manner.

    Science.gov (United States)

    Fan, Junkai; Liu, Yajuan; Jia, Jianhang

    2012-06-15

    The activation of Smoothened (Smo) requires phosphorylation at three clusters of Serine residues in Drosophila Hedgehog (Hh) signaling. However, the mechanism by which phosphorylation promotes Smo conformational change and subsequently activates Smo in response to Hh gradient remains unclear. Here, we show that the conformational states of Smo are determined by not only the amount but also the position of the negative charges provided by phosphorylation. By using a Smo phospho-specific antibody, we demonstrate that Smo is differentially phosphorylated at three clusters of serine residues in response to levels of Hh activity. Mutating the first cluster, compared to mutating the other clusters, impairs Smo activity more severely, whereas mutating the last cluster prohibits C-terminus dimerization. In addition, phosphorylation of the membrane proximal cluster promotes phosphorylation of the distal cluster. We propose a zipper-lock model in which the gradual phosphorylation at these clusters induces a gradual conformational change in the Smo cytoplasmic tail, which promotes the interaction between Smo and Costal2 (Cos2). Moreover, we show that Hh regulates both PKA and CK1 phosphorylation of Smo. Thus, the differential phosphorylation of Smo mediates the thresholds of Hh activity. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Advances in Optical Adjunctive Aids for Visualisation and Detection of Oral Malignant and Potentially Malignant Lesions

    Directory of Open Access Journals (Sweden)

    Nirav Bhatia

    2013-01-01

    Full Text Available Traditional methods of screening for oral potentially malignant disorders and oral malignancies involve a conventional oral examination with digital palpation. Evidence indicates that conventional examination is a poor discriminator of oral mucosal lesions. A number of optical aids have been developed to assist the clinician to detect oral mucosal abnormalities and to differentiate benign lesions from sinister pathology. This paper discusses advances in optical technologies designed for the detection of oral mucosal abnormalities. The literature regarding such devices, VELscope and Identafi, is critically analysed, and the novel use of Narrow Band Imaging within the oral cavity is also discussed. Optical aids are effective in assisting with the detection of oral mucosal abnormalities; however, further research is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant and malignant lesions.

  19. Impression cytology diagnosis of ulcerative eyelid malignancy.

    Science.gov (United States)

    Sen, S; Lyngdoh, A D; Pushker, N; Meel, R; Bajaj, M S; Chawla, B

    2015-02-01

    The utility of impression cytology in ocular diseases has predominantly been restricted to the diagnosis of dry eye, limbal stem cell deficiency and conjunctival neoplasias. Its role in malignant eyelid lesions remains largely unexplored. Although scrape cytology is more popular for cutaneous lesions, impression cytology, being non-traumatic, has an advantage in small and delicate areas such as the eyelid. The present study has been designed to evaluate its role in the diagnosis and management of malignant eyelid lesions. Thirty-two histopathologically proven malignant eyelid lesions diagnosed over a 2-year period, including 13 basal cell carcinomas, 11 sebaceous carcinomas, four squamous cell carcinomas, two malignant melanomas and two poorly differentiated carcinomas, formed the study group. The results of impression cytology were compared with those of histopathology in the study group and with an age- and sex-matched group of benign cases as controls. The sensitivity of impression cytology was 84% (27/32) for the diagnosis of malignancy and 28% (9/32) for categorization of the type of malignancy. Impression cytology is a simple, useful, non-invasive technique for the detection of malignant ulcerative eyelid lesions. It is especially useful as a follow-up technique for the detection of recurrences. © 2014 John Wiley & Sons Ltd.

  20. Terminal ballistics

    CERN Document Server

    Rosenberg, Zvi

    2016-01-01

    This book comprehensively discusses essential aspects of terminal ballistics, combining experimental data, numerical simulations and analytical modeling. Employing a unique approach to numerical simulations as a measure of sensitivity for the major physical parameters, the new edition also includes the following features: new figures to better illustrate the problems discussed; improved explanations for the equation of state of a solid and for the cavity expansion process; new data concerning the Kolsky bar test; and a discussion of analytical modeling for the hole diameter in a thin metallic plate impacted by a shaped charge jet. The section on thick concrete targets penetrated by rigid projectiles has now been expanded to include the latest findings, and two new sections have been added: one on a novel approach to the perforation of thin concrete slabs, and one on testing the failure of thin metallic plates using a hydrodynamic ram.

  1. Advances in diffuse malignant peritoneal mesothelioma

    Directory of Open Access Journals (Sweden)

    Tristan D. Yan

    2011-12-01

    Full Text Available Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. A great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated median survival of 40 to 90 months and 5-year survival of 30% to 60% after the combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This improvement in survival has prompted new searches into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade.

  2. Dynorphin 1-17 and Its N-Terminal Biotransformation Fragments Modulate Lipopolysaccharide-Stimulated Nuclear Factor-kappa B Nuclear Translocation, Interleukin-1beta and Tumor Necrosis Factor-alpha in Differentiated THP-1 Cells.

    Directory of Open Access Journals (Sweden)

    Siti Sarah Fazalul Rahiman

    Full Text Available Dynorphin 1-17, (DYN 1-17 opioid peptide produces antinociception following binding to the kappa-opioid peptide (KOP receptor. Upon synthesis and release in inflamed tissues by immune cells, DYN 1-17 undergoes rapid biotransformation and yields a unique set of opioid and non-opioid fragments. Some of these major fragments possess a role in immunomodulation, suggesting that opioid-targeted therapeutics may be effective in diminishing the severity of inflammatory disorders. This study aimed to examine the immunomodulatory effects of DYN 1-17 and major N-terminal fragments found in the inflammatory environment on nuclear factor-kappaB/p65 (NF-κB/p65 nuclear translocation and the release of interleukin-1beta (IL-1β and tumor necrosis factor-alpha (TNF-α from lipopolysaccharide (LPS-stimulated, differentiated THP-1 cells. The results demonstrate that NF-κB/p65 nuclear translocation was significantly attenuated following treatment with DYN 1-17 and a specific range of fragments, with the greatest reduction observed with DYN 1-7 at a low concentration (10 nM. Antagonism with a selective KOP receptor antagonist, ML-190, significantly reversed the inhibitory effects of DYN 1-17, DYN 1-6, DYN 1-7 and DYN 1-9, but not other DYN 1-17 N-terminal fragments (DYN 1-10 and 1-11 on NF-κB/p65 nuclear translocation. DYN 1-17 and selected fragments demonstrated differential modulation on the release of IL-1β and TNF-α with significant inhibition observed with DYN 1-7 at low concentrations (1 nM and 10 pM. These effects were blocked by ML-190, suggesting a KOP receptor-mediated pathway. The results demonstrate that DYN 1-17 and certain N-terminal fragments, produced in an inflamed environment, play an anti-inflammatory role by inhibiting NF-κB/p65 translocation and the subsequent cytokine release through KOP receptor-dependent and independent pathways.

  3. Topology of the C-terminal tail of HIV-1 gp41: differential exposure of the Kennedy epitope on cell and viral membranes.

    Directory of Open Access Journals (Sweden)

    Jonathan D Steckbeck

    2010-12-01

    Full Text Available The C-terminal tail (CTT of the HIV-1 gp41 envelope (Env protein is increasingly recognized as an important determinant of Env structure and functional properties, including fusogenicity and antigenicity. While the CTT has been commonly referred to as the "intracytoplasmic domain" based on the assumption of an exclusive localization inside the membrane lipid bilayer, early antigenicity studies and recent biochemical analyses have produced a credible case for surface exposure of specific CTT sequences, including the classical "Kennedy epitope" (KE of gp41, leading to an alternative model of gp41 topology with multiple membrane-spanning domains. The current study was designed to test these conflicting models of CTT topology by characterizing the exposure of native CTT sequences and substituted VSV-G epitope tags in cell- and virion-associated Env to reference monoclonal antibodies (MAbs. Surface staining and FACS analysis of intact, Env-expressing cells demonstrated that the KE is accessible to binding by MAbs directed to both an inserted VSV-G epitope tag and the native KE sequence. Importantly, the VSV-G tag was only reactive when inserted into the KE; no reactivity was observed in cells expressing Env with the VSV-G tag inserted into the LLP2 domain. In contrast to cell-surface expressed Env, no binding of KE-directed MAbs was observed to Env on the surface of intact virions using either immune precipitation or surface plasmon resonance spectroscopy. These data indicate apparently distinct CTT topologies for virion- and cell-associated Env species and add to the case for a reconsideration of CTT topology that is more complex than currently envisioned.

  4. Metastatic Malignant Melanoma With Complete Loss of Differentiation Markers (Undifferentiated/Dedifferentiated Melanoma): Analysis of 14 Patients Emphasizing Phenotypic Plasticity and the Value of Molecular Testing as Surrogate Diagnostic Marker.

    Science.gov (United States)

    Agaimy, Abbas; Specht, Katja; Stoehr, Robert; Lorey, Thomas; Märkl, Bruno; Niedobitek, Gerald; Straub, Melanie; Hager, Thomas; Reis, Anna-Carinna; Schilling, Bastian; Schneider-Stock, Regine; Hartmann, Arndt; Mentzel, Thomas

    2016-02-01

    Metastatic malignant melanoma is notorious for its phenotypic diversity and loss of differentiation markers. We herein summarized our experience with 14 metastatic melanomas showing complete loss of immunohistochemical melanocytic markers (with or without heterologous differentiation). Patients included 11 men and 3 women aged 24 to 78 years (median, 67 y). Thirteen patients had histologically confirmed primary skin melanoma, and 1 had metastatic melanoma of unknown primary. Undifferentiated metastasis was diagnosed synchronous to primary tumor (n=1), following skin melanoma by 3 months to 9 years (n=11) and preceding it by 1 year (n=1). Sites of undifferentiated metastases were axillary (3), inguinal (1), or submandibular (1) lymph nodes, digestive tract (2), bone/soft tissue (2), lung/pleura (2), and disseminated (n=3). Histology of metastases mimicked undifferentiated pleomorphic or spindle cell sarcoma with variable myxoid and giant cell areas (n=10) and cytokeratin-positive undifferentiated small cell sarcoma (n=1). Three cases showed heterologous dedifferentiation: pleomorphic rhabdomyosarcoma (n=1), teratocarcinosarcoma-like with prominent rhabdomyoblasts (n=1), and adenocarcinoma-like with metaplastic bone (n=1). All cases were negative for S100, melanoma cocktail, HMB45, Melan A, and SOX10. Other markers showed following results: smooth muscle actin (1/14), p16 (1/14), TP53 (2/12), pancytokeratin (4/14), desmin (5/14), h-caldesmon (0/9), and MDM2/CDK4 (0/5). SMARCB1 was intact in 8/8 cases. Genotyping showed BRAF(V600E) mutation (5/14), NRAS mutation (5/14), and BRAF/NRAS wild-type (4/14). In conclusion, undifferentiated/dedifferentiated metastatic melanoma is likely underrecognized and frequently mistaken for undifferentiated sarcoma or other neoplasms. Diagnosis of undifferentiated sarcoma at sites where melanoma metastasis are frequent (eg, inguinal and axillary region) should be made with great caution and warrants exploration of the remote history

  5. Aggressive malignant phyllodes tumor

    OpenAIRE

    Nathan Roberts; Dianne M. Runk

    2015-01-01

    Introduction: Originally described in 1838 by Muller, phyllodes tumor is a rare fibroepithelial neoplasm which represents roughly 0.3–0.9% of all breast cancers. Phyllodes tumor are divided into benign, borderline and malignant histologic categories. Malignant phyllodes tumor represent anywhere from 10–30% of all phyllodes tumors. This group has both the potential to recur locally and metastasize, however not all malignant phyllodes behave this way. The challenge lays in predicting which tumo...

  6. Clustered microcalcifications without mass on mammography : benignancy vs. malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yoon Hee; Do, Young Soo; Oh, Hoon Il; Kim, Ki Hwan; Chin, Soo Yil [Korean Cancer Center Hostpital, Seoul (Korea, Republic of); Cho, Byung Jae [Chung Dam Radiologic Clinics, Seoul (Korea, Republic of); Han, Heon [Chungang Gil Hospital, Seoul (Korea, Republic of); Choi, Yeun Hyeun; Han, Boo Kyung [Sam Sung Medical Center, Seoul (Korea, Republic of); Park, Jung Mi [Asan Medical Center, Seoul (Korea, Republic of)

    1996-11-01

    The purpose of this study is to evaluate the accuracy of differentiation between benign and malignant clustered microcalcifications without mass on mammogram. Fourty six mammograms of 44 patients showing clustered microcalcifications without mass were interpreted blindly by five independent observers majoring in breast imaging from different institutions. Twenty two were malignant (10 infiltrating ductal carcinomas, 12 intraductal carcinomas) and 24 were benign (all fibrocystic disease). The observers judge benignancy or malignancy of microcalcifications. The authors assess the accuracy of differential diagnosis of clustered microcalcifications. Of 24 cases proved benign microcalcifications, five radiologists correctly interpreted 20 on average as benign and of malignant 22 cases, 16 on average were correctly interpreted as malignant. The diagnostic accuracy of malignant microcalcifications was 71.8% on average(63.6%{approx}81.8%) and the diagnostic accuracy for benign microcalcifications was 83% on average(71%{approx}92%). It was 9 among total 46 cases that were misinterpreted by more than three radiologists. Among these 9 cases, malignant microcalcifications that had been misinterpreted as benign were seven, benign microcalcifications misinterpreted as malignant were two. The diagnostic accuracy of clustered malignant microcalcifications(71.8%) without mass on mammogram was lower than that of benign microcalcifications(83.3%). So, in case of suspected malignant microcalcification on mammogram, it is preferable that along with magnification view, histopathologic confirmation by core biopsy must be obtained.

  7. Infarcted Tarsal Pyogenic Granuloma Simulating Malignant Melanoma.

    Science.gov (United States)

    Charles, Norman C; Kahn, Jonathan B

    The authors describe a rapidly enlarging, pedunculated brown tarsal lesion in a 34-year-old man with a history of chalazia. Following excision, histopathologic analysis showed the features of a necrotic pyogenic granuloma. This unique case expands the differential diagnosis of conjunctival malignant melanoma.

  8. Ovarian Thecoma with Meigs Syndrome Mimicking Malignancy in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Chun-Chieh Chia

    2005-12-01

    Conclusion: Meigs syndrome is not uncommon in gynecology. The clinical signs and symptoms, and imaging and laboratory findings may not sufficiently differentiate Meigs syndrome from malignancy. An exploratory laparotomy is essential for the final diagnosis of this syndrome.

  9. Role of fibulin-3 in the diagnosis of malignant mesothelioma

    Directory of Open Access Journals (Sweden)

    Mohammed A. Agha

    2014-01-01

    Conclusions: Fibulin-3 in the serum and pleural fluid is a good biomarker in the diagnosis of MPM and in differentiation between MPM from malignant pleural metastasis other than mesothelioma and also from benign pleural effusions.

  10. Malignant vasovagal syndrome?

    Science.gov (United States)

    Kala, G K; Lee, C; Coatesworth, A P

    2004-01-01

    We present the management of a patient with nasopharyngeal carcinoma with a history of recurrent syncopal attacks diagnosed as malignant vasovagal syndrome. We discuss clinical presentation as well as the resolution of disease symptoms. The importance of metastatic nasopharyngeal malignancy in relation to syncope is discussed.

  11. BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

    Energy Technology Data Exchange (ETDEWEB)

    Goupille, Olivier [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Penglong, Tipparat [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Lefevre, Carine; Granger, Marine; Kadri, Zahra [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Fucharoen, Suthat [Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Maouche-Chretien, Leila [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Leboulch, Philippe [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Genetics Division, Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Chretien, Stany, E-mail: stany.chretien@cea.fr [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer UT7 erythroleukemia cells are known to be refractory to differentiate. Black-Right-Pointing-Pointer Brief JQ1 treatment initiates the first steps of erythroid differentiation program. Black-Right-Pointing-Pointer Engaged UT7 cells then maturate in the presence of erythropoietin. Black-Right-Pointing-Pointer Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

  12. Malignancy-Induced Hypercalcemia—Diagnostic Challenges

    Directory of Open Access Journals (Sweden)

    Claire Hoyoux

    2017-11-01

    Full Text Available Hypercalcemia in children is a rare metabolic finding. The clinical picture is usually non-specific, and the etiology includes several entities (metabolic, nutritional, drug-induced, inflammatory, cancer-associated, or genetic depending on the age at presentation, but severe hypercalcemia is associated mainly with malignancy in childhood and sepsis in neonates. Severe parathyroid hormone (PTH-suppressed hypercalcemia is challenging and requires multidisciplinary diagnostic and therapeutic approaches to (i confirm or rule out a malignant cause, (ii treat it and its potentially dangerous complications. We report a case of severe and complicated PTH-independent hypercalcemia in a symptomatic 3-year-old boy. His age, severity of hypercalcemia and its complicated course, and the first imaging reports were suggestive of malignancy. The first bone and kidney biopsies and bone marrow aspiration were normal. The definitive diagnosis was a malignant-induced hypercalcemia, and we needed 4 weeks to assess other differential diagnoses and to confirm, on histopathological and immunochemical base, the malignant origin of hypercalcemia. Using this case as an illustrative example, we suggest a diagnostic approach that underlines the importance of repeated histology if the clinical suspicion is malignancy-induced hypercalcemia. Effective treatment is required acutely to restore calcium levels and to avoid complications.

  13. O uso da difusão por ressonância magnética na diferenciação das lesões mamárias benignas e malignas The use of diffusion-weighted magnetic resonance imaging in the differentiation between benign and malignant breast lesions

    Directory of Open Access Journals (Sweden)

    Fernanda Philadelpho Arantes Pereira

    2009-10-01

    Full Text Available OBJETIVO: Estudar a utilidade da sequência pesada em difusão na diferenciação das lesões mamárias benignas e malignas. MATERIAIS E MÉTODOS: Quarenta e cinco mulheres (idade média de 46,1 anos com 52 nódulos de mama foram submetidas a ressonância magnética acrescida da sequência difusão. O coeficiente de difusão aparente (ADC foi calculado através do mapa de ADC obtido pelo uso de cinco valores de b (0, 250, 500, 750 e 1.000 s/mm². O valor de ADC médio de cada lesão foi correlacionado com achados de imagem e resultados histopatológicos. Valores de ADC de corte, sensibilidade e especificidade da sequência difusão na diferenciação das lesões benignas e malignas foram calculados. P OBJECTIVE: To study the utility of diffusion-weighted magnetic resonance imaging in the differentiation between benign and malignant breast lesions. MATERIALS AND METHODS: Forty-five women (mean age, 46.1 years with 52 focal breast lesions underwent diffusionweighted magnetic resonance imaging. The calculation of apparent diffusion coefficient (ADC was based on the ADC map reflecting five b values (0, 250, 500, 750, and 1000 s/mm². The mean ADC value of each lesion was correlated with imaging findings and histopathologic results. Cutoff ADC, sensitivity and specificity of diffusion-weighted imaging in the differentiation between benign and malignant lesions were calculated. P < 0.05 was considered as statistically significant. RESULTS: The mean ADC was significantly lower for malignant lesions (0.92 ± 0.26 × 10-3 mm²/s as compared with benign lesions (1.50 ± 0.34 × 10-3 mm²/s (P < 0.0001. Diffusion-weighted imaging showed high sensitivity and specificity (both, 92.3% in the differentiation between benign and malignant lesions. CONCLUSION: Diffusion-weighted imaging is a potential resource as an adjuvant to breast magnetic resonance imaging to differentiate benign from malignant lesions. Such sequence can be easily added to the standard

  14. Positron emission tomography-computed tomography and 4-hydroxynonenal-histidine immunohistochemistry reveal differential onset of lipid peroxidation in primary lung cancer and in pulmonary metastasis of remote malignancies.

    Science.gov (United States)

    Živković, Nevenka Piskač; Petrovečki, Mladen; Lončarić, Čedna Tomasović; Nikolić, Igor; Waeg, Georg; Jaganjac, Morana; Žarković, Kamelija; Žarković, Neven

    2017-04-01

    The Aim of the study was to reveal if PET-CT analysis of primary and of secondary lung cancer could be related to the onset of lipid peroxidation in cancer and in surrounding non-malignant lung tissue. Nineteen patients with primary lung cancer and seventeen patients with pulmonary metastasis were involved in the study. Their lungs were analyzed by PET-CT scanning before radical surgical removal of the cancer. Specific immunohistochemistry for the major bioactive marker of lipid peroxidation, 4-hydroxynonenal (HNE), was done for the malignant and surrounding non-malignant lung tissue using genuine monoclonal antibody specific for the HNE-histidine adducts. Both the intensity of the PET-CT analysis and the HNE-immunohistochemistry were in correlation with the size of the tumors analyzed, while primary lung carcinomas were larger than the metastatic tumors. The intensity of the HNE-immunohistochemistry in the surrounding lung tissue was more pronounced in the metastatic than in the primary tumors, but it was negatively correlated with the cancer volume determined by PET-CT. The appearance of HNE was more pronounced in non-malignant surrounding tissue than in cancer or stromal cells, both in case of primary and metastatic tumors. Both PET-CT and HNE-immunohistochemistry reflect the size of the malignant tissue. However, lipid peroxidation of non-malignant lung tissue in the vicinity of cancer is more pronounced in metastatic than in primary malignancies and might represent the mechanism of defense against cancer, as was recently revealed also in case of human liver cancer. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Malignant Triton Tumor of the Sciatic Nerve as a Secondary Malignancy after Extended Field Radiotherapy and Chemotherapy of Hodgkin's Disease

    Directory of Open Access Journals (Sweden)

    Mirko Nitsche

    2014-03-01

    Full Text Available Late effects of therapy for Hodgkin's disease include secondary malignancies like leukemia, lymphoma or solid tumors developing after long periods of latency. Ionizing radiation often causes the last group. The highest risks have been described for induced breast and lung cancers. We are the first to report a malignant triton tumor (MTT as a secondary malignancy after radiotherapy and chemotherapy for Hodgkin's lymphoma. MTT is a very rare subtype of malignant peripheral nerve sheath tumors with rhabdomyoblastic differentiation and an aggressive course of disease.

  16. Intravoxel incoherent motion diffusion-weighted imaging as an adjunct to dynamic contrast-enhanced MRI to improve accuracy of the differential diagnosis of benign and malignant breast lesions.

    Science.gov (United States)

    Ma, Dejing; Lu, Feng; Zou, Xuexue; Zhang, Hu; Li, Yangyang; Zhang, Lin; Chen, Liang; Qin, Dongjing; Wang, Bin

    2017-02-01

    To investigate the value of use of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) as an adjunct to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to distinguish benign from malignant breast lesions. Retrospective analysis of data pertaining to 117 patients with breast lesions who underwent DCE-MRI and IVIM-DWI examination with 3.0T MRI was conducted. A total of 128 lesions were pathologically confirmed (47 benign and 81 malignant). Between-group differences in DCE-MRI parameters (Morphology, enhancement pattern, maximum slope of increase (MSI) and time-signal curve (TIC) type) and IVIM-DWI parameters (f value, D value and D* value) were assessed. Multivariate logistic regression was performed to identify variables that distinguished benign from malignant breast lesions. The diagnostic performance of DCE-MRI and DCE-MRI plus IVIM-DWI, to distinguish benign from malignant breast lesions, was evaluated using pathology results as the gold standard. Lesion morphology, MSI, and TIC type (P0.05), were significantly different between the benign and malignant groups. The f (8.53±2.14) and D* (7.64±2.07) values in the malignant group were significantly higher than those in the benign group (7.68±1.97 and 6.83±2.13, respectively), while the D value (0.99±0.22) was significantly lower than that (1.34±0.17) in the benign group (Pbreast. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Large fibroadenoma mimicking malignancy

    African Journals Online (AJOL)

    Enrique

    looking features that can mimic malignancy. ... breast. Due to the fact that there was a positive family history of breast carci- noma and the mass ... Histological diagnosis confirmed a fibroadenoma. ... texture with regular, lobulated or irregular ...

  18. Stages of Malignant Mesothelioma

    Science.gov (United States)

    ... malignant mesothelioma, and may also be used as palliative therapy to relieve symptoms and improve quality of life . ... and decortication , with or without radiation therapy , as palliative therapy to relieve symptoms and improve quality of life . ...

  19. Chromatin condensation during terminal erythropoiesis.

    Science.gov (United States)

    Zhao, Baobing; Yang, Jing; Ji, Peng

    2016-09-02

    Mammalian terminal erythropoiesis involves gradual but dramatic chromatin condensation steps that are essential for cell differentiation. Chromatin and nuclear condensation is followed by a unique enucleation process, which is believed to liberate more spaces for hemoglobin enrichment and enable the generation of a physically flexible mature red blood cell. Although these processes have been known for decades, the mechanisms are still unclear. Our recent study reveals an unexpected nuclear opening formation during mouse terminal erythropoiesis that requires caspase-3 activity. Major histones, except H2AZ, are partially released from the opening, which is important for chromatin condensation. Block of the nuclear opening through caspase inhibitor or knockdown of caspase-3 inhibits chromatin condensation and enucleation. We also demonstrate that nuclear opening and histone release are cell cycle regulated. These studies reveal a novel mechanism for chromatin condensation in mammalia terminal erythropoiesis.

  20. Aggressive malignant phyllodes tumor.

    Science.gov (United States)

    Roberts, Nathan; Runk, Dianne M

    2015-01-01

    Originally described in 1838 by Muller, phyllodes tumor is a rare fibroepithelial neoplasm which represents roughly 0.3-0.9% of all breast cancers. Phyllodes tumor are divided into benign, borderline and malignant histologic categories. Malignant phyllodes tumor represent anywhere from 10-30% of all phyllodes tumors. This group has both the potential to recur locally and metastasize, however not all malignant phyllodes behave this way. The challenge lays in predicting which tumor will recur locally or metastasize. Distinguishing this subset of malignant phyllodes tumor is paramount. We present a case of malignant phyllodes which presented with metastatic disease. What is fascinating about this case is not only the initial presentation but also the aggressiveness of this variation of phyllodes tumor. The patient initially presented with a large mass which encompassed her whole right breast. On surgical pathology the mass measured roughly 31cm in diameter and weighed over 10kg. Within 5 weeks from surgery the patient had suffered brain metastases and also 6 local recurrent tumors. The patient passed roughly 11 weeks after her first visit to our office. Despite biopsy proven malignant phyllodes tumor, it was near impossible to predict such a rapid course of disease progression in our patient. Our case illustrates the unpredictable nature of this disease in general and it possibly sheds light on a variant of the disease which had undergone an aggressive transformation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. The case of malignancy mimicking legionella pneumonia

    Directory of Open Access Journals (Sweden)

    Ali Karakuş

    2013-09-01

    Full Text Available Legionella pneumophila is a bacterium, which can grow inwater pipe networks and climate systems. Contaminationoccurs by aspiration of infected water or aerosol inhalation.It is usually presented with fever, bradycardia, andchange in mental status, hyponatremia, elevation of liverenzymes and deterioration of renal function. The definitediagnosis is established by detection of the antigens andcultivating in the culture medium. Also, malign lung tumorscan encounter with the same clinical findings, so lungcancer should be remembered in differential diagnosis.The patient hospitalized for the Legionella pneumophiladue to the physical examination and laboratory findingsduring the first evaluation in the emergency department.However, further examinations pointed to the cancer. Weaimed to emphasize the probability of malignant tumorsin terms of hyponatremia, increase in the liver enzymes,and failure in the renal functions, which were usually experiencedin emergency unit. J Clin Exp Invest 2013; 4(3: 390-392Key words: Legionella pneumophila, pneumonia, lung malignancy

  2. Clinician's Update on the Benign, Premalignant, and Malignant Skin Tumours of the Vulva

    DEFF Research Database (Denmark)

    Sand, Freja Lærke; Thomsen, Simon Francis

    2017-01-01

    Correct and rapid diagnosis of skin tumours often requires biopsy and histopathological examination to differentiate benign lesions such as seborrhoeic keratoses or melanocytic naevi from premalignant and malignant lesions such as malignant melanoma. Particularly, to the untrained eye, any benign...... skin tumour-pigmented or nonpigmented-is easily mistaken for a malignant lesion. Qualified clinical evaluation is paramount in order to reduce the frequency of unwarranted skin biopsies. Herein, the most common benign, premalignant, and malignant vulvar skin tumours are reviewed....

  3. Unusual malignant solid neoplasms of the kidney: Cross-sectional imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Karaosmanoglu, Ali Devrim; Hahn, Peter F. [Dept. of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston (United States); Shirkhoda, Ali [Dept. of Radiology, University of California School of Medicine, Irvine (United States); Onur, Mehmet Ruhi; Ozmen, Mustafa [Dept. of Radiology, University of Hacettepe School of Medicine, Ankara (Turkmenistan)

    2015-08-15

    Malignant kidney neoplasms are the most frequently encountered solid kidney masses. Although renal cell carcinoma is the major renal malignancy, other solid malignant renal masses should be considered in the differential diagnosis of solid renal masses that do not contain a macroscopic fatty component. In this pictorial essay, we present the imaging findings of a primitive neuroectodermal tumor, primary liposarcoma of the kidney, primary neuroendocrine tumor, leiomyosarcoma, synovial sarcoma, malignant fibrous histiocytoma, sclerosing fibrosarcoma and renal metastasis of osteosarcoma.

  4. Giant hydronephrosis mimicking progressive malignancy

    Directory of Open Access Journals (Sweden)

    Heidenreich Axel

    2003-10-01

    Full Text Available Abstract Background Cases of giant hydronephroses are rare and usually contain no more than 1–2 litres of fluid in the collecting system. We report a remarkable case of giant hydronephrosis mimicking a progressive malignant abdominal tumour. Case presentation A 78-year-old cachectic woman presented with an enormous abdominal tumour, which, according to the patient, had slowly increased in diameter. Medical history was unremarkable except for a hysterectomy >30 years before. A CT scan revealed a giant cystic tumour filling almost the entire abdominal cavity. It was analysed by two independent radiologists who suspected a tumour originating from the right kidney and additionally a cystic ovarian neoplasm. Subsequently, a diagnostic and therapeutic laparotomy was performed: the tumour presented as a cystic, 35 × 30 × 25 cm expansive structure adhesive to adjacent organs without definite signs of invasive growth. The right renal hilar vessels could finally be identified at its basis. After extirpation another tumourous structure emerged in the pelvis originating from the genital organs and was also resected. The histopathological examination revealed a >15 kg hydronephrotic right kidney, lacking hardly any residual renal cortex parenchyma. The second specimen was identified as an ovary with regressive changes and a large partially calcified cyst. There was no evidence of malignant growth. Conclusion Although both clinical symptoms and the enormous size of the tumour indicated malignant growth, it turned out to be a giant hydronephrosis. Presumably, a chronic obstruction of the distal ureter had caused this extraordinary hydronephrosis. As demonstrated in our case, an accurate diagnosis of giant hydronephrosis remains challenging due to the atrophy of the renal parenchyma associated with chronic obstruction. Therefore, any abdominal cystic mass even in the absence of other evident pathologies should include the differential diagnosis of a

  5. Urological malignancies in Port Harcourt, Nigeria: a 14-year review ...

    African Journals Online (AJOL)

    Background: Urological malignancies are complex, covering the urinary system in both sexes and the genital system of males. They are common in this setting and posing a lot of problems to the patients. In most cases, the disease terminates in the death of the patient. Aim: To study the pattern and frequency of urological ...

  6. Management of malignant pleural effusions.

    LENUS (Irish Health Repository)

    Uzbeck, Mateen H

    2010-06-01

    Malignant pleural effusions are a common clinical problem in patients with primary thoracic malignancy and metastatic malignancy to the thorax. Symptoms can be debilitating and can impair tolerance of anticancer therapy. This article presents a comprehensive review of pharmaceutical and nonpharmaceutical approaches to the management of malignant pleural effusion, and a novel algorithm for management based on patients\\' performance status.

  7. Simulants of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Gérald E. Piérard

    2015-08-01

    Full Text Available During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN of the skin. Beyond this clinical procedure, AMN histopathology remains mandatory for establishing their precise diagnosis. Of note, panels of experts in AMN merely report moderate agreement in various puzzling cases. Divergences in opinion and misdiagnosis are likely increased when histopathological criteria are not fine-tuned and when facing a diversity of AMN types. Furthermore, some AMN have been differently named in the literature including atypical Spitz tumor, metastasizing Spitz tumor, borderline and intermediate melanocytic tumor, malignant Spitz nevus, pigmented epithelioid melanocytoma or animal-type melanoma. Some acronyms have been further suggested such as MELTUMP (after melanocytic tumor of uncertain malignant potential and STUMP (after Spitzoid melanocytic tumor of uncertain malignant potential. In this review, such AMN at the exclusion of cutaneous malignant melanoma (MM variants, are grouped under the tentative broad heading skin melanocytoma. Such set of AMN frequently follows an indolent course, although they exhibit atypical and sometimes worrisome patterns or cytological atypia. Rare cases of skin melanocytomas progress to loco regional clusters of lesions (agminate melanocytomas, and even to regional lymph nodes. At times, the distinction between a skin melanocytoma and MM remains puzzling. However, multipronged immunohistochemistry and emerging molecular biology help profiling any malignancy risk if present.

  8. Malignancy following kidney transplantation.

    Science.gov (United States)

    Arichi, N; Kishikawa, H; Nishimura, K; Mitsui, Y; Namba, Y; Tokugawa, S; Ichikawa, Y

    2008-09-01

    A cohort of 429 patients who received kidney grafts between 1973 and 2007 at our hospital was studied for the incidence and sites of malignancy. Sixty-two malignant diseases developed in 57 of 429 patients (13.3%). The cumulative incidences of malignancy increased markedly in the second and third posttransplantation decades. The overall rates were 1.8% at 5 years, 6.7% at 10 years, 12.5% at 15 years, 17.3% at 20 years, and 25.6% at 25 years. In the second and third posttransplantation decades, patients without malignancy showed significantly superior survival versus than those with cancer (P = .0002). Their survival rates were 83.4% versus 86.9% at 10 years and 63.1% versus 80.3% at 20 years, respectively. Skin cancer, renal cell carcinoma of the native kidney, hepatocellular carcinoma, posttransplantation lymphoproliferative disease, uterine cancer, and colorectal cancer were common in our series. The 5-year survival rates after the treatment of malignancy were better for skin cancer and renal cell carcinoma of the native kidney. Concerning the effects of immunosuppression, the tacrolimus-based group displayed a higher incidence among 3 groups (P = .0044).

  9. Cystic partially differentiated nephroblastoma.

    Science.gov (United States)

    Puvaneswary, M; Macintosh, J; Cassey, J

    2006-06-01

    Cystic partially differentiated nephroblastoma is a relatively rare tumour of the kidney usually affecting infants. Cystic Wilms' tumour and multilocular cystic nephroma should be distinguished from cystic partially differentiated nephroblastoma. Multilocular cystic nephroma is a benign tumour whereas cystic Wilms' tumour is at the malignant end of the range of classification of such tumours. Cystic partially differentiated nephroblastoma may undergo local recurrence but there is no report of metastasis.

  10. Differential effect of shear stress on extracellular signal-regulated kinase and N-terminal Jun kinase in endothelial cells. Gi2- and Gbeta/gamma-dependent signaling pathways.

    Science.gov (United States)

    Jo, H; Sipos, K; Go, Y M; Law, R; Rong, J; McDonald, J M

    1997-01-10

    Shear stress differentially regulates production of many vasoactive factors at the level of gene expression in endothelial cells that may be mediated by mitogen-activated protein kinases, including extracellular signal-regulated kinase (ERK) and N-terminal Jun kinase (JNK). Here we show, using bovine aortic endothelial cells (BAEC), that shear stress differentially regulates ERK and JNK by mechanisms involving Gi2 and pertussis toxin (PTx)-insensitive G-protein-dependent pathways, respectively. Shear activated ERK with a rapid, biphasic time course (maximum by 5 min and basal by 30-min shear exposure) and force dependence (minimum and maximum at 1 and 10 dyn/cm2 shear stress, respectively). PTx treatment prevented shear-dependent activation of ERK1/2, consistent with a Gi-dependent mechanism. In contrast, JNK activity was maximally turned on by a threshold level of shear force (0.5 dyn/cm2 or higher) with a much slower and prolonged time course (requiring at least 30 min to 4 h) than that of ERK. Also, PTx had no effect on shear-dependent activation of JNK. To further define the shear-sensitive ERK and JNK pathways, vectors expressing hemagglutinin epitope-tagged ERK (HA-ERK) or HA-JNK were co-transfected with other vectors by using adenovirus-polylysine in BAEC. Expression of the mutant (alpha)i2(G203), antisense G(alpha)i2 and a dominant negative Ras (N17Ras) prevented shear-dependent activation of HA-ERK, while that of (alpha)i2(G204) and antisense (alpha)i3 did not. Expression of a Gbeta/gamma scavenger, the carboxyl terminus of beta-adrenergic receptor kinase (betaARK-ct), and N17Ras inhibited shear-dependent activation of HA-JNK. Treatment of BAEC with genistein prevented shear-dependent activation of ERK and JNK, indicating the essential role of tyrosine kinase(s) in both ERK and JNK pathways. These results provide evidence that 1) Gi2-protein, Ras, and tyrosine kinase(s) are upstream regulators of shear-dependent activation of ERK and 2) that shear

  11. Immunotherapy of Genitourinary Malignancies

    Directory of Open Access Journals (Sweden)

    Teruo Inamoto

    2012-01-01

    Full Text Available Most cancer patients are treated with some combination of surgery, radiation, and chemotherapy. Despite recent advances in local therapy with curative intent, chemotherapeutic treatments for metastatic disease often remain unsatisfying due to severe side effects and incomplete long-term remission. Therefore, the evaluation of novel therapeutic options is of great interest. Conventional, along with newer treatment strategies target the immune system that suppresses genitourinary (GU malignancies. Metastatic renal cell carcinoma and non-muscle-invasive bladder caner represent the most immune-responsive types of all human cancer. This review examines the rationale and emerging evidence supporting the anticancer activity of immunotherapy, against GU malignancies.

  12. Rheumatologic Manifestations of Malignancy.

    Science.gov (United States)

    Hashefi, Mandana

    2017-02-01

    A variety of conditions mimicking rheumatologic syndromes may be associated with an underlying malignancy. Therefore, distinguishing these syndromes from more common, nonparaneoplastic rheumatologic conditions can be perplexing. Some autoimmune conditions and the medications used for their management can be associated with increased future risk of malignancy. Some cancers can directly involve the musculoskeletal structures, whereas others present with systemic manifestations at sites away from the tumor and its metastases. Better awareness and timely recognition of these associations may lead to earlier cancer detection and hopefully better long-term survival. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Productive lifecycle of human papillomaviruses that depends upon squamous epithelial differentiation.

    Directory of Open Access Journals (Sweden)

    Naoko eKajitani

    2012-04-01

    Full Text Available The target of human papillomaviruses (HPVs is stratified epidermis, and the infection causes diseases ranging from benign condylomas to malignant tumors. Infection of HPVs in genital tracts is one of common sexually transmitted infections, and is a major risk factor of cervical cancer. The infection of HPV targets the epithelial cells in the basal layer of epithelium, while progeny virions egress from terminally differentiated cells in the cornified layer, most surface layer of epithelium. In the infected basal cells, viruses maintain their genome DNAs at low copy number, where their productive lifecycle cannot proceed. Progression of viral productive lifecycle requires differentiation of the host cell, indicating there is tight crosstalk between viral replication and host differentiation programs. In this review, we discuss the regulation of the HPV lifecycle controlled by the differentiation program of the host cells.

  14. Intermodal freight terminals : terminal business planning

    NARCIS (Netherlands)

    Nijkamp, Peter; Wiegmans, Bart W.

    2000-01-01

    The main purpose of this paper is to provide a framework for existing- and newly proposedinter-modal freight terminals in their business planning process. This framework is importantfor constructing- and improving the central terminal service portfolio of handling (loading,discharging, and

  15. Quantification of the magnetization-transfer contrast effect: can it yield additional information in differentiation of musculoskeletal lesions particularly in separation of benign from malignant lesions; Quantifizierung des Magnetization Transfer Contrast (MTC) Effektes durch Berechnung von MT-Quotienten: Ergeben sich Zusatzinformationen fuer die Differenzierung benigner und maligner Erkrankungen des Bewegungsapparates?

    Energy Technology Data Exchange (ETDEWEB)

    Vahlensieck, M.; Traeber, F.; Schild, H. [Radiologische Universitaetsklinik Bonn (Germany); Gieseke, J. [Philips Medizinsysteme (Germany)

    1999-12-01

    Purpose: To investigate the potential information of the amount of magnetization-transfer effect in musculoskeletal lesions and to compare MT ratios from benign and malignant musculoskeletal lesions. Material and Method: 49 patients with malignant tumors (3 osteosarcoma, 3 malignant fibrous histiocytoma, 4 chondrosarcoma, 2 Ewing sarcomas) and benign lesions (8 chondroma, 2 fibrous dysplasia, 3 osteoid-osteoma, 6 ganglion cyst, 3 cyst, 3 osteomyelitis, 4 tendinitis, 3 rotator cuff tear, 5 scar tissue) were scanned using routine MRI protocols including T{sub 1}- and T{sub 2}-weighted spin echo as well as T{sub 2}*-weighted gradient echo (FFE) sequences at 1.5 Tesla (ACS II, Philips Medical). Additionally MTC images were generated by combining the FFE sequence and the off-resonance MT technique (-1500 Hz off-resonance frequency, 1770 flip angle and 50 ms pulse duration). MT ratios were calculated as SI{sub o}-SI{sub m}/SI{sub o}. Results: The MT ratio of benign lesions was 26{+-}15%, that of malignant lesions was 22{+-}6%. The difference was statistically not significant. As expected muscle showed a high MT ratio of 50{+-}8%. Scar tissue demonstrated an MT ratio of 39{+-}16% which was significantly higher than the tumor MT ratios. Conclusion: MTC (MT ratios) failed to show significant differences between benign and malignant lesions as was expected due to basic differences in cellularity, rate of mitosis and chromatin content. MTC might however gain more importance in separating scar tissue from recurrent tumor in the future. (orig.) [German] Zielsetzung: Durch die Quantifizierung des Magnetization Transfer Contrastes sollte untersucht werden, ob sich Zusatzinformationen in der Magnetresonanztomographie des Stuetz- und Bewegungsapparates ergeben. Insbesondere sollte ermittelt werden, ob gut- und boesartige Laesionen unterschiedliche MT-Quotienten aufweisen. Material und Methode: 49 Patienten mit boesartigen Tumoren (3 Osteosarkom, 4 Chondrosarkom, 3 Malignes

  16. Angiogenesis in malignant lymphoma.

    NARCIS (Netherlands)

    Koster, A.; Raemaekers, J.M.M.

    2005-01-01

    PURPOSE OF REVIEW: Angiogenesis plays an important role in the pathophysiology of both solid tumors and hematologic malignancies. Angiogenesis-associated parameters are important prognosticators, and tumor blood vessels are an emerging target for therapy. This review addresses the evidence of the

  17. Aggressive malignant phyllodes tumor

    Directory of Open Access Journals (Sweden)

    Nathan Roberts

    2015-01-01

    Conclusion: Despite biopsy proven malignant phyllodes tumor, it was near impossible to predict such a rapid course of disease progression in our patient. Our case illustrates the unpredictable nature of this disease in general and it possibly sheds light on a variant of the disease which had undergone an aggressive transformation.

  18. Susceptibility to malignant hyperthermia

    NARCIS (Netherlands)

    Snoeck, Marcus Matheus Johannes

    2004-01-01

    In this thesis the author studied the diagnostic procedures for susceptibility to malignant hyperthermia (MH), with special emphasis upon refining the biological diagnostic test and improving protocols and guidelines for investigation of MH susceptibility. MH is a pharmacogenetic disease of skeletal

  19. Trauma - the malignant epidemic

    African Journals Online (AJOL)

    life are lost annually from trauma than malignant disease, heart disease, and AIDS combined, and by the ... diffused and rapidly spreading condition affecting many people in anyone region at the same time and tending ... upon inadequate and overcrowded methods of transportation. TABLE I. INTERPERSONAL VIOLENCE ...

  20. Role of DR-70 immunoassay in suspected malignant pleural effusion

    Science.gov (United States)

    Sengupta, Amitabha; Saha, Kaushik; Jash, Debraj; Banerjee, Sourindra Nath; Biswas, Nirendra Mohan; Dey, Atin

    2013-01-01

    Context: A good proportion of patients with undiagnosed pleural effusion (PE) turn into malignancy over a period of time. Identification of positive biomarker may help in selecting the individuals who require close follow-up. Aims: The aims of this study were to evaluate the role of DR-70 immunoassay in suspected malignant PE. Settings and Design: We conducted a cross-sectional study among 89 patients of suspected malignant PE and 50 normal subjects (NS) were taken as control. Materials and Methods: Patients with exudative PE; who had pleural fluid lymphocyte count greater than 50% and adenosine deaminase less than 30 U/L were taken as cases. We had selected NSs among relatives of patients having normal blood chemistry and radiological investigations. Sensitivity and specificity of the test to differentiate malignant and non-malignant PE and also to identify PE with underlying malignancy was analyzed. Results: Mean value of DR-70 in NS was found to be 0.83 ± 0.273 mg/L without any significant difference between males (0.82 mg/L) and females (0.85 mg/L). Mean value of DR-70 in PE with underlying cancer was 5.03 ± 3.79 mg/L. Sensitivity (80%) and specificity (77.78%) of the test was maximum in PE with underlying cancer using cut-off value of 2 mg/L. Mean value DR-70 in malignant PE was 5.18 ± 3.75 mg/L and in non-malignant PE was 3.73 ± 3.74 mg/L without any statistically significant difference (P = 0.08). Conclusions: DR-70 assay has high sensitivity in detecting underlying lung cancer, but has no role in differentiating malignant PE from non-malignant PE. PMID:24339491

  1. Clinical Presentation of Pelvic Tuberculosis Imitating Ovarian Malignancy

    OpenAIRE

    Yun-Ju Huang; Lin-Hung Wei; Chang-Yao Hsieh

    2004-01-01

    Objective: Pelvic tuberculosis is rare, but is problematic for differential diagnosis. In this communication, we report a case series of pelvic tuberculosis clinically presenting as ovarian malignancy. Case Series: Over the past 10 years in our hospital, six cases of pelvic tuberculosis were seen. Five were thought to be ovarian malignancies, presenting either with ascites, an elevation of serum CA-125, or an adnexal tumor. Four patients underwent exploratory laparotomy and one received on...

  2. Malignant lymphoma in a west Indian manatee (Trichechus manatus)

    DEFF Research Database (Denmark)

    Hammer, Anne Sofie; Klausen, Bjarne; Knold, Steffen

    2005-01-01

    We identified a malignant lymphoma infiltrating the lung, liver, kidney, mesenteric lymph nodes, and eye as the cause of death in a male West Indian manatee (Trichechus manatus). Diagnosis was based on gross histopathologic, and immunohistochemical studies. Tissue samples from ten organs were inc......-cell differentiation. The cause of this neoplasm was not determined. This is the first report of malignant lymphoma in the mammal order Sirenia....

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  4. Terminated Multifamily Mortgages Database

    Data.gov (United States)

    Department of Housing and Urban Development — Includes all terminated HUD Multifamily insured mortgages. It includes the Holder and Servicer at the time the mortgage was terminated. The data is good as of...

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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  16. Terminated Multifamily Mortgages Database

    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

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    Data.gov (United States)

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    Data.gov (United States)

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

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    Data.gov (United States)

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

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    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  19. katl Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  20. kmth Terminal Aerodrome Forecast

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TAF (terminal aerodrome forecast or terminal area forecast) is a format for reporting weather forecast information, particularly as it relates to aviation. TAFs are...

  1. International Joint Venture Termination: An Empirical Investigation

    DEFF Research Database (Denmark)

    Nielsen, Ulrik B.; Rasmussen, Erik Stavnsager; Siersbæk, Nikolaj

    for the article stems from data from the project portfolio of a Danish Investment Fund for Developing Countries with a total of 773 investments. A number of hypotheses are established from the literature review and tested related to the empirical data. The result indicates that the most important factor...... the difference between intended termination and unintended termination has left a significant gap in the literature. The purpose of this article is to contribute to a better understanding of IJV exit literature by differentiating empirically between intended and unintended IJV termination. The empirical data...

  2. Oral potentially malignant disorders: is malignant transformation predictable and preventable?

    NARCIS (Netherlands)

    van der Waal, I.

    2014-01-01

    Leukoplakia is the most common potentially malignant disorder of the oral mucosa. The prevalence is approximately 1% while the annual malignant transformation ranges from 2% to 3%. At present, there are no reliable clinicopathological or molecular predicting factors of malignant transformation that

  3. Accuracy of magnetic resonance imaging in differentiating between benign and malignant vertebral lesions: role of diffusion-weighted imaging, in-phase/opposed-phase imaging and apparent diffusion coefficient.

    Science.gov (United States)

    Martel Villagrán, J; Bueno Horcajadas, Á; Pérez Fernández, E; Martín Martín, S

    2015-01-01

    To determine the ability of MRI to distinguish between benign and malignant vertebral lesions. We included 85 patients and studied a total of 213 vertebrae (both pathologic and normal). For each vertebra, we determined whether the lesion was hypointense in T1-weighted sequences and whether it was hyperintense in STIR and in diffusion-weighted sequences. We calculated the in-phase/out-of-phase quotient and the apparent diffusion coefficient for each vertebra. We combined parameters from T1-weighted, diffusion-weighted, and STIR sequences to devise a formula to distinguish benign from malignant lesions. The group comprised 60 (70.6%) women and 25 (29.4%) men with a mean age of 67±13.5 years (range, 33-90 y). Of the 85 patients, 26 (30.6%) had a known primary tumor. When the lesion was hypointense on T1-weighted sequences, hyperintense on STIR and diffusion-weighted sequences, and had a signal intensity quotient greater than 0.8, the sensitivity was 97.2%, the specificity was 90%, and the diagnostic accuracy was 91.2%. If the patient had a known primary tumor, these values increased to 97.2%, 99.4%, and 99%, respectively. Benign lesions can be distinguished from malignant lesions if we combine the information from T1-weighted, STIR, and diffusion-weighted sequences together with the in-phase/out-of-phase quotient of the lesion detected in the vertebral body on MRI. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  4. Malignant mesenchymoma of the scrotum

    DEFF Research Database (Denmark)

    Møller, P; Bernstein, Inge Thomsen; Brynitz, S

    1991-01-01

    Paratesticular sarcomas are rare, especially the malignant mesenchymoma. To our knowledge only four cases of paratesticular malignant mesenchymoma have been described previously. All were localized to the spermatic cord. We present a case of malignant mesenchymoma in the scrotum free of the sperm...

  5. Intermodal freight terminals : terminal business planning

    OpenAIRE

    Nijkamp, Peter; Bart W Wiegmans

    2000-01-01

    The main purpose of this paper is to provide a framework for existing- and newly proposedinter-modal freight terminals in their business planning process. This framework is importantfor constructing- and improving the central terminal service portfolio of handling (loading,discharging, and transhipping) and storage of containerised cargo. Supportive activities (e.g. administration, customs) are taken into account as well.In particular, its aim is to investigate whether business planning offer...

  6. Squash preparation of a malignant triton tumor in a rare location

    Directory of Open Access Journals (Sweden)

    Sundaram Sandhya

    2008-01-01

    Full Text Available Malignant peripheral nerve sheath tumors (MPNST are rare malignant mesenchymal neoplasms of neural origin. Malignant peripheral nerve sheath tumors arising in a cranial nerve are rare with only a few cases being reported in literature. An MPNST with rhabdomyosarcomatous differentiation is also known as malignant triton tumor (MTT. MTT has a worse prognosis than the classic MPNST. The cytomorphological patterns of these tumors are insufficiently documented in literature. We present here the cytohistological features of an MPNST with focal rhabdomyomatous differentiation arising in the trigeminal nerve, which was confirmed by immunohistochemistry.

  7. Differentiation of malignant and benign breast lesions: Added value of the qualitative analysis of breast lesions on diffusion-weighted imaging (DWI) using readout-segmented echo-planar imaging at 3.0 T.

    Science.gov (United States)

    An, Yeong Yi; Kim, Sung Hun; Kang, Bong Joo

    2017-01-01

    To determine the added value of qualitative analysis as an adjunct to quantitative analysis for the discrimination of benign and malignant lesions in patients with breast cancer using diffusion-weighted imaging (DWI) with readout-segmented echo-planar imaging (rs-EPI). A total of 99 patients with 144 lesions were reviewed from our prospectively collected database. DWI data were obtained using rs-EPI acquired at 3.0 T. The diagnostic performances of DWI in the qualitative, quantitative, and combination analyses were compared with that of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Additionally, the effect of lesion size on the diagnostic performance of the DWI combination analysis was evaluated. The strongest indicators of malignancy on DWI were a heterogeneous pattern (P = 0.005) and an apparent diffusion coefficient (ADC) value 1 cm group (80% vs. 95.6%, P = 0.034). Qualitative analysis of tumor morphology was diagnostically applicable on DWI using rs-EPI. This qualitative analysis adds value to quantitative analyses for lesion characterization in patients with breast cancer.

  8. [Malignant cartilage tumors].

    Science.gov (United States)

    Geirnaerdt, M J; Hogendoorn, P C; Taminiau, A H; Bloem, J L

    1998-06-01

    Malignant cartilaginous tumors (chondrosarcomas) are, with a relative frequency of 20%, the second most common malignant tumors of bone after osteosarcoma. The diagnosis of chondrosarcoma can usually be made confidently based on combination of clinical information, radiographs, Gd-enhanced MR imaging, and histologic examination of a biopsy sample. The combination of these parameters is important because accuracy of histologic diagnosis is adversely affected by unrepresentative sampling of these usually large tumors. The prognosis of patients with chondrosarcoma becomes poorer with more axial location, higher histologic grade, larger tumor size and inadequate resection. By careful analysis of radiographs and Gd-enhanced MR imaging the radiologist has the ability to improve the management of patients with chondrosarcoma.

  9. Telomerase in hematologic malignancies.

    Science.gov (United States)

    Bruedigam, Claudia; Lane, Steven W

    2016-07-01

    The activation of telomere maintenance pathways has long been regarded as a key hallmark of cancer and this has propelled the development of novel inhibitors of telomerase. In this review, we detail the background biology on telomere maintenance in health and disease, then concentrate on the recent preclinical and clinical development behind targeting telomerase in blood cancers. Preclinical and clinical studies have shown that imetelstat, a competitive inhibitor of telomerase, has activity in certain hematologic malignancies, in particular the myeloproliferative neoplasms and acute myeloid leukemia. Telomerase inhibition has shown remarkable efficacy in myeloid malignancies, and current and future preclinical and clinical studies are necessary to comprehensively investigate its underlying mechanism of action. Future work should identify the potential genetic susceptibilities to telomerase inhibition therapy, and evaluate rational combinations of telomerase inhibitors with chemotherapy and other novel agents. Robust preclinical evaluation is essential to best translate these new agents successfully into our clinical treatment algorithm for myeloid and other blood cancers.

  10. Intravascular malignant lymphomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Duverneuil, N.; Lafitte, F.; Chiras, J. [Service de Neuroradiologie Charcot, Batiment Babinski, Hopital de la Salpetriere, 75013 Paris (France); Mokhtari, K. [Service de Neuropathologie, Hopital de la Salpetriere, 75013 Paris (France); Behin, A.; Hoang-Xuan, K. [Departement de Neurologie, Hopital de la Salpetriere, 75013 Paris (France)

    2002-09-01

    Intravascular malignant lymphomatosis is a rare and probably often overlooked disease characterised by massive intravascular proliferation of lymphoid cells, usually with a poor prognosis. CT and MRI appearances are nonspecific; the most suggestive finding being both asymmetrical, bilateral, contrast enhancing high-signal areas on T2 weighting and infarct-like lesions of the cortex and basal ganglia. We report two patients with previously unreported dural and spinal cord involvement. (orig.)

  11. Candidiasis in Malignancy

    OpenAIRE

    Taher, Diany N; Syam, Ari Fahrial; Abdullah, Murdani; Atmakusuma, Jumhana; Chen, Khie

    2006-01-01

    Esophageal candidiasis presents with a range of clinical findings and is rarely found among immunocompetent patient without predisposing factors. Between 20-50% of patient may be asymptomatic. One of predisposing factor of candidiasis is immunocompromised condition due to Malignancy. Dysphagia is the most frequently presented feature of esophageal carcinoma. We demonstrated a case of esophageal candidiasis as one of early clinical presentation in patient with esophageal carcinoma.

  12. Lymphoscintigraphy in gynecologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Bloomer, W.D.

    1983-01-01

    Lymphoscintigraphy is an easily performed noninvasive procedure that offers the potential to detect small numbers of ascitic tumor cells and early diaphragmatic tumor involvement. Moreover, it can be used to delineate and define abnormalities in lymph nodes that are not routinely visualized by bipedal contrast lymphangiography, ultrasound or computed tomography. Lymphoscintigraphy is recommended as an important investigative and adjunctive procedure in diagnosing gynecologic malignancies; there does not appear to be sufficient sensitivity and specificity to justify its routine clinical use.

  13. Malignant histiocytosis. Case report

    OpenAIRE

    Ruiz, Oscar; Instituto de Investigaciones Clínicas, Facultad de Medicina, UNMSM, y Hospital Nacional Dos de Mayo; QUIÑONES, WILLY; Servicio Hematologia Clínica, Hospital Dos de Mayo; MISAD, OSCAR; Laboratorio de Anatomia Patológica “Oscar Misad; DELGADO, CARLOS; Instituto de Investigaciones Clínicas, UNMSM; Servicio Hematologia Clínica, Hospital Dos de Mayo; Ronceros, Sergio; Instituto de Investigaciones Clínicas, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú.; Marangoni, Manuela; Departamento de Enfermería, Hospital Nacional Dos de Mayo. Lima, Perú; BARDALES, LUZ; Servicio Hematologia Clínica, Hospital Dos de Mayo; REYES, RAFAEL; Servicio Hematologia Clínica, Hospital Dos de Mayo; CASTILLO, ALFREDO; Servicio Hematologia Clínica, Hospital Dos de Mayo; URRUTIA, KATIA; Servicio Hematologia Clínica, Hospital Dos de Mayo

    2013-01-01

    Fourteen year-old male patient referred from Huancayo who presented one month gastric intolerance, jaundice, fever and a lymph proliferative syndrome. Laboratory tests revealed severe pancytopenia due to phagocytosis. Haematologic and anatomy-pathology diagnosis was human malignant histiocytosis. We present this case due to its low frequency and the emergency character of the disease. Paciente varón de 14 años, procedente de Huancayo, que presenta un mes antes de su hospitalización intoler...

  14. Immunotherapy for gastrointestinal malignancies.

    Science.gov (United States)

    Toomey, Paul G; Vohra, Nasreen A; Ghansah, Tomar; Sarnaik, Amod A; Pilon-Thomas, Shari A

    2013-01-01

    Gastrointestinal (GI) cancers are the most common human tumors encountered worldwide. The majority of GI cancers are unresectable at the time of diagnosis, and in the subset of patients undergoing resection, few are cured. There is only a modest improvement in survival with the addition of modalities such as chemotherapy and radiation therapy. Due to an increasing global cancer burden, it is imperative to integrate alternative strategies to improve outcomes. It is well known that cancers possess diverse strategies to evade immune detection and destruction. This has led to the incorporation of various immunotherapeutic strategies, which enable reprogramming of the immune system to allow effective recognition and killing of GI tumors. A review was conducted of the results of published clinical trials employing immunotherapy for esophageal, gastroesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers. Monoclonal antibody therapy has come to the forefront in the past decade for the treatment of colorectal cancer. Immunotherapeutic successes in solid cancers such as melanoma and prostate cancer have led to the active investigation of immunotherapy for GI malignancies, with some promising results. To date, monoclonal antibody therapy is the only immunotherapy approved by the US Food and Drug Administration for GI cancers. Initial trials validating new immunotherapeutic approaches, including vaccination-based and adoptive cell therapy strategies, for GI malignancies have demonstrated safety and the induction of antitumor immune responses. Therefore, immunotherapy is at the forefront of neoadjuvant as well as adjuvant therapies for the treatment and eradication of GI malignancies.

  15. Ocular metastasis of cutaneous malignant melanoma.

    Science.gov (United States)

    Ullah, Tehseena; Gurwood, Andrew S; Myers, Marc D

    2009-10-01

    Metastatic melanoma to the eye and orbit are rare. Patients at greatest risk often have disseminated metastases in the setting of advanced disease. Because the prognosis for orbital metastatic disease is poor, emphasis must be placed on early detection and prevention. Although cutaneous malignancies include basal cell carcinoma, squamous cell carcinoma, sebaceous cell carcinoma, and malignant melanoma, the majority of cases that result in metastasis, ocular morbidity, and mortality are from sebaceous cell carcinoma and malignant melanoma. A 72-year-old white woman presented emergently with a chief complaint of sudden, painless vision loss in her left eye of 2 weeks' duration. Her best-corrected visual acuities measured 20/30 in the right eye and 20/400 in the left eye with no improvement on refraction. Her systemic medical history was significant for the diagnosis of a cutaneous malignant melanoma. Examination of the left eye found grade II disc edema with all other posterior pole and peripheral structures intact and unremarkable. Magnetic resonance imaging confirmed the diagnosis of metastatic lesions involving structures of the left orbit ultimately causing reduced visual ability. The patient opted to avoid aggressive care and "hope for the best." Denying significant medical intervention, the woman lived in hospice where she died 6 months later. The primary care optometric setting, by the way a patient's visual symptoms present or the appearance of fundus abnormalities, can offer the capability of first detection and referral for the discovery of metastatic lesions. Although orbital metastasis is considered a terminal finding in these cases, timely diagnosis enables, while limited, the best options for management.

  16. 29 CFR 4043.24 - Termination or partial termination.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Termination or partial termination. 4043.24 Section 4043.24....24 Termination or partial termination. (a) Reportable event. A reportable event occurs when the Secretary of the Treasury determines that there has been a termination or partial termination of a plan...

  17. Epigenetic modifiers in normal and malignant hematopoiesis.

    Science.gov (United States)

    Haladyna, Jessica N; Yamauchi, Taylor; Neff, Tobias; Bernt, Kathrin M

    2015-01-01

    Genome scale sequencing in patients with cancer has revealed a lower frequency of genetic aberrations in hematologic disorders compared with most other malignancies, suggesting a prominent role for epigenetic mechanisms. In parallel, epigenetic modifiers that are altered in cancer play critical roles in normal hematopoietic development, influencing both self-renewal of hematopoietic stem cells and differentiation into the different lineages. In this review, we aim to compare the role of several key DNA or histone modifying enzymes and complexes in normal development and hematopoietic malignancies, including DNMT3A, TET2, IDH1, IDH2, MLL1, MLL4, DOT1L, PRC1/2 and WSHC1/NSD2/MMSET. Insights into their biological mechanisms led to the development of therapies designed to target mutant IDH1 and IDH2, DOT1L in MLL-rearranged leukemias and EZH2 in several cancer types including lymphomas. Inhibitors for these enzymes are currently in clinical trials.

  18. Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma cell differentiation mediated by XBP-1.

    Science.gov (United States)

    Jiang, Hua; Zou, Jianfeng; Zhang, Hui; Fu, Weijun; Zeng, Tianmei; Huang, Hejing; Zhou, Fan; Hou, Jian

    2015-02-01

    The unfolded protein response (UPR) is an essential pathway for both normal and malignant plasma cells to maintain endoplasmic reticulum (ER) homeostasis in response to the large amount of immunoglobulin (Ig) output. The inositol-requiring enzyme 1-X-box binding protein-1 (IRE1-XBP-1) arm of the UPR pathway has been shown to play crucial roles not only in relieving the ER stress by up-regulating a series of genes favoring ER-associated protein degradation and protein folding, but in mediating terminal plasmacytic differentiation and maturation. Myeloma cells comprise various subsets arrested in diverse differentiated phases, and the immaturity of myeloma cells has been taken as a marker for poor prognosis, suggesting that differentiation induction would be a promising therapeutic strategy for myeloma. Herein, we used low-dose pharmacological UPR inducers such as tunicamycin (TM) and dithiothreitol (DTT) to efficiently activate the IRE1-XBP-1 pathway in myeloma cells characterized by transcriptional expression increase in spliced XBP-1 and molecular chaperons, accompanied by significant differentiation and maturation of these myeloma cells, without concomitant cytotoxicity. These differentiated myeloma cells exhibited a more mature appearance with well-developed cytoplasm and a reduced nucleocytoplasmic ratio, and a further differentiated phenotype with markedly increased expression of CD49e together with significantly elevated cellular secretion of Ig light chain as shown by flow cytometry and ELISA, in contrast to the control myeloma cells without exposed to TM or DTT. Moreover, siRNA knockdown of XBP-1 disrupted TM- or DTT-induced myeloma cell differentiation and maturation. Our study, for the first time, validated that the modest activation of the UPR pathway enables myeloma cells to further differentiate, and identified that XBP-1 plays an indispensable role in UPR-mediated myeloma cell differentiation and maturation. Thus, we provided the rationale and

  19. Meningioma maligno Malignant meningioma

    Directory of Open Access Journals (Sweden)

    Yvei González Orlandi

    2011-03-01

    Full Text Available Los meningiomas intracraneales son tumores por lo general benignos, de crecimiento lento, y se originan en la capa de células aracnoideas, especialmente en las granulaciones aracnoideas. Los meningiomas anaplásicos o malignos representen solo el 1-3 %. En ocasiones simulan lesiones tumorales neuroepiteliales malignas, por su crecimiento rápido y la frecuente invasión al tejido cerebral vecino; suelen recidivar con mayor frecuencia y muchas veces requieren terapia coadyuvante. Las imágenes topográficas de este tipo de tumores suelen ser hiperdensas, con muy buena captación del contraste, regulares y bien delimitadas con poco o ningún edema asociado, todo lo contrario a lo visto en el caso que se presenta, en el cual las imágenes parecían corresponder a las de un glioma maligno (glioblastoma multiforme.The intracranial meningiomas are tumors in general of benign type of a slow growth originating in the arachnoid cells layer, especially in arachnoid granulations. The anaplastic or malignant meningiomas accounted for only the 1-3%. Sometimes they simulate malignant neuroepithelial lesions due to its fast growth and the frequent invasion of surrounding cerebral tissue with very frequent relapses and many times they required adjuvant therapy. The topographic images of this type of tumor are hyper-denses with a good contrast capture, regular and well defined with not much or not associated edema, quite the contrary that observed in present case where images seems to correspond with those of a malignant glioma (multiforme glioblastoma.

  20. [Malignant tumors of thyroid gland].

    Science.gov (United States)

    Uhliarová, B; Bugová, G; Hajtman, A

    2015-01-01

    The incidence of thyroid cancer has been increasing. The aim of this work was to determine risk factors, diagnostic methods and extent of surgical treatment of malignant goiter. The authors retrospectively analyzed patients who were surgically treated for thyroid disease at the Department of Otorhinolaryngology, Head and Neck Surgery, Comenius University, Jessenius Faculty of Medicine, Teaching Hospital in Martin, Slovakia, from the January 1st, 2006 to December 31st, 2013, for thyroid disease. The incidence, risk factors of malignant thyroid tumors, indication for surgery and its complications were evaluated. A total of 1,620 adult patients were surgically treated for thyroid disease at the Department of ENT, Head and Neck Surgery, CU JMF, UH in Martin, Slovakia, between 2006- 2013. Malignant tumors were identified in 238 patients (15%). Microcarcinoma (incidentally detected malignant tumor 1 cm) occurred in 78 cases (5%). Malignant thyroid tumor was more common in younger patients (p = 0.002). Newly created and larger nodules positively correlated with the occurrence of malignancy (p = 0.003, p = 0.041, resp.). Gender, family history of thyroid disorder, previous radiation therapy, and previous malignancy did not affect the incidence of malignant tumor of thyroid gland. High sensitivity and specificity in the dia-gnosis of malignant thyroid nodule was observed using aspiration cytology (75%, 97%, resp.) and intraoperative histopathological examination (88%, 100%, resp.). Malignant tumor of thyroid gland is more common in younger patients with newly developed nodule. The risk factors of malignancy increase with the size of the thyroid nodule. Aspiration cytology and peroperative histopathology have high sensitivity and specificity in the dia-gnosis of malignant thyroid tumor; therefore, they should be a standard method in the dia-gnosis of nodular goiter. The method of choice in the treatment of thyroid malignancy is total thyroidectomy.

  1. Oral potentially malignant disorders: is malignant transformation predictable and preventable?

    OpenAIRE

    Van der Waal, Isaäc

    2014-01-01

    Leukoplakia is the most common potentially malignant disorder of the oral mucosa. The prevalence is approximately 1% while the annual malignant transformation ranges from 2% to 3%. At present, there are no reliable clinicopathological or molecular predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented. Furthermore, follow-up programs are of questionable value in this respect. Cessation of smoking habits may result in ...

  2. Helminths and malignancy

    DEFF Research Database (Denmark)

    Vennervald, Birgitte J; Polman, K.

    2009-01-01

    It has been estimated that chronic infections with viruses, bacteria and parasites contribute to 17.8% of the global burden of cancer, although only a relatively small proportion of the infection-related cancers can be attributed to helminth infections. These are important because of the high...... oxidize and damage DNA and lead to genetic instabilities and malignant transformation. Physical damage caused by the parasites, their eggs or secreted products leads to restorative hyperplasia of the damaged tissue. This may promote the propagation of cells, in which genotoxic damage and pre...

  3. Maligne adnekstumorer i huden

    DEFF Research Database (Denmark)

    Klit, Anders; Hærskjold, Ann; Lei, Ulrikke

    2016-01-01

    types entirely on their clinical appearance. The histologic diagnosis is troublesome, and the lesions are often mistaken for their benign counterpart, basal cell carcinoma or squamous cell carcinoma. The lesions are treated with surgery. Radiotherapy and chemotherapy may play a role in treatment......Malignant adnexal carcinomas of the skin are rare but associated with high propensity for local recurrence, and for some of the distinct subgroups they are known to metastasize regionally or distant. Biopsy is necessary for correct diagnosis, as the lesions cannot be separated from other tumour...

  4. Neuroleptic malignant syndrome

    Directory of Open Access Journals (Sweden)

    Bino Rajamani

    2016-01-01

    Full Text Available Neuroleptic malignant syndrome (NMS is a life-threatening emergency that is often seen as a complication of antipsychotic agents. It is characterized by a tetrad of motor, behavioral, autonomic, and laboratory abnormalities. We report a case of a 34-year-old man with a history of newly diagnosed Type 2 diabetes mellitus, mental retardation, and behavioral abnormalities who developed NMS after starting on antipsychotic agents. He presented with high temperature, muscle rigidity, tachycardia, and elevated blood pressure. After a week of hospital treatment in the general ward of a secondary care unit, he was discharged in a hemodynamically and mentally stable state.

  5. CONTAINER TERMINALS IN EUROPE

    Directory of Open Access Journals (Sweden)

    Bart W. WIEGMANS

    2001-01-01

    Full Text Available This paper aims to address the linkage between logistics (in particular, the management of marketing channel flows and transport markets, while also the interaction between these two markets and intermodal container terminals is analysed. The marketing channel theory is used to describe all relevant actors and flows that run through marketing channels, starting with customer needs and ending with customer satisfaction. Porter's theory of competitive advantages is used to review competitive forces in both markets. Finally, a competitor analysis is performed for the logistics and transport market. These theories are applied so as to be able to determine the competitive position of intermodal container terminals with a view to the management of marketing channel flows and the physical transport of freight flows. Hence, the central question of this paper is: Which markets are served by intermodal container terminals and with whom are they competing? At present, neither the maritime container terminals nor the continental container terminals appear to have a significant influence in the logistics service market; they concentrate mainly on the physical movement of containers (transshipment. Furthermore, maritime container terminals and continental container terminals are not dominant players in the transport service market. Our conclusion is that continental terminals are predominantly competing with unimodal road transport, with neighbouring continental terminals and with barge transport companies.

  6. Prognostic Significance of Melanoma Differentiation and Trans-Differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Maddodi, Nityanand; Setaluri, Vijayasaradhi, E-mail: setaluri@wisc.edu [Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, B25, Madison WI 53706 (United States)

    2010-05-26

    Cutaneous malignant melanomas share a number of molecular attributes such as limitless replicative potential that define capabilities acquired by most malignancies. Accordingly, much effort has been focused on evaluating and validating protein markers related to these capabilities to function as melanoma prognostic markers. However, a few studies have also highlighted the prognostic value of markers that define melanocytic differentiation and the plasticity of melanoma cells to trans-differentiate along several other cellular pathways. Here, we provide a comprehensive review and evaluation of the prognostic significance of melanocyte-lineage markers such as MITF and melanogenic proteins, as well as markers of vascular epithelial and neuronal differentiation.

  7. A clinicopathological study of eyelid malignancies from central India

    Directory of Open Access Journals (Sweden)

    Jahagirdar Sameer

    2007-01-01

    Full Text Available Background: Eyelid malignancies are completely treatable if detected early. The treatment depends on the invasiveness of the cancer which in turn depends on the type of malignancy. Aim: The aim of the study was to characterize the distribution of the types of eyelid malignancies in central India. Settings and Design: The study was conducted in the Department of Plastic and Maxillofacial Surgery at a tertiary care hospital. Materials and Methods: We report a series of 27 cases of eyelid malignancies. In the same case series, we also include a case of malignant hemangiopericytoma which is an extremely rare form of eyelid malignancy worldwide. Statistical Analysis: Depending on the underlying statistical distribution, either analysis of variance (ANOVA or the Kruskal-Wallis (K-W test was used to assess the differential distribution of these variables across the types of eyelid malignancies observed in this study. Results: We observed that sebaceous cell carcinoma (~37% was almost as prevalent as basal cell carcinoma (~44% in the study subjects and had an earlier age of occurrence and a more rapid clinical course. Conclusions: Sebaceous cell carcinoma of the eyelid is almost as common as basal cell carcinoma in a large tertiary care centre in central India.

  8. [Pathologic characteristics of malignant neoplasms occurring in the elderly].

    Science.gov (United States)

    Arai, Tomio; Matsuda, Yoko; Aida, Junko; Takubo, Kaiyo

    2015-08-01

    Malignant neoplasm preferentially occurs in the elderly. Common cancers in the elderly are gastric, colorectal, lung and prostate cancers in men whereas colorectal, lung, gastric and pancreatic cancers in women. There are several characteristic features such as tumor location, histology, biological behavior and pathway of carcinogenesis in malignant neoplasms occurring in the elderly. Multiple cancers increase with aging. Although it is generally believed that carcinoma in the elderly shows well differentiation, slow growth, low incidence of metastasis and favorable prognosis, the tumor does not always show such features. Regarding biological behavior of malignant tumor in the elderly, age-related alterations of the host such as stromal weakness and decreased immune response against cancer cell invasion should be considered as well as characteristics of tumor cell itself. Thus, we need a specific strategy for treatment for malignant neoplasms in the elderly.

  9. 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.

  10. A rare case of malignant paraganglioma of urinary bladder.

    Science.gov (United States)

    Shah, Vinaya B; Bhandare, Amit T

    2015-01-01

    Paraganglioma of the urinary bladder is a rare pathologic entity with no definitive histological, immunohistochemical or molecular features to determine its malignant potential. Malignancy is essentially determined by the presence of deep local invasion, invasion of adjacent structures and lymph node or distant metastases. So far, up to 180 cases of paraganglioma have been reported, with bladder mass was given as invasive urothelial carcinoma. Patient underwent radical cystectomy with pelvic lymphadenectomy. The gross morphological brown discoloration of mass on formalin fixation was suspicious of paraganglioma and was confirmed on immunohistochemistry. The diagnosis of malignant paraganglioma was made based on regional lymph node metastases. We describe a rare case of a patient with malignant urinary bladder paraganglioma with main differential diagnostic considerations on the histomorphology.

  11. Metastatic lung malignancy to mandibular gingiva

    Directory of Open Access Journals (Sweden)

    Moharil Rohit

    2010-01-01

    Full Text Available Metastatic tumors of oral cavity are uncommon and may occur in oral soft tissues or jaw bones. Because of their rarity, metastasis to oral cavity are challenging to diagnose and difficult to treat. They often have vague symptoms that mimic dental infections. These lesions generally show poorly differentiated histopathologic picture and have poor prognosis. We reported a case of a 40-year-old male patient of metastatic lesion to the oral cavity and brain with primary tumor, diagnosed as an undifferentiated epithelial malignancy of lung.

  12. Are All Highly Malignant Cancer Cells Identical?

    Science.gov (United States)

    1979-01-01

    ADA3665 ARE AL HIGHL MAGNANTCANCER CELLS DENOIALU) PENNSYLVANIA HOSPITAL PHILADELPHIA DEPT OF MOLECULAR BIOLOGY G NIGET AL 199 N00014-ACA026 UNCLASFE...embryo cells or even the original fertilized ovum . If this speculation has validity, the carcinogenesis and differentiation have the same destinies but...F/G /5 N 1111 2Z111117 1 125iiI 1 1. 1111_L6. -11 O=M 1 MrCROCOP RErSOLUTICN TEST CHART N, APoP SN A’ ,- ARE ALL HIGHLY MALIGNANT CANCER CELLS

  13. Ovarian tuberculosis mimicking a malignant tumour

    Directory of Open Access Journals (Sweden)

    Eric Yebouet

    2015-01-01

    Full Text Available There has been reported increased incidence of ovarian tuberculosis in the tropics since the advent of HIV/AIDS disease. We report a case of bilateral ovarian tuberculosis associated with a single right kidney of uncertain origin in an immunocompetent 15-year-old generally healthy-looking girl. Abdominopelvic scan was equivocal about the diagnosis of the lesion as it failed to differentiate it from malignancy. Tuberculin and histopathology were necessary to confirm the diagnosis of ovarian tuberculosis. Antituberculous medical therapy successfully resolved the disease.

  14. 5 CFR 575.111 - Termination of a service agreement.

    Science.gov (United States)

    2010-01-01

    ... official may unilaterally terminate a recruitment incentive service agreement based solely on the... a result of failing to meet employment qualifications, the employee must repay all recruitment... RECRUITMENT, RELOCATION, AND RETENTION INCENTIVES; SUPERVISORY DIFFERENTIALS; AND EXTENDED ASSIGNMENT...

  15. Organizational Relationship Termination Competence

    DEFF Research Database (Denmark)

    Ritter, Thomas; Geersbro, Jens

    2011-01-01

    that a firm's percentage of unwanted customers decreases significantly as acceptance of termination increases, if the firm's definition of unwanted customers is well understood, and if a firm has clear termination routines. In addition, general focus on profitability and external constraints on relationship...

  16. EZH2 in normal hematopoiesis and hematological malignancies

    OpenAIRE

    Herviou, Laurie; Cavalli, Giacomo; Cartron, Guillaume; Klein, Bernard; Moreaux, J?r?me

    2015-01-01

    Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2, inhibits gene expression through methylation on lysine 27 of histone H3. EZH2 regulates normal hematopoietic stem cell self-renewal and differentiation. EZH2 also controls normal B cell differentiation. EZH2 deregulation has been described in many cancer types including hematological malignancies. Specific small molecules have been recently developed to exploit the oncogenic addiction of tumor cell...

  17. Are irregular hypoechoic breast masses on ultrasound always malignancies?: A Pictorial essay

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Youe Ree; Kim, Hun Soo; Kim, Hye Won [Wonkwang University Hospital, Iksan (Korea, Republic of)

    2015-12-15

    Irregular hypoechoic masses in the breast do not always indicate malignancies. Many benign breast diseases present with irregular hypoechoic masses that can mimic carcinoma on ultrasonography. Some of these diseases such as inflammation and trauma-related breast lesions could be suspected from a patient's symptoms and personal history. Careful ultrasonographic examination and biopsy could help to differentiate these from malignancies.

  18. Eosinophilia in routine blood samples and the subsequent risk of hematological malignancies and death

    DEFF Research Database (Denmark)

    Andersen, Christen Bertel L; Siersma, Volkert Dirk; Hasselbalch, HC

    2013-01-01

    Eosinophilia may represent an early paraclinical sign of hematological malignant disease, but no reports exist on its predictive value for hematological malignancies. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one...

  19. An amelanotic malignant melanoma masquerading as hypergranulation tissue.

    Science.gov (United States)

    Cahill, S; Cryer, J R; Otter, S J; Ramesar, K

    2009-01-01

    We report a case of amelanotic malignant melanoma occurring in the nail sulcus of the hallux, which on initial presentation was mistaken for hypergranulation tissue due to an in-growing toenail. We highlight the importance of this differential diagnosis as such lesions can have serious sequelae.

  20. Giant cardiac myxoma with malignant transformed glandular structures

    Energy Technology Data Exchange (ETDEWEB)

    Eckhardt, Boris P.; Stuckmann, Gerd; Zollikofer, Christoph L. [Institute of Radiology, Cantonal Hospital, Brauerstrasse 15, 8401 Winterthur (Switzerland); Dommann-Scherrer, Corina C. [Insitute of Pathology, Cantonal Hospital, Brauerstrasse 15, 8401 Winterthur (Switzerland); Wentz, Klaus U. [Institute of Radiology, Cantonal Hospital, Brauerstrasse 15, 8401 Winterthur (Switzerland); Medical Faculty, University of Witten/Herdecke, Alfred-Herrhausen-Strasse 50, 58448 Witten (Germany)

    2003-09-01

    A case of a right-sided giant cardiac myxoma with malignant transformation of glandular structures causing systemic metastases is described. Plain chest radiography and computed tomography localized the tumor within the heart. Exact depiction of the origin of the tumor using subtracted 2D-projection MR angiography is documented. Radiologic findings and differential diagnosis of this unique tumor are discussed. (orig.)

  1. Temozolomide in malignant glioma

    Directory of Open Access Journals (Sweden)

    Gregor Dresemann

    2010-07-01

    Full Text Available Gregor DresemannCenter for Neurooncology at Aerztehaus Velen, Velen, GermanyAbstract: Glioblastoma multiforme WHO grade IV (GBM is the most aggressive ­malignant glioma and the most frequent primary tumor of the central nervous system. The median ­survival of newly diagnosed GBM patients was between 9 to 12 months prior to treatment with ­temozolomide being introduced. Primary resection that is as complete as possible is recommended for malignant glioma. Conventional fractionated irradiation 55 to 60 gy with concomitant temozolomide followed by standard temozolomide 6 cycles (5/28 (EORTC/NCIC-regime published by R Stupp in 2005 is the standard of care for newly diagnosed GBM after surgery, independent of the methylation status of the MGM-T gene promoter. Age is no ­contraindication for treatment with temozolomide, although comorbidity and performance status have to be ­considered. For temozolomide naive GBM and astrocytoma grade III patients with disease progression, temozolomide is still the treatment of choice outside of clinical studies. A ­general consensus regarding the schedule of choice has not yet been achieved; so far the 5 out of 28 days regimen (5/28 is the standard of care in most countries. Patients with disease progression after standard temozolomide (5/28 are candidates for clinical studies. Outside of clinical ­studies, dose-dense (7/7, prolonged (21/28, or metronomic (28/28 temozolomide, or alternatively a nitrosourea-based regimen can be an option. The excellent toxicity profile of ­temozolomide allows for various combinations with antitumor agents. None of these ­combinations, however, have been demonstrated to be statistically significantly superior compared to temozolomide alone. The role of lower dosed, dose-dense, or continuous regimen with or without drug combination and the role of temozolomide for newly diagnosed astrocytoma grade III and low grade glioma still has to be determined.Keywords: glioblastoma

  2. Oral potentially malignant disorders: Is malignant transformation predictable and preventable?

    Science.gov (United States)

    van der Waal, Isaäc

    2014-01-01

    Leukoplakia is the most common potentially malignant disorder of the oral mucosa. The prevalence is approximately 1% while the annual malignant transformation ranges from 2% to 3%. At present, there are no reliable clinicopathological or molecular predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented. Furthermore, follow-up programs are of questionable value in this respect. Cessation of smoking habits may result in regression or even disappearance of the leukoplakia and will diminish the risk of cancer development either at the site of the leukoplakia or elsewhere in the mouth or the upper aerodigestive tract. The debate on the allegedly potentially malignant character of oral lichen planus is going on already for several decades. At present, there is a tendency to accept its potentially malignant behaviour, the annual malignant transformation rate amounting less than 0.5%. As in leukoplakia, there are no reliable predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented either. Follow-up visits, e.g twice a year, may be of some value. It is probably beyond the scope of most dentists to manage patients with these lesions in their own office. Timely referral to a specialist seems most appropriate, indeed. Key words:Oral potentially malignant disorders, oral leukoplakia, oral lichen planus. PMID:24905952

  3. Gastric malignancies and associated pre-malignant lesions in a ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-07-04

    Jul 4, 2008 ... lesions like chronic gastritis, glandular atrophy, intestinal metaplasia, H. pylori infection play some role in the pathogenesis of gastric malignancies. The aims of this investigation were to study the histological type of gastric malignancies seen in the. Department of Morbid Anatomy and Forensic Medicine,.

  4. Benign versus malignant lymphadenopathy : the usefulness of color doppler sonography

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Yun Woo; Hong, Hyun Sook; Park, Jae Ho; Lee, Yong Il; Lee, Hae Kyung; Kwon, Kui Hyang; Choi, Deuk Lin [Soonchunhyang Univ. Hospital, Asan (Korea, Republic of)

    1999-04-01

    To evaluate the vascular pattern of lymph nodes, and the usefulness of color Doppler sonogaphy in differentiating benign from malignant superficial lymphadenopathy. Twenty-six patients were pathologically and clinically confirmed to be suffering from benign reactive lymphadenitis and tuberculosis (n=16) or lymphoma and malignant lymphadenitis (n=10). Lymph node shape was assessed by the ratio of longitudinal diameter to transverse diameter(L/T), and patients were thus assigned to one of two groups : L/T{>=}2, or L/T<2. The hilar vascular pattern of lymph node was assessed by color Doppler sonography and classified as central, eccentric, or absent. On the basis of peripheral vascularity, patients were divided into three groups according to circumferental linear vascularity. An absence of peripheral vascularity was classified as grade 0. If less than half the periphery was covered by linear vascularity, a patient was assigned to as grade I, and if more than half was covered by a vessel, the classification was grade II. Statistically significant differences in L/T ratio were noted between malignant and benign node (p<.001). Of the 16 benign reactive nodes, 13 showed L/T{>=}2, and 3 L/T<2. while in nine of the ten malignant nodes, L/T<2 was noted. Among 16 benign reactive nodes, hilar vascularity was central in 13, eccentric in one, and absent in two. Among the ten malignant nodes, the corresponding totals were nil, four, and Six. The hilar vascular pattern showed statistically significant differentiation between malignant and benign node (p<.05). Among 16 benign reactive nodes, 13 were grade 0, two were grade I, and one was grade II, while among ten malignant nodes, two were grade 0 and eight were grade I. On the basis of vascular pattern, the difference between benign and malignant nodes was statistically significant (p<.05). L/T ratio<2, absent or eccentric hilar vascularity, and the presence of peripheral vascularity are suggestive of malignant lymph node. The

  5. Malignant pleural effusion

    OpenAIRE

    Teixeira, Lisete Ribeiro; Pinto, José Antonio de Figueiredo; Marchi, Evaldo

    2006-01-01

    O derrame pleural neoplásico é uma complicação freqüente nos pacientes portadores de tumores avançados. A presença de células malignas no líquido pleural ou na biópsia da pleura é indicativa de disseminação da doença primária, com conseqüente redução da expectativa de vida. O diagnóstico e tratamento precoce do derrame pleural maligno são fundamentais para promover uma melhor qualidade de vida aos pacientes portadores de câncer avançado.The malignant pleural effusion is a frequent complicatio...

  6. Targeting cell cycle regulators in hematologic malignancies

    Directory of Open Access Journals (Sweden)

    Eiman eAleem

    2015-04-01

    Full Text Available Hematologic malignancies represent the fourth most frequently diagnosed cancer in economically developed countries. In hematologic malignancies normal hematopoiesis is interrupted by uncontrolled growth of a genetically altered stem or progenitor cell (HSPC that maintains its ability of self-renewal. Cyclin-dependent kinases (CDKs not only regulate the mammalian cell cycle, but also influence other vital cellular processes, such as stem cell renewal, differentiation, transcription, epigenetic regulation, apoptosis, and DNA repair. Chromosomal translocations, amplification, overexpression and altered CDK activities have been described in different types of human cancer, which have made them attractive targets for pharmacological inhibition. Mouse models deficient for one or more CDKs have significantly contributed to our current understanding of the physiological functions of CDKs, as well as their roles in human cancer. The present review focuses on selected cell cycle kinases with recent emerging key functions in hematopoiesis and in hematopoietic malignancies, such as CDK6 and its role in MLL-rearranged leukemia and acute lymphocytic leukemia, CDK1 and its regulator WEE-1 in acute myeloid leukemia, and cyclin C/CDK8/CDK19 complexes in T-cell acute lymphocytic leukemia. The knowledge gained from gene knockout experiments in mice of these kinases is also summarized. An overview of compounds targeting these kinases, which are currently in clinical development in various solid tumors and hematopoietic malignances, is presented. These include the CDK4/CDK6 inhibitors (palbociclib, LEE011, LY2835219, pan-CDK inhibitors that target CDK1 (dinaciclib, flavopiridol, AT7519, TG02, P276-00, terampeprocol and RGB 286638 as well as the WEE-1 kinase inhibitor, MK-1775. The advantage of combination therapy of cell cycle inhibitors with conventional chemotherapeutic agents used in the treatment of AML, such as cytarabine, is discussed.

  7. Malign katatoni, et neuropsykiatrisk syndrom

    DEFF Research Database (Denmark)

    Moltke, Katinka; Lublin, Henrik

    2010-01-01

    This case report describes a 36-year-old schizophrenic man who developed malignant catatonia during a hospital stay. He was treated with benzodiazepines (BZD) and 26 sessions of electroconvulsive therapy (ECT). After the therapy his condition normalised. Malignant catatonia is a rare condition...

  8. Malignant Melanoma of the Foot

    Science.gov (United States)

    ... page. Please enable Javascript in your browser. Malignant Melanoma of the Foot What Is Malignant Melanoma? Melanoma is a cancer that begins in the ... people of all age groups, even the young. Melanoma in the Foot Melanoma that occurs in the ...

  9. Malignant priapism: a case report.

    LENUS (Irish Health Repository)

    Ellanti, P

    2011-12-01

    Metastatic involvement of the penis is most commonly from a primary malignant genitourinary tumour. It is a rare phenomenon usually reflecting disseminated malignancy associated with a poor prognosis. Metastasis to the penis mimicking priapism is extremely rare, particularly in the absence of disseminated disease.

  10. Malignant ameloblastoma or ameloblastic carcinoma

    NARCIS (Netherlands)

    Slootweg, P.J.; Müller, H.

    1984-01-01

    The World Health Organization defines malignant ameloblastoma as a lesion exhibiting features of an ameloblastoma in primary and metastatic growths. To cases collected from the literature we have added two of our own cases in which features of an ameloblastoma were coupled with malignant behavior.

  11. Comsat's TDMA traffic terminal

    Science.gov (United States)

    Benjamin, M. C.; Bogaert, W. M.

    1985-06-01

    Comsat has installed two traffic terminals in the Etam earth-station and is currently installing a third in the new Roaring Creek earth-station to access the Intelsat TDMA network. This paper describes the Comsat TDMA traffic terminal equipment from the supergroup interface to the antenna. Comsat's 1: N redundancy approach for terrestrial interface equipment and DSI unit back-up is described as well as electrical path length, amplitude and group delay equalization techniques, special on-line RF monitoring and failure reporting facilities and the operation and maintenance center which can operate and perform diagnostic testing on up to four traffic terminals from a central location.

  12. The block of adipocyte differentiation by a C-terminally truncated, but not by full-length, simian virus 40 large tumor antigen is dependent on an intact retinoblastoma susceptibility protein family binding domain.

    OpenAIRE

    Higgins, C; Chatterjee, S.; Cherington, V

    1996-01-01

    Simian virus 40 (SV40) can promote cell transformation and suppress differentiation. It does this partly by targeting tumor suppressors such as p53 and members of the retinoblastoma susceptibility protein (Rb) family. This work concentrates on mechanisms by which SV40 large tumor antigen (SVLT) suppresses adipocyte differentiation. We created cell lines derived from murine 3T3-L1 preadipocytes expressing different versions of SV40 early-region sequences. SVLT-expressing cells failed to exhibi...

  13. Imaging Findings of Primary Tubal Malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Sang Been; Park, Jun Young; Park, Dong Hee; Kim, Kie Hwan [Dept. of Radiology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Cho, Kyoung Sik [Dept. of Radiology and Research Institute of Radiology, Ulsan University College of Medicine, Asan Medical Center, Seoul (Korea, Republic of)

    2012-02-15

    To describe the radiologic findings of primary tubal malignancy. This study described the imaging findings of 27 patients with 28 cases of primary tubal malignancy. Of the 27 patients examined, 23 underwent CT, 3 underwent MRI and 4 underwent ultrasonography. Image findings were analyzed according to size, proportion of cyst, shape, and associated findings of tumor. The mean tumor diameter was 5.3 cm (range 2.0-13.1 cm). According to proportion of cyst within the tumor, each case was categorized in one of the four types: 10 cases (35.7%) of type I ({>=} 75 of cystic portion), 2 cases (7.1%) of type II (50-75%), 3 cases (10.7%) of type III (25-50%) and 13 cases (46.4%) of type IV ({<=} 25%). According to the shape of the tumor, 7 cases (25%) were round, 12 cases (42.9%) were lobular, and 9 cases (32.1%) were tubular. Moreover, septa were observed in 8 cases (28.6%), wall thickening was observed in 13 cases (46.4%), and hydrosalpinx was observed in 11 cases (39.3%). The imaging findings of tubal cancer manifests from a solid to a cystic mass. It is a challenge to differentiate primary tubal cancer from ovarian cancer, but when it is associated with hydrosalpinx or the shape of the tumor is lobular or tubular, primary tubal cancer can be suggested as part of the differential diagnosis.

  14. The malignant conversion step of mouse skin carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Yuspa, S.H.; Hennings, H.; Roop, D.; Strickland, J.; Greenhalgh, D.A. (National Cancer Institute, Bethesda, MD (USA))

    1990-08-01

    Multiple benign squamous papillomas commonly precede the development of an occasional squamous cell carcinoma in mouse skin carcinogenesis. The incidence of carcinomas can be enhanced by treating papilloma-bearing mice with mutagens such as urethane, nitroquinoline-N-oxide, or cisplatinum. This observation suggests that a genetic change is required for malignant conversion. The malignant phenotype is characterized by a marked reduction in the transcription of specific epidermal differentiation markers, a pattern which is useful for the early diagnosis of malignant conversion. Cells expressing a benign phenotype can be obtained by introducing the v-ras{sup Ha} oncogene into cultured epidermal cells by a replication-defective retrovirus. Alternatively, benign tumor cells can be cultured from papillomas induced by chemical carcinogens in vivo or from carcinogen-treated mouse epidermis. In all cases, the benign phenotype in vitro is characterized by an altered biological response to changes in extracellular calcium, an important determinant of the differentiation state of cultured normal keratinocytes. Transfection of cloned plasmid DNA into benign tumor cells has revealed that transforming constructs of the fos oncogene induce malignant conversion, whereas myc and adenovirus E1A oncogenes do not. Cultured normal epidermal cells, exposed to the v-ras and the v-fos oncogenes simultaneously, are malignantly transformed. Alone, the fos oncogene does not detectably alter the phenotype of normal keratinocytes. These studies indicate that a limited number of genes is involved in epidermal carcinogenesis.

  15. Oral potentially malignant disorders: is malignant transformation predictable and preventable?

    Science.gov (United States)

    van der Waal, Isaäc

    2014-07-01

    Leukoplakia is the most common potentially malignant disorder of the oral mucosa. The prevalence is approximately 1% while the annual malignant transformation ranges from 2% to 3%. At present, there are no reliable clinicopathological or molecular predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented. Furthermore, follow-up programs are of questionable value in this respect. Cessation of smoking habits may result in regression or even disappearance of the leukoplakia and will diminish the risk of cancer development either at the site of the leukoplakia or elsewhere in the mouth or the upper aerodigestive tract. The debate on the allegedly potentially malignant character of oral lichen planus is going on already for several decades. At present, there is a tendency to accept its potentially malignant behaviour, the annual malignant transformation rate amounting less than 0.5%. As in leukoplakia, there are no reliable predicting factors of malignant transformation that can be used in an individual patient and such event can not truly be prevented either. Follow-up visits, e.g twice a year, may be of some value. It is probably beyond the scope of most dentists to manage patients with these lesions in their own office. Timely referral to a specialist seems most appropriate, indeed.

  16. Terminated Multifamily Mortgages Database

    Data.gov (United States)

    Department of Housing and Urban Development — This dataset includes all terminated HUD Multifamily mortgages except those from the Hospital Mortgage Insurance Program. It includes the Holder and Servicer at the...

  17. Malignant peripheral nerve sheath tumor of the breast: case report

    Directory of Open Access Journals (Sweden)

    Roy Somak

    2007-12-01

    Full Text Available Abstract Background Malignant peripheral nerve sheath tumor is a rare soft tissue sarcoma of ectomesenchymal origin. It is the malignant counterpart of benign soft tissue tumors like neurofibromas and schwannomas and may often follow them. Common sites include deeper soft tissues, usually in the proximity of a nerve trunk. Breast is an extremely rare location of this lesion and presentation as a breast lump in the absence of pain or previous benign neural tumor is even rarer. Case presentation A 38-year-old female presented with complaints of painless, hard breast lump for three months which was clinically suspected to be a ductal carcinoma with inconclusive fine needle aspiration cytology. Histopathology revealed a malignant spindle cell tumor which was confirmed to be malignant peripheral nerve sheath tumor on the basis of immunopositivity for vimentin, neurone specific enolase and S-100. Conclusion To the best of our knowledge only six such case reports have been published in literature. The differential diagnosis of malignant peripheral nerve sheath tumor should be considered by the clinician as well as the pathologists in the work-up of a breast neoplasm as treatment and prognosis of this rare malignancy is different.

  18. Antecedents of Customer Relationship Termination

    DEFF Research Database (Denmark)

    Geersbro, Jens; Ritter, Thomas

    relationships as a managerial task. This paper contributes by (1) developing a conceptualization of relationship termination competence and (2) analyzing its antecedents. The empirical results identify termination acceptance, definition non-customers, organizational relationship termination routines...

  19. Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia

    Science.gov (United States)

    dos Santos, Guilherme Augusto; Kats, Lev

    2013-01-01

    Acute promyelocytic leukemia (APL) is a hematological malignancy driven by a chimeric oncoprotein containing the C terminus of the retinoic acid receptor-a (RARa) fused to an N-terminal partner, most commonly promyelocytic leukemia protein (PML). Mechanistically, PML-RARa acts as a transcriptional repressor of RARa and non-RARa target genes and antagonizes the formation and function of PML nuclear bodies that regulate numerous signaling pathways. The empirical discoveries that PML-RARa–associated APL is sensitive to both all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO), and the subsequent understanding of the mechanisms of action of these drugs, have led to efforts to understand the contribution of molecular events to APL cell differentiation, leukemia-initiating cell (LIC) clearance, and disease eradication in vitro and in vivo. Critically, the mechanistic insights gleaned from these studies have resulted not only in a better understanding of APL itself, but also carry valuable lessons for other malignancies. PMID:24344243

  20. Immunotherapy in genitourinary malignancies

    Directory of Open Access Journals (Sweden)

    Kathan Mehta

    2017-04-01

    Full Text Available Abstract Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents. These cytotoxic agents have good response rates and achieve palliation; however, complete responses are rarely seen. The field of cancer immunology has made rapid advances in the past 20 years. Recently, a number of agents and vaccines, which modulate the immune system to allow it to detect and target cancer cells, are being developed. The benefit of these agents is twofold, it enhances the ability the body’s own immune system to fight cancer, thus has a lower incidence of side effects compared to conventional cytotoxic chemotherapy. Secondly, a small but substantial number of patients with metastatic disease are cured by immunotherapy or achieve durable responses lasting for a number of years. In this article, we review the FDA-approved immunotherapy agents in the field of genitourinary malignancies. We also summarize new immunotherapy agents being evaluated in clinical studies either as single agents or as a combination.