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Sample records for aggressive malignant tumor

  1. Deregulation of miR-183 and KIAA0101 in Aggressive and Malignant Pituitary Tumors

    PubMed Central

    Roche, Magali; Wierinckx, Anne; Croze, Séverine; Rey, Catherine; Legras-Lachuer, Catherine; Morel, Anne-Pierre; Fusco, Alfredo; Raverot, Gérald; Trouillas, Jacqueline; Lachuer, Joel

    2015-01-01

    Changes in microRNAs (miRNAs) expression in many types of cancer suggest that they may be involved in crucial steps during tumor progression. Indeed, miRNAs deregulation has been described in pituitary tumorigenesis, but few studies have described their role in pituitary tumor progression toward aggressiveness and malignancy. To assess the role of miRNAs within the hierarchical cascade of events in prolactin (PRL) tumors during progression, we used an integrative genomic approach to associate clinical–pathological features, global miRNA expression, and transcriptomic profiles of the same human tumors. We describe the specific down-regulation of one principal miRNA, miR-183, in the 8 aggressive (A, grade 2b) compared to the 18 non-aggressive (NA, grades 1a, 2a) PRL tumors. We demonstrate that it acts as an anti-proliferative gene by directly targeting KIAA0101, which is involved in cell cycle activation and inhibition of p53–p21-mediated cell cycle arrest. Moreover, we show that miR-183 and KIAA0101 expression significantly correlate with the main markers of pituitary tumors aggressiveness, Ki-67 and p53. These results confirm the activation of proliferation in aggressive and malignant PRL tumors compared to non-aggressive ones. Importantly, these data also demonstrate the ability of such an integrative genomic strategy, applied in the same human tumors, to identify the molecular mechanisms responsible for tumoral progression even from a small cohort of patients. PMID:26322309

  2. MIB-1 labeling indices in benign, aggressive, and malignant meningiomas: a study of 90 tumors.

    PubMed

    Abramovich, C M; Prayson, R A

    1998-12-01

    Predicting tumor behavior in meningiomas based on histology alone has been problematic. This study retrospectively compares histology and MIB-1 (cell proliferation marker) labeling indices (LI) in benign, aggressive, and malignant meningiomas. Six histological features, including mitoses, necrosis, loss of pattern, hypervascularity/hemosiderin deposition, prominent nucleoli, and nuclear pleomorphism, were compared in 90 meningiomas (Fisher's exact test). Tumors with two or more of the above features were designated as aggressive meningiomas. Malignant meningiomas were characterized by brain invasion or metastasis. The MIB-1 LIs (% positive tumor cell nuclei) were compared between the three groups (Kruskal-Wallis test, Wilcoxon two-sample test). Of the benign meningiomas (n=37; mean age, 54 years), 41% had one of the six histological features, with nuclear pleomorphism (n=10) being the most frequent. The aggressive tumors (n=29; mean age, 61 years) were characterized by nuclear pleomorphism (n=28), mitoses (n=20), necrosis (n=16), loss of pattern (n=16), prominent nucleoli (n=6), and hypervascularity/hemosiderin deposition (n=5). Malignant tumors (n=24; mean age, 59 years) were characterized by nuclear pleomorphism (n=22), mitoses (n=21), loss of pattern (n=21), necrosis (n=21), nucleoli (n=17), and hypervascularity/hemosiderin deposition (n=3). Significant differences were found between the aggressive and malignant groups with regard to loss of pattern, necrosis, and nucleoli (P=.0043, .011, and .00029, respectively). Mean MIB-1 LIs for the benign, aggressive, and malignant groups were 1.0% (range, 0 to 5.5%),5.5% (range, 0.1 to 32.5%), and 12.0% (range, 0.3 to 32.5%), respectively. Differences in the mean MIB-1 LI between groups were statistically significant, with P values of <.0001 (benign v aggressive) and .0012 (aggressive v malignant). Mean MIB-1 LIs for recurrent versus nonrecurrent tumors were 7.1% (range, 0 to 32.5%) versus 3.8% (range, 0 to 20.9%) (P=.32

  3. Primary vertebral tumors: a review of epidemiologic, histological and imaging findings, part II: locally aggressive and malignant tumors.

    PubMed

    Ropper, Alexander E; Cahill, Kevin S; Hanna, John W; McCarthy, Edward F; Gokaslan, Ziya L; Chi, John H

    2012-01-01

    This second part of a comprehensive review of primary vertebral tumors focuses on locally aggressive and malignant tumors. As discussed in the earlier part of the review, both benign and malignant types of these tumors affect the adult and the pediatric population, and an understanding of their subtleties may increase their effective resection. In this review, we discuss the epidemiologic, histological, and imaging features of the most common locally aggressive primary vertebral tumors (chordoma and giant-cell tumor) and malignant tumors (chondrosarcoma, Ewing sarcoma, multiple myeloma or plasmacytoma, and osteosarcoma). The figures used for illustration are from operative patients of the senior authors (Z.L.G. and J.H.C.). Taken together, parts 1 and 2 of this article provide a thorough and illustrative review of primary vertebral tumors. PMID:21768918

  4. ACR Appropriateness Criteria Follow-Up of Malignant or Aggressive Musculoskeletal Tumors.

    PubMed

    Roberts, Catherine C; Kransdorf, Mark J; Beaman, Francesca D; Adler, Ronald S; Amini, Behrang; Appel, Marc; Bernard, Stephanie A; Fries, Ian Blair; Germano, Isabelle M; Greenspan, Bennett S; Holly, Langston T; Kubicky, Charlotte D; Shek-Man Lo, Simon; Mosher, Timothy J; Sloan, Andrew E; Tuite, Michael J; Walker, Eric A; Ward, Robert J; Wessell, Daniel E; Weissman, Barbara N

    2016-04-01

    Appropriate imaging modalities for the follow-up of malignant or aggressive musculoskeletal tumors include radiography, MRI, CT, (18)F-2-fluoro-2-deoxy-D-glucose PET/CT, (99m)Tc bone scan, and ultrasound. Clinical scenarios reviewed include evaluation for metastatic disease to the lung in low- and high-risk patients, for osseous metastatic disease in asymptomatic and symptomatic patients, for local recurrence of osseous tumors with and without significant hardware present, and for local recurrence of soft tissue tumors. The timing for follow-up of pulmonary metastasis surveillance is also reviewed. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID:26922595

  5. IL-1β promotes malignant transformation and tumor aggressiveness in oral cancer.

    PubMed

    Lee, Chia-Huei; Chang, Jeffrey Shu-Ming; Syu, Shih-Han; Wong, Thian-Sze; Chan, Jimmy Yu-Wai; Tang, Ya-Chu; Yang, Zhi-Ping; Yang, Wen-Chan; Chen, Chiung-Tong; Lu, Shao-Chun; Tang, Pei-Hua; Yang, Tzu-Ching; Chu, Pei-Yi; Hsiao, Jenn-Ren; Liu, Ko-Jiunn

    2015-04-01

    Chronic inflammation, coupled with alcohol, betel quid, and cigarette consumption, is associated with oral squamous cell carcinoma (OSCC). Interleukin-1 beta (IL-1β) is a critical mediator of chronic inflammation and implicated in many cancers. In this study, we showed that increased pro-IL-1β expression was associated with the severity of oral malignant transformation in a mouse OSCC model induced by 4-Nitroquinolin-1-oxide (4-NQO) and arecoline, two carcinogens related to tobacco and betel quid, respectively. Using microarray and quantitative PCR assay, we showed that pro-IL-1β was upregulated in human OSCC tumors associated with tobacco and betel quid consumption. In a human OSCC cell line TW2.6, we demonstrated nicotine-derived nitrosamine ketone (NNK) and arecoline stimulated IL-1β secretion in an inflammasome-dependent manner. IL-1β treatment significantly increased the proliferation and dysregulated the Akt signaling pathways of dysplastic oral keratinocytes (DOKs). Using cytokine antibodies and inflammation cytometric bead arrays, we found that DOK and OSCC cells secreted high levels of IL-6, IL-8, and growth-regulated oncogene-α following IL-1β stimulation. The conditioned medium of IL-1β-treated OSCC cells exerted significant proangiogenic effects. Crucially, IL-1β increased the invasiveness of OSCC cells through the epithelial-mesenchymal transition (EMT), characterized by downregulation of E-cadherin, upregulation of Snail, Slug, and Vimentin, and alterations in morphology. These findings provide novel insights into the mechanism underlying OSCC tumorigenesis. Our study suggested that IL-1β can be induced by tobacco and betel quid-related carcinogens, and participates in the early and late stages of oral carcinogenesis by increasing the proliferation of dysplasia oral cells, stimulating oncogenic cytokines, and promoting aggressiveness of OSCC. PMID:25204733

  6. Non-Hodgkin's Malignant Lymphoma with Aggressive Development

    PubMed Central

    DANCIU, Cezara Elisabeta; HEROIU (CATALOIU), Adriana-Daniela; POPESCU, Cristian Radu

    2014-01-01

    Non-Hodgkin's malignant lymphoma is a hematologic malignant disease which usually responds to the polychemotherapy. We present a clinical case report of a 50 years old patient who develops an aggressive type of lymphoma. Patient develops a nodal Non-Hodgkin's malignant lymphoma who present at hospital admission as a huge tumor at the right side of the neck. Any type of treatment was a failure, the patient having a particularly aggressive form of lymphoma, resistant to all three chemotherapy regimens tested. Death occurs quickly, about one year after diagnosis and initiation of therapy. PMID:25553129

  7. Malignant transformation of aggressive osteoblastoma to ostesarcoma.

    PubMed

    Görgün, Ömer; Salduz, Ahmet; Kebudi, Rejin; Özger, Harzem; Bilgiç, Bilge

    2016-08-01

    Osteoblastoma is a rare, bone-forming tumor, characterized by osteoid and woven bone production. A 13-year-old boy patient presented to our clinic with complaint of pain in his left proximal tibia. We performed curettage and bone grafting for the lesion diagnosed as osteoblastoma. Two years later, the patient admitted to the hospital with a mass in the same region which was diagnosed by biopsy to be osteosarcoma. Patient was performed reconstruction operation with local resection and mega prosthesis. Fourteen months after termination of chemotherapy, lung metastasis developed and the patient died consequently. In this article, we reported a patient with aggressive osteoblastoma of the left proximal tibia which recurred as an osteosarcoma and discussed the difficulties in the histopathological diagnosis and management of these patients. As some other cases in the literature, our case indicates that osteoblastomas may undergo malignant transformation. PMID:27499324

  8. CD44 enhances tumor aggressiveness by promoting tumor cell plasticity.

    PubMed

    Paulis, Yvette W J; Huijbers, Elisabeth J M; van der Schaft, Daisy W J; Soetekouw, Patricia M M B; Pauwels, Patrick; Tjan-Heijnen, Vivianne C G; Griffioen, Arjan W

    2015-08-14

    Aggressive tumor cells can obtain the ability to transdifferentiate into cells with endothelial features and thus form vasculogenic networks. This phenomenon, called vasculogenic mimicry (VM), is associated with increased tumor malignancy and poor clinical outcome. To identify novel key molecules implicated in the process of vasculogenic mimicry, microarray analysis was performed to compare gene expression profiles of aggressive (VM+) and non-aggressive (VM-) cells derived from Ewing sarcoma and breast carcinoma. We identified the CD44/c-Met signaling cascade as heavily relevant for vasculogenic mimicry. CD44 was at the center of this cascade, and highly overexpressed in aggressive tumors. Both CD44 standard isoform and its splice variant CD44v6 were linked to increased aggressiveness in VM. Since VM is most abundant in Ewing sarcoma tumors functional analyses were performed in EW7 cells. Overexpression of CD44 allowed enhanced adhesion to its extracellular matrix ligand hyaluronic acid. CD44 expression also facilitated the formation of vasculogenic structures in vitro, as CD44 knockdown experiments repressed migration and vascular network formation. From these results and the observation that CD44 expression is associated with vasculogenic structures and blood lakes in human Ewing sarcoma tissues, we conclude that CD44 increases aggressiveness in tumors through the process of vasculogenic mimicry. PMID:26189059

  9. Podocalyxin expression in malignant astrocytic tumors.

    PubMed

    Hayatsu, Norihito; Kaneko, Mika Kato; Mishima, Kazuhiko; Nishikawa, Ryo; Matsutani, Masao; Price, Janet E; Kato, Yukinari

    2008-09-19

    Podocalyxin is an anti-adhesive mucin-like transmembrane sialoglycoprotein that has been implicated in the development of aggressive forms of cancer. Podocalyxin is also known as keratan sulfate (KS) proteoglycan. Recently, we revealed that highly sulfated KS or another mucin-like transmembrane sialoglycoprotein podoplanin/aggrus is upregulated in malignant astrocytic tumors. The aim of this study is to examine the relationship between podocalyxin expression and malignant progression of astrocytic tumors. In this study, 51 astrocytic tumors were investigated for podocalyxin expression using immunohistochemistry, Western blot analysis, and quantitative real-time PCR. Immunohistochemistry detected podocalyxin on the surface of tumor cells in six of 14 anaplastic astrocytomas (42.9%) and in 17 of 31 glioblastomas (54.8%), especially around proliferating endothelial cells. In diffuse astrocytoma, podocalyxin expression was observed only in vascular endothelial cells. Podocalyxin might be associated with the malignant progression of astrocytic tumors, and be a useful prognostic marker for astrocytic tumors. PMID:18639524

  10. Podocalyxin expression in malignant astrocytic tumors

    SciTech Connect

    Hayatsu, Norihito; Kaneko, Mika Kato; Mishima, Kazuhiko; Nishikawa, Ryo; Matsutani, Masao; Price, Janet E.; Kato, Yukinari

    2008-09-19

    Podocalyxin is an anti-adhesive mucin-like transmembrane sialoglycoprotein that has been implicated in the development of aggressive forms of cancer. Podocalyxin is also known as keratan sulfate (KS) proteoglycan. Recently, we revealed that highly sulfated KS or another mucin-like transmembrane sialoglycoprotein podoplanin/aggrus is upregulated in malignant astrocytic tumors. The aim of this study is to examine the relationship between podocalyxin expression and malignant progression of astrocytic tumors. In this study, 51 astrocytic tumors were investigated for podocalyxin expression using immunohistochemistry, Western blot analysis, and quantitative real-time PCR. Immunohistochemistry detected podocalyxin on the surface of tumor cells in six of 14 anaplastic astrocytomas (42.9%) and in 17 of 31 glioblastomas (54.8%), especially around proliferating endothelial cells. In diffuse astrocytoma, podocalyxin expression was observed only in vascular endothelial cells. Podocalyxin might be associated with the malignant progression of astrocytic tumors, and be a useful prognostic marker for astrocytic tumors.

  11. Sternal Resection and Reconstruction for Malignant Phylloides Tumor.

    PubMed

    Selvakumar, Veda Padma Priya; Poonia, Dharmaram; Agrawal, Juhi; Goel, Ashish; Mehta, Sandeep; Kumar, Kapil

    2015-08-01

    Malignant phylloides tumor is a locally aggressive breast neoplasm constituting less than 1 % of all breast cancers. It has a tendency for local recurrence and management is multidisciplinary. We hereby report a case of total sternal resection and reconstruction using Biopore HDPE prosthesis for Malignant Phylloides tumor. PMID:26702245

  12. Malignant Peripheral Nerve Sheath Tumor -A Rare Malignancy in Mandible

    PubMed Central

    Majumdar, Sumit; Kotina, Sreekanth; Uppala, Divya; Kumar, Singam Praveen

    2016-01-01

    Malignant Peripheral Nerve Sheath Tumor (MPNST) is biologically an aggressive tumor that is usually found in the extremities, trunk and infrequently found in the head and neck area particularly in the jaws, arising from the cells allied with nerve sheath. Mandibular MPNST may either arise from a preexisting neurofibroma or develop de novo. Because of the greater variability from case to case in overall appearance both clinically and histologically, a case of MPNST of the mandible in a 25-year-old female patient is reported. The lesion was excised and immunohistological studies (S-100 & Neuron specific enolase) were conducted to confirm the neural origin. PMID:27504425

  13. Malignant Peripheral Nerve Sheath Tumor -A Rare Malignancy in Mandible.

    PubMed

    Majumdar, Sumit; Kotina, Sreekanth; Mahesh, Nirujogi; Uppala, Divya; Kumar, Singam Praveen

    2016-06-01

    Malignant Peripheral Nerve Sheath Tumor (MPNST) is biologically an aggressive tumor that is usually found in the extremities, trunk and infrequently found in the head and neck area particularly in the jaws, arising from the cells allied with nerve sheath. Mandibular MPNST may either arise from a preexisting neurofibroma or develop de novo. Because of the greater variability from case to case in overall appearance both clinically and histologically, a case of MPNST of the mandible in a 25-year-old female patient is reported. The lesion was excised and immunohistological studies (S-100 & Neuron specific enolase) were conducted to confirm the neural origin. PMID:27504425

  14. Calpains: markers of tumor aggressiveness?

    PubMed

    Roumes, Hélène; Leloup, Ludovic; Dargelos, Elise; Brustis, Jean-Jacques; Daury, Laetitia; Cottin, Patrick

    2010-05-15

    Rhabdomyosarcoma (RMS) are soft-tissue sarcoma commonly encountered in childhood. RMS cells can acquire invasive behavior and form metastases. The metastatic dissemination implicates many proteases among which are mu-calpain and m-calpain. Study of calpain expression and activity underline the deregulation of calpain activity in RMS. Analysis of kinetic characteristics of RMS cells, compared to human myoblasts LHCN-M2 cells, shows an important migration velocity in RMS cells. One of the major results of this study is the positive linear correlation between calpain activity and migration velocity presenting calpains as a marker of tumor aggressiveness. The RMS cytoskeleton is disorganized. Specifying the role of mu- and m-calpain using antisense oligonucleotides led to show that both calpains up-regulate alpha- and beta-actin in ARMS cells. Moreover, the invasive behavior of these cells is higher than that of LHCN-M2 cells. However, it is similar to that of non-treated LHCN-M2 cells, when calpains are inhibited. In summary, calpains may be involved in the anarchic adhesion, migration and invasion of RMS. The direct relationship between calpain activity and migration velocities or invasive behavior indicates that calpains could be considered as markers of tumor aggressiveness and as potential targets for limiting development of RMS tumor as well as their metastatic behavior. PMID:20193680

  15. [Genodermatoses with malignant skin tumors].

    PubMed

    Hübinger, L; Frank, J

    2014-06-01

    Cutaneous malignancies can manifest as isolated and sporadic tumors as well as multiple and disseminated tumors. In the latter case they often point to a genetic disease, which either can be restricted to the skin exclusively or also involve extracutaneous organs in the context of a hereditary tumor syndrome. Such hereditary tumor syndromes are clinically and genetically very heterogeneous. Therefore, the prevailing specific skin tumors play an important diagnostic role in the case of complex symptom constellations. Elucidation of the genetic basis of rare monogenetically inherited disorders and syndromes can contribute to a better understanding of the pathogenesis of frequently occurring cutaneous malignancies because the mutated genes often encode proteins, which have a key position in metabolic signaling pathways that are of high significance for the development of targeted therapies. Here we provide an overview of genodermatoses, which are associated with basal cell carcinomas, sebaceous carcinomas, keratoacanthomas, squamous cell carcinomas and malignant melanomas. PMID:24898507

  16. Malignant phylloides tumor in pregnancy.

    PubMed

    Blaker, Kristen M; Sahoo, Sunati; Schweichler, Maria R; Chagpar, Anees B

    2010-03-01

    Malignant phylloides tumors are exceedingly rare with few cases being reported in pregnancy. We describe the first case ever reported of a malignant phylloides tumor presenting in the first trimester of pregnancy and provide insight into the complexities of management as well as a review of the known literature. An extensive PubMed literature search for "cystosarcoma," "phylloides," and "pregnancy" was performed. References of each citation were reviewed. Only six previous cases of phylloides tumor in pregnancy were found, none of which were in the first trimester. Medical records of a patient presenting to our institution at 9 weeks gestation with a malignant phylloides tumor were reviewed. We further provide a review of the current literature of the management of phylloides tumor in pregnancy. A 27-year-old white G2P0SA1 woman with no family history of breast cancer presented with a right breast mass at her first prenatal examination at 9 weeks of pregnancy. Ultrasound confirmed a solid mass measuring 24 mm. Core needle biopsy demonstrated a malignant phylloides tumor. She previously had a fibroadenoma removed from the same breast 7 years previously. The current tumor was excised to clear margins. Histopathological examination revealed a 4-cm fibroepithelial tumor with marked stromal cellularity and a high mitotic count (five to seven mitoses/high-power field), confirming the diagnosis of malignant phylloides tumor. The patient continued her pregnancy without complications. Six other cases of phylloides tumor presenting in pregnancy have been reported in the literature, one of which had bilateral disease. Of these, the average patient age was 32 years (range, 28 to 35 years). The majority of these patients presented in their third trimester (mean, 29 weeks; range, 20 to 36 weeks) and often had large tumors (mean, 15 cm; range, 5 to 21 cm). Four of the seven tumors (57%) required a mastectomy. Previous cases have shown phylloides tumors to present in the third

  17. Glucocorticoid Receptor-Targeted Liposomal Codelivery of Lipophilic Drug and Anti-Hsp90 Gene: Strategy to Induce Drug-Sensitivity, EMT-Reversal, and Reduced Malignancy in Aggressive Tumors.

    PubMed

    Mondal, Sujan Kumar; Jinka, Sudhakar; Pal, Krishnendu; Nelli, Swetha; Dutta, Shamit Kumar; Wang, Enfeng; Ahmad, Ajaz; AlKharfy, Khalid M; Mukhopadhyay, Debabrata; Banerjee, Rajkumar

    2016-07-01

    Many cancers including the late stage ones become drug-resistant and undergo epithelial-to-mesenchymal transition (EMT). These lead to enhanced invasion, migration, and metastasis toward manifesting its aggressiveness and malignancy. One of the key hallmarks of cancer is its overdependence on glycolysis as its preferred energy metabolism pathway. The strict avoidance of alternate energy pathway gluconeogenesis by cancer cells points to a yet-to-be hoisted role of glucocorticoid receptor (GR) especially in tumor microenvironment, where cells are known to become drug-sensitive through induction of gluconeogenesis. However, since GR is involved in metabolism, anti-inflammatory reactions, immunity besides inducing gluconeogenesis, a greater role of GR in tumor microenvironment is envisaged. We have shown previously that GR, although ubiquitously expressed in all cells; afford to be an effective cytoplasmic target for killing cancer cells selectively. Herein, we report the therapeutic use of a newly developed GR-targeted liposomal concoction (DXE) coformulating a lipophilic drug (ESC8) and an anti-Hsp90 anticancer gene against aggressive tumor models. This induced drug-sensitivity and apoptosis while reversing EMT in tumor cells toward effective retardation of aggressive growth in pancreas and skin tumor models. Additionally, the ESC8-free lipid formulation upon cotreatment with hydrophilic drugs, gemcitabine and doxorubicin, could effectively sensitize and kill pancreatic cancer and melanoma cells, respectively. The formulation-triggered EMT-reversal was GR-dependent. Overall, we found a new strategy for drug sensitization that led to the advent of new GR-targeted anticancer therapeutics. PMID:27184196

  18. Imaging probe for tumor malignancy

    NASA Astrophysics Data System (ADS)

    Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Hasahiro

    2009-02-01

    Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions ("tumor hypoxia"). Although more than half a century has passed since it was suggested that tumor hypoxia correlated with poor treatment outcomes and contributed to cancer recurrence, a fundamental solution to this problem has yet to be found. Hypoxia-inducible factor (HIF-1) is the main transcription factor that regulates the cellular response to hypoxia. It induces various genes whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important targets of cancer therapy, particularly in therapy against refractory cancers. Imaging of the HIF-1-active microenvironment is therefore important for cancer therapy. To image HIF-1activity in vivo, we developed a PTD-ODD fusion protein, POHA, which was uniquely labeled with near-infrared fluorescent dye at the C-terminal. POHA has two functional domains: protein transduction domain (PTD) and VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of the alpha subunit of HIF-1 (HIF-1α). It can therefore be delivered to the entire body and remain stabilized in the HIF-1-active cells. When it was intravenously injected into tumor-bearing mice, a tumor-specific fluorescence signal was detected in the tumor 6 h after the injection. These results suggest that POHA can be used an imaging probe for tumor malignancy.

  19. Malignant Peripheral Nerve Sheath Tumor.

    PubMed

    James, Aaron W; Shurell, Elizabeth; Singh, Arun; Dry, Sarah M; Eilber, Fritz C

    2016-10-01

    Malignant peripheral nerve sheath tumor (MPNST) is the sixth most common type of soft tissue sarcoma. Most MPNSTs arise in association with a peripheral nerve or preexisting neurofibroma. Neurofibromatosis type is the most important risk factor for MPNST. Tumor size and fludeoxyglucose F 18 avidity are among the most helpful parameters to distinguish MPNST from a benign peripheral nerve sheath tumor. The histopathologic diagnosis is predominantly a diagnosis of light microscopy. Immunohistochemical stains are most helpful to distinguish high-grade MPNST from its histologic mimics. Current surgical management of high-grade MPNST is similar to that of other high-grade soft tissue sarcomas. PMID:27591499

  20. Tumor Metabolism of Malignant Gliomas

    PubMed Central

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang

    2013-01-01

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation. PMID:24217114

  1. Malignant Peripheral Nerve Sheath Tumors.

    PubMed

    Durbin, Adam D; Ki, Dong Hyuk; He, Shuning; Look, A Thomas

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are tumors derived from Schwann cells or Schwann cell precursors. Although rare overall, the incidence of MPNST has increased with improved clinical management of patients with the neurofibromatosis type 1 (NF1) tumor predisposition syndrome. Unfortunately, current treatment modalities for MPNST are limited, with no targeted therapies available and poor efficacy of conventional radiation and chemotherapeutic regimens. Many murine and zebrafish models of MPNST have been developed, which have helped to elucidate the genes and pathways that are dysregulated in MPNST tumorigenesis, including the p53, and the RB1, PI3K-Akt-mTOR, RAS-ERK and Wnt signaling pathways. Preclinical results have suggested that new therapies, including mTOR and ERK inhibitors, may synergize with conventional chemotherapy in human tumors. The discovery of new genome editing technologies, like CRISPR-cas9, and their successful application to the zebrafish model will enable rapid progress in the faithful modeling of MPNST molecular pathogenesis. The zebrafish model is especially suited for high throughput screening of new targeted therapeutics as well as drugs approved for other purposes, which may help to bring enhanced treatment modalities into human clinical trials for this devastating disease. PMID:27165368

  2. Multicentric malignant gastrointestinal stromal tumor.

    PubMed

    Shukla, Shailaja; Singh, Sanjeet K; Pujani, Mukta

    2009-01-01

    Malignant gastrointestinal stromal tumor (GIST) is a rare type of sarcoma that is found in the digestive system, most often in the wall of the stomach. Multiple GISTs are extremely rare and usually associated with type 1 neurofibromatosis and familial GIST.We report here a case of a 70-year-old woman who reported pain in the abdomen, loss of appetite, and weight loss for six months. Ultrasound examination showed a small bowel mass along with multiple peritoneal deposits and a mass within the liver. Barium studies were suggestive of a neoplastic pathology of the distal ileum. A differential diagnosis of adenocarcinoma/lymphoma with metastases was entertained. Perioperative findings showed two large growths arising from the jejunum and the distal ileum, along with multiple smaller nodules on the serosal surface and adjoining mesentery of the involved bowel segments. Segmental resection of the involved portions of the intestine was performed. Histopathological features were consistent with those of multicentric malignant GIST-not otherwise specified (GIST-NOS). Follow-up examination three months after surgery showed no evidence of recurrence. PMID:19568556

  3. Radiosensitized treatment of malignant brain tumors

    NASA Astrophysics Data System (ADS)

    Bloznelyte-Plesniene, Laima

    2003-12-01

    Around 12,000 deaths from glioblastoma occurs within the European Community annually. At present, the best available treatment for malignant brain tumors results in a median survival of patients of 15 months despite surgery, radiotherapy, and chemotherapy. The purpose of this paper is to review our results of radiosensitized treatment of malignant brain tumors.

  4. Malignant peripheral nerve sheath tumor of the parotid gland.

    PubMed

    Chis, Octavian; Albu, Silviu

    2014-09-01

    Malignant peripheral nerve sheath tumor (MPNST) refers to spindle cell sarcomas arising from or separating in the direction of cells of the peripheral nerve sheath. The MPNST of the parotid gland is an extremely rare tumor, usually having a poor prognosis, and only a few cases been described in the literature. In this article, we report the diagnostic and therapeutic challenges related to a new case of MPNST of the parotid. Diagnosis was made based on clinical, imaging (computed tomography scan), histologic, and immunohistochemistry findings. Despite comprehensive treatment--complete surgical resection and radiotherapy--the tumor displayed a highly aggressive course. PMID:25153067

  5. Malignant mammary tumor in female dogs: environmental contaminants

    PubMed Central

    2010-01-01

    Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7%) as having complex carcinoma and three (33.3%) with simple carcinoma. From these tumors, seven (77.8%) presented aggressiveness degree III and two (22.2%) degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits. PMID:20587072

  6. Extracorporeal Irradiation in Malignant Bone Tumors.

    PubMed

    Bhandari, R B; Jha, A K; Neupane, P; Chaurasia, P P; Sigdel, A

    2015-01-01

    Extracorporeal irradiation (ECI) is relatively a rare method used in the management of malignant bone tumors (MBT). It consists of en block removal of the tumor bearing bone segment, removal of the tumor from the bone, irradiation and re implantation back in the body. PMID:27549504

  7. Malignant Triton Tumors in Sisters with Clinical Neurofibromatosis Type 1

    PubMed Central

    Alina, Basnet; Sebastian, Jofre A.; Gerardo, Capo

    2015-01-01

    Malignant triton tumors (MTTs) are rare and aggressive sarcomas categorized as a subgroup of malignant peripheral nerve sheath tumors (MPNSTs). MTTs arise from Schwann cells of peripheral nerves or existing neurofibromas and have elements of rhabdomyoblastic differentiation. We report the occurrence of MTTs in two sisters. The first patient is a 36-year-old female who presented with left sided chest wall swelling. She also had clinical features consistent with neurofibromatosis type 1 (NF-1). Debulking of the mass showed high-grade malignant peripheral nerve sheath tumor with skeletal muscle differentiation (MTT). The patient was treated with ifosfamide and adriamycin along with radiation. Four years after treatment, she still has no evidence of disease recurrence. Her sister subsequently presented to us at the age of 42 with left sided lateral chest wall pain. Imaging showed a multicompartmental retroperitoneal cystic mass with left psoas involvement. The tumor was resected and, similarly to her sister, it showed high-grade malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation (MTT). The patient was started on chemotherapy and radiation as described above. PMID:26114002

  8. Genetics of Bladder Malignant Tumors in Childhood.

    PubMed

    Zangari, Andrea; Zaini, Johan; Gulìa, Caterina

    2016-02-01

    Bladder masses are represented by either benign or malignant entities. Malignant bladder tumors are frequent causes of disease and death in western countries. However, in children they are less common. Additionally, different features are found in childhood, in which non epithelial tumors are more common than epithelial ones. Rhabdomyosarcoma is the most common pediatric bladder tumor, but many other types of lesions may be found, such as malignant rhabdoid tumor (MRT), inflammatory myofibroblastic tumor and neuroblastoma. Other rarer tumors described in literature include urothelial carcinoma and other epithelial neoplasms. Rhabdomyosarcoma is associated to a variety of genetic syndromes and many genes are involved in tumor development. PAX3-FKHR and PAX7-FKHR (P-F) fusion state has important implications in the pathogenesis and biology of RMS, and different genes alterations are involved in the pathogenesis of P-F negative and embryonal RMS, which are the subsets of tumors most frequently affecting the bladder. These genes include p53, MEF2, MYOG, Ptch1, Gli1, Gli3, Myf5, MyoD1, NF1, NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, FBXW7, IGF1R, PDGFRA, ERBB2/4, MET, BCOR. Malignant rhabdoid tumor (MRT) usually shows SMARCB1/INI1 alterations. Anaplastic lymphoma kinase (ALK) gene translocations are the most frequently associated alterations in inflammatory myofibroblastic tumor (IMT). Few genes alterations in urothelial neoplasms have been reported in the paediatric population, which are mainly related to deletion of p16/lnk4, overexpression of CK20 and overexpression of p53. Here, we reviewed available literature to identify genes associated to bladder malignancies in children and discussed their possible relationships with these tumors. PMID:27013922

  9. Genetics of Bladder Malignant Tumors in Childhood

    PubMed Central

    Zangari, Andrea; Zaini, Johan; Gulìa, Caterina

    2016-01-01

    Bladder masses are represented by either benign or malignant entities. Malignant bladder tumors are frequent causes of disease and death in western countries. However, in children they are less common. Additionally, different features are found in childhood, in which non epithelial tumors are more common than epithelial ones. Rhabdomyosarcoma is the most common pediatric bladder tumor, but many other types of lesions may be found, such as malignant rhabdoid tumor (MRT), inflammatory myofibroblastic tumor and neuroblastoma. Other rarer tumors described in literature include urothelial carcinoma and other epithelial neoplasms. Rhabdomyosarcoma is associated to a variety of genetic syndromes and many genes are involved in tumor development. PAX3-FKHR and PAX7-FKHR (P-F) fusion state has important implications in the pathogenesis and biology of RMS, and different genes alterations are involved in the pathogenesis of P-F negative and embryonal RMS, which are the subsets of tumors most frequently affecting the bladder. These genes include p53, MEF2, MYOG, Ptch1, Gli1, Gli3, Myf5, MyoD1, NF1, NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, FBXW7, IGF1R, PDGFRA, ERBB2/4, MET, BCOR. Malignant rhabdoid tumor (MRT) usually shows SMARCB1/INI1 alterations. Anaplastic lymphoma kinase (ALK) gene translocations are the most frequently associated alterations in inflammatory myofibroblastic tumor (IMT). Few genes alterations in urothelial neoplasms have been reported in the paediatric population, which are mainly related to deletion of p16/lnk4, overexpression of CK20 and overexpression of p53. Here, we reviewed available literature to identify genes associated to bladder malignancies in children and discussed their possible relationships with these tumors. PMID:27013922

  10. Malignant phyllodes tumor of the left atrium.

    PubMed

    Bhambhani, Anupam; Ayyagari, Sudha; Mohapatra, Tushar; Rehman, Syed Abdul; Shah, Milap; Rao, Sudhakar; Rangashamanna, Vital; Rajasekhar, V; Chittimilla, Santosh

    2014-01-01

    Metastatic tumors to the heart usually involve right sided chambers. We report a rare case of malignant phyllodes tumor of breast with metastatic involvement of left atrium occurring through direct invasion from mediastinal micro-metastasis and presenting as a left atrial mass causing arrhythmia. PMID:24814127

  11. Malignant Rhabdoid Tumor of the Liver: A Case Report and Literature Review

    PubMed Central

    Oita, Satoru; Terui, Keita; Komatsu, Syugo; Hishiki, Tomoro; Saito, Takeshi; Mitsunaga, Tetsuya; Nakata, Mitsuyuki; Yoshida, Hideo

    2015-01-01

    Malignant rhabdoid tumor (MRT) is a rare and aggressive malignancy associated with poor outcomes. MRT of the liver is even rarer, and little information has been described. We report the case of an 8-month-old boy with MRT of the liver. The tumor showed aggressive progression despite a multidisciplinary approach, and the patient died due to multiple organ failure 14 days after admission. Autopsy revealed the liver tumor and multiple metastases with negative immunohistochemistry for INI1/BAF47. A review of 53 cases of pediatric MRT of the liver is provided. PMID:25918621

  12. Tumor initiating cells in malignant gliomas

    PubMed Central

    Hadjipanayis, Costas G.; Van Meir, Erwin G.

    2009-01-01

    A rare subpopulation of cells within malignant gliomas, which shares canonical properties with neural stem cells (NSCs), may be integral to glial tumor development and perpetuation. These cells, also known as tumor initiating cells (TICs), have the ability to self-renew, develop into any cell in the overall tumor population (multipotency), and proliferate. A defining property of TICs is their ability to initiate new tumors in immunocompromised mice with high efficiency. Mounting evidence suggests that TICs originate from the transformation of NSCs and their progenitors. New findings show that TICs may be more resistant to chemotherapy and radiation than the bulk of tumor cells, thereby permitting recurrent tumor formation and accounting for the failure of conventional therapies. The development of new therapeutic strategies selectively targeting TICs while sparing NSCs may provide for more effective treatment of malignant gliomas. PMID:19189072

  13. Malignant triton tumor of the chest wall invading the lung. A case report and literature review

    PubMed Central

    Kamperis, E; Barbetakis, N; Asteriou, C; Kleontas, A; Christoforidou, V

    2013-01-01

    Background: Malignant triton tumor (MTT) is an histological deviation of malignant peripheral nerve sheath tumor with additional rhabdomyosarcomatous elements. It is very rare, profoundly aggressive, with a tendency to recur locally and metastasize early. If manifests itself more often in individuals with neurofibromatosis type I (NF-1) disease but also sporadically or post radiotherapy. Description of case: A 57-year-old male was admitted with a history of malignant triton tumor of the chest wall. Despite prior aggressive locoregional treatment including wide excision and adjuvant consolidating radiotherapy, the tumor recurred. The patient underwent a new operation and systemic chemotherapy, but expired a few months later due to disease progression. Conclusion: MTT is exceedingly malignant requiring multimodality treatment. The cornerstone of management is radical surgical resection with clear margins. Nevertheless, the overall prognosis remains dismal. PMID:24470743

  14. Autocrine growth factors and solid tumor malignancy.

    PubMed Central

    Walsh, J. H.; Karnes, W. E.; Cuttitta, F.; Walker, A.

    1991-01-01

    The ability of malignant cells to escape the constraint that normally regulate cell growth and differentiation has been a primary focus of attention for investigators of cancer cell biology. An outcome of this attention has been the discovery that the protein products of oncogenes play a role in the activation of growth signal pathways. A second outcome, possibly related to abnormal oncogene expression, has been the discovery that malignant cells frequently show an ability to regulate their own growth by the release of autocrine growth modulatory substances. Most important, the growth of certain malignant cell types has been shown to depend on autocrine growth circuits. A malignant tumor whose continued growth depends on the release of an autocrine growth factor may be vulnerable to treatment with specific receptor antagonists or immunoneutralizing antibodies designed to break the autocrine circuit. Information is rapidly emerging concerning autocrine growth factors in selected human solid tissue malignancy. Images PMID:1926844

  15. Massive exophytic malignant peripheral nerve sheath tumor.

    PubMed

    Khorsand, Derek; Porrino, Jack; Flaherty, Erin; Bandhlish, Anshu; Davidson, Darin

    2016-06-01

    We present a case of a solitary neurofibroma involving the right posterior shoulder of a 69-year-old man with degeneration into a massive, malignant peripheral nerve sheath tumor measuring more than 3 times the average reported size. The radiographic, magnetic resonance imaging, and computed tomographic features are compared with the gross appearance and pathology. PMID:27257459

  16. Arsenic trioxide inhibits tumor cell growth in malignant rhabdoid tumors in vitro and in vivo by targeting overexpressed Gli1.

    PubMed

    Kerl, Kornelius; Moreno, Natalia; Holsten, Till; Ahlfeld, Julia; Mertins, Julius; Hotfilder, Marc; Kool, Marcel; Bartelheim, Kerstin; Schleicher, Sabine; Handgretinger, Rupert; Schüller, Ulrich; Meisterernst, Michael; Frühwald, Michael C

    2014-08-15

    Rhabdoid tumors are highly aggressive tumors occurring in infants and very young children. Despite multimodal and intensive therapy prognosis remains poor. Molecular analyses have uncovered several deregulated pathways, among them the CDK4/6-Rb-, the WNT- and the Sonic hedgehog (SHH) pathways. The SHH pathway is activated in rhabdoid tumors by GLI1 overexpression. Here, we demonstrate that arsenic trioxide (ATO) inhibits tumor cell growth of malignant rhabdoid tumors in vitro and in a mouse xenograft model by suppressing Gli1. Our data uncover ATO as a promising therapeutic approach to improve prognosis for rhabdoid tumor patients. PMID:24420698

  17. Malignant metastatic carcinoid presenting as brain tumor

    PubMed Central

    Sundar, I. Vijay; Jain, S. K.; Kurmi, Dhrubajyoti; Sharma, Rakesh; Chopra, Sanjeev; Singhvi, Shashi

    2016-01-01

    Carcinoid tumors are rarely known to metastasise to the brain. It is even more rare for such patients to present with symptoms related to metastases as the initial and only symptom. We present a case of a 60-year-old man who presented with hemiparesis and imaging features suggestive of brain tumor. He underwent surgery and the histopathology revealed metastatic malignant lesion of neuroendocrine origin. A subsequent work up for the primary was negative. Patient was treated with adjuvant radiotherapy. We present this case to highlight the pathophysiological features, workup and treatment options of this rare disease and discuss the methods of differentiating it from more common brain tumors. PMID:27366273

  18. Malignant metastatic carcinoid presenting as brain tumor.

    PubMed

    Sundar, I Vijay; Jain, S K; Kurmi, Dhrubajyoti; Sharma, Rakesh; Chopra, Sanjeev; Singhvi, Shashi

    2016-01-01

    Carcinoid tumors are rarely known to metastasise to the brain. It is even more rare for such patients to present with symptoms related to metastases as the initial and only symptom. We present a case of a 60-year-old man who presented with hemiparesis and imaging features suggestive of brain tumor. He underwent surgery and the histopathology revealed metastatic malignant lesion of neuroendocrine origin. A subsequent work up for the primary was negative. Patient was treated with adjuvant radiotherapy. We present this case to highlight the pathophysiological features, workup and treatment options of this rare disease and discuss the methods of differentiating it from more common brain tumors. PMID:27366273

  19. General Information about Ovarian Low Malignant Potential Tumors

    MedlinePlus

    ... Malignant Potential Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Low Malignant Potential Tumors Go to ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  20. All children with malignant rhabdoid tumors should be treated initially with intensive chemotherapy.

    PubMed

    Hernández-Marqués, C; Lassaletta, A; Cormenzana, M; García-Esparza, E; Madero-López, L

    2015-04-01

    Malignant rhabdoid tumors (MRT) of soft tissues are aggressive tumors, which can be detected in almost any part of the body. MRT are rare, and very few cases have been reported in the literature. Prognosis of these tumors is extremely poor despite intensive therapy. Some risk factors such as young age or disseminated disease are associated with an aggressive and almost always lethal clinical course. Some clinicians even recommend initial palliative care due to this outcome. We report a case of metastatic MRT in a 6-month-old child with excellent initial response to chemotherapy. PMID:24852450

  1. Malignant Solitary Fibrous Tumor of the Scalp.

    PubMed

    Shirley, Brett M; Kang, David R; Sakamoto, Aya Hamao

    2016-07-01

    Solitary fibrous tumors are an uncommon slow growing benign neoplasm originally described as a pleural neoplasm but can also be found in the lung, mediastinum, peritoneum, or any other sites including the head and neck. Malignant solitary fibrous tumors (MSFT) are extremely rare and only few cases have been published in the literature. There have been 19 cases reported of MSFT in the head and neck, but there are no reports of MSFT located within the scalp in the English language literature. We present a case of MSFT arising in the scalp and describe our experience with the clinical presentation, surgical management, and outcome in this pathological condition. PMID:27408445

  2. Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib.

    PubMed

    Wei, Lei; Liu, Song; Conroy, Jeffrey; Wang, Jianmin; Papanicolau-Sengos, Antonios; Glenn, Sean T; Murakami, Mitsuko; Liu, Lu; Hu, Qiang; Conroy, Jacob; Miles, Kiersten Marie; Nowak, David E; Liu, Biao; Qin, Maochun; Bshara, Wiam; Omilian, Angela R; Head, Karen; Bianchi, Michael; Burgher, Blake; Darlak, Christopher; Kane, John; Merzianu, Mihai; Cheney, Richard; Fabiano, Andrew; Salerno, Kilian; Talati, Chetasi; Khushalani, Nikhil I; Trump, Donald L; Johnson, Candace S; Morrison, Carl D

    2015-10-01

    Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise <2% of all granular cell tumors, are associated with aggressive behavior and poor clinical outcome, and are poorly understood in terms of tumor etiology and systematic treatment. Because of its rarity, the genetic basis of malignant granular cell tumor remains unknown. We performed whole-genome sequencing of one malignant granular cell tumor with metabolic response to pazopanib. This tumor exhibited a very low mutation rate and an overall stable genome with local complex rearrangements. The mutation signature was dominated by C>T transitions, particularly when immediately preceded by a 5' G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation. PMID:27148567

  3. Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib

    PubMed Central

    Wei, Lei; Liu, Song; Conroy, Jeffrey; Wang, Jianmin; Papanicolau-Sengos, Antonios; Glenn, Sean T.; Murakami, Mitsuko; Liu, Lu; Hu, Qiang; Conroy, Jacob; Miles, Kiersten Marie; Nowak, David E.; Liu, Biao; Qin, Maochun; Bshara, Wiam; Omilian, Angela R.; Head, Karen; Bianchi, Michael; Burgher, Blake; Darlak, Christopher; Kane, John; Merzianu, Mihai; Cheney, Richard; Fabiano, Andrew; Salerno, Kilian; Talati, Chetasi; Khushalani, Nikhil I.; Trump, Donald L.; Johnson, Candace S.; Morrison, Carl D.

    2015-01-01

    Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise <2% of all granular cell tumors, are associated with aggressive behavior and poor clinical outcome, and are poorly understood in terms of tumor etiology and systematic treatment. Because of its rarity, the genetic basis of malignant granular cell tumor remains unknown. We performed whole-genome sequencing of one malignant granular cell tumor with metabolic response to pazopanib. This tumor exhibited a very low mutation rate and an overall stable genome with local complex rearrangements. The mutation signature was dominated by C>T transitions, particularly when immediately preceded by a 5′ G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation. PMID:27148567

  4. Oral malignant melanoma: An aggressive clinical entity - Report of a rare case with review of literature

    PubMed Central

    Hasan, Shamimul; Jamdar, Sami Faisal; Jangra, Jogender; Al Beaiji, Sadun Mohammad Al Ageel

    2016-01-01

    Melanomais one of the most dreaded and aggressive neoplasms, being derived from epidermal melanocytes. The majority of melanomas are seen to involve the skin, and primary mucosal melanomas account for less than 1% of all melanomas. Oral malignant melanomas (OMM) are asymptomatic at the initial presentation, but later they become painful with growth and expansion. In the late stages, the patient may present with ulceration, bleeding, tooth mobility, paresthesia, ill-fitting prosthesis, and delayed healing of the extraction sockets. Diagnosis is often delayed due to asymptomatic clinical presentation, with silent progression of the lesion. OMM are associated with poor prognosis due to their invasive and metastasizing tendencies. The condition has poor survival rates, and metastatic melanomas show even worse prognosis. The 5-year survival rate for OMM ranges 4.5–29%, with 18.5 months being the mean survival rate. The tumor is best managed by wide surgical resection; however, consideration should also be made for adjunctive therapies such as chemotherapy, immunotherapy, and radiotherapy. Recurrences may be seen even 10–15 years after the primary therapy. This paper aims to present an interesting report of aggressive OMM in a 50-year-old male patient and emphasizes the role of dental professionals in maintaining a high degree of vigilance for the pigmented lesions of the oral cavity. Pigmented lesions of uncertain origin should be routinely biopsied to rule out malignancy. Early diagnosis of this dreadful entity entails thorough history taking, physical examination, and radiographic features coupled with histopathology. PMID:27114959

  5. Oral malignant melanoma: An aggressive clinical entity - Report of a rare case with review of literature.

    PubMed

    Hasan, Shamimul; Jamdar, Sami Faisal; Jangra, Jogender; Al Beaiji, Sadun Mohammad Al Ageel

    2016-01-01

    Melanomais one of the most dreaded and aggressive neoplasms, being derived from epidermal melanocytes. The majority of melanomas are seen to involve the skin, and primary mucosal melanomas account for less than 1% of all melanomas. Oral malignant melanomas (OMM) are asymptomatic at the initial presentation, but later they become painful with growth and expansion. In the late stages, the patient may present with ulceration, bleeding, tooth mobility, paresthesia, ill-fitting prosthesis, and delayed healing of the extraction sockets. Diagnosis is often delayed due to asymptomatic clinical presentation, with silent progression of the lesion. OMM are associated with poor prognosis due to their invasive and metastasizing tendencies. The condition has poor survival rates, and metastatic melanomas show even worse prognosis. The 5-year survival rate for OMM ranges 4.5-29%, with 18.5 months being the mean survival rate. The tumor is best managed by wide surgical resection; however, consideration should also be made for adjunctive therapies such as chemotherapy, immunotherapy, and radiotherapy. Recurrences may be seen even 10-15 years after the primary therapy. This paper aims to present an interesting report of aggressive OMM in a 50-year-old male patient and emphasizes the role of dental professionals in maintaining a high degree of vigilance for the pigmented lesions of the oral cavity. Pigmented lesions of uncertain origin should be routinely biopsied to rule out malignancy. Early diagnosis of this dreadful entity entails thorough history taking, physical examination, and radiographic features coupled with histopathology. PMID:27114959

  6. Giant malignant phylloides tumor: case report.

    PubMed

    Arcuri, M F; Del Rio, P; Martella, E M; Bezer, L; Sianesi, M

    2007-01-01

    The incidence of phylloides breast tumors is less than 1% in the population affected by breast cancers. The age at higher risk is between 35 and 45 years. These neoplasms are characterized by a proliferation of mesenchimal and epithelial cells. We present a rare case of giant malignant phylloides tumor (28 x 21 x 15 cm) with a complet substitution of the gland. The clinical presentation of phylloides tumors is heterogenous; the surgical treatment is a conservative one of the gland if the neoplastic lesion size is less than 5 cm with a free margin of 1 cm and a mastectomy if the diameter of lesion is more than 5 cm. Complementary therapies still remain controversial. PMID:17626767

  7. Immature Teratoma with Embryonal Carcinoma; a Rare Malignant Mixed Germ Cell Tumor in a 13-Year-Old Girl.

    PubMed

    Rana, Shweta; Gill, Manmeet Kaur; Kalhan, Shivani; Satarkar, Rahul N; Sangwaiya, Ashok; Singh, Pawan

    2016-01-01

    Malignant mixed germ cell tumors,though rare overall, are the most common type of malignant ovarian neoplasms in young and adolescent girls. These tumors are rapidly growing and can metastasize. We report a case of 13-yr-old girl who presented at SHKM GMC, Nalhar, Mewat, Haryana, India in December 2013 with huge abdominal lump of a malignant mixed germ cell tumor comprising both immature teratoma and embryonal carcinoma. This report illustrates the aggressiveness of this tumor and emphasises the need of early diagnosis and treatment. PMID:26870146

  8. Immature Teratoma with Embryonal Carcinoma; a Rare Malignant Mixed Germ Cell Tumor in a 13-Year-Old Girl

    PubMed Central

    Rana, Shweta; Gill, Manmeet¬_Kaur; Kalhan, Shivani¬; Satarkar, Rahul N; Sangwaiya, Ashok; Singh, Pawan

    2016-01-01

    Malignant mixed germ cell tumors,though rare overall, are the most common type of malignant ovarian neoplasms in young and adolescent girls. These tumors are rapidly growing and can metastasize. We report a case of 13-yr-old girl who presented at SHKM GMC, Nalhar, Mewat, Haryana, India in December 2013 with huge abdominal lump of a malignant mixed germ cell tumor comprising both immature teratoma and embryonal carcinoma. This report illustrates the aggressiveness of this tumor and emphasises the need of early diagnosis and treatment. PMID:26870146

  9. Photodynamic Therapy for Malignant Brain Tumors.

    PubMed

    Akimoto, Jiro

    2016-04-15

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area. PMID:26888042

  10. Photodynamic Therapy for Malignant Brain Tumors

    PubMed Central

    AKIMOTO, Jiro

    2016-01-01

    Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women’s Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area. PMID:26888042

  11. Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy.

    PubMed

    Morrone, Fernanda B; Gehring, Marina P; Nicoletti, Natália F

    2016-09-01

    Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calcium-permeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca(2+) activity plays an important role in the regulation of cell proliferation, and Ca(2+) signaling is altered in proliferating tumor cells. A series of previous studies emphasized the importance of the T-type low-voltage-gated calcium channels (VGCC) in different cancer types, including gliomas, and remarkably, pharmacologic inhibition of T-type VGCC caused antiproliferative effects and triggered apoptosis of human glioma cells. Other calcium permeable channels, such as transient receptor potential (TRP) channels, contribute to changes in Ca(2+) by modulating the driving force for Ca(2+) entry, and some TRP channels are required for proliferation and migration in gliomas. Furthermore, recent evidence shows that TRP channels contribute to the progression and survival of the glioblastoma patients. Likewise, the purinergic P2X7 receptor acts as a direct conduit for Ca(2+)-influx and an indirect activator of voltage-gated Ca(2+)-channel. Evidence also shows that P2X7 receptor activation is linked to elevated expression of inflammation promoting factors, tumor cell migration, an increase in intracellular mobilization of Ca(2+), and membrane depolarization in gliomas. Therefore, this review summarizes the recent findings on calcium channels and associated receptors as potential targets to treat malignant gliomas. PMID:27418672

  12. Photodynamic therapy of advanced malignant tumors

    NASA Astrophysics Data System (ADS)

    Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

    1993-03-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

  13. PTEN: Multiple Functions in Human Malignant Tumors

    PubMed Central

    Milella, Michele; Falcone, Italia; Conciatori, Fabiana; Cesta Incani, Ursula; Del Curatolo, Anais; Inzerilli, Nicola; Nuzzo, Carmen M. A.; Vaccaro, Vanja; Vari, Sabrina; Cognetti, Francesco; Ciuffreda, Ludovica

    2015-01-01

    PTEN is the most important negative regulator of the PI3K signaling pathway. In addition to its canonical, PI3K inhibition-dependent functions, PTEN can also function as a tumor suppressor in a PI3K-independent manner. Indeed, the PTEN network regulates a broad spectrum of biological functions, modulating the flow of information from membrane-bound growth factor receptors to nuclear transcription factors, occurring in concert with other tumor suppressors and oncogenic signaling pathways. PTEN acts through its lipid and protein phosphatase activity and other non-enzymatic mechanisms. Studies conducted over the past 10 years have expanded our understanding of the biological role of PTEN, showing that in addition to its ability to regulate proliferation and cell survival, it also plays an intriguing role in regulating genomic stability, cell migration, stem cell self-renewal, and tumor microenvironment. Changes in PTEN protein levels, location, and enzymatic activity through various molecular mechanisms can generate a continuum of functional PTEN levels in inherited syndromes, sporadic cancers, and other diseases. PTEN activity can indeed, be modulated by mutations, epigenetic silencing, transcriptional repression, aberrant protein localization, and post-translational modifications. This review will discuss our current understanding of the biological role of PTEN, how PTEN expression and activity are regulated, and the consequences of PTEN dysregulation in human malignant tumors. PMID:25763354

  14. Proprotein Convertases in Tumor Progression and Malignancy

    PubMed Central

    Khatib, Abdel-Majid; Siegfried, Géraldine; Chrétien, Michel; Metrakos, Peter; Seidah, Nabil G.

    2002-01-01

    The mammalian subtilisin/kexin-like proprotein convertase (PC) family has been implicated in the activation of a wide spectrum of proteins. These proteins are usually synthesized as inactive precursors before their conversion to fully mature bioactive forms. A large majority of these active proteins such as matrix metalloproteases, growth factors, and adhesion molecules are crucial in the processes of cellular transformation, acquisition of the tumorigenic phenotype, and metastases formation. Inhibition of PCs significantly affects the malignant phenotype of various tumor cells. In addition to direct tumor cell proliferation and migration blockade, PC inhibitors can also be used to target tumor angiogenesis. In this Review article we discuss a number of recent findings on the clinical relevance of PCs in cancer patients, their implication in the regulation of multiple cellular functions that impact on the invasive/metastatic potential of cancer cells. Thus, PC inhibitors may constitute new promising agents for the treatment of multiple tumors and/or in adjuvant therapy to prevent recurrence. PMID:12057895

  15. Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness

    PubMed Central

    Adamo, Hanibal Hani; Strömvall, Kerstin; Nilsson, Maria; Halin Bergström, Sofia; Bergh, Anders

    2015-01-01

    In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues. PMID:26536349

  16. More Complete Removal of Malignant Brain Tumors by Fluorescence-Guided Surgery

    ClinicalTrials.gov

    2016-05-13

    Benign Neoplasms, Brain; Brain Cancer; Brain Neoplasms, Benign; Brain Neoplasms, Malignant; Brain Tumor, Primary; Brain Tumor, Recurrent; Brain Tumors; Intracranial Neoplasms; Neoplasms, Brain; Neoplasms, Intracranial; Primary Brain Neoplasms; Primary Malignant Brain Neoplasms; Primary Malignant Brain Tumors; Gliomas; Glioblastoma

  17. Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

    PubMed Central

    Ford, Catriona A.; Petrova, Sofia; Pound, John D.; Voss, Jorine J.L.P.; Melville, Lynsey; Paterson, Margaret; Farnworth, Sarah L.; Gallimore, Awen M.; Cuff, Simone; Wheadon, Helen; Dobbin, Edwina; Ogden, Carol Anne; Dumitriu, Ingrid E.; Dunbar, Donald R.; Murray, Paul G.; Ruckerl, Dominik; Allen, Judith E.; Hume, David A.; van Rooijen, Nico; Goodlad, John R.; Freeman, Tom C.; Gregory, Christopher D.

    2015-01-01

    Summary Background Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Results Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. Conclusions In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. PMID:25702581

  18. PDT for malignant tumors: a clinical analysis of 152 cases

    NASA Astrophysics Data System (ADS)

    Zhuang, Shi-Zhang; Wang, Yun-Zhen; Li, Xin; Zhang, Changjun; Wang, Jian-Zhao; Zhang, Da-Ren

    1993-03-01

    Hematoporphyrin derivative (HPD) laser photodynamic therapy (PDT) was applied for the patients of 152 cases of malignant tumors, including tumors of the lip, tongue, esophagus, urinary bladder, skin, larynx, vagina, etc. Since early 1981 good results have been obtained.

  19. [Pelvic actinomycosis simulating adnexal malignant tumor].

    PubMed

    Benkiran, L; Gamra, L; Lamalmi, N; Essouyeh, M; Regragui, A; Amrani, M; Souadka, A; Melabbas, M A

    2002-01-01

    The purpose of this report is to describe the case of a 35-year-old patient admitted to the National Oncology Institute in Rabat, Morocco for pelvic pain and deteriorating general status ongoing for 8 months. Clinical and ultrasonographic examination showed a heterogenous mass measuring 7 cm in maximum width located inferior and lateral to the inferior aspect of the right side of the uterus. These findings were suggestive of a malignant tumor of the right ovary. Ovariectomy and omentectomy were performed. Histological examination of surgical specimens demonstrated right tubo-ovarian actinomycosis associated with peritonitis. Genital tract actinomycosis is an uncommon finding in women of childbearing age. It is due to colonization by a pyogenic bacteria (Actinomyces) usually secondary to a gastrointestinal infection, e.g. ileocecum, and sometimes in association with the presence of an intrauterine device or foreign body. Based on this case report, the authors discuss abdominopelvic actinomyocosis with emphasis on tumor-like findings that can lead to misdiagnosis by clinicians and radiologists. PMID:12038184

  20. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    ClinicalTrials.gov

    2016-04-12

    Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

  1. A colonization of basal cell carcinoma by malignant melanoma in situ resembling a malignant basomelanocytic tumor.

    PubMed

    Goeser, Megan; DiMaio, Dominick J

    2014-11-01

    We report a case of colonization of basal cell carcinoma (BCC) by malignant melanoma in situ (MIS) simulating a malignant basomelanocytic tumor. A biopsy of a pigmented lesion present on an 83-year-old man's scalp displayed intimate admixing of basaloid and melanocytic cells. This seemingly inseparable combination of BCC and neoplastic melanocytes has been referred to as a malignant basomelanocytic tumor. However, our case also displays an adjacent component of MIS, thus favoring colonization of BCC by MIS as the etiology. To our knowledge, this is the third case report of colonization of BCC by MIS resembling a malignant basomelanocytic tumor. PMID:24752214

  2. Primary malignant small bowel tumors: an atypical abdominal emergency.

    PubMed Central

    Mitchell, K. J.; Williams, E. S.; Leffall, L. D.

    1995-01-01

    Primary malignant tumors of the small bowel are uncommon in the United States. They comprise less than 1% of all gastrointestinal malignancies, with an incidence of 2200 cases per year. The clinical presentation of small bowel tumors is frequently insidious and often overlooked by physicians. The low incidence and lack of pathognomonic symptoms are the reasons that the early diagnosis of malignant small bowel tumor is uncommon. To better understand the clinical presentation, diagnostic evaluation, management, and outcome, a review of Howard University patients with primary malignant small bowel tumors between 1970 and 1990 was conducted. Our experience concurs with the reported literature and supports the conclusion that a high index of suspicion is necessary. The diagnosis of a malignant small bowel tumor should be considered in patients with vague chronic abdominal complaints. Images Figure 1 Figure 2 PMID:7752280

  3. Uterine malignant mixed Müllerian tumor camouflaging as pelvic sarcoma.

    PubMed

    Monappa, Vidya; Kudva, Ranjini; Hasan, Roumina

    2015-01-01

    Malignant mixed Müllerian tumors (MMMTs) of the uterus are rare, aggressive tumors that present at an advanced stage and are associated with poor prognosis. They arise as a result of divergent carcinomatous and mesenchymal differentiation of tumor stem cells. Rarely one of the components may predominate contributing to diagnostic confusion. We present a rare case of uterine MMMT arising in endometrial adenocarcinoma, camouflaging as pelvic sarcoma with a major sarcomatous component. This case report highlights the importance of thorough tissue sampling and the role of immunohistochemistry (IHC) in arriving at an accurate diagnosis. This case also demonstrates the conversion theory of histogenesis of MMMTs. PMID:26881567

  4. Radiation-induced malignant and atypical peripheral nerve sheath tumors

    SciTech Connect

    Foley, K.M.; Woodruff, J.M.; Ellis, F.T.; Posner, J.B.

    1980-04-01

    The reported peripheral nerve complications of therapeutic irradiation in humans include brachial and lumbar plexus fibrosis and cranial and peripheral nerve atrophy. We have encountered 9 patients with malignant (7) and atypical (2) peripheral nerve tumors occurring in an irradiated site suggesting that such tumors represent another delayed effect of radiation treatment on peripheral nerve. In all instances the radio-theray was within an acceptable radiation dosage, yet 3 patients developed local radiation-induced skin and bony abnormalities. The malignant peripheral nerve sheath tumors developed only in the radiation port. Animal studies support the clinical observation that malignant peripheral nerve sheath tumors can occur as a delayed effect of irradiation.

  5. Basosquamous carcinoma: is it an aggressive tumor?

    PubMed

    Kececi, Yavuz; Argon, Asuman; Kebat, Tulug; Sir, Emin; Gungor, Melike; Vardar, Enver

    2015-04-01

    Basosquamous carcinoma is a rare cutaneous tumour that is considered an aggressive type of basal cell carcinoma with an increased risk of recurrence and metastases. This impression has been perpetuated in the literature, despite limited scientific data and conflicting results of some authors. This present study was aimed to evaluate the clinical-pathological features of this tumour and follow-up of a series of basosquamous carcinoma. Basosquamous carcinoma patients who underwent surgical excision between January 2000 and February 2012 were analyzed retrospectively. Their medical files were reviewed and the corresponding routinely stained sections (with hematoxylin-eosin) were re-evaluated by two pathologists. Thirty-five patients with basosquamous carcinoma were operated on in this period. Most tumurs were located in the head and neck area (94%), and the mean age of the patients was 69.8 years. Margin involvements were seen in 11 patients (31.4%) and all of them underwent re-excision. There was only one local recurrence. There was neither regional lymph node nor distant metastasis in this series. The recurrence rate of basosquamous carcinoma is found as 4%, lower than that of most other similar studies. Further pathologic studies are needed to better classify basosquamous carcinoma and to increase consistency between the results of studies. Surgical excision and regular follow-up are considered as the treatment of choice. PMID:25139415

  6. Malignant Tenosynovial Giant Cell Tumor of the Leg: A Radiologic-Pathologic Correlation and Review of the Literature

    PubMed Central

    Richman, Danielle M; Bresler, Scott C; Rosenthal, Michael H; Howard, Stephanie Anne Holler

    2015-01-01

    Malignant tenosynovial giant cell tumor (TGCT) is a rare clinical entity that can arise as a recurrent lesion or can co-exist with a benign TGCT lesion. Malignant TGCT most commonly arises in the lower extremity and tends to be clinically aggressive, with most patients developing recurrent lesions or dying. Much of the literature describes the histopathologic features and classifies this broad group of tumors, with little description of the imaging characteristics of this disease. We present the multimodality appearance of a case of malignant diffuse-type TGCT that recurred 2 months after resection with subsequent rapid clinical progression. PMID:25861547

  7. Malignant tenosynovial giant cell tumor of the leg: a radiologic-pathologic correlation and review of the literature.

    PubMed

    Richman, Danielle M; Bresler, Scott C; Rosenthal, Michael H; Howard, Stephanie Anne Holler

    2015-01-01

    Malignant tenosynovial giant cell tumor (TGCT) is a rare clinical entity that can arise as a recurrent lesion or can co-exist with a benign TGCT lesion. Malignant TGCT most commonly arises in the lower extremity and tends to be clinically aggressive, with most patients developing recurrent lesions or dying. Much of the literature describes the histopathologic features and classifies this broad group of tumors, with little description of the imaging characteristics of this disease. We present the multimodality appearance of a case of malignant diffuse-type TGCT that recurred 2 months after resection with subsequent rapid clinical progression. PMID:25861547

  8. Caveolin-1 overexpression in benign and malignant salivary gland tumors.

    PubMed

    Jaafari-Ashkavandi, Zohreh; Ashraf, Mohammad Javad; Nazhvani, Ali Dehghani; Azizi, Zahra

    2016-02-01

    Caveolin-1, a tyrosine-phosphorylated protein, is supposed to have different regulatory roles as promoter or suppressor in many human cancers. However, no published study concerned its expression in benign and malignant salivary gland tumors. The aim of this study was to evaluate and compare the expression of Cav-1 in the most common benign and malignant salivary gland tumors and evaluate its correlation with proliferation activity. In this cross-sectional retrospective study, immunohistochemical expression of caveolin-1 and Ki67 were evaluated in 49 samples, including 11 normal salivary glands, 15 cases of pleomorphic adenoma (PA), 13 adenoid cystic carcinomas (AdCC), and 10 mucoepidermoid carcinomas (MEC). The expression of Cav-1 was seen in 18 % of normal salivary glands and 85 % of tumors. The immunoreaction in the tumors was significantly higher than normal tissues (P = 0.001), but the difference between benign and malignant tumors was not significant (P = 0.07). Expression of Cav-1 was correlated with Ki67 labeling index in PAs, but not in malignant tumors. Cav-1 expression was not in association with tumor size and stage. Overexpression of Cav-1 was found in salivary gland tumors in comparison with normal tissues, but no significant difference was observed between benign and malignant tumors. Cav-1 was inversely correlated with proliferation in PA. Therefore, this marker may participate in tumorigenesis of salivary gland tumors and may be a potential biomarker for cancer treatments. PMID:26323261

  9. Transformation of benign fibroadenoma to malignant phyllodes tumor.

    PubMed

    Sanders, Linda M; Daigle, Megan E; Tortora, Matthew; Panasiti, Ryane

    2015-07-01

    The transformation of a benign fibroadenoma into a phyllodes tumor is uncommon and unpredictable. We report the case of a 40-year-old woman with a core biopsy proven fibroadenoma that underwent transformation into a malignant phyllodes tumor after 3 years of size stability. We present ultrasound and magnetic resonance images, as well as pathology slides from core biopsy and surgical excision, to illustrate this transformation. It has been suggested that phyllodes tumors may be misdiagnosed as fibroadenomas by core biopsy. However, in this case, pathology supports correct initial diagnosis of fibroadenoma and demonstrates a portion of the original fibroadenoma along the periphery of the malignant phyllodes tumor. PMID:26331090

  10. Rare Malignant Tumors of the Breast

    PubMed Central

    Miller, Trevor; Albarracin, Constance; Carkaci, Selin; Whitman, Gary J; Adrada, Beatriz E

    2015-01-01

    While the more common forms of breast cancer are well understood and recognized, there are many important rare malignancies that are less appreciated. Many of these cancers have imaging findings that, when understood, help to formulate a more educated differential diagnosis. In this article, the clinical features, imaging, and pathologic findings of rare breast malignancies will be discussed. PMID:26664775

  11. Delay in treatment of primary malignant and aggressive musculoskeletal tumours.

    PubMed

    Pan, K L; Zolqarnain, A; Chia, Y Y

    2006-02-01

    Patients with aggressive musculoskeletal tumours often arrive at specialised treatment centres late. Such a delay could mean disfavour for potentially curable or long-term disease-free outcome of limb preserving surgery. This study was undertaken to identify the underlying problem-related delay with a view to propose solution for solving it. We reviewed 30 patients to determine the periods of delay between onset of the first symptom and the definitive treatment. The delays were categorized as 'patient' delay, 'referral' delay and 'treatment' delay. There was 'patient' delay in 57% of patients (n=17), ranging from 1 to 18 months; 'referral' delay in 67% of patients (n=20) ranging from 1 to 19 months and 23% of patients (n=7) had treatment delay (average 23 days) at the treatment centre. The causes of late arrival are not solely patient-related but are multifactorial. Measures to minimize such delays include enhancing awareness only with high index of suspicion among primary care practitioners, creating a special lane specialized imaging studies and establishing a dedicated musculoskeletal tumour unit. PMID:17042231

  12. [Classification of malignant tumors of suprarenal glands].

    PubMed

    Komissarenko, I V; Rybakov, S I; Kvacheniuk, A N

    2004-09-01

    The extent of diagnostic possibilities of medical technique, permitting to reveal the majority of suprarenal tumors, and the most modem information technologies as well demands creation of the suprarenal tumors applicable classification, well-adopted for physician in practice and also for scientist dealing with analysis of the investigation results in these pathology. Taking into account hormonal activity of majority of tumors, influencing the patients management tactic, the authors propose the insight on suprarenal tumor diagnosis of their own. PMID:15560595

  13. Malignant mast cell tumor in an African hedgehog (Atelerix albiventris).

    PubMed

    Raymond, J T; White, M R; Janovitz, E B

    1997-01-01

    In November 1995, a malignant mast cell tumor (mastocytoma) was diagnosed in an adult African hedgehog (Atelerix albiventris) from a zoological park (West Lafayette, Indiana, USA). The primary mast cell tumor presented as a firm subcutaneous mass along the ventrum of the neck. Metastasis to the right submandibular lymph node occurred. PMID:9027702

  14. Malignant giant cell tumor of soft parts in a mare

    PubMed Central

    Marryatt, Paige A.

    2003-01-01

    Two subcutaneous masses were removed from the elbow of a mare. Histologically they were composed of islands of polygonal to plump spindlelioid cells with large nuclei, coarsely stippled chromatin, and eosinophilic cytoplasm. Findings were diagnostic for a malignant giant cell tumor of soft parts, a rare tumor with a fair prognosis. PMID:14524631

  15. Reconstruction after resection of malignant parapharyngeal space tumor

    PubMed Central

    Umezawa, Hiroki; Nakamizo, Munenaga; Yokoshima, Kazuhiko; Nara, Shimpei; Ogawa, Rei; Hyakusoku, Hiko

    2014-01-01

    Abstract Primary malignant tumor of the parapharyngeal space (PPS) is rare. After surgical resection, primary closure could be considered if the oropharynx mucosa remains. This report describes two patients who underwent reconstruction by free tissue transfer after the resection of PPS tumors. This report was presented at the 56th annual meeting of the Japanese Society of Plastic and Reconstructive Surgery, 4 April, 2013.

  16. Applications of Nanomaterials in Radiotherapy for Malignant Tumors.

    PubMed

    Wang, Yanchao; Liang, Ruichao; Fang, Fang

    2015-08-01

    Malignant tumors are tremendous heath problems facing by the medical world. In order to achieve the purpose of curing malignant tumor, numerous therapeutic strategies have been developed. Radiotherapy is one of the main therapeutic strategies for malignant tumors. Current imaging strategies cannot display exact infiltrating margins, radio-resistance generated by irradiated tissue, and intercurrent damage to healthy tissues during radiotherapy. Therefore, novel strategies to solve these problems are urgently needed. Nanomaterials have specific physical and biological properties that can help clinician to distinguish margins of infiltrating tumors as a novel contrast agent. Besides, nanoparticles can significantly enhance the effect of radiotherapy by generating reactive oxygen species (ROS) or influence cell cycle. In addition, nanomaterials can also help in diminishing the intercurrent damage caused by radiotherapy. So nanomaterials have very promising prospect in the radiotherapy of malignant tumors. This review mainly focuses on the applications of nanomaterials in radiotherapy for malignant tumors; especially it applies to lesion imaging and their radiosensitizing effects. PMID:26369108

  17. Galectin-3 as a Potential Therapeutic Target in Tumors Arising from Malignant Endothelia1

    PubMed Central

    Johnson, Kim D; Glinskii, Olga V; Mossine, Valeri V; Turk, James R; Mawhinney, Thomas P; Anthony, Douglas C; Henry, Carolyn J; Huxley, Virginia H; Glinsky, Gennadi V; Pienta, Kenneth J; Raz, Avraham; Glinsky, Vladislav V

    2007-01-01

    Angiosarcoma (ASA) in humans and hemangiosarcoma (HSA) in dogs are deadly neoplastic diseases characterized by an aggressive growth of malignant cells with endothelial phenotype, widespread metastasis, and poor response to chemotherapy. Galectin-3 (Gal-3), a β-galactoside-binding lectin implicated in tumor progression and metastasis, endothelial cell biology and angiogenesis, and regulation of apoptosis and neoplastic cell response to cytotoxic drugs, has not been studied before in tumors arising from malignant endothelia. Here, we tested the hypothesis that Gal-3 could be widely expressed in human ASA and canine HSA and could play an important role in malignant endothelial cell biology. Immunohistochemical analysis demonstrated that 100% of the human ASA (10 of 10) and canine HSA (17 of 17) samples analyzed expressed Gal-3. Two carbohydrate-based Gal-3 inhibitors, modified citrus pectin (MCP) and lactulosyl-l-leucine (LL), caused a dose-dependent reduction of SVR murine ASA cell clonogenic survival through the inhibition of Gal-3 antiapoptotic function. Furthermore, both MCP and LL sensitized SVR cells to the cytotoxic drug doxorubicin to a degree sufficient to reduce the in vitro IC50 of doxorubicin by 10.7-fold and 3.6-fold, respectively. These results highlight the important role of Gal-3 in the biology of ASA and identify Gal-3 as a potential therapeutic target in tumors arising from malignant endothelial cells. PMID:17786185

  18. Immunotherapy of Malignancy by in vivo Gene Transfer into Tumors

    NASA Astrophysics Data System (ADS)

    Plautz, Gregory E.; Yang, Zhi-Yong; Wu, Bei-Yue; Gao, Xiang; Huang, Leaf; Nabel, Gary J.

    1993-05-01

    The immune system confers protection against a variety of pathogens and contributes to the surveillance and destruction of neoplastic cells. Several cell types participate in the recognition and lysis of tumors, and appropriate immune stimulation provides therapeutic effects in malignancy. Foreign major histocompatibility complex (MHC) proteins also serve as a potent stimulus to the immune system. In this report, a foreign MHC gene was introduced directly into malignant tumors in vivo in an effort to stimulate tumor rejection. In contrast to previous attempts to induce tumor immunity by cell-mediated gene transfer, the recombinant gene was introduced directly into tumors in vivo. Expression of the murine class I H-2K^s gene within the CT26 mouse colon adenocarcinoma (H-2K^d) or the MCA 106 fibrosarcoma (H-2K^b) induced a cytotoxic T-cell response to H-2K^s and, more importantly, to other antigens present on unmodified tumor cells. This immune response attenuated tumor growth and caused complete tumor regression in many cases. Direct gene transfer in vivo can therefore induce cell-mediated immunity against specific gene products, which provides an immunotherapeutic effect for malignancy, and potentially can be applied to the treatment of cancer and infectious diseases in man.

  19. MMSET is overexpressed in cancers: Link with tumor aggressiveness

    SciTech Connect

    Kassambara, Alboukadel; Klein, Bernard Moreaux, Jerome

    2009-02-20

    MMSET is expressed ubiquitously in early development and its deletion is associated with the malformation syndrome called Wolf-Hirschhorn syndrome. It is involved in the t(4; 14) (p16; q32) chromosomal translocation, which is the second most common translocation in multiple myeloma (MM) and is associated with the worst prognosis. MMSET expression has been shown to promote cellular adhesion, clonogenic growth and tumorigenicity in multiple myeloma. MMSET expression has been recently shown to increase with ascending tumor proliferation activity in glioblastoma multiforme. These data demonstrate that MMSET could be implicated in tumor emergence and/or progression. Therefore, we compared the expression of MMSET in 40 human tumor types - brain, epithelial, lymphoid - to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database. We found significant overexpression of MMSET in 15 cancers compared to their normal counterparts. Furthermore MMSET is associated with tumor aggressiveness or prognosis in many types of these aforementioned cancers. Taken together, these data suggest that MMSET potentially acts as a pathogenic agent in many cancers. The identification of the targets of MMSET and their role in cell growth and survival will be key to understand how MMSET is associated with tumor development.

  20. Serous Ovarian Carcinoma Recurring as Malignant Mixed Mullerian Tumor

    PubMed Central

    Hale, Demir; Senem, Demiroz Ahu; Ovgu, Aydin; Hakan, Erenel; Sennur, Ilvan; Zerrin, Calay; Fuat, Demirkiran

    2015-01-01

    Only five cases of recurrence of malignant mixed Mullerian tumor (carcinosarcoma) from the ovarian carcinoma have been published in the literature to our knowledge. A 64-year-old woman first underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy because of pelvic mass. Histological diagnosis was serous papillary carcinoma of the left ovary. After six courses of chemotherapy, CA125 level returned to normal range. However, she had persistent multiple mediastinal and para-aortic lymphadenopathies in spite of additional six courses of chemotherapy. Then she underwent the second operation about 2 years after primary surgery. Multiple excisional biopsies were taken from subcutaneous tissue, over the bowels and the left external iliac artery. The histopathological diagnosis which was confirmed by immunohistochemical study was malignant mixed Mullerian tumor for all metastatic foci. A rare case of ovarian serous papillary carcinoma recurring as malignant mixed Mullerian tumor is reported. PMID:26713165

  1. Endometriosis Mimicking an Advanced Malignant Tumor.

    PubMed

    Wang, Taisong; Xing, Yan; Zhao, Jinhua

    2016-08-01

    A 27-year-old woman with swelling left leg, groin pain, and increased serum CA125 level underwent FDG PET/CT to evaluate a pelvic mass revealed by an MRI performed from an outside hospital. A large hypermetabolic solid mass in the left pelvic wall and several lymph nodes with elevated FDG activity were noted, which indicated malignancy. However, histopathological examination demonstrated endometriosis. PMID:27187736

  2. Large malignant ovarian tumors during pregnancy: two cases

    PubMed Central

    Xu, Dong; Liang, Cheng; He, Jing

    2014-01-01

    The present study reports two cases of large ovarian malignancy during pregnancy, which is very rare. The two patients were received between Nov 2012 and Feb 2013 at Gynecological and Obstetrical Department, Women’s Hospital, School of Medicine, Zhejiang University (People’s Republic of China). Both cases present tumor sized more than 20 cm, with one case of 40 cm. Both patients underwent timely cesarean section, with survival of the Child, and successful removal of the tumor. All patients showed good outcome in the follow-up period. Therefore the large ovarian malignancy during pregnancy could be well treated after careful clinical evaluation. PMID:25484595

  3. Magnetic resonance imaging of less common pancreatic malignancies and pancreatic tumors with malignant potential

    PubMed Central

    Franz, D.; Esposito, I.; Kapp, A.-C.; Gaa, J.; Rummeny, E.J.

    2014-01-01

    Pancreatic tumors are an increasingly common finding in abdominal imaging. Various kinds of pathologies of the pancreas are well known, but it often remains difficult to classify the lesions radiologically in respect of type and grade of malignancy. Magnetic resonance imaging (MRI) is the method of choice for the evaluation of pancreatic pathologies due to its superior soft tissue contrast. In this article we present a selection of less common malignant and potentially malignant pancreatic neoplasms with their characteristic appearance on established MRI sequences with and without contrast enhancement. PMID:26937427

  4. APRIL promotes breast tumor growth and metastasis and is associated with aggressive basal breast cancer.

    PubMed

    García-Castro, Araceli; Zonca, Manuela; Florindo-Pinheiro, Douglas; Carvalho-Pinto, Carla E; Cordero, Alex; Gutiérrez del Fernando, Burgo; García-Grande, Aránzazu; Mañes, Santos; Hahne, Michael; González-Suárez, Eva; Planelles, Lourdes

    2015-05-01

    APRIL (a proliferation-inducing ligand) is a cytokine of the tumor necrosis factor family associated mainly with hematologic malignancies. APRIL is also overexpressed in breast carcinoma tissue lesions, although neither its role in breast tumorigenesis nor the underlying molecular mechanism is known. Here, we show that several breast cancer cell lines express APRIL and both its receptors, B cell maturation antigen (BCMA) and transmembrane activator and CAML-interactor (TACI), independently of luminal or basal tumor cell phenotype, and that the mitogen-activated protein kinases p38, ERK1/2, and JNK1/2 are activated in response to APRIL. The inflammatory stimulus poly I:C, a toll-like receptor (TLR) 3 ligand, enhanced APRIL secretion. Silencing experiments decreased cell proliferation, demonstrating that APRIL is a critical autocrine factor for breast tumor growth. Studies of 4T1 orthotopic breast tumors in APRIL transgenic mice showed that an APRIL-enriched environment increased tumor growth and promoted lung metastasis associated with enhanced tumor cell proliferation; BCMA and TACI expression suggests that both participate in these processes. We detected APRIL, BCMA and TACI in human luminal, triple-negative breast carcinomas and HER2 breast carcinomas, with increased levels in more aggressive basal tumors. APRIL was observed near Ki67(+) nuclei and was distributed heterogeneously in the cancer cells, in the leukocyte infiltrate, and in the myoepithelial layer adjacent to the tumor area; these results imply that APRIL provides proliferation signals to tumor cells through paracrine and autocrine signaling. Our study identifies participation of APRIL signaling in breast cancer promotion; we propose impairment of this pathway as a potential therapeutic strategy. PMID:25750171

  5. Adenoviral virotherapy for malignant brain tumors

    PubMed Central

    Nandi, Suvobroto; Lesniak, Maciej S

    2009-01-01

    Glioblastoma multiforme (GBM) is the most common form of primary brain cancer. In the past decade, virotherapy of tumors has gained credence, particularly in glioma management, as these tumors are not completely resectable and tend to micro-metastasize. Adenoviral vectors have an advantage over other viral vectors in that they are relatively non-toxic and do not integrate in the genome. However, the lack of coxsackie and adenovirus receptors (CAR) on surface of gliomas provides for inefficient transduction of wild-type adenoviral vectors in these tumors. By targeting receptors that are over-expressed in gliomas, modified adenoviral constructs have been shown to efficiently infect glioma cells. In addition, by taking advantage of tumor specific promoter (TSP) elements, oncolytic adenoviral vectors offer the promise of selective tumor-specific replication. This dual targeting strategy has enabled specificity in both laboratory and pre-clinical settings. This review looks at current trends in adenoviral virotherapy of gliomas, with an emphasis on targeting modalities and future clinical applications. PMID:19456208

  6. Adenoviral virotherapy for malignant brain tumors.

    PubMed

    Nandi, Suvobroto; Lesniak, Maciej S

    2009-06-01

    Glioblastoma multiforme is the most common form of primary brain cancer. In the past decade, virotherapy of tumors has gained credence, particularly in glioma management, as these tumors are not completely resectable and tend to micro-metastasize. Adenoviral vectors have an advantage over other viral vectors in that they are relatively non-toxic and do not integrate in the genome. However, the lack of coxsackie and adenovirus receptors on surface of gliomas provides for inefficient transduction of wild-type adenoviral vectors in these tumors. By targeting receptors that are overexpressed in gliomas, modified adenoviral constructs have been shown to efficiently infect glioma cells. In addition, by taking advantage of tumor-specific promoter elements, oncolytic adenoviral vectors offer the promise of selective tumor-specific replication. This dual targeting strategy has enabled specificity in both laboratory and pre-clinical settings. This review examines current trends in adenoviral virotherapy of gliomas, with an emphasis on targeting modalities and future clinical applications. PMID:19456208

  7. Ovarian mucinous tumor with malignant mural nodules: dedifferentiation or collision?

    PubMed

    Desouki, Mohamed M; Khabele, Dineo; Crispens, Marta A; Fadare, Oluwole

    2015-01-01

    Ovarian mucinous tumors with mural nodules are rare surface epithelial-stromal tumors. The mural nodules are divergent neoplasms that may be benign or malignant. The latter may be in the form of a sarcoma, carcinosarcoma, anaplastic carcinoma, or a variety of other recognized histotypes of carcinoma, which raises the question of whether malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors or whether they represent collision tumors. We recently reported the K-RAS gene mutation status in a case of ovarian mucinous adenocarcinoma with mural nodule of high-grade sarcoma. The mucinous and sarcomatous components revealed a mutation in codon 12 of the K-RAS gene of a different nucleotide substitution, indicating that these 2 tumor components were different clones of the same tumor. Herein, we are reporting another case of a 20-yr-old woman who presented with 22 cm pelvic mass, omental caking, and ascites. A diagnosis of invasive mucinous carcinoma with mural nodules of anaplastic carcinoma was rendered. K-RAS gene mutation studies revealed p.G12V, c.35G>T mutation in the 2 components of the tumor, which is the most common mutation reported in mucinous tumors of the ovary. The fact that sarcomatous or anaplastic carcinomatous mural nodules in ovarian mucinous tumors display the same K-RAS mutations as their underlying mucinous neoplasms provides supportive evidence that at least some malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors, rather than a collision of 2 divergent tumor types. PMID:25473748

  8. Updated Management of Malignant Biliary Tract Tumors: An Illustrative Review.

    PubMed

    Cannavale, Alessandro; Santoni, Mariangela; Gazzetti, Marianna; Maher, Ben; Fanelli, Fabrizio; Fiocca, Fausto; Catalano, Carlo

    2016-07-01

    The management of malignant biliary tumors (MBTs) is complex and requires a multidisciplinary approach. Guidelines and methods of staging for biliary tumors have recently been released by main international societies, altering the clinical and radiologic approach to this pathologic condition. The aim of the present review is to detail the updated role of imaging in preoperative staging and follow-up and to illustrate clinical/therapeutic pathways. In addition, future perspectives on imaging and targeted/embolization therapies are outlined. PMID:27107982

  9. MTA1 Expression in Benign and Malignant Salivary gland Tumors

    PubMed Central

    Andisheh-Tadbir, Azadeh; Dehghani-Nazhvani, Ali; Ashraf, Mohammad Javad; Khademi, Bijan; Mirhadi, Hosein; Torabi-Ardekani, Shima

    2016-01-01

    Introduction: Salivary gland tumors (SGTs) are important parts of human neoplasms. The most common SGT is pleomorphic adenoma and the most common malignant SGTs are mucoepidermoid carcinoma and adenoid cystic carcinoma (ACC). Metastasis-associated genes 1 (MTA1), a member of the nucleosome remodeling and histone deacetylation complex, is one newly discovered gene which recruits histone deacetylation, causing ATP-dependent chromosome remodeling, and regulating transcription. MTA1 had been shown to be overexpressed in malignant tumors with the enhancement of invasion and metastasis. Materials and Methods: Fifty-six samples of salivary gland tumors from the Khalili Hospital archive, including 20 cases of pleomorphic adenoma, 17 cases of mucoepidermoid carcinoma, 19 cases of ACC, and 23 cases of normal salivary gland tissues were chosen for immunohistochemical analysis of MTA1. Results: MTA1 expression in the malignant tumors was significantly higher than that in pleomorphic adenoma (P<0.001), and higher in pleomorphic adenoma than the normal salivary glands(P< 0.001). In total, 69.6% of normal salivary gland tissues showed MTA1, but all cases of salivary gland tumors were positive for MTA1. High nuclear expression of MTA1 was detected in 83.3% (30/36) of the malignant salivary gland tumors and 45% (9/20) of pleomorphic adenoma, while low MTA1 expression was seen in all of the normal salivary gland tissues. No statistically significant correlation was found between MTA1 protein expression and any clinicopathological features (P>0.05). Conclusion: Our findings demonstrate that MTA1 was significantly overexpressed in malignant salivary gland neoplasm in comparison to a lower level in benign pleomorphic adenoma, suggesting that MTA1 protein might be involved in carcinogenesis. PMID:26878004

  10. [Glutamate and malignant gliomas, from epilepsia to biological aggressiveness: therapeutic implications].

    PubMed

    Blecic, Serge; Rynkowski, Michal; De Witte, Olivier; Lefranc, Florence

    2013-09-01

    In this review article, we describe the unrecognized roles of glutamate and glutamate receptors in malignant glioma biology. The neurotransmitter glutamate released from malignant glioma cells in the extracellular matrix is responsible for seizure induction and at higher concentration neuronal cell death. This neuronal cell death will create vacated place for tumor growth. Glutamate also stimulates the growth and the migration of glial tumor cells by means of the activation of glutamate receptors on glioma cells in a paracrine and autocrine manner. The multitude of effects of glutamate in glioma biology supports the rationale for pharmacological targeting of glutamate receptors and transporters in the adjuvant treatment of malignant gliomas in neurology and neuro-oncology. Using the website www.clinicaltrials.gov/ as a reference - a service developed by the National Library of Medicine for the National Health Institute in USA - we have evoked the few clinical trials completed and currently ongoing with therapies targeting the glutamate receptors. PMID:23883552

  11. Vascular patterns provide therapeutic targets in aggressive neuroblastic tumors

    PubMed Central

    Tadeo, Irene; Bueno, Gloria; Berbegall, Ana P.; Fernández-Carrobles, M. Milagro; Castel, Victoria; García-Rojo, Marcial; Navarro, Samuel; Noguera, Rosa

    2016-01-01

    Angiogenesis is essential for tumor growth and metastasis, nevertheless, in NB, results between different studies on angiogenesis have yielded contradictory results. An image analysis tool was developed to characterize the density, size and shape of total blood vessels and vascular segments in 458 primary neuroblastic tumors contained in tissue microarrays. The results were correlated with clinical and biological features of known prognostic value and with risk of progression to establish histological vascular patterns associated with different degrees of malignancy. Total blood vessels were larger, more abundant and more irregularly-shaped in tumors of patients with associated poor prognostic factors than in the favorable cohort. Tumor capillaries were less abundant and sinusoids more abundant in the patient cohort with unfavorable prognostic factors. Additionally, size of post-capillaries & metarterioles as well as higher sinusoid density can be included as predictive factors for survival. These patterns may therefore help to provide more accurate pre-treatment risk stratification, and could provide candidate targets for novel therapies. PMID:26918726

  12. TUMOR CONTAMINATION IN THE BIOPSY PATH OF PRIMARY MALIGNANT BONE TUMORS

    PubMed Central

    Oliveira, Marcelo Parente; Lima, Pablo Moura de Andrade; de Mello, Roberto José Vieira

    2015-01-01

    Objective: To study factors possibly associated with tumor contamination in the biopsy path of primary malignant bone tumors. Method: Thirty-five patients who underwent surgical treatment with diagnoses of osteosarcoma, Ewing's tumor and chondrosarcoma were studied retrospectively. The sample was analyzed to characterize the biopsy technique used, histological type of the tumor, neoadjuvant chemotherapy used, local recurrences and tumor contamination in the biopsy path. Results: Among the 35 patients studied, four cases of contamination occurred (11.43%): one from osteosarcoma, two from Ewing's tumor and one from chondrosarcoma. There was no association between the type of tumor and presence of tumor contamination in the biopsy path (p = 0.65). There was also no association between the presence of tumor contamination and the biopsy technique (p = 0.06). On the other hand, there were associations between the presence of tumor contamination and local recurrence (p = 0.01) and between tumor contamination and absence of neoadjuvant chemotherapy (p = 0.02). Conclusion: Tumor contamination in the biopsy path of primary malignant bone tumors was associated with local recurrence. On the other hand, the histological type of the tumor and the type of biopsy did not have an influence on tumor contamination. Neoadjuvant chemotherapy had a protective effect against this complication. Despite these findings, tumor contamination is a complication that should always be taken into consideration, and removal of the biopsy path is recommended in tumor resection surgery. PMID:27047877

  13. Chemotherapy for malignant brain tumors of childhood

    PubMed Central

    Gottardo, Nicholas G.; Gajjar, Amar

    2009-01-01

    During the past 3 decades, chemotherapeutic agents have been extensively evaluated for the treatment of pediatric brain tumors in a myriad of schedules, doses, and combinations. Remarkable advances in outcome have been achieved for certain groups of children, notably those with medulloblastoma, and chemotherapy has played a key role. However, improvements in survival are obtained at a high cost to quality of life. In addition, the success achieved for medulloblastoma is offset by a lack of progress for high-grade glioma. Despite decades of intensive investigation, no single chemotherapeutic regimen stands out as particularly beneficial for children with high-grade glioma, with the vast majority of these patients succumbing to their disease. A plateau in efficacy has been reached. Further treatment intensification using conventional nonspecific chemotherapy is more likely to result in additional toxicity without major advances in survival. Genomewide analysis using microarray technology has contributed significantly to our understanding of tumor biology. This knowledge has shifted the focus onto novel agents that target molecular changes crucial for tumor proliferation or survival. These selective agents are likely to be less toxic to normal cells and it is anticipated they will be more effective than the nonspecific chemotherapeutic agents currently used. PMID:18952581

  14. Inhibition of PAI-1 Limits Tumor Angiogenesis Regardless of Angiogenic Stimuli in Malignant Pleural Mesothelioma.

    PubMed

    Takayama, Yusuke; Hattori, Noboru; Hamada, Hironobu; Masuda, Takeshi; Omori, Keitaro; Akita, Shin; Iwamoto, Hiroshi; Fujitaka, Kazunori; Kohno, Nobuoki

    2016-06-01

    Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor that secretes various angiogenic factors. The main inhibitor of plasminogen activators, PAI-1 (SERPINE1), has been implicated in tumor progression and angiogenesis, and high PAI-1 expression has been associated with poor prognosis in MPM patients. In this study, we examined the antiangiogenic effects of PAI-1 inhibition in MPM. We administered the PAI-1 inhibitor, SK-216, to orthotopic mouse models in which MPM cells expressing high levels of VEGF (VEGFA) or bFGF (FGF2) were intrapleurally transplanted. SK-216 administration reduced tumor weights and the degree of angiogenesis in intrapleural tumors, irrespective of their angiogenic expression profiles. In addition, a combination of SK-216 and the chemotherapeutic agent cisplatin significantly reduced tumor weights compared with monotherapy, prolonging the survival of animals compared with cisplatin treatment alone. Furthermore, SK-216 inhibited migration and tube formation of cultured human umbilical vein endothelial cells induced by various angiogenic factors known to be secreted by MPM. These findings suggest that PAI-1 inactivation by SK-216 may represent a general strategy for inhibiting angiogenesis, including for the treatment of MPM. Cancer Res; 76(11); 3285-94. ©2016 AACR. PMID:27197170

  15. A Rare Case of Breast Malignant Phyllodes Tumor With Metastases to the Kidney: Case Report.

    PubMed

    Karczmarek-Borowska, Bożenna; Bukala, Agnieszka; Syrek-Kaplita, Karolina; Ksiazek, Mariusz; Filipowska, Justyna; Gradalska-Lampart, Monika

    2015-08-01

    Phyllodes tumors are rare breast neoplasms. Surgery is the treatment of choice. The role of postoperative radiotherapy and chemotherapy is still under dispute, as there are no equivocal prognostic factors. Treatment failure results in the occurrence of distant metastasis-mainly to the lungs, bones, liver, and brain. We have described the case of a woman with a malignant phyllodes tumor of the breast that was surgically treated. She did not receive adjuvant therapy because there is no consensus on the role of postoperative chemotherapy and radiotherapy. One year following the surgery, the patient had left-sided nephrectomy performed because of a rapidly growing tumor of the kidney. Renal cancer was suspected; however, a histopathological examination revealed that it was a metastatic phyllodes tumor. At the same time, the patient was diagnosed as having metastases in the other kidney, the lungs, liver, and bones.Our case report describes not only an unusual localization of the metastases (in the kidneys), but also failure of the chemotherapy and the aggressive course of malignant phyllodes tumor. Identification of patients with high risk for distant metastasis and the introduction of uniform rules for the management of adjuvant chemotherapy and radiotherapy would make planning treatment as efficacious as possible. PMID:26287414

  16. A Rare Case of Breast Malignant Phyllodes Tumor With Metastases to the Kidney

    PubMed Central

    Karczmarek-Borowska, Bożenna; Bukala, Agnieszka; Syrek-Kaplita, Karolina; Ksiazek, Mariusz; Filipowska, Justyna; Gradalska-Lampart, Monika

    2015-01-01

    Abstract Phyllodes tumors are rare breast neoplasms. Surgery is the treatment of choice. The role of postoperative radiotherapy and chemotherapy is still under dispute, as there are no equivocal prognostic factors. Treatment failure results in the occurrence of distant metastasis—mainly to the lungs, bones, liver, and brain. We have described the case of a woman with a malignant phyllodes tumor of the breast that was surgically treated. She did not receive adjuvant therapy because there is no consensus on the role of postoperative chemotherapy and radiotherapy. One year following the surgery, the patient had left-sided nephrectomy performed because of a rapidly growing tumor of the kidney. Renal cancer was suspected; however, a histopathological examination revealed that it was a metastatic phyllodes tumor. At the same time, the patient was diagnosed as having metastases in the other kidney, the lungs, liver, and bones. Our case report describes not only an unusual localization of the metastases (in the kidneys), but also failure of the chemotherapy and the aggressive course of malignant phyllodes tumor. Identification of patients with high risk for distant metastasis and the introduction of uniform rules for the management of adjuvant chemotherapy and radiotherapy would make planning treatment as efficacious as possible. PMID:26287414

  17. Malignant Clear Cell Acanthoma: Report of a Rare Case of Clear Cell Acanthoma-Like Tumor With Malignant Features.

    PubMed

    Lin, Chien-Yio; Lee, Li-Yu; Kuo, Tseng-Tong

    2016-07-01

    An erythematous and moist tumor nodule on the left temple of a 92-year-old woman was biopsied and identified as a clear cell acanthoma (CCA)-like tumor with malignant cytology and high proliferation activity. This case is similar to 2 cases reported previously as atypical CCA. The authors believe that these tumors are malignant counterparts of CCA and propose to call them malignant CCA. The clinicopathologic features of the present case are described along with dermoscopic findings. PMID:26885606

  18. Mutational Landscape of Aggressive Prostate Tumors in African American Men.

    PubMed

    Lindquist, Karla J; Paris, Pamela L; Hoffmann, Thomas J; Cardin, Niall J; Kazma, Rémi; Mefford, Joel A; Simko, Jeffrey P; Ngo, Vy; Chen, Yalei; Levin, Albert M; Chitale, Dhananjay; Helfand, Brian T; Catalona, William J; Rybicki, Benjamin A; Witte, John S

    2016-04-01

    Prostate cancer is the most frequently diagnosed and second most fatal nonskin cancer among men in the United States. African American men are two times more likely to develop and die of prostate cancer compared with men of other ancestries. Previous whole genome or exome tumor-sequencing studies of prostate cancer have primarily focused on men of European ancestry. In this study, we sequenced and characterized somatic mutations in aggressive (Gleason ≥7, stage ≥T2b) prostate tumors from 24 African American patients. We describe the locations and prevalence of small somatic mutations (up to 50 bases in length), copy number aberrations, and structural rearrangements in the tumor genomes compared with patient-matched normal genomes. We observed several mutation patterns consistent with previous studies, such as large copy number aberrations in chromosome 8 and complex rearrangement chains. However, TMPRSS2-ERG gene fusions and PTEN losses occurred in only 21% and 8% of the African American patients, respectively, far less common than in patients of European ancestry. We also identified mutations that appeared specific to or more common in African American patients, including a novel CDC27-OAT gene fusion occurring in 17% of patients. The genomic aberrations reported in this study warrant further investigation of their biologic significant role in the incidence and clinical outcomes of prostate cancer in African Americans. Cancer Res; 76(7); 1860-8. ©2016 AACR. PMID:26921337

  19. Recurrent Intrapulmonary Solitary Fibrous Tumor With Malignant Transformation.

    PubMed

    Inoue, Takuya; Owada, Yuki; Watanabe, Yuzuru; Muto, Satoshi; Okabe, Naoyuki; Yonechi, Atsushi; Kanno, Ryuzo; Suzuki, Hiroyuki

    2016-07-01

    Intrapulmonary solitary fibrous tumor (SFT) of the pleura; the so-called inverted pattern, which appears to grow into the lung parenchyma, is extremely rare. We experienced a 66-year-old woman with an intrapulmonary SFT that recurred locally with malignant transformation 2 years after wedge resection of the left upper lobe for the primary tumor. Subsequently, she underwent a lobectomy of the residual left upper lobe. Six years after the second operation she was well, without rerecurrence. Complete excision and long-term follow-up of intrapulmonary SFTs of the pleura are important, even when the primary tumor displays benign histopathologic features. PMID:27343529

  20. Study of grows of spontaneous malignant tumors using LASCA microscopy

    NASA Astrophysics Data System (ADS)

    Golova, Alina; Laskavy, Vladislav; Ulianova, Onega; Polyanina, Tatyana; Bogoutdinov, Nail; Feodorova, Valentina; Ulyanov, Sergey

    2014-01-01

    Methods t-LASCA and s-LASCA has been adopted for diagnostics of malignant tissue on animal models. Investigations of tumors on inbred mice (line BALB/c) after the inoculation of syngeneic myeloma cells (line Sp.2/0-Ag.8) and on inbred mice (line SHK) with spontaneous tumors have been carried out. The efficiency of application of t-LASCA with illumination by wide laser beam for tumor investigations has been proven. It also has been found that method of LASCA with illumination of tissue by strongly focused laser beam is absolutely non-productive.

  1. Molecular subtypes of serous borderline ovarian tumor show distinct expression patterns of benign tumor and malignant tumor-associated signatures.

    PubMed

    Curry, Edward W J; Stronach, Euan A; Rama, Nona R; Wang, Yuepeng Y P; Gabra, Hani; El-Bahrawy, Mona A

    2014-03-01

    Borderline ovarian tumors show heterogeneity in clinical behavior. Most have excellent prognosis, although a small percentage show recurrence or progressive disease, usually to low-grade serous carcinoma. The aim of this study was to understand the molecular relationship between these entities and identify potential markers of tumor progression and therapeutic targets. We studied gene expression using Affymetrix HGU133plus2 GeneChip microarrays in 3 low-grade serous carcinomas, 13 serous borderline tumors and 8 serous cystadenomas. An independent data set of 18 serous borderline tumors and 3 low-grade serous carcinomas was used for validation. Unsupervised clustering revealed clear separation of benign and malignant tumors, whereas borderline tumors showed two distinct groups, one clustering with benign and the other with malignant tumors. The segregation into benign- and malignant-like borderline molecular subtypes was reproducible on applying the same analysis to an independent publicly available data set. We identified 50 genes that separate borderline tumors into their subgroups. Functional enrichment analysis of genes that separate borderline tumors to the two subgroups highlights a cell adhesion signature for the malignant-like subset, with Claudins particularly prominent. This is the first report of molecular subtypes of borderline tumors based on gene expression profiling. Our results provide the basis for identification of biomarkers for the malignant potential of borderline ovarian tumor and potential therapeutic targets for low-grade serous carcinoma. PMID:23948749

  2. Malignant soft tissue tumors in children.

    PubMed

    Thacker, Mihir M

    2013-10-01

    Soft tissue masses are frequently seen in children. Although most are benign or reactive, soft tissue sarcomas (STS)-both rhabdomyosarcoma (most common) and non-rhabdo STS, do occur in the extremities. Appropriate evaluation of extremity soft tissue tumors often includes a biopsy as the clinical and imaging features may not be enough to establish a definitive diagnosis. Much needs to be done for improving the treatment of these rare but often devastating sarcomas. Given the small numbers of these cases seen at various centers, collaborative efforts should be made to further our understanding and improve the management of these challenging cases. PMID:24095080

  3. Tumor type influences the effectiveness of pleurodesis in malignant effusions.

    PubMed

    Bielsa, Silvia; Hernández, Paula; Rodriguez-Panadero, Francisco; Taberner, Teresa; Salud, Antonieta; Porcel, José M

    2011-04-01

    Pleurodesis is commonly indicated for symptom relief in patients with malignant pleural effusions. A number of factors may influence pleurodesis outcome, but whether tumor type is one of them is a matter of debate. This study investigates the impact of tumor type on the efficacy of bedside doxycycline and thoracoscopic talc poudrage pleurodesis in order to determine which patients may benefit most from these procedures. A retrospective study of 138 and 450 doxycycline and talc poudrage pleurodesis procedures, respectively, evaluated their overall successes and failures, according to primary tumor types. In addition, a logistic regression model addressed whether the pleurodesis outcome in different tumor types was influenced by or attributable to pleural tumor burden. In the talc group, patients with lung cancer and mesothelioma had significantly lower complete response rates (63 and 61%, respectively) as compared with breast (77%) and other metastatic effusions (74%, p = 0.012). In the doxycycline group, the data followed the same trend in that complete response rates were lower in patients with lung carcinomas (31%) than in those with breast cancer (54%) or metastases from other primary sites (74%, p = 0.001). The regression analysis showed pleural burden and tumor type as independent predictors of pleurodesis failure in the talc group. The tumor type involving the pleural surfaces influences the success of a pleurodesis, regardless of the sclerosing agent used. Malignant effusions due to mesothelioma and lung cancer are particularly prone to a failed procedure. PMID:21331598

  4. No Detectable Hypoxia in Malignant Salivary Gland Tumors: Preliminary Results

    SciTech Connect

    Wijffels, Karien; Hoogsteen, Ilse J.; Lok, Jasper; Rijken, Paulus F.J.W.; Marres, Henri A.M.; Wilde, Peter C.M. de; Kogel, Albert J. van der; Kaanders, Johannes H.A.M.

    2009-04-01

    Purpose: Hypoxia is detected in most solid tumors and is associated with malignant progression and adverse treatment outcomes. However, the oxygenation status of malignant salivary gland tumors has not been previously studied. The aim of this study was to investigate the potential clinical relevance of hypoxia in this tumor type. Methods and Materials: Twelve patients scheduled for surgical resection of a salivary gland tumor were preoperatively injected with the hypoxia marker pimonidazole and the proliferation marker iododeoxyuridine. Tissue samples of the dissected tumor were immunohistochemically stained for blood vessels, pimonidazole, carbonic anhydrase-IX, glucose transporters-1 and -3 (Glut-1, Glut-3), hypoxia-inducible factor-1{alpha}, iododeoxyuridine, and epidermal growth factor receptor. The tissue sections were quantitatively assessed by computerized image analysis. Results: The tissue material from 8 patients was of sufficient quality for quantitative analysis. All tumors were negative for pimonidazole binding, as well as for carbonic anhydrase-IX, Glut-1, Glut-3, and hypoxia-inducible factor-1{alpha}. The vascular density was high, with a median value of 285 mm{sup -2} (range, 209-546). The iododeoxyuridine-labeling index varied from <0.1% to 12.2% (median, 2.2%). Epidermal growth factor receptor expression levels were mostly moderate to high. In one-half of the cases, nuclear expression of epidermal growth factor receptor was observed. Conclusion: The absence of detectable pimonidazole binding, as well as the lack of expression of hypoxia-associated proteins in all tumors, indicates that malignant salivary gland tumors are generally well oxygenated. It is unlikely that hypoxia is a relevant factor for their clinical behavior and treatment responsiveness.

  5. Targeting CSCs in Tumor Microenvironment: The Potential Role of ROS-Associated miRNAs in Tumor Aggressiveness

    PubMed Central

    Bao, Bin; Azmi, Asfar S.; Li, Yiwei; Ahmad, Aamir; Ali, Shadan; Banerjee, Sanjeev; Kong, Dejuan; Sarkar, Fazlul H.

    2015-01-01

    Reactive oxygen species (ROS) have been widely considered as critical cellular signaling molecules involving in various biological processes such as cell growth, differentiation, proliferation, apoptosis, and angiogenesis. The homeostasis of ROS is critical to maintain normal biological processes. Increased production of ROS, namely oxidative stress, due to either endogenous or exogenous sources causes irreversible damage of bio-molecules such as DNA, proteins, lipids, and sugars, leading to genomic instability, genetic mutation, and altered gene expression, eventually contributing to tumorigenesis. A great amount of experimental studies in vitro and in vivo have produced solid evidence supporting that oxidative stress is strongly associated with increased tumor cell growth, treatment resistance, and metastasis, and all of which contribute to tumor aggressiveness. More recently, the data have indicated that altered production of ROS is also associated with cancer stem cells (CSCs), epithelial-to-mesenchymal transition (EMT), and hypoxia, the most common features or phenomena in tumorigenesis and tumor progression. However, the exact mechanism by which ROS is involved in the regulation of CSC and EMT characteristics as well as hypoxia- and, especially, HIF-mediated pathways is not well known. Emerging evidence suggests the role of miRNAs in tumorigenesis and progression of human tumors. Recently, the data have indicated that altered productions of ROS are associated with deregulated expression of miRNAs, suggesting their potential roles in the regulation of ROS production. Therefore, targeting ROS mediated through the deregulation of miRNAs by novel approaches or by naturally occurring anti-oxidant agents such as genistein could provide a new therapeutic approach for the prevention and/or treatment of human malignancies. In this article, we will discuss the potential role of miRNAs in the regulation of ROS production during tumorigenesis. Finally, we will discuss

  6. Boron Neutron Capture Therapy for Malignant Brain Tumors

    PubMed Central

    MIYATAKE, Shin-Ichi; KAWABATA, Shinji; HIRAMATSU, Ryo; KUROIWA, Toshihiko; SUZUKI, Minoru; KONDO, Natsuko; ONO, Koji

    2016-01-01

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

  7. Boron Neutron Capture Therapy for Malignant Brain Tumors.

    PubMed

    Miyatake, Shin-Ichi; Kawabata, Shinji; Hiramatsu, Ryo; Kuroiwa, Toshihiko; Suzuki, Minoru; Kondo, Natsuko; Ono, Koji

    2016-07-15

    Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID:27250576

  8. Autofluorescence of tissue surrounding malignant tumors

    NASA Astrophysics Data System (ADS)

    Lohmann, Wolfgang; Bohle, Rainer M.; Schill, Wolf-Bernhard; Vahrson, H.; Mussmann, J.

    1998-04-01

    In vitro fluorescence measurements on pap smears of ascites, pleura, or Douglas confirmed results obtained previously with different types of tissue: Cancer tissue fluoresces hardly and is surrounded by a 'fluorescence belt.' Investigations of cytological smears (e.g. Pap smears) have revealed the possible participation of granulocytes in this 'immune' reaction. Furthermore, there seems to be obvious differences in the fluorescence response of pap smears between ovarial- carcinomas and peritoneal carcinomas based on ovarial carcinoma. This observation cannot be explained yet. Because of its sensitivity and specificity the fluorescence method can be used as an additional tool for the evaluation of the tumor invasion front. Preferably it might be used for frozen sections of biopsies and surgical excisions.

  9. Lipiodol enhanced CT scanning of malignant hepatic tumors.

    PubMed

    Eurvilaichit, C

    2000-04-01

    From August 1984 to March 1991, 41 patients with malignant liver tumors, 30 males and 11 females, aged 30-75 years were treated at Ramathibodi Hospital with injection of mitomycin-C lipiodol emulsion into the tumor via the feeding artery followed by embolization of the feeding artery with gelfoam particles. The patients comprised 30 cases of hepatocellular carcinoma, 4 cases of cholangiocarcinoma and 7 cases of metastatic tumors of which one was from CA stomach, three were from CA breast, and three from CA colon. The vascularity of the tumor was assessed in angiogram obtained prior to treatment and retention pattern of lipiodol in the tumor was evaluated in lipiodol-enhanced CT scan images taken 2-4 weeks following therapy. The results showed that lipiodol CT scan images exhibited four patterns of lipiodol retention in the tumor appearing as opacity as follows (1) homogenous (2) heterogeneous (3) ring-like and (4) none. Lipiodol retention pattern appeared to be somewhat related to vascularity of the tumor. Most of the hypervascular tumors such as hepatocellular carcinoma had homogeneous lipiodol accumulation pattern if the tumor size was less than 5 cm. Metastatic tumors and cholangiocarcinoma showed heterogeneous or ring-like pattern of lipiodol accumulation because they were relatively hypovascular. Hypervascular hepatocellular carcinoma may exhibit heterogeneous or ring-like pattern if they are larger than 5 cms, and have multiple feeding arteries, necrosis or AV shunting. Hepatocellular carcinoma with AV shunting may not show any lipiodol accumulation at all. PMID:10808700

  10. Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy

    PubMed Central

    Williams, Carly Bess; Yeh, Elizabeth S; Soloff, Adam C

    2016-01-01

    Deleterious inflammation is a primary feature of breast cancer. Accumulating evidence demonstrates that macrophages, the most abundant leukocyte population in mammary tumors, have a critical role at each stage of cancer progression. Such tumor-associated macrophages facilitate neoplastic transformation, tumor immune evasion and the subsequent metastatic cascade. Herein, we discuss the dynamic process whereby molecular and cellular features of the tumor microenvironment act to license tissue-repair mechanisms of macrophages, fostering angiogenesis, metastasis and the support of cancer stem cells. We illustrate how tumors induce, then exploit trophic macrophages to subvert innate and adaptive immune responses capable of destroying malignant cells. Finally, we discuss compelling evidence from murine models of cancer and early clinical trials in support of macrophage-targeted intervention strategies with the potential to dramatically reduce breast cancer morbidity and mortality. PMID:26998515

  11. Simian virus 40 transformation, malignant mesothelioma and brain tumors

    PubMed Central

    Qi, Fang; Carbone, Michele; Yang, Haining; Gaudino, Giovanni

    2011-01-01

    Simian virus 40 (SV40) is a DNA virus isolated in 1960 from contaminated polio vaccines, that induces mesotheliomas, lymphomas, brain and bone tumors, and sarcomas, including osteosarcomas, in hamsters. These same tumor types have been found to contain SV40 DNA and proteins in humans. Mesotheliomas and brain tumors are the two tumor types that have been most consistently associated with SV40, and the range of positivity has varied about from 6 to 60%, although a few reported 100% of positivity and a few reported 0%. It appears unlikely that SV40 infection alone is sufficient to cause human malignancy, as we did not observe an epidemic of cancers following the administration of SV40-contaminated vaccines. However, it seems possible that SV40 may act as a cofactor in the pathogenesis of some tumors. In vitro and animal experiments showing cocarcinogenicity between SV40 and asbestos support this hypothesis. PMID:21955238

  12. Phase II Study of Intraventricular Methotrexate in Children With Recurrent or Progressive Malignant Brain Tumors

    ClinicalTrials.gov

    2016-06-30

    Recurrent Childhood Medulloblastoma; Recurrent Childhood Ependymoma; Childhood Atypical Teratoid/Rhabdoid Tumor; Embryonal Tumor With Abundant Neuropil and True Rosettes; Metastatic Malignant Neoplasm to the Leptomeninges

  13. Expression of Notch 1 receptor associated with tumor aggressiveness in papillary thyroid carcinoma

    PubMed Central

    Fu, Hongliang; Ma, Chao; Guan, Wenbin; Cheng, Weiwei; Feng, Fang; Wang, Hui

    2016-01-01

    Aim The aim of this study was to assess if the expression of Notch 1 receptor is associated with tumor aggressiveness in papillary thyroid carcinomas (PTCs). Patients and methods By searching the electronic medical record system of Xin Hua Hospital, all cases of PTC patients who underwent thyroidectomy in the hospital between 2013 and 2014 were retrieved. Then, the cases of patients who had a history of any other malignancy or whose thyroid tumor specimen was not available for assay were rejected. Finally, 68 cases of PTC patients were obtained. Formalin-fixed paraffin-embedded tissue blocks of these patients were studied by immunohistochemistry to learn the expression of Notch 1 receptor. Meanwhile, the clinical data of these patients including sex, age, size of the tumor, presence of node metastasis or distant metastasis, and presence of capsule invasion and tumor multicentricity were collected. Pearson’s chi-square test or Fisher’s exact test was used for measuring statistical differences in categorical variables. All the statistical tests were two-sided. A P-value <0.05 was considered to be statistically significant. Results A total of 19 male and 49 female PTC patients with a mean age of 44.8±13.6 years (range 18–78 years) were studied. Notch 1 receptor expression was found in 15/68 (22%) samples of PTC. The expression of Notch 1 receptor was significantly associated with tumor size (P=0.021), distant metastasis (P=0.008), capsule invasion (P=0.001), tumor multicentricity (P=0.018), and age (P=0.033). However, the expression of Notch 1 receptor was not significantly correlated with node metastasis (P=0.096) and sex (P=0.901). Conclusion The expression of Notch 1 receptor is associated with tumor aggressiveness in PTC, and may be used as a molecular marker of tumor invasiveness in PTC. PTC patients who show positive expression of Notch 1 receptor may benefit from radioiodine remnant ablation. PMID:27042120

  14. Malignant perivascular epithelioid cell tumor of the uterus

    PubMed Central

    Bleeker, Jonathan S.; Quevedo, J. Fernando; Folpe, Andrew L.

    2012-01-01

    Perivascular epithelioid cell tumors (PEComas) are a rare collection of tumors arising in a wide array of anatomic locations and characterized by a myomelanocytic phenotype. PEComas which occur in non-classic anatomic distributions are known as perivascular epithelioid cell tumor-not otherwise specified (PEComa-NOS), and one of the most common primary sites for PEComa-NOS is the uterus. The risk of aggressive behavior of these tumors has been linked to a number of factors evaluable on pathologic review following initial surgical resection. We report a case of PEComa-NOS of the uterus with multiple high-risk features, including frank vascular invasion, with no evidence of recurrent disease 18 months following initial surgical resection. PMID:22532912

  15. HuR in pheochromocytomas and paragangliomas - overexpression in verified malignant tumors.

    PubMed

    Leijon, Helena; Salmenkivi, Kaisa; Heiskanen, Ilkka; Hagström, Jaana; Louhimo, Johanna; Heikkilä, Päivi; Ristimäki, Ari; Paavonen, Timo; Metso, Saara; Mäenpää, Hanna; Haglund, Caj; Arola, Johanna

    2016-09-01

    Pheochromocytomas and paragangliomas are rare, neural crest-originating, neuroendocrine tumors. HuR is an mRNA-binding protein of the ELAV/Hu-protein family, which participates in posttranscriptional regulation of many cancer-associated genes. HuR expression has been connected with aggressive behavior of several malignancies. Cyclooxygenase-2 (COX-2) is also expressed in several malignant tumors, and its expression is regulated by HuR. Tissue microarray of 153 primary pheochromocytomas and paragangliomas was investigated for the expression of HuR and COX-2 proteins by immunohistochemistry using two different HuR antibodies (HuR19F12 and HuR3A). In these tumors, the expression of both intranuclear and cytoplasmic HuR was detectable. Increased cytoplasmic HuR expression was significantly associated with metastatic tumors. Increased COX-2 and MIB-1 expression also was associated with metastatic potential, and moreover, HuR and COX-2 expression correlated with each other. Our data suggest that increased expression of HuR protein is associated with metastatic potential of paragangliomas and pheochromocytomas, and COX-2 seems to be a target of HuR. PMID:27357268

  16. Malignant peripheral nerve sheath tumor of kidney—A case report☆

    PubMed Central

    Alharbi, Badr

    2013-01-01

    INTRODUCTION Malignant peripheral nerve sheath tumors (MPNSTs) are very rare soft-tissue tumors. These tumors originate from Schwann cells or pluripotent perineural cells of the neural crest. An isolated MPNST of the kidney is extremely rare and has been reported in only six cases to date. PRESENTATION OF CASE A 30-year-old female with an unremarkable past medical and surgical history presented with an enlarging, right-sided abdominal mass for the last 3 months. A CT scan of the abdomen and pelvis showed a large exophytic mass arising from the right kidney. A metastatic work-up was negative, so a right radical nephrectomy was performed. Histopathological and immunohistochemical studies confirmed the diagnosis of an MPNST. DISCUSSION MPNSTs are rare and aggressive soft-tissue sarcomas that are usually associated with neurofibromatosis type 1 (NF-1) but that also occur post-radiation and sporadically. These tumors are highly malignant neoplasms with a high recurrence rate and distant metastases. Complete surgical excision remains the mainstay of treatment due to the limited response of MPNSTs to both chemotherapy and radiotherapy. CONCLUSION MPNSTs arising from the kidney are very rare. Complete surgical resection provides the only hope for cure. Postoperative chemotherapy and radiotherapy are still controversial, although postoperative radiotherapy is currently recommended by an oncology consensus group. PMID:23995478

  17. Radial expansion rates and tumor growth kinetics predict malignant transformation in contrast-enhancing low-grade diffuse astrocytoma

    PubMed Central

    Hathout, Leith; Pope, Whitney B; Lai, Albert; Nghiemphu, Phioanh L; Cloughesy, Timothy F; Ellingson, Benjamin M

    2015-01-01

    Summary Background Contrast-enhancing low-grade diffuse astrocytomas are an understudied, aggressive subtype at increased risk because of few radiographic indications of malignant transformation. In the current study, we tested whether tumor growth kinetics could identify tumors that undergo malignant transformation to higher grades. Methods Thirty patients with untreated diffuse astrocytomas (WHO II) that underwent tumor progression were enrolled. Contrast-enhancing and T2 hyperintense tumor regions were segmented and the radius of tumor at two time points leading to progression was estimated. Radial expansion rates were used to estimate proliferation and invasion rates using a biomathematical model. Results Radial expansion rates for both contrast-enhancing (p = 0.0040) and T2 hyperintense regions (p = 0.0016) were significantly higher in WHO II–IV tumors compared with nontransformers. Similarly, model estimates showed a significantly higher proliferation (p = 0.0324) and invasion rate (p = 0.0050) in WHO II–IV tumors compared with nontransformers. Conclusion Tumor growth kinetics can identify contrast-enhancing diffuse astrocytomas undergoing malignant transformation. PMID:26095141

  18. EGFR-STAT3 signaling promotes formation of malignant peripheral nerve sheath tumors

    PubMed Central

    Wu, Jianqiang; Patmore, Deanna M.; Jousma, Edwin; Eaves, David W.; Breving, Kimberly; Patel, Ami V.; Schwartz, Eric B.; Fuchs, James R.; Cripe, Timothy P.; Stemmer-Rachamimov, Anat O.; Ratner, Nancy

    2014-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) develop sporadically or in the context of neurofibromatosis type 1 (NF1). EGFR overexpression has been implicated in MPNST formation, but its precise role and relevant signaling pathways remain unknown. We found that EGFR overexpression promotes mouse neurofibroma transformation to aggressive MPNST (GEM-PNST). Immunohistochemistry demonstrated phosphorylated STAT3 (Tyr705) in both human MPNST and mouse GEM-PNST. A specific JAK2/STAT3 inhibitor FLLL32 delayed MPNST formation in an MPNST xenograft nude mouse model. STAT3 knockdown by shRNA prevented MPNST formation in vivo. Finally, reducing EGFR activity strongly reduced pSTAT3 in vivo. Thus, an EGFR-STAT3 pathway is necessary for MPNST transformation and establishment of MPNST xenografts growth but not for tumor maintenance. Efficacy of the FLLL32 pharmacological inhibitor in delaying MPNST growth suggests that combination therapies targeting JAK/STAT3 might be useful therapeutics. PMID:23318430

  19. EGFR-STAT3 signaling promotes formation of malignant peripheral nerve sheath tumors.

    PubMed

    Wu, J; Patmore, D M; Jousma, E; Eaves, D W; Breving, K; Patel, A V; Schwartz, E B; Fuchs, J R; Cripe, T P; Stemmer-Rachamimov, A O; Ratner, N

    2014-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) develop sporadically or in the context of neurofibromatosis type 1. Epidermal growth factor receptor (EGFR) overexpression has been implicated in MPNST formation, but its precise role and relevant signaling pathways remain unknown. We found that EGFR overexpression promotes mouse neurofibroma transformation to aggressive MPNST (GEM-PNST). Immunohistochemistry demonstrated phosphorylated STAT3 (Tyr705) in both human MPNST and mouse GEM-PNST. A specific JAK2/STAT3 inhibitor FLLL32 delayed MPNST formation in an MPNST xenograft nude mouse model. STAT3 knockdown by shRNA prevented MPNST formation in vivo. Finally, reducing EGFR activity strongly reduced pSTAT3 in vivo. Thus, an EGFR-STAT3 pathway is necessary for MPNST transformation and establishment of MPNST xenografts growth but not for tumor maintenance. Efficacy of the FLLL32 pharmacological inhibitor in delaying MPNST growth suggests that combination therapies targeting JAK/STAT3 might be useful therapeutics. PMID:23318430

  20. Malignant transformation in human chondrosarcoma cells supported by telomerase activation and tumor suppressor inactivation.

    PubMed

    Martin, James A; Forest, Erin; Block, Joel A; Klingelhutz, Aloysius J; Whited, Brent; Gitelis, Steven; Wilkey, Andrew; Buckwalter, Joseph A

    2002-09-01

    Human chondrosarcomas do not respond to current chemotherapies or radiation therapy, and their size and histological appearance do not reliably predict the risk of local recurrence and metastases, making selection of surgical treatment difficult. Identifying mechanisms responsible for the proliferation and invasive behavior of these tumors would be of immense clinical value. We hypothesized that telomerase expression is one of these mechanisms. We detected telomerase expression in 7 of 16 chondrosarcomas, but cells cultured from telomerase-negative chondrosarcomas acquired strong telomerase activity and lost tumor suppressor activity after their establishment in culture. These changes were associated with accelerated indefinite cell proliferation, morphological transition, and increased invasive activity, indicating that telomerase activation and loss of cell cycle control leads to the emergence of aggressive cells from chondrosarcoma cell populations. These observations may lead to better understanding of the factors responsible for malignant transformation, local recurrence, and metastases of cartilage neoplasms. PMID:12354749

  1. [Benign and malignant granular cell tumors. An immunohistochemical classification of tumor cells].

    PubMed

    Kuhn, A; Mahrle, G; Steigleder, G K

    1987-06-15

    Eight benign and three malignant granular cell tumors were characterized by means of antibodies and antisera against keratin, desmin, epithelial membrane antigen, factor VIII-related protein, lysozyme, myelin basic protein, myoglobin, neurone-specific enolase, S 100 protein, myelin-associated protein (Leu 7), glial fibrillary acidic protein, vimentin, and neurofilament. All benign granular cell tumours showed positive staining of the tumor cells to antibodies against vimentin, S 100 protein, and neurone-specific enolase; myelin-associated protein (Leu 7), in contrast, was only detectable in a few tumor sections. Histogenetically the granular cells may be classified as Schwann's cells which lost their expression of laminin. The three malignant granular cell tumors showed a staining pattern significantly different from that of the benign tumours. Thus, only neurone-specific enolase was detectable in all the tumors, whereas S 100 protein and vimentin could not be demonstrated but in one and two, resp., out of three tumors. PMID:3303714

  2. Expression of autophagy-related protein beclin-1 in malignant canine mammary tumors

    PubMed Central

    2013-01-01

    Background Autophagy is a self-catabolic mechanism that degrades unnecessary cellular components through lysosomal enzymes. Beclin-1, an autophagy-related protein, establishes the first connection between autophagy and tumorigenesis. The purpose of this study is to assess the Beclin-1 expression pattern and to determine its prognostic significance in patients with malignant canine mammary tumor (CMT). Results We examined Beclin-1 expression in 70 cases of malignant CMTs by immunohistochemistry. Cytoplasmic Beclin-1 expression was significantly weaker in cancer cells than in nearby normal mammary glands (p < 0.001). Low cytoplasmic expression (57.14%) was associated with older age, lower degree of tubular formation, increased mitotic activity, higher histologic grade, and extensive necrosis. Low nuclear expression (40%) was connected with older age, lower degree of tubular formation, extensive necrosis, and negative for Her2/neu overexpression. Univariate survival analysis showed that Beclin-1 cytoplasmic expression was a poor prognostic factor for overall survival rate (p < 0.001). Multivariate survival analysis demonstrated that Beclin-1 cytoplasmic expression is an independent prognostic factor (p = 0.016). Conclusions Loss of Beclin-1 is associated with aggressive clinicopathologic features and poor overall survival. The results suggest that Beclin-1 plays an important role in tumor progression of malignant CMTs. PMID:23578251

  3. Tetraspanins: Spanning from solid tumors to hematologic malignancies.

    PubMed

    Yang, Ying-Gui; Sari, Ita Novita; Zia, Mohammad Farid; Lee, Sung Ryul; Song, Su Jung; Kwon, Hyog Young

    2016-05-01

    Tetraspanins (tetraspans or TM4SF) are a family of integral membrane proteins with four transmembrane helices, a small extracellular loop, and a large extracellular loop. Although tetraspanins are expressed in many types of cells, including immune cells, their biological roles are not fully defined. Nonetheless, recent studies have revealed the important roles of tetraspanins in solid tumors and hematologic malignancies, and expression of tetraspanins is associated with the malignancy of human tumors. Furthermore, genetic mouse models of tetraspanins highlight their contribution to tumorigenesis. In this review, we summarize the implication of tetraspanins in cancer with a special focus on tetraspanin 3 in myeloid leukemia. Our increasing knowledge of tetraspanins and the pathologies that alter their function will undoubtedly inform the rational design of novel cancer therapies. PMID:26930362

  4. Acoustic Radiation Force Impulse Elastography for Focal Hepatic Tumors: Usefulness for Differentiating Hemangiomas from Malignant Tumors

    PubMed Central

    Kim, Ji Eun; Bae, Kyung Soo; Han, Joon Koo; Choi, Byung Ihn

    2013-01-01

    Objective The purpose of this study is to investigate whether acoustic radiation force impulse (ARFI) elastography with ARFI quantification and ARFI 2-dimensional (2D) imaging is useful for differentiating hepatic hemangiomas from malignant hepatic tumors. Materials and Methods One-hundred-and-one tumors in 74 patients were included in this study: 28 hemangiomas, 26 hepatocellular carcinomas (HCCs), three cholangiocarcinomas (CCCs), 20 colon cancer metastases and 24 other metastases. B-mode ultrasound, ARFI 2D imaging, and ARFI quantification were performed in all tumors. Shear wave velocities (SWVs) of the tumors and the adjacent liver and their SWV differences were compared among the tumor groups. The ARFI 2D images were compared with B-mode images regarding the stiffness, conspicuity and size of the tumors. Results The mean SWV of the hemangiomas was significantly lower than the malignant hepatic tumor groups: hemangiomas, 1.80 ± 0.57 m/sec; HCCs, 2.66 ± 0.94 m/sec; CCCs, 3.27 ± 0.64 m/sec; colon cancer metastases, 3.70 ± 0.61 m/sec; and other metastases, 2.82 ± 0.96 m/sec (p < 0.05). The area under the receiver operating characteristics curve of SWV for differentiating hemangiomas from malignant tumors was 0.86, with a sensitivity of 96.4% and a specificity of 65.8% at a cut-off value of 2.73 m/sec (p < 0.05). In the ARFI 2D images, the malignant tumors except HCCs were stiffer and more conspicuous as compared with the hemangiomas (p < 0.05). Conclusion ARFI elastography with ARFI quantification and ARFI 2D imaging may be useful for differentiating hepatic hemangiomas from malignant hepatic tumors. PMID:24043967

  5. Primary hepatic solitary fibrous tumor with histologically benign and malignant areas.

    PubMed

    Silvanto, Anna; Karanjia, Nariman D; Bagwan, Izhar N

    2015-12-01

    Extrapleural solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm, presenting most commonly in the intrathoracic sites but which has been reported at numerous extrathoracic locations. The majority of intra-thoracic SFTs are benign, but 10%-15% behave aggressively. We report a case of primary hepatic SFT with histologically benign and malignant areas. A 65-year-old man underwent an abdominal CT scan following a cerebrovascular accident, which demonstrated a sharply demarcated large liver mass with a heterogenous enhancing area and occupying most of the left lobe of the liver. Histological examination following a hemihepatectomy showed an SFT with morphological patterns ranging from benign to malignant areas, including pleomorphism, increased cellularity, herringbone pattern, necrosis and a raised mitotic count. On review of the literature, only an occasional case report with malignant areas in a hepatic SFT was identified. This case highlights that SFT should be included in the differential diagnosis of a hepatic spindle cell lesion, and that on rare occasions, malignant areas can occur in this already uncommon neoplasm. PMID:26663016

  6. A Case of Malignant Gastrointestinal Stromal Tumor Initially Misdiagnosed as Malignant B-Cell Lymphoma

    PubMed Central

    Suh, Byoung Jo

    2016-01-01

    Errors that occur in anatomic pathology influence the treatment strategy of patients with malignancy. There are four general types of error with three subtypes in the category of defective interpretation. The first subtype is a false-negative diagnosis or undercall of the extent or severity of the lesion, the second is a false-positive diagnosis, and the third is misclassification. We herein report a 65-year-old female patient with malignant gastrointestinal stromal tumor that was diagnosed after reevaluation of the lesion at our hospital – and treated with proximal gastrectomy – after initial diagnosis as malignant B-cell lymphoma on esophagogastroduodenoscopy biopsy of a small gastric fundic mass and subsequent treatment with six cycles of CHOP chemotherapy with aggravation of the mass at another hospital. PMID:27462236

  7. Training stem cells for treatment of malignant brain tumors

    PubMed Central

    Li, Shengwen Calvin; Kabeer, Mustafa H; Vu, Long T; Keschrumrus, Vic; Yin, Hong Zhen; Dethlefs, Brent A; Zhong, Jiang F; Weiss, John H; Loudon, William G

    2014-01-01

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for patients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution (i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system. PMID:25258664

  8. Classification and grading of canine malignant mammary tumors

    PubMed Central

    Tavasoly, Abbas; Golshahi, Hannaneh; Rezaie, Annahita; Farhadi, Mohammad

    2013-01-01

    Histological grading is a good parameter to stratify tumors according to their biological aggressiveness. The Elston and Ellis grading method in humans, invasive ductal breast carcinomas and other invasive tumors are routinely used. The aims of this study were classification of mammary gland tumors and also application of a human grading method in canine mammary carcinoma. The samples included 37 tumors of mammary glands. Mammary tumors were carcinomas (n = 32) and sarcomas (n = 5). The carcinomas were classified as simple carcinoma 56.8% (n = 21), complex carcinoma 13.5% (n = 5), carcinoma arising from benign tumor 10.8% (n= 4) and special type of carcinoma 5.4% (n = 2). Out of 32 carcinomas studied, 37.5% (n = 12) grade I, 46.9% (n = 15) grade II and 15.6% (n = 5) grade III. This study demonstrated that the Elston and Ellis method of histological grading in canine mammary tumor is a reliable prognostic factor which is correlated with histopathological classification. PMID:25593682

  9. Denosumab-treated Giant Cell Tumor of Bone Exhibits Morphologic Overlap With Malignant Giant Cell Tumor of Bone.

    PubMed

    Wojcik, John; Rosenberg, Andrew E; Bredella, Miriam A; Choy, Edwin; Hornicek, Francis J; Nielsen, G Petur; Deshpande, Vikram

    2016-01-01

    Giant cell tumor (GCT) of bone is a locally aggressive benign neoplasm characterized by an abundance of osteoclastic giant cells that are induced by the neoplastic mononuclear cells; the latter express high levels of receptor activator of nuclear factor κ-B ligand (RANKL). Denosumab, a RANKL inhibitor, which is clinically used to treat GCT, leads to a marked alteration in the histologic appearance of the tumor with giant cell depletion and new bone deposition, leading to substantial histologic overlap with other primary tumors of bone. Most significantly, denosumab-treated GCT (tGCT) with abundant bone deposition may mimic de novo osteosarcoma, or GCT that has undergone malignant transformation. To histologically characterize tGCT, we identified 9 cases of GCT biopsied or resected after denosumab treatment. tGCT cases included 16 specimens from 9 patients including 6 female and 3 male individuals aged 16 to 47 (median 32) years. Duration of treatment varied from 2 to 55 months. We compared these tumors with malignant neoplasms arising in GCTs (n=9). The histology of tGCT was variable but appeared to relate to the length of therapy. All tGCTs showed marked giant cell depletion. Early lesions were highly cellular, and the combination of cellularity, atypia, and haphazard bone deposition caused the lesion to resemble high-grade osteosarcoma. Unlike de novo high-grade osteosarcoma or malignancies arising in GCT, however, tGCT showed less severe atypia, reduced mitotic activity, and lack of infiltrative growth pattern. Tumor in patients on prolonged therapy showed decreased cellularity and abundant new bone, deposited as broad, rounded cords or long, curvilinear arrays. The latter morphology was reminiscent of low-grade central osteosarcoma, but, unlike low-grade central osteosarcoma, tGCT was negative for MDM2 and again lacked an infiltrative growth pattern. Overall, tGCT may have a wide range of morphologic appearances. Because the treated tumors bear little

  10. Optically measured microvascular blood flow contrast of malignant breast tumors.

    PubMed

    Choe, Regine; Putt, Mary E; Carlile, Peter M; Durduran, Turgut; Giammarco, Joseph M; Busch, David R; Jung, Ki Won; Czerniecki, Brian J; Tchou, Julia; Feldman, Michael D; Mies, Carolyn; Rosen, Mark A; Schnall, Mitchell D; DeMichele, Angela; Yodh, Arjun G

    2014-01-01

    Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS), a near-infrared optical method that quantifies deep tissue microvascular blood flow. Tumor-to-normal perfusion ratios are derived from thirty-two human subjects. Mean (95% confidence interval) tumor-to-normal ratio using surrounding normal tissue was 2.25 (1.92-2.63); tumor-to-normal ratio using normal tissues at the corresponding tumor location in the contralateral breast was 2.27 (1.94-2.66), and using normal tissue in the contralateral breast was 2.27 (1.90-2.70). Thus, the mean tumor-to-normal ratios were significantly different from unity irrespective of the normal tissue chosen, implying that tumors have significantly higher blood flow than normal tissues. Therefore, the study demonstrates existence of breast cancer contrast in blood flow measured by DCS. The new, optically accessible cancer contrast holds potential for cancer detection and therapy monitoring applications, and it is likely to be especially useful when combined with diffuse optical spectroscopy/tomography. PMID:24967878

  11. Contribution of Soft Substrates to Malignancy and Tumor Suppression during Colon Cancer Cell Division

    PubMed Central

    Rabineau, Morgane; Kocgozlu, Leyla; Dujardin, Denis; Senger, Bernard; Haikel, Youssef; Voegel, Jean-Claude; Freund, Jean-Noel; Schaaf, Pierre; Lavalle, Philippe; Vautier, Dominique

    2013-01-01

    In colon cancer, a highly aggressive disease, progression through the malignant sequence is accompanied by increasingly numerous chromosomal rearrangements. To colonize target organs, invasive cells cross several tissues of various elastic moduli. Whether soft tissue increases malignancy or in contrast limits invasive colon cell spreading remains an open question. Using polyelectrolyte multilayer films mimicking microenvironments of various elastic moduli, we revealed that human SW480 colon cancer cells displayed increasing frequency in chromosomal segregation abnormalities when cultured on substrates with decreasing stiffness. Our results show that, although decreasing stiffness correlates with increased cell lethality, a significant proportion of SW480 cancer cells did escape from the very soft substrates, even when bearing abnormal chromosome segregation, achieve mitosis and undergo a new cycle of replication in contrast to human colonic HCoEpiC cells which died on soft substrates. This observation opens the possibility that the ability of cancer cells to overcome defects in chromosome segregation on very soft substrates could contribute to increasing chromosomal rearrangements and tumor cell aggressiveness. PMID:24167628

  12. Molecular biology of malignant melanoma and other cutaneous tumors.

    PubMed

    Pons, M; Quintanilla, M

    2006-07-01

    Skin cancer is the most common cancer worldwide. Its incidence is doubling every 15-20 years likely because of an aging population, changes in behaviour towards sun exposure, and increased UV light fluency at the earth surface due to ozone depletion. In this review, we summarize the most important genetic changes contributing to the development of malignant melanoma, basal cell carcinoma and squamous cell carcinoma, the main tumor entities arising in the skin. While our understanding of the oncogenes and tumor suppressor genes involved in the development and progression of skin tumors is still fragmentary, recent advances have shown alterations affecting conserved signalling pathways that control cellular proliferation and viability. These pathways include INK4alpha/Rb, ARF/p53, RAS/MAPKs, and sonic hedgehog/Gli. PMID:16870533

  13. Tet1 is a tumor suppressor of hematopoietic malignancy

    PubMed Central

    Cimmino, Luisa; Dawlaty, Meelad M.; Ndiaye-Lobry, Delphine; Yap, Yoon Sing; Bakogianni, Sofia; Yu, Yiting; Bhattacharyya, Sanchari; Shaknovich, Rita; Geng, Huimin; Lobry, Camille; Mullenders, Jasper; King, Bryan; Trimarchi, Thomas; Aranda-Orgilles, Beatriz; Liu, Cynthia; Shen, Steven; Verma, Amit K.; Jaenisch, Rudolf; Aifantis, Iannis

    2015-01-01

    The TET methylcytosine dioxygenase 1 (TET1) enzyme is an important regulator of 5-hydroxymethylcytosine (5hmC) in embryonic stem cells. Decreased expression of TET proteins and loss of 5hmC in many tumors suggests a critical role for the maintenance of this epigenetic modification. Here we show that deletion of Tet1 promoted the development of B cell lymphoma in mice. Tet1 was required for maintaining normal content of 5hmC, preventing DNA hypermethylation and in the regulation of B cell lineage, chromosome maintenance and DNA repair genes. Whole-exome sequencing of Tet1-deficient tumors revealed mutations frequently found in Non-Hodgkin B cell lymphoma, where TET1 was hypermethylated and transcriptionally silenced. These findings provide in vivo evidence of TET1 function as a tumor suppressor of hematopoietic malignancy. PMID:25867473

  14. Solid pseudopapillary tumor of the pancreas: emphasis on differential diagnosis from aggressive tumors of the pancreas.

    PubMed

    Aydiner, Fatma; Erinanç, Hilal; Savaş, Berna; Erden, Esra; Karayalçin, Kaan

    2006-09-01

    Solid pseudopapillary tumor is an unusual primary tumor of the pancreas with a low potential for malignancy and unknown cell origin, seen mostly in young women. Although it is discussed among pancreatic epithelial tumors, many cases do not express cytokeratin but show neuroendocrine differentiation. Three cases (2 female, 1 male, aged 24, 45 and 50 years, respectively) of solid pseudopapillary tumor localized in the pancreas are presented. All cases displayed a well-circumscribed tumor, with an average diameter of 6 cm and a red-brown colored, hemorrhagic, cystic cut surface. Microscopically they were encapsulated with large areas composed of thin papillary formations and solid areas focally. Tumor cells were dyscohesive with small, round- to-oval, central nuclei, and vacuolated, clear or eosinophilic cytoplasm without mitotic activity. NSE, vimentin, synaptophysin, ER, PR, Ki-67, S-100, Pan CK, a1-antitrypsin, a2-antichymotrypsin, and antibodies were used in the immunohistochemical study. Vimentin, synaptophysin, NSE, PR, and a1-antitrypsin showed expression in all cases, while Pan-CK was expressed in two cases. Ki-67 expression was below 1% in all cases. Morphologic features of solid pseudopapillary tumor may be confused with pancreatic endocrine neoplasm and ductal adenocarcinoma. All cases showed features of histiocytic and neuroendocrine differentiation. Epithelial differentiation was identified in two cases. We conclude that immunohistochemistry is incapable of giving additional information for the diagnosis of solid pseudopapillary tumor due to different lines of differentiation of tumor cells. We believe that macroscopic and microscopic features (using hematoxylin and eosin stain) are more important for the diagnosis and differential diagnosis of this tumor. PMID:16941259

  15. The impact of dietary isoflavonoids on malignant brain tumors.

    PubMed

    Sehm, Tina; Fan, Zheng; Weiss, Ruth; Schwarz, Marc; Engelhorn, Tobias; Hore, Nirjhar; Doerfler, Arnd; Buchfelder, Michael; Eyüpoglu, Iiker Y; Savaskan, Nic E

    2014-08-01

    Poor prognosis and limited therapeutic options render malignant brain tumors one of the most devastating diseases in clinical medicine. Current treatment strategies attempt to expand the therapeutic repertoire through the use of multimodal treatment regimens. It is here that dietary fibers have been recently recognized as a supportive natural therapy in augmenting the body's response to tumor growth. Here, we investigated the impact of isoflavonoids on primary brain tumor cells. First, we treated glioma cell lines and primary astrocytes with various isoflavonoids and phytoestrogens. Cell viability in a dose-dependent manner was measured for biochanin A (BCA), genistein (GST), and secoisolariciresinol diglucoside (SDG). Dose-response action for the different isoflavonoids showed that BCA is highly effective on glioma cells and nontoxic for normal differentiated brain tissues. We further investigated BCA in ex vivo and in vivo experimentations. Organotypic brain slice cultures were performed and treated with BCA. For in vivo experiments, BCA was intraperitoneal injected in tumor-implanted Fisher rats. Tumor size and edema were measured and quantified by magnetic resonance imaging (MRI) scans. In vascular organotypic glioma brain slice cultures (VOGIM) we found that BCA operates antiangiogenic and neuroprotective. In vivo MRI scans demonstrated that administered BCA as a monotherapy was effective in reducing significantly tumor-induced brain edema and showed a trend for prolonged survival. Our results revealed that dietary isoflavonoids, in particular BCA, execute toxicity toward glioma cells, antiangiogenic, and coevally neuroprotective properties, and therefore augment the range of state-of-the-art multimodal treatment approach. PMID:24898306

  16. Composite pheochromocytoma with a malignant peripheral nerve sheath tumor: Case report and review of the literature.

    PubMed

    Namekawa, Takeshi; Utsumi, Takanobu; Imamoto, Takashi; Kawamura, Koji; Oide, Takashi; Tanaka, Tomoaki; Nihei, Naoki; Suzuki, Hiroyoshi; Nakatani, Yukio; Ichikawa, Tomohiko

    2016-07-01

    Adrenal tumors with more than one cellular component are uncommon. Furthermore, an adrenal tumor composed of a pheochromocytoma and a malignant peripheral nerve sheath tumor is extremely rare. A composite pheochromocytoma with malignant peripheral nerve sheath tumor in a 42-year-old man is reported here. After adequate preoperative control, left adrenalectomy was performed simultaneously with resection of the ipsilateral kidney for spontaneous rupture of the left adrenal tumor. Pathological findings demonstrated pheochromocytoma and malignant peripheral nerve sheath tumor in a ruptured adrenal tumor. To date, there have been only four reported cases of composite pheochromocytoma with malignant peripheral nerve sheath tumor, so the present case is only the fifth case in the world. Despite the very poor prognosis of patients with pheochromocytoma and malignant peripheral nerve sheath tumors reported in the literature, the patient remains well without evidence of recurrence or new metastatic lesions at 36 months postoperatively. PMID:27338175

  17. Total Humeral Endoprosthetic Replacement following Excision of Malignant Bone Tumors

    PubMed Central

    Kotwal, Suhel; Moon, Bryan; Lin, Patrick; Satcher, Robert; Lewis, Valerae

    2016-01-01

    Humerus is a common site for malignant tumors. Advances in adjuvant therapies and reconstructive methods provide salvage of the upper limb with improved outcomes. Reports of limb salvage with total humeral replacement in extensive humeral tumors are sparse. We undertook a retrospective study of 20 patients who underwent total humeral endoprosthetic replacement as limb salvage following excision of extensile malignant tumor from 1990 to 2011. With an average followup of 42.9, functional and oncological outcomes were analyzed. Ten patients were still alive at the time of review. Mean estimated blood loss was 1131 mL and duration of surgery was 314 minutes. Deep infection was encountered in one patient requiring debridement while mechanical loosening of ulnar component was identified in one patient. Subluxation of prosthetic humeral head was noted in 3 patients. Mean active shoulder abduction was 12.5° and active flexion was 15°. Incompetence of abduction mechanism was the major determinant of poor active functional outcome. Mean elbow flexion was 103.5° with 30.5° flexion contracture in 10 patients with good and useful hand function. Average MSTS score was 71.5%. Total humeral replacement is a reliable treatment option in restoring mechanical stability and reasonable functional results without compromising patient survival, with low complication rate. PMID:27042158

  18. Molecular sublocalization and characterization of the 11; 22 translocation breakpoint in a malignant rhabdoid tumor

    SciTech Connect

    Newsham, I.; Daub, D.; Besnard-Guerin, C.; Cavenee, W. )

    1994-02-01

    Malignant rhabdoid tumors are extremely aggressive soft-tissue sarcomas that tend to be widely metastatic at diagnosis. These tumors were first described as variants of the kidney neoplasm Wilms' tumor, although tumors of similar clinicopathologic features have been cited in a variety of extrarenal sites. Here, the authors have characterized the chromosomal translocation t(11;22)(p15.5;q11.23) from a retroperitoneal rhabdoid tumor. Somatic cell hybrids with segregated copies of the derivative 11 and derivative 22 chromosomes allowed sublocalization of the chromosome 11 breakpoint to a 1- to 2-Mb region between the proximal marker D11S12 and the distal locus tyrosine hydroxylase (TH). Translocation-associated aberrant fragments were identified by pulsed-field gel electrophoresis, with the smallest resulting from BssHII digestion as detected with a probe for TH. These data indicate that the locus or loci disrupted by this genetic abnormality might lie less than 60 kb proximal to this marker and place it in the chromosomal vicinity of genes involved in the etiologies of rhabdomyosarcoma, Wilms' tumor, and the congenital overgrowth disorder, Beckwith-Wiedemann syndrome. Analysis of two other tumor-associated loci, EWS1 and NF2, that have been mapped to the general region of 22q11.2 indicated that they were not involved in this translocation breakpoint. Isolation of the genes present at this translocation junction on both chromosomes 11 and 22 may yield important clinicopathologic and genetic markers for this enigmatic tumor as well as other pediatric diseases. 45 refs., 3 figs.

  19. Malignant phyllodes tumor metastasized to the right ventricle: a case report.

    PubMed

    Yoshidaya, Fumi; Hayashi, Naoki; Takahashi, Katsuhito; Suzuki, Koyu; Akiyama, Futoshi; Ishiyama, Mitsutomi; Takahashi, Yuko; Yoshida, Atsushi; Yagata, Hiroshi; Nakamura, Seigo; Tsunoda, Hiroko; Yamauchi, Hideko

    2015-12-01

    Cardiac metastasis of malignant phyllodes tumor is very rare. We herein report a rare case that developed cardiac metastasis from malignant phyllodes tumor. A 38-year-old woman underwent lumpectomy, and the final pathological findings showed the 5-cm malignant phyllodes tumor partially containing 1 cm of squamous cell carcinoma. Four months after the first surgery, a local recurrence of malignant phyllodes tumor and distant metastases to the bone, lung, pulmonary main trunk, and right ventricle were detected. Mass reduction surgery of cardiac metastasis of the malignant phyllodes tumor was performed to avoid sudden death. In immunohistochemical findings, the tumor was suspected to be originated in myoepithelial cells because of the expression of smooth muscle lineage including α-smooth muscle actin and Calponin1 and highly malignant characteristics showing MIB-1 and p53 highly positive with angiogenesis. Further studies are needed to clarify the effective treatment to these tumors. PMID:26943445

  20. Gall bladder carcinoma: Aggressive malignancy with protean loco-regional and distant spread.

    PubMed

    Dwivedi, Amit Nandan Dhar; Jain, Shivi; Dixit, Ruhi

    2015-03-16

    The most common malignancy of biliary tract is gallbladder cancer (GBC) which is the third most common cancer in gastrointestinal tract. It is a lethal disease for most patients in spite of growing awareness and improved diagnostic techniques. GBC has a very poor prognosis and the 5 year survival rate is < 10%. Although etiology of the carcinoma of the gallbladder is still obscure, various factors have been implicated, cholelithiasis being the most frequent. The incidence of GBC worldwide is based on the gender, geography and ethnicity which suggest that both genetic and environmental factors can cause GBC. The major route of spread of gallbladder cancer (GC) is loco-regional rather than distant. It spreads by lymphatic, vascular, neural, intraperitoneal, and intraductal routes. Sonography is usually the most common imaging test to evaluate symptoms of biliary tract disease including suspected GC. With recent advances in imaging modalities like multi-detector computed tomography (CT) scanners, magnetic resonance imaging-positron emission tomography/CT diagnosis of gallbladder cancer has improved. Studies have also targeted molecular and genetic pathways. Treatment options have included extended and radical surgeries and adjuvant chemotherapy. This review article deals in detail with important aspects of carcinoma gallbladder and its manifestations and challenges. Role of various imaging modalities in characterization and accurate staging has been discussed. The loco-regional spread of this aggressive malignancy is dealt explicitly. PMID:25789296

  1. Gall bladder carcinoma: Aggressive malignancy with protean loco-regional and distant spread

    PubMed Central

    Dwivedi, Amit Nandan Dhar; Jain, Shivi; Dixit, Ruhi

    2015-01-01

    The most common malignancy of biliary tract is gallbladder cancer (GBC) which is the third most common cancer in gastrointestinal tract. It is a lethal disease for most patients in spite of growing awareness and improved diagnostic techniques. GBC has a very poor prognosis and the 5 year survival rate is < 10%. Although etiology of the carcinoma of the gallbladder is still obscure, various factors have been implicated, cholelithiasis being the most frequent. The incidence of GBC worldwide is based on the gender, geography and ethnicity which suggest that both genetic and environmental factors can cause GBC. The major route of spread of gallbladder cancer (GC) is loco-regional rather than distant. It spreads by lymphatic, vascular, neural, intraperitoneal, and intraductal routes. Sonography is usually the most common imaging test to evaluate symptoms of biliary tract disease including suspected GC. With recent advances in imaging modalities like multi-detector computed tomography (CT) scanners, magnetic resonance imaging-positron emission tomography/CT diagnosis of gallbladder cancer has improved. Studies have also targeted molecular and genetic pathways. Treatment options have included extended and radical surgeries and adjuvant chemotherapy. This review article deals in detail with important aspects of carcinoma gallbladder and its manifestations and challenges. Role of various imaging modalities in characterization and accurate staging has been discussed. The loco-regional spread of this aggressive malignancy is dealt explicitly. PMID:25789296

  2. Simulating ‘structure-function’ patterns of malignant brain tumors

    NASA Astrophysics Data System (ADS)

    Mansury, Yuri; Deisboeck, Thomas S.

    2004-01-01

    Rapid growth and extensive tissue infiltration are characteristics of highly malignant neuroepithelial brain tumors. Very little is known, however, about the existence of structure-function relationships in these types of neoplasm. Therefore, using a previously developed two-dimensional agent-based model, we have investigated the emergent patterns of multiple tumor cells that proliferate and migrate on an adaptive grid lattice, driven by a local-search mechanism and guided by the presence of distinct environmental conditions. Numerical results indicate a strong correlation between the fractal dimensions of the tumor surface and the average velocity of the tumor's spatial expansion. In particular, when the so called ‘beaten-path advantage’ intensifies, i.e., rising ‘mechanical rewards’ for cells to follow each other along preformed pathways, it results in an increase of the tumor system's fractal dimensions leading to a concomitant acceleration of its spatial expansion. Whereas cell migration is the dominant phenotype responsible for the more extensive branching patterns exhibiting higher fractal dimensions, cell proliferation appears to become more active primarily at lower fracticality associated with stronger mechanical confinements. Implications of these results for experimental and clinical cancer research are discussed.

  3. Malignant Eccrine Poroma of the Vulva: An Intriguing Case of a Rare Tumor at an Unusual Site.

    PubMed

    Mishra, Pranshu; Sen, Sumit; Sharma, Neha; Sen, Debasish

    2016-01-01

    Malignant eccrine poroma is a rare malignancy of the eccrine sweat glands, occurring most frequently on the lower extremities. It affects both sexes equally usually in the 6(th) to 7(th) decade of life. Metastasis to regional lymph nodes may occur in 20% that may be fatal in 60% cases. Its aggressive nature, rarity of occurrence, and unusual presentations make it very important to be evaluated properly by the clinician. We hereby report a case of a 75-year-old female presenting with two exophytic tumors over her vulva with local extension. On histopathological examination, it was diagnosed as malignant eccrine poroma. On magnetic resonance imaging of the pelvic region, metastatic extension in regional lymph nodes was found. She was treated by radical vulvectomy with bilateral inguinal and femoral lymph node dissection followed by radiotherapy. PMID:27512190

  4. Malignant Eccrine Poroma of the Vulva: An Intriguing Case of a Rare Tumor at an Unusual Site

    PubMed Central

    Mishra, Pranshu; Sen, Sumit; Sharma, Neha; Sen, Debasish

    2016-01-01

    Malignant eccrine poroma is a rare malignancy of the eccrine sweat glands, occurring most frequently on the lower extremities. It affects both sexes equally usually in the 6th to 7th decade of life. Metastasis to regional lymph nodes may occur in 20% that may be fatal in 60% cases. Its aggressive nature, rarity of occurrence, and unusual presentations make it very important to be evaluated properly by the clinician. We hereby report a case of a 75-year-old female presenting with two exophytic tumors over her vulva with local extension. On histopathological examination, it was diagnosed as malignant eccrine poroma. On magnetic resonance imaging of the pelvic region, metastatic extension in regional lymph nodes was found. She was treated by radical vulvectomy with bilateral inguinal and femoral lymph node dissection followed by radiotherapy. PMID:27512190

  5. Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis.

    PubMed

    Miller, S J; Lan, Z D; Hardiman, A; Wu, J; Kordich, J J; Patmore, D M; Hegde, R S; Cripe, T P; Cancelas, J A; Collins, M H; Ratner, N

    2010-01-21

    Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas without effective therapeutics. Bioinformatics was used to identify potential therapeutic targets. Paired Box (PAX), Eyes Absent (EYA), Dachsund (DACH) and Sine Oculis (SIX) genes, which form a regulatory interactive network in Drosophila, were found to be dysregulated in human MPNST cell lines and solid tumors. We identified a decrease in DACH1 expression, and increases in the expressions of PAX6, EYA1, EYA2, EYA4, and SIX1-4 genes. Consistent with the observation that half of MPNSTs develop in neurofibromatosis type 1 (NF1) patients, subsequent to NF1 mutation, we found that exogenous expression of the NF1-GTPase activating protein-related domain normalized DACH1 expression. EYA4 mRNA was elevated more than 100-fold as estimated by quantitative real-time PCR in most MPNST cell lines. In vitro, suppression of EYA4 expression using short hairpin RNA reduced cell adhesion and migration and caused cellular necrosis without affecting cell proliferation or apoptotic cell death. MPNST cells expressing shEYA4 either failed to form tumors in nude mice or formed very small tumors, with extensive necrosis but similar levels of proliferation and apoptosis as control cells. Our findings identify a role of EYA4 and possibly interacting SIX and DACH proteins in MPNSTs and suggest the EYA4 pathway as a rational therapeutic target. PMID:19901965

  6. [Chest wall reconstruction after resection of malignant chest wall tumors].

    PubMed

    Ayabe, H; Oka, T; Akamine, S; Takahashi, T; Nagayasu, T

    1998-05-01

    Full-thickness chest wall resection is performed for complete removal of primary and secondary malignant chest wall tumors. Large defects of the chest wall after resection must be repaired to maintain adequate ventilation, to protect important intrathoracic structures, and to preserve cosmetic integrity. Various materials have been utilized over the years to replace the rigid chest wall. At present, Marlex mesh and a composite of Marlex mesh and methylmethacrylate are frequently used to reconstruct rigid chest wall defects. On the other hand, to replace the soft part of the chest wall and cover the rigid materials, pedicled muscle flaps, myocutaneous flaps, or omentum are used. Major pedicled flaps include the pectoralis major, rectus abdominis and latissimus dorsi muscular, and musculocutaneous flaps. Techniques are now available to repair any chest wall site, and to restore chest continuity in patients whose tumors are curatively resected. PMID:9656244

  7. An unusual long-term survey of a patient with widespread malignant urachal tumor, not given chemotherapy or radiotherapy.

    PubMed

    Ormeci, Tugrul; Kiremit, Murat Can; Erkurt, Bulent; Örmeci, Aslı

    2015-01-01

    The urachus establishes a connection between the dome of the bladder and the umbilicus throughout fetal life. If the urachus does not close completely, malignancy is a potential complication. The primary treatment for malignant urachal tumor is surgical excision. A 61-year-old male patient diagnosed with urachal carcinoma had undergone partial cystectomy 25 years previously. Twenty years later, local recurrence was treated with another partial cystectomy without umbilical remnant excision. Recurrence at the umbilical site was excised 2 years later, but intraperitoneal invasion had occurred, and the patient underwent a total colectomy at that time. Local disease and disseminated metastases in the thorax and intra- and extraperitoneal areas were noted upon admission to our hospital. Urachal carcinomas are usually aggressive tumors, and surgical treatment should include partial or radical cystectomy and excision of the urachus and umbilicus, to prevent local recurrence and distant metastasis. PMID:25838960

  8. Synchronous congenital malignant rhabdoid tumor of the orbit and atypical teratoid/rhabdoid tumor--feasibility and efficacy of multimodal therapy in a long-term survivor.

    PubMed

    Seeringer, Angela; Reinhard, Harald; Hasselblatt, Martin; Schneppenheim, Reinhard; Siebert, Reiner; Bartelheim, Kerstin; Leuschner, Ivo; Frühwald, Michael C

    2014-09-01

    Among infant malignancies, congenital tumors, especially those of the central nervous system (CNS), constitute a rather unique subgroup. Poor survival rates (28% in CNS tumors) may be attributed to the aggressive biology as well as specific therapeutic limitations innate to the young age of affected patients. Our patient developed synchronous congenital tumors: an atypical teratoid/rhabdoid tumor (AT/RT) localized in the right lateral ventricle of the brain and a malignant rhabdoid tumor (MRT) in the soft tissue of the right orbit. A de novo germline chromosomal deletion in 22q encompassing the SMARCB1 gene was detected, prompting the diagnosis of a de novo rhabdoid tumor predisposition syndrome 1 (RTPS1). The patient was reported to the European Rhabdoid Registry (EU-RHAB) and treated according to the Rhabdoid 2007 recommendation. Despite the very young age of the patient, the initially desperate situation of RTPS1, and the synchronous localization of congenital rhabdoid tumors, intensive chemotherapy was well tolerated; the child is still in complete remission 5 years following diagnosis. In conclusion, RTPS1 with congenital synchronous MRTs is not necessarily associated with a detrimental outcome. Intensive multidrug chemotherapy, including high dose chemotherapy, may be feasible and justified. PMID:25262118

  9. Malignant Peripheral Nerve Sheath Tumor of the Infraorbital Nerve.

    PubMed

    D'Addino, José Luis; Piccoletti, Laura; Pigni, María Mercedes; de Gordon, Maria José Rodriguez Arenas

    2016-06-01

    The objective of this study is to report a large, rare, and ulcerative infiltrated skin lesion. Its diagnosis, therapeutic management, and progress are described. The patient is a 78-year-old white man, who presented with a 12-month ulcerative perforated lesion that had affected and infiltrated the skin, with easy bleeding. He had a history of hypertension, although controlled, was a 40-year smoker, had chronic atrial fibrillation, diabetes, and microangiopathy. During the consultation, the patient also presented with ocular obstruction due to an inability to open the eye. He mentioned having reduced vision. The computed tomography scan showed upper maxilla osteolysis without eye involvement. We underwent a radical resection in which upper maxilla and the anterior orbital margin were included. We used a Becker-type flap that allowed us to rebuild the cheek and to complete a modified neck dissection. Progress was favorable; the patient recovered ocular motility and his vision improved to 20/200. The final biopsy result was "malignant peripheral nerve sheath tumor, malignant schwannoma." Malignant schwannoma of the peripheral nerve is extremely rare. The total resection and reconstruction being completed in one surgery represented a challenge due to the difficulty in obtaining tissues in addition to the necessity of an oncological resection. PMID:27162577

  10. Pediatric Malignant Bone Tumors: A Review and Update on Current Challenges, and Emerging Drug Targets.

    PubMed

    Jackson, Twana M; Bittman, Mark; Granowetter, Linda

    2016-07-01

    Osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT) are the most common malignant bone tumors in children and adolescents. While significant improvements in survival have been seen in other pediatric malignancies the treatment and prognosis for pediatric bone tumors has remained unchanged for the past 3 decades. This review and update of pediatric malignant bone tumors will provide a general overview of osteosarcoma and the Ewing sarcoma family of tumors, discuss bone tumor genomics, current challenges, and emerging drug targets. PMID:27265835

  11. Maintenance Therapy with Interferon Alfa 2b Improves Outcome in Aggressive Malignant Lymphoma.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; García, E L; Nambo, M J

    1998-01-01

    To assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with malignant lymphoma on complete response after conventional chemotherapy we start a randomized clinical trial. One hundred and seventy patients were randomized to received either IFN 5.0 MU three time at week by one year or no further treatment, as control group. At a median follow-up of 9.0 years (range 4.3 to 11 years) median freedom from relapse (FFR) has not been reached in patients who received IFN, it is statistically significant to patients in control group with a median FFR of 60 months (p <.001). Actuarial curves show that at 10-years, 58 patients (66%, 95% confidence interval (CI) 53% to 79%) remain in first remission, statistical different to control group 33 patients (40%, 95% Cl: 33% to 57%) (p <.001). Event free survival (EFS) shown that a 10-years 63 patients (71%, 95% CI: 59% to 81%) are alive free of disease in the IFN arm compared to only 38 patients (45%, 95% CI: 37% to 57%) in the control group (p <.001). Toxicity was mild, 81 patients received the planned doses of IFN on time and 6 patients had transitory delay secondary to hematological toxicity (grade 1 or 2) and completed the treatment on 13 months. No late side effects has been observed. After a long term follow-up we confirm that IFN used as maintenance therapy improves outcome in patients with aggressive malignant lymphoma who were in complete remission after conventional chemotherapy without excessive toxicity. We feld that IFN will be consider in controlled clinical trials to define the role of this therapeutic option. PMID:27414082

  12. Fibroblast Growth Factor Receptors as Novel Therapeutic Targets in SNF5-Deleted Malignant Rhabdoid Tumors

    PubMed Central

    Wöhrle, Simon; Jagani, Zainab; Thuery, Anne; Bauer-Probst, Beatrice; Reimann, Flavia; Stamm, Christelle; Pornon, Astrid; Romanet, Vincent; Guagnano, Vito; Brümmendorf, Thomas; Sellers, William R.; Hofmann, Francesco; Roberts, Charles W. M.; Graus Porta, Diana

    2013-01-01

    Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers arising in brain, kidney and soft tissues, which are characterized by loss of the tumor suppressor SNF5/SMARCB1. MRTs are poorly responsive to chemotherapy and thus a high unmet clinical need exists for novel therapies for MRT patients. SNF5 is a core subunit of the SWI/SNF chromatin remodeling complex which affects gene expression by nucleosome remodeling. Here, we report that loss of SNF5 function correlates with increased expression of fibroblast growth factor receptors (FGFRs) in MRT cell lines and primary tumors and that re-expression of SNF5 in MRT cells causes a marked repression of FGFR expression. Conversely, siRNA-mediated impairment of SWI/SNF function leads to elevated levels of FGFR2 in human fibroblasts. In vivo, treatment with NVP-BGJ398, a selective FGFR inhibitor, blocks progression of a murine MRT model. Hence, we identify FGFR signaling as an aberrantly activated oncogenic pathway in MRTs and propose pharmacological inhibition of FGFRs as a potential novel clinical therapy for MRTs. PMID:24204904

  13. Malignant Peripheral Nerve Sheath Tumors in Children with Neurofibromatosis Type 1

    PubMed Central

    Pourtsidis, Apostolos; Baka, Margarita; Bouhoutsou, Despina; Varvoutsi, Maria; Synodinou, Maria; Giamarelou, Panagiota; Kosmidis, Helen

    2014-01-01

    Purpose. Malignant peripheral nerve sheath tumors (MPNSTs) are rare in children and account for approximately 5–10% of all soft tissue sarcomas in adults. MPNSTs may occur independently but individuals with neurofibromatosis type 1 (NF1) have a significantly increased risk. Our aim is to present patients with MPNST treated in our department. Cases and Results. In this report we present 4 cases of MPNSTs (3 females: 13, 12, and 13 years old and 1 male: 10 years old) arising in patients with NF1. All of them presented with an enlarging mass and pain at diagnosis. Tumor was located in the buttock, the spinal cord, the trunk, and the left leg proximal to the heel. Wide excision of the tumor and radiotherapy were applied to all and adjuvant chemotherapy was given to three of them after the disease was progressed. All four died 32, 18, 10, and 22 months after diagnosis with progressive disease locally and pulmonary metastases in two of them. Conclusions. In conclusion, MPNSTs arising in patients with NF1 are high grade sarcomas with short survival. Individuals with NF1 should be followed closely in order to identify early the development of MPNSTs. Aggressive surgery and complete excision significantly improves disease-free survival. The usefulness of radiation therapy in MPNSTs is not determined although all patients will receive radiation therapy at some stage of the disease. The role of chemotherapy is unclear. PMID:25317349

  14. Malignant peripheral nerve sheath tumors in children with neurofibromatosis type 1.

    PubMed

    Pourtsidis, Apostolos; Doganis, Dimitrios; Baka, Margarita; Bouhoutsou, Despina; Varvoutsi, Maria; Synodinou, Maria; Giamarelou, Panagiota; Kosmidis, Helen

    2014-01-01

    Purpose. Malignant peripheral nerve sheath tumors (MPNSTs) are rare in children and account for approximately 5-10% of all soft tissue sarcomas in adults. MPNSTs may occur independently but individuals with neurofibromatosis type 1 (NF1) have a significantly increased risk. Our aim is to present patients with MPNST treated in our department. Cases and Results. In this report we present 4 cases of MPNSTs (3 females: 13, 12, and 13 years old and 1 male: 10 years old) arising in patients with NF1. All of them presented with an enlarging mass and pain at diagnosis. Tumor was located in the buttock, the spinal cord, the trunk, and the left leg proximal to the heel. Wide excision of the tumor and radiotherapy were applied to all and adjuvant chemotherapy was given to three of them after the disease was progressed. All four died 32, 18, 10, and 22 months after diagnosis with progressive disease locally and pulmonary metastases in two of them. Conclusions. In conclusion, MPNSTs arising in patients with NF1 are high grade sarcomas with short survival. Individuals with NF1 should be followed closely in order to identify early the development of MPNSTs. Aggressive surgery and complete excision significantly improves disease-free survival. The usefulness of radiation therapy in MPNSTs is not determined although all patients will receive radiation therapy at some stage of the disease. The role of chemotherapy is unclear. PMID:25317349

  15. Fibroblast growth factor receptors as novel therapeutic targets in SNF5-deleted malignant rhabdoid tumors.

    PubMed

    Wöhrle, Simon; Weiss, Andreas; Ito, Moriko; Kauffmann, Audrey; Murakami, Masato; Jagani, Zainab; Thuery, Anne; Bauer-Probst, Beatrice; Reimann, Flavia; Stamm, Christelle; Pornon, Astrid; Romanet, Vincent; Guagnano, Vito; Brümmendorf, Thomas; Sellers, William R; Hofmann, Francesco; Roberts, Charles W M; Graus Porta, Diana

    2013-01-01

    Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers arising in brain, kidney and soft tissues, which are characterized by loss of the tumor suppressor SNF5/SMARCB1. MRTs are poorly responsive to chemotherapy and thus a high unmet clinical need exists for novel therapies for MRT patients. SNF5 is a core subunit of the SWI/SNF chromatin remodeling complex which affects gene expression by nucleosome remodeling. Here, we report that loss of SNF5 function correlates with increased expression of fibroblast growth factor receptors (FGFRs) in MRT cell lines and primary tumors and that re-expression of SNF5 in MRT cells causes a marked repression of FGFR expression. Conversely, siRNA-mediated impairment of SWI/SNF function leads to elevated levels of FGFR2 in human fibroblasts. In vivo, treatment with NVP-BGJ398, a selective FGFR inhibitor, blocks progression of a murine MRT model. Hence, we identify FGFR signaling as an aberrantly activated oncogenic pathway in MRTs and propose pharmacological inhibition of FGFRs as a potential novel clinical therapy for MRTs. PMID:24204904

  16. Evaluation of ornithine decarboxylase activity as a marker for tumor growth rate in malignant tumors.

    PubMed

    Westin, T; Edström, S; Lundholm, K; Gustafsson, B

    1991-10-01

    Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the synthesis of polyamines. Polyamines regulate DNA synthesis by a mechanism that is not fully understood. High levels of polyamines and ODC activity are associated with rapid cell growth, particularly in tumor tissues. The aim of this study was to determine whether ODC activity as a marker for rapid alterations in tumor growth could be used to investigate whether nutritional support in cancer patients stimulates tumor cell proliferation. Weight-losing head and neck cancer patients and tumor-bearing mice (MCG 101, C57/BL) were studied during different feeding regimens. The ODC activity in tumor tissue was investigated in relation to the following variables: (1) histopathologic differentiation; (2) DNA content; and (3) bromodeoxyuridine (BrdUrd) incorporation into DNA. After the animals were starved for 24 hours, a significant reduction of tumor growth was demonstrated in the experimental tumor along with a reduction of ODC activity, an accumulation of cells in the G0G1 phase, and a reduction of cells incorporating BrdUrd into DNA. Refeeding after 24 hours generated a response by all variables. Tumor biopsy specimens from patients with head and neck cancer malignancies demonstrated aneuploidy in the cells of 70% of the patients. High ODC activity in tumor tissue was demonstrated mainly among poorly differentiated tumors, and ODC activity was correlated with the compartment size of aneuploidic cells in the tumor. High ODC activity indicated a poor short-term survival (1 year). It was concluded that experimental tumor growth is highly dependent on host feeding. However, there was no evidence supporting the claim that nutritional support to cancer patients stimulates tumor cell proliferation. Determination of ODC activity may be used to monitor rapid changes in DNA synthesis and may have prognostic significance for survival. PMID:1951878

  17. Case Report: Two-step Malignant Transformation of a Liposclerosing Myxofibrous Tumor of Bone

    PubMed Central

    Campbell, Kirk

    2008-01-01

    We present the case of a patient with malignant transformation of a liposclerosing myxofibrous tumor. The patient had a histologically confirmed liposclerosing myxofibrous tumor that, during a course of 22 months, spontaneously transformed into a lesion appearing like a benign giant cell reactive lesion and subsequently into a high-grade bone sarcoma. Few such cases of spontaneous malignant transformation of liposclerosing myxofibrous tumor have been reported. We report what we believe to be the first case documenting spontaneous transformation of a liposclerosing myxofibrous tumor into an intermediate lesion with benign-appearing histologic features and then into a high-grade malignant tumor. PMID:18607664

  18. Phyllodes Tumor of the Breast With Malignant Melanoma Component: A Case Report.

    PubMed

    Vergine, Marco; Guy, Catherine; Taylor, Mark R

    2015-09-01

    Phyllodes tumors of the breast display a wide variation in histological appearance and are classified into benign, borderline, and malignant categories based on a combination of histological parameters. These tumors may include a malignant heterologous component that is believed to originate through a process of multidirectional differentiation from a cancer stem cell. In these cases, the tumor is classified as a malignant phyllodes tumor. Among the heterologous elements that have been described in malignant phyllodes tumors are rhabdomyosarcoma, chondrosarcoma, osteosarcoma, liposarcoma and angiosarcoma. We present the first case of a phyllodes tumor with a malignant melanoma component in the breast of a 71-year-old lady, discussing the clinical implications of this diagnosis. PMID:26113664

  19. Teratoma: from spontaneous tumors to the pluripotency/malignancy assay.

    PubMed

    Bulic-Jakus, Floriana; Katusic Bojanac, Ana; Juric-Lekic, Gordana; Vlahovic, Maja; Sincic, Nino

    2016-01-01

    A teratoma is a benign tumor containing a mixture of differentiated tissues and organotypic derivatives of the three germ layers, while a teratocarcinoma also contains embryonal carcinoma cells (EC cells). Experimental teratomas and teratocarcinomas have been derived from early mammalian embryos transplanted into the adult animal (ectopic sites). In the rat, the pluripotency of the transplanted epiblast was demonstrated and a quantifiable restriction of developmental potential persisted after subsequent transplantation of chemically defined cultivated postimplantation embryos. The rat is nonpermissive for teratocarcinoma development and rat pluripotent cell lines have been established only recently. Transplantation of mouse embryos, epiblast, or embryonic stem cells (mESCs) gave rise to teratocarcinomas. The pluripotency of reprogrammed human cells has been tested by a 'gold standard' trilaminar teratoma assay in immunocompromised mice in vivo. Human pluripotent stem cells proposed for use in regenerative medicine such as human embryonic stem cell (hESC), human nuclear-transfer/therapeutic cloning embryonic stem cell (NT-ESC), or human induced pluripotent stem cell (hiPSC) lines, once differentiated in vitro to the desired cell type, should be again tested in a long-term animal teratoma assay to exclude their malignancy. Such an approach led to a recently implemented human therapy with retinal pigmented epithelium. For greater biosafety, the teratoma assay should be standardized and complemented by assessments of mutations/epimutations, RNA/protein expression, and possible immunogenicity of autologous pluripotent cells. Furthermore, the standardized teratoma assay should be directed more to the assessment of EC/malignant cell features than of differentiated tissues, especially after a unique case of human therapy with neural stem cells was found to lead to malignancy. For further resources related to this article, please visit the WIREs website. PMID:26698368

  20. Epstein-Barr Virus MicroRNA Expression Increases Aggressiveness of Solid Malignancies

    PubMed Central

    Pandya, Deep; Mariani, Marisa; He, Shiquan; Andreoli, Mirko; Spennato, Manuela; Dowell-Martino, Candice; Fiedler, Paul; Ferlini, Cristiano

    2015-01-01

    The Cancer Genome Atlas (TCGA) microRNA (miRNA) initiative has revealed a pivotal role for miRNAs in cancer. Utilizing the TCGA raw data, we performed the first mapping of viral miRNA sequences within cancer and adjacent normal tissues. Results were integrated with TCGA RNA-seq to link the expression of viral miRNAs to the phenotype. Using clinical data and viral miRNA mapping results we also performed outcome analysis. Three lines of evidence lend credence to an active role of viral miRNAs in solid malignancies. First, expression of viral miRNA is consistently higher in cancerous compared to adjacent noncancerous tissues. Second, viral miRNA expression is associated with significantly worse clinical outcome among patients with early stage malignancy. These patients are also featured by increased expression of PD1/PD-L1, a pathway implicated in tumors escaping immune destruction. Finally, a particular cluster of EBV-miRNA (miR-BART2, miR-BART4, miR-BART5, miR-BART18, and miR-BART22) is associated with expression of cytokines known to inhibit host response to cancer. Quantification of specific viral miRNAs may help identify patients who are at risk of poor outcome. These patients may be candidates for novel therapeutic strategies incorporating antiviral agents and/or inhibitors of the PD-1/PD-L1 pathway. PMID:26375401

  1. Primary malignant chest wall tumors: analysis of 40 patients

    PubMed Central

    2014-01-01

    Background Primary chest wall tumors originate from different constructions of thoracic wall. We report our multidisciplinary experience on primary thoracic tumor resection and thoracic reconstruction, the need to additional therapy and evaluating prognostic factors affecting survival. Methods We performed a retrospective review of our prospectively maintained database of 40 patients treated for malignant primary chest wall tumor from 1989 to 2009. Patients were evaluated in terms of age, sex, clinical presentation, type of imaging, tissue diagnosis methods, pathology, surgical technique, early complications, hospital mortality, prevalence of recurrence and distant metastases, additional treatment, 3 years survival and factors affecting survival. Results Male/Female (F/M) = 1, with median age of 43.72 years. Mass was the most common symptoms and the soft tissue sarcoma was the most common pathology. Resection without reconstruction was performed in 5 patients and Thirty-five patients (87.5%) had extensive resection and reconstruction with rotatory muscular flap, prosthetic mesh and/or cement. Overall, 12.5% (5/40) of patients received neoadjuvant therapy and 75% (30/40) of patients were treated with adjuvant therapy. The 3-year survival rate was 65%. Recurrences occurred in 24 patients (60%), 14 developed local recurrences, and 10 developed distant metastases. The primary treatment modality for both local and distant recurrences was surgical resection; among them, 10 underwent repeated resection, 9 adjuvant therapy and 5 were treated with lung metastasectomy. The most common site of distant metastasis was lung (n = 7). Factors that affected survival were type of pathology and evidence of distant metastasis. Conclusion Surgery with wide margin is the safe and good technique for treatment of primary chest wall tumors with acceptable morbidity and mortality. PMID:24947314

  2. Malignant phylloides tumor of breast in a pregnant woman with coincidental nulliparous vaginal prolapse.

    PubMed

    Ray, Sabyasachi; Basak, Subhadeep; Das, Subhabrata; Pal, Mallika; Konar, Hiralal

    2011-12-01

    Malignant phylloides tumor is a relatively rare and rapidly growing tumor of the breast. Presentation during pregnancy is uncommon. Reports regarding malignancy in these tumors differ greatly in incidence, and most of them are stromal malignancies. We report this case in which 24-year old primigravid patient in the 36(th) week of her pregnancy had a malignant phylloides tumor of breast with sudden growth and fine needle aspiration cytology of the breast was positive for malignancy. Ultimately after her caesarean delivery, excision biopsy was in favor of a malignant process. Pregnancy with nulliparous prolapse is also a rare condition. Those conditions are not associated with each other, but presence of two rare conditions in the same time in the same person is unique. PMID:23115419

  3. Malignant Phylloides Tumor of Breast in a Pregnant Woman with Coincidental Nulliparous Vaginal Prolapse

    PubMed Central

    Ray, Sabyasachi; Basak, Subhadeep; Das, Subhabrata; Pal, Mallika; Konar, Hiralal

    2011-01-01

    Malignant phylloides tumor is a relatively rare and rapidly growing tumor of the breast. Presentation during pregnancy is uncommon. Reports regarding malignancy in these tumors differ greatly in incidence, and most of them are stromal malignancies. We report this case in which 24-year old primigravid patient in the 36th week of her pregnancy had a malignant phylloides tumor of breast with sudden growth and fine needle aspiration cytology of the breast was positive for malignancy. Ultimately after her caesarean delivery, excision biopsy was in favor of a malignant process. Pregnancy with nulliparous prolapse is also a rare condition. Those conditions are not associated with each other, but presence of two rare conditions in the same time in the same person is unique. PMID:23115419

  4. Genomic profiling of malignant phyllodes tumors reveals aberrations in FGFR1 and PI-3 kinase/RAS signaling pathways and provides insights into intratumoral heterogeneity.

    PubMed

    Liu, Su-Yang; Joseph, Nancy M; Ravindranathan, Ajay; Stohr, Bradley A; Greenland, Nancy Y; Vohra, Poonam; Hosfield, Elizabeth; Yeh, Iwei; Talevich, Eric; Onodera, Courtney; Van Ziffle, Jessica A; Grenert, James P; Bastian, Boris C; Chen, Yunn-Yi; Krings, Gregor

    2016-09-01

    Malignant phyllodes tumors of the breast are poorly understood rare neoplasms with potential for aggressive behavior. Few efficacious treatment options exist for progressed or metastatic disease. The molecular features of malignant phyllodes tumors are poorly defined, and a deeper understanding of the genetics of these tumors may shed light on pathogenesis and progression and potentially identify novel treatment approaches. We sequenced 510 cancer-related genes in 10 malignant phyllodes tumors, including 5 tumors with liposarcomatous differentiation and 1 with myxoid chondrosarcoma-like differentiation. Intratumoral heterogeneity was assessed by sequencing two separate areas in 7 tumors, including non-heterologous and heterologous components of tumors with heterologous differentiation. Activating hotspot mutations in FGFR1 were identified in 2 tumors. Additional recurrently mutated genes included TERT promoter (6/10), TP53 (4/10), PIK3CA (3/10), MED12 (3/10), SETD2 (2/10) and KMT2D (2/10). Together, genomic aberrations in FGFR/EGFR PI-3 kinase and RAS pathways were identified in 8 (80%) tumors and included mutually exclusive and potentially actionable activating FGFR1, PIK3CA and BRAF V600E mutations, inactivating TSC2 mutation, EGFR amplification and PTEN loss. Seven (70%) malignant phyllodes tumors harbored TERT aberrations (six promoter mutations, one amplification). For comparison, TERT promoter mutations were identified by Sanger sequencing in 33% borderline (n=12) and no (0%, n=8) benign phyllodes tumors (P=0.391 and P=0.013 vs malignant tumors, respectively). Genetic features specific to liposarcoma, including CDK4/MDM2 amplification, were not identified. Copy number analysis revealed intratumoral heterogeneity and evidence for divergent tumor evolution in malignant phyllodes tumors with and without heterologous differentiation. Tumors with liposarcomatous differentiation revealed more chromosomal aberrations in non-heterologous components compared with

  5. Dermatofibrosarcoma protuberans, a rare but locally aggressive tumor on finger: clinical and aeromedical considerations

    PubMed Central

    Chiang, Kwo-Tsao; Lee, Shih-Yu; Chu, Hsin

    2015-01-01

    Abstract Dermatofibrosarcoma protuberans (DFSP) is a rare, slow growing, locally infiltrative tumor of intermediate malignancy. It is mostly found on the trunk and head, rarely on hands. The course of evaluation and treatment of a young pilot with DFSP on left middle finger is reported. The clinical issues and aeromedical considerations of this rare tumor is discussed.

  6. A rare case of recurrent malignant triton tumor in a male with NF1: Case report and mini-review

    PubMed Central

    Aykut, B.; Wieczorek, K.; Schirmacher, P.; Büchler, M.W.; Hoffmann, K.

    2016-01-01

    Background Malignant triton tumors (MTT) represent a rare subset of tumors with rhabdomyoblastic differentiation within the heterogeneous group of malignant peripheral nerve sheath tumors (MPNST). Case presentation Here, we report on a case of a 25 year-old male with a history of neurofibromatosis type I and MTT of the mediastinal wall who presented in our clinic with a pelvic tumor and multiple hypervascular mesenteric masses and underwent resection. Upon resection, histological findings revealed an MTT of the omentum and an atypical neurofibroma of the pelvis with focal transitions to a low-grade MPNST. The patient relapsed just one month later and died 3 months after the surgery. Conclusion Clinically, MTTs are characterized as highly aggressive tumors that are fast-growing and prone to local recurrence and distant metastasis. To date, there is no treatment consensus available yet and many patients succumb to the disease shortly after diagnosis. This is because the pathogenesis of MTT remains unknown and patients with MTT are often diagnosed at a late stage of disease. Our case presents valuable teaching points in terms of providing a possible progression model based on the coexistence of a low-grade MPNST and MTT in the context of NF1 and an atypical neurofibroma in this patient. Close monitoring of patients with NF1 and atypical neurofibromas or MPNST might therefore help to diagnose MTT at an earlier stage. PMID:26975033

  7. Subacute brain atrophy after radiation therapy for malignant brain tumor

    SciTech Connect

    Asai, A.; Matsutani, M.; Kohno, T.; Nakamura, O.; Tanaka, H.; Fujimaki, T.; Funada, N.; Matsuda, T.; Nagata, K.; Takakura, K.

    1989-05-15

    Brain atrophy with mental and neurologic deterioration developing a few months after radiation therapy in patients without residual or recurrent brain tumors has been recognized. Two illustrative case reports of this pathologic entity are presented. Six autopsy cases with this entity including the two cases were reviewed neurologically, radiographically, and histopathologically. All patients presented progressive disturbances of mental status and consciousness, akinesia, and tremor-like involuntary movement. Computerized tomography (CT) demonstrated marked enlargement of the ventricles, moderate widening of the cortical sulci, and a moderately attenuated CT number for the white matter in all six patients. Four of the six patients had CSF drainage (ventriculoperitoneal shunt or continuous lumbar drainage), however, none of them improved. Histologic examination demonstrated swelling and loss of the myelin sheath in the white matter in all patients, and reactive astrocytosis in three of the six patients. Neither prominent neuronal loss in the cerebral cortex or basal ganglia, nor axonal loss in the white matter was generally identified. The blood vessels of the cerebral cortex and white matter were normal. Ependymal layer and the surrounding brain tissue were normal in all patients. These findings suggested that this pathologic condition results from demyelination secondary to direct neurotoxic effect of irradiation. The authors' previous report was reviewed and the differential diagnoses, the risk factors for this pathologic entity, and the indication for radiation therapy in aged patients with a malignant brain tumor are discussed.

  8. Primary mixed malignant tumor of bone in an 18-year-old male: Report of a case with radiologic-pathologic correlation

    PubMed Central

    Courtier, Jesse; Robbins, Elizabeth; Soares, Bruno; Horvai, Andrew; Mackenzie, John D.

    2012-01-01

    We report a case of primary malignant mixed tumor (MMT) of bone in an 18-year-old boy with X-ray, CT, MR, scintigraphic, FDG PET, and pathologic correlation. Primary MMT of bone is a highly aggressive tumor and presents both a diagnostic and clinical treatment challenge. This tumor is extremely rare and to the best of our knowledge, this is the first report of the diagnostic imaging findings for primary MMT arising from bone in a patient of this age group. PMID:26909264

  9. Breast metastases from a malignant peripheral nerve sheath tumor of the kidney: An unusual presentation

    PubMed Central

    Koppisetty, Shalini; Alessio, Ricardo C.; Rajpurkar, Atul

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare soft tissue sarcomas of ectomesenchymal origin. They are commonly seen in association with neurofibromatosis type 1 (NF-1), but can also occur without a history of NF (isolated MPNST). MPNSTs are most commonly located on the extremities (brachial and sacral plexus), head and neck, and trunk regions and are rarely reported in genitourinary organs. These tumors are aggressive, with a high recurrence rate and distant metastases. MPNST involving the kidney is extremely rare, and review of the literature using PubMed from 2001 to 2014 revealed eight cases of MPNST involving the kidney (seven, primarily involving the kidney and one metastatic MPNST of the kidney). Herein, we describe a case of breast metastases from an MPNST of the kidney without a history of NF-1. The patient was initially diagnosed with a spindle cell neoplasm of the kidney with peripheral nerve sheath differentiation. Eventually, the patient developed a right breast mass that was diagnosed as metastatic MPNST. The patient refused any kind of treatment and died 6 months later in hospice care. PMID:27453670

  10. Defective apical extrusion signaling contributes to aggressive tumor hallmarks.

    PubMed

    Gu, Yapeng; Shea, Jill; Slattum, Gloria; Firpo, Matthew A; Alexander, Margaret; Mulvihill, Sean J; Golubovskaya, Vita M; Rosenblatt, Jody

    2015-01-01

    When epithelia become too crowded, some cells are extruded that later die. To extrude, a cell produces the lipid, Sphingosine 1-Phosphate (S1P), which activates S1P₂ receptors in neighboring cells that seamlessly squeeze the cell out of the epithelium. Here, we find that extrusion defects can contribute to carcinogenesis and tumor progression. Tumors or epithelia lacking S1P₂ cannot extrude cells apically and instead form apoptotic-resistant masses, possess poor barrier function, and shift extrusion basally beneath the epithelium, providing a potential mechanism for cell invasion. Exogenous S1P₂ expression is sufficient to rescue apical extrusion, cell death, and reduce orthotopic pancreatic tumors and their metastases. Focal Adhesion Kinase (FAK) inhibitor can bypass extrusion defects and could, therefore, target pancreatic, lung, and colon tumors that lack S1P₂ without affecting wild-type tissue. PMID:25621765

  11. MICROBIAL DRIVEN TLR5-DEPENDENT SIGNALING GOVERNS DISTAL MALIGNANT PROGRESSION THROUGH TUMOR-PROMOTING INFLAMMATION

    PubMed Central

    Rutkowski, Melanie R.; Stephen, Tom L.; Svoronos, Nikolaos; Allegrezza, Michael J.; Tesone, Amelia J.; Perales-Puchalt, Alfredo; Brencicova, Eva; Escovar-Fadul, Ximena; Nguyen, Jenny M.; Cadungog, Mark G.; Zhang, Rugang; Salatino, Mariana; Tchou, Julia; Rabinovich, Gabriel A.; Conejo-Garcia, Jose R.

    2014-01-01

    The dominant TLR5R392X polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extra-mucosal locations by increasing systemic IL-6, which drives mobilization of myeloid derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening anti-tumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently up-regulated in TLR5-unresponsive tumor-bearing mice, but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, anti-tumor immunity and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism. PMID:25533336

  12. Clinical aggressiveness of malignant gliomas is linked to augmented metabolism of amino acids.

    PubMed

    Panosyan, Eduard H; Lasky, Joseph L; Lin, Henry J; Lai, Albert; Hai, Yang; Guo, Xiuqing; Quinn, Michael; Nelson, Stanley F; Cloughesy, Timothy F; Nghiemphu, P Leia

    2016-05-01

    Glutamine, glutamate, asparagine, and aspartate are involved in an enzyme-network that controls nitrogen metabolism. Branched-chain-amino-acid aminotransferase-1 (BCAT1) promotes proliferation of gliomas with wild-type IDH1 and is closely connected to the network. We hypothesized that metabolism of asparagine, glutamine, and branched-chain-amino-acids is associated with progression of malignant gliomas. Gene expression for asparagine synthetase (ASNS), glutaminase (GLS), and BCAT1 were analyzed in 164 gliomas from 156 patients [33-anaplastic gliomas (AG) and 131-glioblastomas (GBM), 64 of which were recurrent GBMs]. ASNS and GLS were twofold higher in GBMs versus AGs. BCAT1 was also higher in GBMs. ASNS expression was twofold higher in recurrent versus new GBMs. Five patients had serial samples: 4-showed higher ASNS and 3-higher GLS at recurrence. We analyzed grade and treatment in 4 groups: (1) low ASNS, GLS, and BCAT1 (n = 96); (2) low ASNS and GLS, but high BCAT1 (n = 26); (3) high ASNS or GLS, but low BCAT1 (n = 25); and (4) high ASNS or GLS and high BCAT1 (n = 17). Ninety-one  % of patients (29/32) with grade-III lesions were in group 1. In contrast, 95 % of patients (62/65) in groups 2-4 had GBMs. Treatment was similar in 4 groups (radiotherapy-80 %; temozolomide-30 %; other chemotherapy-50 %). High expression of ASNS, GLS, and BCAT1 were each associated with poor survival in the entire group. The combination of lower ASNS, GLS, and BCAT1 levels correlated with better survival for newly diagnosed GBMs (66 patients; P = 0.0039). Only tumors with lower enzymes showed improved outcome with temozolomide. IDH1(WT) gliomas had higher expression of these genes. Manipulation of amino acid metabolism in malignant gliomas may be further studied for therapeutics development. PMID:26922345

  13. Uterine adenolipoleiomyoma: a tumor with potential of aggressive behavior.

    PubMed

    Shaco-Levy, Ruthy; Piura, Benjamin

    2008-04-01

    An unusual uterine adenolipoleiomyoma forming intramural and subserosal masses and recurring within 16 months in the form of huge coalescent uterine masses is described. Histology showed the mass to be composed of benign-appearing smooth muscle, mature adipose tissue, and bland endocervical-type glands. The recurrent adenolipoleiomyoma contained, in addition, benign-appearing endometrial-type glands and stroma and showed small foci of atypically proliferating endocervical-type epithelium. This is the fourth report of adenolipoleiomyoma within the uterus, the second with an intramural location, and the first with an aggressive behavior in the form of massive local recurrence. PMID:18317215

  14. A retroperitoneal NF1-independent malignant peripheral nerve sheath tumor with elevated serum CA125: case report and discussion.

    PubMed

    Yan, Bing; Meng, Xianze; Shi, Bian; Shi, Jun; Qin, Zhifeng; Wei, Pinkang

    2012-08-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are usually located in the trunk, extremities, head, or neck, and most occur with neurofibromatosis type 1 (NF1; von Recklinghausen's disease). No biomarkers have previously been found to be associated with their progression. Retroperitoneal NF1-independent MPNSTs are rare; they are considered to be less aggressive and to have better prognoses compared to NF1-related tumors. Currently, en bloc excision is the only consensus treatment approach. In a 27-year-old male with a giant retroperitoneal MPNST and no stigmata or family history of neurofibromatosis type-1 (NF1), a remarkable elevation of serum CA125 was detected. The high-grade tumor displayed a striking progression: the primary lesion, 25 cm in diameter, recurred in its previous site as a 17-cm MPNST less than 50 days after total excision. Subsequent treatment with microwave ablation and huachansu, a traditional Chinese medication, proved ineffective, and the patient died within 3 months. Our case suggests that retroperitoneal MPNSTs can deteriorate rapidly even if NF1 independent, that aggressive treatment may not benefit large high-grade MPNSTs, and that novel and effective treatment is urgently needed. Our case also suggests the possibility of using serum tumor markers in the early detection and monitoring of MPNSTs. PMID:22528792

  15. Malignant proliferating pilar tumors arising in KID syndrome: a report of two patients.

    PubMed

    Nyquist, Gurston G; Mumm, Christina; Grau, Renee; Crowson, A Neil; Shurman, Daniel L; Benedetto, Paul; Allen, Pamela; Lovelace, Kelli; Smith, David W; Frieden, Ilona; Hybarger, C Patrick; Richard, Gabriele

    2007-04-01

    We report on two young adults with KID syndrome and follicular hyperkeratosis, hidradenitis suppurativa of the groin, progressive development of proliferative pilar cysts and dissecting cellulitis of the scalp, who developed metastatic malignant pilar tumors. Based on our findings, we believe that cancer surveillance in patients with KID syndrome should include screening for pilar tumors and their early removal to avoid development of malignant proliferating pilar tumors with poor prognosis. PMID:17330861

  16. Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors

    PubMed Central

    Sarin, Hemant

    2009-01-01

    Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous blood-brain tumor barrier of malignant brain tumor microvasculature. Small molecule systemic chemotherapy drugs maintain peak blood concentrations for only minutes, and therefore, do not accumulate to therapeutic concentrations within individual brain tumor cells. The physiologic upper limit of pore size in the blood-brain tumor barrier of malignant brain tumor microvasculature is approximately 12 nanometers. Spherical nanoparticles ranging between 7 nm and 10 nm in diameter maintain peak blood concentrations for several hours and are sufficiently smaller than the 12 nm physiologic upper limit of pore size in the blood-brain tumor barrier to accumulate to therapeutic concentrations within individual brain tumor cells. Therefore, nanoparticles bearing chemotherapy that are within the 7 to 10 nm size range can be used to deliver therapeutic concentrations of small molecule chemotherapy drugs across the blood-brain tumor barrier into individual brain tumor cells. The initial therapeutic efficacy of the Gd-G5-doxorubicin dendrimer, an imageable nanoparticle bearing chemotherapy within the 7 to 10 nm size range, has been demonstrated in the orthotopic RG-2 rodent malignant glioma model. Herein I discuss this novel strategy to improve the effectiveness of systemic chemotherapy for the treatment of malignant brain tumors and the therapeutic implications thereof. PMID:19723323

  17. Malignant melanoma maxilla

    PubMed Central

    Devi, Seema; Sinha, Richi; Singh, Rakesh Kumar

    2015-01-01

    A malignant melanoma is a highly lethal melanocytic neoplasm. A neoplasm usually affects the skin. Malignant melanomas in the head and neck region are rare, accounting for less than 1% of all melanomas. Malignant melanoma of the nose and paranasal sinuses is an aggressive disease typically presenting at an advanced stage, with a 5-year survival rate ranging 20-30%. Melanomas are tumors arising from melanocytes, which are neuroectodermally derived cells located in the basal layers of the skin. This is a case report of a 35-year-old male, who presented with very aggressive disease and developed liver metastasis. PMID:26668467

  18. Malignant Tumors and Forensics – Dilemmas and Proposals

    PubMed Central

    Budimlija, Zoran; Lu, Connie; Axler-DiPerte, Grace; Seifarth, Jessica; Popiolek, Dorota; Fogt, Franz; Prinz, Mechthild

    2009-01-01

    Aim To evaluate the effect of genetic instability and degradation in archived histology samples from cancerous tumors and to investigate the validity of short tandem repeat (STR) typing of these samples and its potential effect on human identification. Methods Two hundred and twenty eight slides of archival pathology tissues from 13 different types of malignant tumors were compared with healthy tissues from the same individuals. DNA analysis was performed using standard techniques for forensic STR analysis, PowerPlex®16 and Identifiler® on 2 distinct sample sets. Genetic instability was assessed by comparing reference tissues with cancerous tissues derived from the same individual. Loss of heterozygosity, a ≥50% reduction in heterozygosity ratio between healthy and diseased samples, and microsatellite instability, the presence of an additional allele not present in reference tissue, were assessed. The quality of profiles obtained with respect to completeness among the archived samples and degradation using the 2 platforms were also compared. Results Profiles obtained using the Identifiler® system were generally more complete, but showed 3-fold higher levels of instability (86%) than those obtained using PowerPlex® 16 (27%). Instances of genetic instability were distributed throughout all loci in both multiplex STR systems. Conclusion After having compared 2 widely used forensic chemistries, we suggest individual validation of each kit for use with samples likely to exhibit instability combined with fixation induced degradation or artifact. A “one size fits all” approach for interpretation of these samples among commercially available multiplexes is not recommended. PMID:19480018

  19. Extra-hepatic fascioliasis with peritoneal malignancy tumor feature.

    PubMed

    Mohammadi-Ghalehbin, Behnam; Chinifroush-Asl, Mir Mehdi; Ramzi, Fatemeh

    2012-04-01

    Fascioliasis is a zoonose parasitic disease caused by Fasciola hepatica and Fasciola gigantica and is widespread in most regions of the world. Ectopic fascioliasis usually caused by juvenile Fasciola spp., but in recent years a few cases of tissue-embedded ova have been reported from different endemic areas. A 79-year-old Iranian man resident in Eird-e-Mousa village from Ardabil Province, north-west of Iran, complained with abdominal pain, nausea, and intestinal obstruction symptoms referred to Ardabil Fatemi hospital. In laparotomy multiple intestinal masses with peritoneal seeding resembling of a malignant lesion were seen. After appendectomy and peritoneal mass biopsy with numerous intraperitoneal adenopathy, paraffin embedded blocks were prepared from each tissues. A blood sample was taken from the patient 5 months later for serological diagnosis. Histopathological examination of sections showed fibrofatty stroma with dense mixed inflammatory cells infiltration and fibrosis in peritoneal masses. Large numbers of ova of Fasciola spp. were noted with typical circumscribed granulomas. Despite of anti-fasciola treatment, IHA test for detecting anti F. hepatica antibodies was positive 5 months after surgery with a titer of 1/128. Due to multiple clinical manifestation of extra-hepatic fascioliasis, its differential diagnosis from intraperitoneal tumors or other similar diseases should be considered. PMID:23542770

  20. Procedure for quantitative determination of effectiveness of photoinduced destruction of malignant tumors

    NASA Astrophysics Data System (ADS)

    Bizyuk, S. A.; Istomin, Yu. P.; Dzhagarov, B. M.

    2006-07-01

    We have developed a procedure for analysis of the functional status of blood vessels in tumor tissues using computer-assisted color scanning of tumor slices and also for a quantitative assessment of the effectiveness of photoinduced destruction of tumor tissues in animal experiments. Its major advantage is direct determination of the size of the tumor necrosis zone. The procedure has been tested in an experiment on three strains of malignant tumors with different morphologies.

  1. Case report of malignant pulmonary parenchymal glomus tumor: imaging features and review of the literature.

    PubMed

    Cunningham, Jane D; Plodkowski, Andrew J; Giri, Dilip D; Hwang, Sinchun

    2016-01-01

    Glomus tumor is rare tumor which arises from glomus body and is most frequently found in the soft tissue of the extremities. The lung is a rare ectopic site, and a malignant glomus tumor arising from pulmonary parenchyma is particularly uncommon. To deepen our understanding on their imaging features, we report a case of malignant glomus tumor of pulmonary parenchyma confirmed with surgical histopathology and immunochemistry and review the medical literature on pulmonary parenchymal glomus tumors with emphasis on their imaging features. PMID:26498485

  2. Small Cell Carcinoma of the Ovary (Hypercalcemic Type): Malignant Rhabdoid Tumor

    PubMed Central

    Kascak, Peter; Zamecnik, Michal; Bystricky, Branislav

    2016-01-01

    We present a rare case of malignant rhabdoid tumor (ovarian small cell carcinoma of hypercalcemic type) in a 24-year-old female with fulminant course. Clinically, hypercalcemia was not found at the time of primary diagnosis. However, it appeared later during the course of tumor progression. Histologically, the tumor showed classical features of small cell carcinoma of hypercalcemic type. Therapy included radical surgery with adjuvant chemotherapy. Despite this intensive therapy, the disease recurred and the patient died 10 months after the diagnosis. We discuss the diagnosis and therapy of this tumor, as well as its recent classification as malignant rhabdoid tumor. PMID:27462229

  3. Primitive neuroectodermal tumor (PNET) in the differential diagnosis of malignant kidney tumors.

    PubMed

    Friedrichs, Nicolaus; Vorreuther, Roland; Poremba, Christopher; Schafer, Karl-Ludwig; Böcking, Alfred; Buettner, Reinhard; Zhou, Hui

    2002-01-01

    Primitive neuroectodermal tumors (PNETs) of the kidney, a rare neoplastic disease of high malignancy with a tendency towards early metastasis, affect young adults (26-30 years) irrespective of the gender. Differential diagnosis from other renal tumors is very important for an effective therapy. Herein, we report on a 24-year-old male patient with a renal tumor consisting of small, round cells, and summarize the diagnostic procedures that establish the diagnosis of PNET. Light microscopy revealed not only areas containing small, round cells forming rosettes and pseudorosettes, but also areas containing spindle cells. Expression of CD 99 in combination with neural markers, such as NSE, was detected by immunohistochemistry, and further evidence of neural differentiation was provided by electron microscopy. Image cytometry revealed a peridiploid DNA-stemline. A reciprocal translocation of the chromosomes 11 and 22 [t(11;22)(q24;q12)] with expression of a EWS/FLI-1 fusion transcript was demonstrated by molecular pathology. Using these methods, the diagnosis of PNET was firmly established, and the tumor was treated by surgical resection and subsequent adjuvant chemotherapy. Eighteen months after therapy, the patient is in excellent health condition without any evidence of tumor recurrence. PMID:12390000

  4. Clinicopathologic Review of 31 Cases of Solid Pseudopapillary Pancreatic Tumors: Can We Use the Scoring System of Microscopic Features for Suggesting Clinically Malignant Potential?

    PubMed

    Kim, Jang-Hee; Lee, Jae-Myeong

    2016-04-01

    A solid pseudopapillary tumor (SPT) is a pancreatic neoplasm of low malignant potential. The potentially malignant pathologic features of SPTs were regarded as angioinvasion, perineural invasion, deep invasion of the surrounding acinar tissue, and nuclear pleomorphism. We retrospectively reviewed 31 cases of SPTs (25 female and 6 male patients, with an average age of 35 ± 14 years). The mean follow-up period was 132.0 ± 55.9 months. To evaluate the clinical impact of above pathological parameters, we analyzed their correlation with actually observed clinical malignancy. In three cases, the SPTs were clearly clinically malignant: one patient had recurrences three times, one showed lymph node metastases, and one deep soft tissue invasion around the gastroduodenal artery. Tumor infiltration to the peripancreatic soft tissue was observed in 17 cases (54.8%). The pathologic features considered suggestive of malignant potential were angioinvasion (25.8%), perineural invasion (6.5%), presence of mitosis in 10 high-power fields (16.1%), and moderate nuclear pleomorphism (19.4%). The presence of at least three of these features was not correlated with clinically confirmed malignant behavior (P = 0.570). Microscopic pathologic features of SPTs cannot be reliably associated with aggressive clinical behavior. Moreover, the absence of these microscopic features cannot exclude clinical malignancy. PMID:27097622

  5. Comprehensive establishment and characterization of orthoxenograft mouse models of malignant peripheral nerve sheath tumors for personalized medicine

    PubMed Central

    Castellsagué, Joan; Gel, Bernat; Fernández-Rodríguez, Juana; Llatjós, Roger; Blanco, Ignacio; Benavente, Yolanda; Pérez-Sidelnikova, Diana; García-del Muro, Javier; Viñals, Joan Maria; Vidal, August; Valdés-Mas, Rafael; Terribas, Ernest; López-Doriga, Adriana; Pujana, Miguel Angel; Capellá, Gabriel; Puente, Xose S; Serra, Eduard; Villanueva, Alberto; Lázaro, Conxi

    2015-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas that can arise either sporadically or in association with neurofibromatosis type 1 (NF1). These aggressive malignancies confer poor survival, with no effective therapy available. We present the generation and characterization of five distinct MPNST orthoxenograft models for preclinical testing and personalized medicine. Four of the models are patient-derived tumor xenografts (PDTX), two independent MPNSTs from the same NF1 patient and two from different sporadic patients. The fifth model is an orthoxenograft derived from an NF1-related MPNST cell line. All MPNST orthoxenografts were generated by tumor implantation, or cell line injection, next to the sciatic nerve of nude mice, and were perpetuated by 7–10 mouse-to-mouse passages. The models reliably recapitulate the histopathological properties of their parental primary tumors. They also mimic distal dissemination properties in mice. Human stroma was rapidly lost after MPNST engraftment and replaced by murine stroma, which facilitated genomic tumor characterization. Compatible with an origin in a catastrophic event and subsequent genome stabilization, MPNST contained highly altered genomes that remained remarkably stable in orthoxenograft establishment and along passages. Mutational frequency and type of somatic point mutations were highly variable among the different MPNSTs modeled, but very consistent when comparing primary tumors with matched orthoxenografts generated. Unsupervised cluster analysis and principal component analysis (PCA) using an MPNST expression signature of ~1,000 genes grouped together all primary tumor–orthoxenograft pairs. Our work points to differences in the engraftment process of primary tumors compared with the engraftment of established cell lines. Following standardization and extensive characterization and validation, the orthoxenograft models were used for initial preclinical drug testing. Sorafenib (a

  6. Intratumoral FoxP3 expression is associated with angiogenesis and prognosis in malignant canine mammary tumors.

    PubMed

    Carvalho, Maria Isabel; Pires, Isabel; Prada, Justina; Gregório, Hugo; Lobo, Luis; Queiroga, Felisbina L

    2016-10-01

    The activity of regulatory T cells (Tregs) is closely associated with the expression of FoxP3 transcription factor. FoxP3 regulatory T cells (FoxP3Treg) have immunosuppressive properties and can work for prevention of harmful autoimmune responses, however can also interfere with beneficial anti-tumor immunity. In human breast cancer these cells play a crucial role in tumor progression. In canine mammary tumors (CMT) this topic is not well-documented. This study included 80 malignant CMT and studied, by immunohistochemistry, the intratumoral FoxP3 expression together with microvessel density (MVD), vascular endothelial growth factor (VEGF) and several clinicopathological characteristics. Abundant FoxP3Treg cells were associated with tumor necrosis (p=0.001), high mitotic grade (p<0.001), more marked nuclear polymorphism (p=0.001), poor differentiation of tumors (p<0.001), high histological grade of malignancy (HGM) (p<0.001), presence of neoplastic intravascular emboli (p<0.001) and presence of lymph node metastasis (p<0.001). Intratumoral FoxP3 was correlated with MVD (r=0.827; p<0.001) and associated with VEGF (p=0.001). Additionally tumors with abundant FoxP3Treg cells were associated with shorter overall survival (OS) time in univariate and multivariate analysis (p<0.001 Kaplan-Meier curves and 7.97 hazard ratio, p<0.001 Cox proportional hazard model). Results suggest that Treg cells play a role in CMT progression and may contribute to increased angiogenesis and aggression in these tumors. The association of intratumoral FoxP3 expression with shorter OS in multivariate analysis suggests the usefulness of Treg cells as an independent prognostic marker. PMID:27496736

  7. Broadening the spectrum of SMARCB1-associated malignant tumors: a case of uterine leiomyosarcoma in a patient with schwannomatosis.

    PubMed

    Paganini, Irene; Sestini, Roberta; Cacciatore, Matilde; Capone, Gabriele L; Candita, Luisa; Paolello, Concetta; Sbaraglia, Marta; Dei Tos, Angelo P; Rossi, Sabrina; Papi, Laura

    2015-08-01

    Schwannomatosis is a tumor predisposition syndrome characterized by development of multiple intracranial, spinal, and peripheral schwannomas. Constitutional alterations in either SMARCB1 or LZTR1 on 22q are responsible of the phenotype. We describe a 34-year-old woman who developed multiple benign peripheral sheath tumors and a uterine leiomyosarcoma. The patient carried a de novo constitutional alteration in exon 8 of SMARCB1, c.1118G > A, which destroyed the splice donor site of intron 8. Two schwannomas and the leiomyosarcoma of the patient retained the SMARCB1 mutation; in addition, the tumors showed loss of the normal chromosome 22. In conclusion, our findings enlarged the spectrum of SMARCB1-predisposing tumors and demonstrated, for the first time, the association of a malignant smooth muscle tumor to schwannomatosis. Therefore, clinicians should definitely be aware that a constitutional SMARCB1 mutation, which mainly predisposes to benign nerve sheath tumors, may also predispose to aggressive neoplasms throughout life, within an unexpected spectrum. PMID:26001331

  8. Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

    PubMed Central

    Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

    2014-01-01

    The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

  9. Prognostic roles for fibroblast growth factor receptor family members in malignant peripheral nerve sheath tumor

    PubMed Central

    Song, Fengju; Zheng, Hong; Chen, Kexin; Zhang, Wei; Yang, Jilong

    2016-01-01

    Background Malignant peripheral nerve sheath tumors (MPNST) are rare, highly malignant, and poorly understood sarcomas. The often poor outcome of MPNST highlights the necessity of identifying prognostic predictors for this aggressive sarcoma. Here, we investigate the role of fibroblast growth factor receptor (FGFR) family members in human MPNSTs. Results aCGH and bioinformatics analysis identified frequent amplification of the FGFR1 gene. FISH analysis revealed that 26.9% MPNST samples had amplification of FGFR1, with both focal and polysomy patterns observed. IHC identified that FGFR1 protein expression was positively correlated with FGFR1 gene amplification. High expression of FGFR1 protein was associated with better overall survival (OS) and was an independent prognostic predictor for OS of MPNST patients. Additionally, combined expression of FGFR1 and FGFR2 protein characterized a subtype of MPNST with better OS. FGFR4 protein was expressed 82.3% of MPNST samples, and was associated with poor disease-free survival. Materials and Methods We performed microarray-based comparative genomic hybridization (aCGH) profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Medical University Cancer Institute and Hospital. Fluorescence in situ hybridization (FISH) was used to validate the gene amplification detected by aCGH analysis. Another cohort of 63 formalin-fixed paraffin-embedded MPNST samples (including 52 samples for FISH assay) was obtained to explore FGFR1, 2, 3, and 4 protein expression by immunohistochemical (IHC) analysis. Conclusions Our integrated genomic and molecular studies provide evidence that FGFRs play different prognostic roles in MPNST. PMID:26993773

  10. Malignant perivascular epithelioid cell tumor of the gallbladder: a case report and review of literature.

    PubMed

    Zhao, Liena; Anders, Karl H

    2014-09-01

    Perivascular epithelioid cell tumors are rare mesenchymal neoplasms composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. The perivascular epithelioid cell tumor family includes angiomyolipoma, clear cell sugar tumor of the lung, lymphangioleiomyomatosis, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and rare clear cell tumors of other anatomic sites. Perivascular epithelioid cell tumors have been reported previously in various sites, but to our knowledge not in the gallbladder. We report here, for the first time, a malignant perivascular epithelioid cell tumor arising in the gallbladder. PMID:25171708

  11. A NOXA/MCL-1 Imbalance Underlies Chemoresistance of Malignant Rhabdoid Tumor Cells.

    PubMed

    Ouchi, Kazutaka; Kuwahara, Yasumichi; Iehara, Tomoko; Miyachi, Mitsuru; Katsumi, Yoshiki; Tsuchiya, Kunihiko; Konishi, Eiichi; Yanagisawa, Akio; Hosoi, Hajime

    2016-09-01

    Malignant rhabdoid tumor (MRT) is a rare aggressive pediatric cancer characterized by inactivation of SNF5, a core subunit of SWI/SNF complexes. Previously, we showed that SNF5 contributes to transcriptional activation of NOXA, a pro-apoptotic protein that binds and inhibits the anti-apoptotic protein MCL-1. In this study, we found that NOXA expression was downregulated in MRT cell lines as well as in clinical MRT samples and that ectopically expressed NOXA bound MCL-1 and increased the sensitivity of MRT cell lines to doxorubicin (DOX) by promoting apoptosis. Consistent with this finding, knockdown of MCL-1 in MRT cell lines induced apoptosis and increased DOX sensitivity in MRT cells, and the MCL-1 inhibitor TW-37 synergized with DOX to induce MRT cell death. Our results suggest that modulation of the NOXA/MCL-1 pathway may be a potential strategy for the treatment of patients with MRT. J. Cell. Physiol. 231: 1932-1940, 2016. © 2015 Wiley Periodicals, Inc. PMID:26680268

  12. Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation.

    PubMed

    Rutkowski, Melanie R; Stephen, Tom L; Svoronos, Nikolaos; Allegrezza, Michael J; Tesone, Amelia J; Perales-Puchalt, Alfredo; Brencicova, Eva; Escovar-Fadul, Ximena; Nguyen, Jenny M; Cadungog, Mark G; Zhang, Rugang; Salatino, Mariana; Tchou, Julia; Rabinovich, Gabriel A; Conejo-Garcia, Jose R

    2015-01-12

    The dominant TLR5(R392X) polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening antitumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently upregulated in TLR5-unresponsive tumor-bearing mice but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, antitumor immunity, and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism. PMID:25533336

  13. Identification of Genes Associated with Local Aggressiveness and Metastatic Behavior in Soft Tissue Tumors12

    PubMed Central

    Cunha, Isabela Werneck; Carvalho, Katia Candido; Martins, Waleska Keller; Marques, Sarah Martins; Muto, Nair Hideko; Falzoni, Roberto; Rocha, Rafael Malagoli; Aguiar, Samuel; Simoes, Ana C. Q.; Fahham, Lucas; Neves, Eduardo Jordão; Soares, Fernando Augusto; Reis, Luiz Fernando Lima

    2010-01-01

    Soft tissue tumors represent a group of neoplasia with different histologic and biological presentations varying from benign, locally confined to very aggressive and metastatic tumors. The molecular mechanisms responsible for such differences are still unknown. The understanding of these molecular alterations mechanism will be critical to discriminate patients who need systemic treatment from those that can be treated only locally and could also guide the development of new drugs' against this tumors. Using 102 tumor samples representing a large spectrum of these tumors, we performed expression profiling and defined differentially expression genes that are likely to be involved in tumors that are locally aggressive and in tumors with metastatic potential. We described a set of 12 genes (SNRPD3, MEGF9, SPTAN-1, AFAP1L2, ENDOD1, SERPIN5, ZWINTAS, TOP2A, UBE2C, ABCF1, MCM2, and ARL6IP5) showing opposite expression when these two conditions were compared. These genes are mainly related to cell-cell and cell-extracellular matrix interactions and cell proliferation and might represent helpful tools for a more precise classification and diagnosis as well as potential drug targets. PMID:20165692

  14. Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients

    SciTech Connect

    Rock, M.G.; Sim, F.H.; Unni, K.K.; Witrak, G.A.; Frassica, F.J.; Schray, M.F.; Beabout, J.W.; Dahlin, D.C.

    1986-09-01

    Twenty-six patients who had a malignant giant-cell tumor of bone--a sarcoma either juxtaposed to a zone of typical benign giant-cell tumor or occurring at the site of a previously documented benign giant-cell tumor--have been seen at the Mayo Clinic. Of the twenty-six tumors, nineteen were secondary to a previous attempt at local control of a benign giant-cell tumor. All but one of these nineteen patients with a secondary tumor had received therapeutic irradiation four to thirty-nine years earlier. The nature and duration of the symptoms and the sites of predilection of the malignant giant-cell tumors were the same as for benign giant-cell tumor. Fibrosarcoma occurred three times as frequently as osteosarcoma. The best results of treatment of the secondary sarcoma were obtained with early ablation.

  15. Malignant peripheral nerve sheath tumor of the orbit: case report and literature review.

    PubMed

    Aydin, Mehmet D; Yildirim, Umran; Gundogdu, Cemal; Dursun, Osman; Uysal, Hasan H; Ozdikici, Mete

    2004-05-01

    A 68-year-old woman with progressive visual loss and exophthalmos in her right eye had been operated on for a mass in her right calf 3 years earlier. Imaging showed a huge mass invading the orbital structures and temporal pole. The presumptive diagnosis was a malignant orbital tumor. The tumor was resected totally and eroded tissues such as the lateral rectus muscle and dural compartments were repaired. The histological diagnosis was a malignant peripheral nerve sheath tumor (MPNST). The patient recovered uneventfully and was discharged 8 days after surgery. Two years later she died from a liver tumor. Few MPNSTs involving the orbit have been reported. PMID:16145592

  16. Aggressive Calcifying Epithelial Odontogenic Tumor of the Maxillary Sinus with Extraosseous Oral Mucosal Involvement: A Case Report

    PubMed Central

    Rani, Vidya; Masthan, Mahaboob Kadar; Aravindha, Babu; Leena, Sankari

    2016-01-01

    Calcifying epithelial odontogenic tumors are benign odontogenic neoplasms whose occurrence in the maxillary sinus is rare. Maxillary tumors tend to be locally aggressive and may rapidly involve the surrounding vital structures. We report a case of a large calcifying epithelial odontogenic tumor of the maxilla, involving the maxillary sinus in a 48-year-old woman. The tumor was largely intraosseous. In the canine and first premolar regions, the loss of bone could be palpated but the oral mucosa appeared normal. Histologically, the tumor tissue could be seen in the connective tissue below the oral epithelium. The most significant finding was the presence of an intraosseous tumor with an extraosseous involvement in a single tumor, indicating aggressive behavior and warranting aggressive treatment. In this article, we discuss the rare presentation of the tumor and its radiological appearance and histological features. We also highlight the importance of a detailed histopathological examination of the excised specimen. PMID:26989286

  17. Aggressive Calcifying Epithelial Odontogenic Tumor of the Maxillary Sinus with Extraosseous Oral Mucosal Involvement: A Case Report.

    PubMed

    Rani, Vidya; Masthan, Mahaboob Kadar; Aravindha, Babu; Leena, Sankari

    2016-03-01

    Calcifying epithelial odontogenic tumors are benign odontogenic neoplasms whose occurrence in the maxillary sinus is rare. Maxillary tumors tend to be locally aggressive and may rapidly involve the surrounding vital structures. We report a case of a large calcifying epithelial odontogenic tumor of the maxilla, involving the maxillary sinus in a 48-year-old woman. The tumor was largely intraosseous. In the canine and first premolar regions, the loss of bone could be palpated but the oral mucosa appeared normal. Histologically, the tumor tissue could be seen in the connective tissue below the oral epithelium. The most significant finding was the presence of an intraosseous tumor with an extraosseous involvement in a single tumor, indicating aggressive behavior and warranting aggressive treatment. In this article, we discuss the rare presentation of the tumor and its radiological appearance and histological features. We also highlight the importance of a detailed histopathological examination of the excised specimen. PMID:26989286

  18. Rat Prostate Tumor Cells Progress in the Bone Microenvironment to a Highly Aggressive Phenotype1

    PubMed Central

    Bergström, Sofia Halin; Rudolfsson, Stina H; Bergh, Anders

    2016-01-01

    Prostate cancer generally metastasizes to bone, and most patients have tumor cells in their bone marrow already at diagnosis. Tumor cells at the metastatic site may therefore progress in parallel with those in the primary tumor. Androgen deprivation therapy is often the first-line treatment for clinically detectable prostate cancer bone metastases. Although the treatment is effective, most metastases progress to a castration-resistant and lethal state. To examine metastatic progression in the bone microenvironment, we implanted androgen-sensitive, androgen receptor–positive, and relatively slow-growing Dunning G (G) rat prostate tumor cells into the tibial bone marrow of fully immune-competent Copenhagen rats. We show that tumor establishment in the bone marrow was reduced compared with the prostate, and whereas androgen deprivation did not affect tumor establishment or growth in the bone, this was markedly reduced in the prostate. Moreover, we found that, with time, G tumor cells in the bone microenvironment progress to a more aggressive phenotype with increased growth rate, reduced androgen sensitivity, and increased metastatic capacity. Tumor cells in the bone marrow encounter lower androgen levels and a higher degree of hypoxia than at the primary site, which may cause high selective pressures and eventually contribute to the development of a new and highly aggressive tumor cell phenotype. It is therefore important to specifically study progression in bone metastases. This tumor model could be used to increase our understanding of how tumor cells adapt in the bone microenvironment and may subsequently improve therapy strategies for prostate metastases in bone. PMID:26992916

  19. A recurrent solitary fibrous tumor of the thigh with malignant transformation: A case report

    PubMed Central

    Yoshimura, Yasuo; Sano, Kenji; Isobe, Ken-ichi; Aoki, Kaoru; Kito, Munehisa; Kato, Hiroyuki

    2016-01-01

    Introduction We describe an unusual case of a uniformly high-grade malignant solitary fibrous tumor (SFT) of the thigh with recurrence after wide resection in a 31-year-old man. Presentation of case Our current case showed a long-term benign course before the operation, although the subcutaneous tumor was larger than 10 cm at presentation. The SFT was diagnosed by needle biopsy, and wide resection was performed. Histological findings showed proliferation of capillaries surrounded by masses of spindle-shaped cells without any cytologic atypia, and the percentage of MIB-1-positive nuclei was 2.1%. However, a rapidly enlarging recurrent tumor was observed 11 months after the operation. A second wide resection for the recurrent tumor was performed. Histologically, the tumor cells uniformly displayed significant cytologic atypia and pleomorphism, and had 40–50 mitoses per 10 high-power fields. The proportion of MIB-1-positive nuclei was 48%. Consequently, the tumor was diagnosed as a SFT with malignant transformation. Discussion The malignant transformation described in past studies showed high-grade areas within benign, low-grade, or intermediate-grade SFTs. Therefore, in contrast to our case, uniformly high-grade malignant histological findings at recurrence were not described. Conclusion Even if a tumor is non-malignant during the clinical course, as confirmed by tissue biopsy, the possibility of tumor progression to high-grade sarcoma at recurrence should be considered, and the treatment strategy should be determined carefully. PMID:26967903

  20. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast

    PubMed Central

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P.; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-01

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast. PMID:26625196

  1. Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics.

    PubMed

    Schaefer, Inga-Marie; Fletcher, Christopher Dm; Hornick, Jason L

    2016-01-01

    The diagnosis of malignant peripheral nerve sheath tumor is challenging, particularly in the sporadic setting. Inactivation of the polycomb repressive complex 2 (PRC2), resulting from inactivating mutations of its constituents SUZ12 or EED1, has recently been identified in 70-90% of malignant peripheral nerve sheath tumors. Homozygous PRC2 inactivation results in loss of histone H3K27 trimethylation (H3K27me3). PRC2 inactivation promotes tumor progression and may render patients sensitive to epigenetic-based targeted therapies. H3K27me3 loss has not yet been validated as a diagnostic marker. We evaluated immunohistochemistry for H3K27me3 in 100 malignant peripheral nerve sheath tumors (70 sporadic, 10 neurofibromatosis type 1-associated, 10 radiation-associated, 10 epithelioid) and 200 other spindle cell neoplasms representing potential mimics (20 each monophasic synovial sarcoma, leiomyosarcoma, dedifferentiated liposarcoma, malignant solitary fibrous tumor, low-grade fibromyxoid sarcoma, cellular schwannoma, spindle cell melanoma, unclassified postradiation sarcoma; 10 each atypical neurofibroma, spindle cell rhabdomyosarcoma, gastrointestinal stromal tumor, fibrosarcomatous dermatofibrosarcoma protuberans). In total, 51 (51%) malignant peripheral nerve sheath tumors, including 34 (49%) sporadic, 7 (70%) neurofibromatosis type 1-associated, and 10 (100%) radiation-associated, but no epithelioid malignant peripheral nerve sheath tumors, were negative for H3K27me3. An additional 6 (6%) tumors showed heterogeneous H3K27me3 expression. Among the 90 sporadic, neurofibromatosis type 1-associated, and radiation-associated malignant peripheral nerve sheath tumors, complete H3K27me3 loss was observed in 29% of low-grade, 59% of intermediate-grade, and 83% of high-grade tumors (low vs intermediate/high grade, P=0.0003). Among other tumor types, 4 (20%) unclassified postradiation sarcomas were negative for H3K27me3, whereas all other neoplasms were positive. Loss of H3K27me

  2. Immunohistochemichal Assessment of the CrkII Proto-oncogene Expression in Common Malignant Salivary Gland Tumors and Pleomorphic Adenoma.

    PubMed

    Askari, Mitra; Darabi, Masoud; Jahanzad, Esa; Mostakhdemian Hosseini, Zahra; Musavi Chavoshi, Marjan; Darabi, Maryam

    2015-01-01

    Background and aims. Various morphologies are seen in different salivary gland tumorsor within an individual tumor, and the lesions show divers biological behaviors. Experimental results support the hypothesis that increased CrkII proto-oncogene is associated with cytokine-induced tumor initiation and progression by altering cell motility signaling pathway. The aim of this study was to assess the CrkII expression in common malignant salivary gland tumors and pleomorphic ade-noma. Materials and methods. Immunohistochemical analysis of CrkII expression was performed on paraffin blocks of 64 car-cinomas of salivary glands, 10 pleomorphic adenomas, and 10 normal salivary glands. Biopsies were subjected to immu-nostaining with EnVision detection system using monoclonal anti-CrkII. Evaluation of immunoreactivity of CrkII was based on the immunoreaction intensity and percentage of stained tumor cells which were scored semi-quantitatively on a scale with four grades 0 to 3. Kruskal-wallis test and additional Mann-Whitney statistical test were used for analysis of CrkII expression levels. Results. Increased expression of CrkII was seen (P=0.005) in malignant tumors including: mucoepidermoid carcinoma, adenoid cystic carcinoma, and carcinoma ex pleomorphic adenoma, but CrkII expression in acinic cell carcinoma was weak. CrkII expression in pleomorphic adenoma was weak or negative. A weak staining was sparsely seen in normal acinar serous cell. Conclusion. Increased expression of CrkII and its higher intensity of staining in tumors with more aggressive biologic behavior in carcinomas of salivary gland is consistent with a role for this proto-oncogene in salivary gland tumorigenesis and cancer progression. PMID:25973151

  3. Diagnosis of Malignancy of Adult Mediastinal Tumors by Conventional and Transesophageal Echocardiography

    PubMed Central

    Zhou, Wei-Wei; Wang, Hong-Wei; Liu, Nan-Nan; Li, Jing-Jing; Yuan, Wei; Zhao, Rui; Xiang, Liang-Bi; Qi, Miao

    2015-01-01

    Background: Transesophageal echocardiography (TEE) is a well-established method for detecting and diagnosing heart tumors. In contrast, its role in assessing the presence, growth and evidence of malignant tumors originating from mediastinal sites remains unclear. The aim of this study was to compare the diagnostic impact of TEE and transthoracic echocardiography (TTE) for determining the localization, growth and malignancy of adult mediastinal tumors (MTs). Methods: In a prospective and investigator-blinded study, we evaluated 144 consecutive patients with MT lesions to assess the diagnostic impact of TEE and TTE for detecting the presence of tumors spreading both inside and outside of the heart and for determining infiltration and invasion using pathological examination results as a reference. Results: All tumor lesions were diagnosed and carefully evaluated by biopsy. Biopsy revealed malignant tumors in 79 patients and benign tumors in 65 patients. When compared to histological findings, TEE predicted malignancy from the presence of tumors spreading both inside and outside of the heart and from infiltration and invasion in 49/79 patients (62.0%). TTE predicted malignancy in only 8/79 patients (10.1%, P < 0.005). TEE visualized tumor lesions in 130 patients (90.3%) while the TTE visualized tumor lesions in 110 patients (76.4%) and was less effective at detecting MT lesions (P < 0.001). TTE and TEE could detect anterior MTs and adequately verified MTs (P > 0.05); TEE detected medium MTs better than TTE (P < 0.001). Conclusions: TEE is effective and superior to TTE for predicting the localization and growth of MTs as well as for accessing evidence of tumor malignancy. TTE and TEE were able to detect anterior MTs; TEE was able to detect medium MT better than TTE. PMID:25881598

  4. Primary hepatic epithelioid angiomyolipoma: A malignant potential tumor which should be recognized

    PubMed Central

    Liu, Jie; Zhang, Cheng-Wu; Hong, De-Fei; Tao, Ran; Chen, Yuan; Shang, Min-Jie; Zhang, Yu-Hua

    2016-01-01

    AIM: To improve the clinical diagnosis and recognition of hepatic epithelioid angiomyolipoma (HEAML). METHODS: Four cases of primary HEAML were confirmed based on the pathology archive system in our hospital from January 2009 to November 2015. The general state, clinical symptoms, imaging manifestations, histological results and immunohistochemistry of these patients were retrospectively reviewed and analyzed. Studies of HEAML published in the last 15 years were collected from PubMed and MEDLINE to summarize the clinical symptoms, imaging characteristics, pathological features and management of HEAML. RESULTS: Four cases of primary HEAML were retrieved from our archives. These included three female patients and one male patient, with a mean age of 41.8 ± 11.5 years (ranging from 31 to 56 years). The mean tumor size was 7.3 ± 5.5 cm (ranging from 3.0 to 15 cm). In the contrast-enhanced imaging, the tumor was obviously enhanced in the arterial phase, but enhanced continuously or exhibited a slow-density masse during the venous and delayed phases. Histologically, the tumors mainly consisted of epithelioid cells that comprised approximately 95% of the total neoplastic mass. Although no metastases occurred in our patients, pathological studies revealed necrosis, mitotic figures and liver invasion in two patients, which indicates aggressive behavior. Immunohistochemical staining revealed that human melanoma black 45 (HMB-45) and Melan-A were positive in 4 cases. We only identified 81 cases with primary HEAML, including our present patients, from 26 articles available from PubMed and MEDLINE. The majority of the papers were published as case reports. Only 5 (5/75, 6%) cases were associated with tuberous sclerosis complex (TSC). More than half (35/66) were discovered incidentally upon physical examination. Approximately 65% (22/34) of the patients were misdiagnosed with HCC or other tumors before surgery. Approximately 10% (8/81) of the patients with HEAML had recurrence

  5. Effect of liver regeneration on malignant hepatic tumors

    PubMed Central

    Shi, Ji-Hua; Line, Pål-Dag

    2014-01-01

    Liver regeneration after major surgery may activate occult micrometastases and facilitate tumor growth, leading to liver tumor recurrence. Molecular changes during liver regeneration can provide a microenvironment that stimulates intrahepatic tumor propagation through alterations in cellular signaling pathways, where activation and proliferation of mature hepatocytes, hepatic progenitor cells, non-parenchymal liver cells might favor both liver regeneration and tumor growth. This review highlights recent advances of tumor growth and development in the regenerating liver, possible mechanisms and clinical implications. PMID:25473170

  6. [A Case of Retroperitoneal Tumor in the Adrenal Area Turned Out to Be Schwannoma Mimicking an Adrenal Malignant Tumor].

    PubMed

    Yumiba, Satoru; Kou, Yoko; Okada, Takayuki; Sato, Mototaka; Nin, Mikio; Tsujihata, Masao

    2015-10-01

    A 76-year-old woman was found to have bilateral suprarenal tumors, 6.5 cm in diameter on the right side, and 2.4 cm in diameter on the left side, by ultrasonography, computed tomography, and magnetic resonance imaging. Strong accumulation of fluorodeoxyglucose in these tumors was found on positron emission tomography. Since it mimicked an adrenal malignant tumor, we performed right adrenalectomy. The pathological diagnosis of the removed mass was benign schwannoma, consistent of the Antoni type A. The left suprarenal tumor was not removed and she has been followed up for 18 months without any recurrence or tumor increase. PMID:26563620

  7. HDAC8, A Potential Therapeutic Target for the Treatment of Malignant Peripheral Nerve Sheath Tumors (MPNST)

    PubMed Central

    Lopez, Gonzalo; Bill, Kate Lynn J.; Bid, Hemant Kumar; Braggio, Danielle; Constantino, Dylan; Prudner, Bethany; Zewdu, Abeba; Batte, Kara; Lev, Dina; Pollock, Raphael E.

    2015-01-01

    Introduction HDAC isoform-specific inhibitors may improve the therapeutic window while limiting toxicities. Developing inhibitors against class I isoforms poses difficulties as they share high homology among their catalytic sites; however, HDAC8 is structurally unique compared to other class I isoforms. HDAC8 inhibitors are novel compounds and have affinity for class I HDAC isoforms demonstrating anti-cancer effects; little is known about their activity in malignant peripheral nerve sheath tumors (MPNST). Recently, we demonstrated anti-MPNST efficacy of HDAC8i in human and murine-derived MPNST pre-clinical models; we now seek to consider the potential therapeutic inhibition of HDAC8 in MPNST. Methods Four Human MPNST cell lines, a murine-derived MPNST cell line, and two HDAC8 inhibitors (PCI-34051, PCI-48012; Pharmacyclics, Inc. Sunnyvale, CA) were studied. Proliferation was determined using MTS and clonogenic assays. Effects on cell cycle were determined via PI FACS analysis; effects on apoptosis were determined using Annexin V-PI FACS analysis and cleaved caspase 3 expression. In vivo growth effects of HDAC8i were evaluated using MPNST xenograft models. 2D gel electrophoresis and mass spectrometry were used to identify potential HDAC8 deacetylation substrates. Results HDAC8i induced cell growth inhibition and marked S-phase cell cycle arrest in human and murine-derived MPNST cells. Relative to control, HDAC8i induced apoptosis in both human and murine-derived MPNST cells. HDAC8i exhibited significant effects on MPNST xenograft growth (p=0.001) and tumor weight (p=0.02). Four potential HDAC8 substrate targets were identified using a proteomic approach: PARK7, HMGB1, PGAM1, PRDX6. Conclusions MPNST is an aggressive sarcoma that is notoriously therapy-resistant, hence the urgent need for improved anti-MPNST therapies. HDAC8 inhibition may be useful for MPNST by improving efficacy while limiting toxicities as compared to pan-HDACis. PMID:26200462

  8. Xanthogranulomatous gastritis of the remnant stomach mimicking a malignant tumor: A case report

    PubMed Central

    OKAMURA, AKIHIKO; TAKAHASHI, TSUNEHIRO; SAIKAWA, YOSHIRO; NAKADAI, JUMPEI; ONO, TAIKI; NAKAMURA, RIEKO; WADA, NORIHITO; KAWAKUBO, HIROFUMI; TAKEUCHI, HIROYA; EMOTO, KATSURA; SASAKI, AYA; KAMEYAMA, KAORI; KITAGAWA, YUKO

    2016-01-01

    Xanthogranulomas are known to develop in the gallbladder and kidney. Xanthogranuloma of the stomach is a rare disease, and to the best of our knowledge, only a few cases have been reported to date. The present patient was a 64-year-old man who underwent a wide resection of the stomach following a Billroth-I reconstruction for a gastric ulcer ~40 years prior to the current presentation. Due to tarry stools, a gastrointestinal endoscopy was performed, leading to identification of an ulcerated gastric lesion located at the previous suture line at the lesser curvature of the remnant stomach. This lesion was elevated, appearing to indicate a submucosal tumor. Positron emission tomography revealed uptake of fluorodeoxyglucose radiotracer by the tumor. Although not indicated by the biopsy specimens, a malignant tumor of the remnant stomach was suspected, in the form of a malignant gastrointestinal tumor or remnant gastric cancer. Curative resection of the tumor was successfully performed. Histological examination of the resected specimens revealed xanthogranulomatous inflammation consisting of foamy histiocytes and plasma cells, however, no cancer cells were observed. The tumor was diagnosed as xanthogranulomatous gastritis that mimicked a malignant tumor of the remnant stomach. The present study therefore indicates that inflammatory tumors should be considered in the differential diagnosis of malignant tumors. PMID:26893759

  9. Malignant Glial Neoplasms: Definition of a Humoral Host Response to Tumor-Associated Antigen(s)

    PubMed Central

    Sheikh, Khalid M.A.; Apuzzo, Michael L.J.; Kochsiek, Kim R.; Weiss, Martin H.

    1977-01-01

    There is increasing evidence that human tumors possess tumor-associated neo-antigens. The host mounts an immunological response to these antigens, as evidenced by the detection of circulating humoral antibodies in a variety of human neoplasia. An indirect immunofluorescent antibody technique was employed to detect antibodies to tumor-associated antigens in the sera of patients with malignant gliomas. Viable single cell suspensions were used to demonstrate antibodies to surface contents of tumor cells and cell preparations were snap-frozen at −160° C to demonstrate antibodies to cytoplasmic components of tumor cells. After incubation with serum, the preparations were treated with polyvalent sheep antihuman globulin conjugated to isomer-1-fluorescein isothiocyanate, washed, and examined with a Leitz incident fluorescent microscope. Of the 17 sera from histologically proven malignant glial neoplasm patients, 2 (11%) were positive for an autologous surface antibody reaction. Five (23%) of 21 were positive for an autologus cytoplasmic antibody, however, 10 (47%) of 21 of the sera gave a positive reaction for cross-reacting cytoplasmic antibodies when tested with a battery of tumor cells obtained from different patients with malignant glial tumors. No reaction was observed with normal brain tissue. Absorption studies indicated the presence of a tumor-associated antigen. This study demonstrated that certain patients with malignant gliomas possess circulating antibodies to cytoplasmic components of their own tumor cells. The fact that a number of sera cross-reacted with tumor cells obtained from different patients suggests that antigenic cross-reactivity exists between malignant glioma cells from different patients. It is suggested that with further refinement, immunofluorescent detection of antibodies could evolve as a useful diagnostic adjunct in malignant glioma. ImagesFIG. 1 PMID:333792

  10. Metachronous Malignant Solitary Fibrous Tumor of Kidney: Case Report and Review of Literature.

    PubMed

    Cheung, Felix; Talanki, Varun R; Liu, Jingxuan; Davis, James E; Waltzer, Wayne C; Corcoran, Anthony T

    2016-01-01

    Solitary fibrous tumors are well described in the pleura, but rare extra-pleural neoplasms have been reported. We describe a patient with a solitary left renal fibrous tumor who after undergoing a nephrectomy, presented 8 years later with a contralateral metachronous solitary fibrous tumor. Malignant metastatic extra-pleural solitary fibrous tumors are extremely rare, and to our knowledge, this is the first case of contralateral recurrence of solitary renal fibrous tumor. The patient underwent a robotic assisted partial nephrectomy of the right renal mass. Both tumors showed overlapping histopathology. PMID:26793578

  11. Metachronous Malignant Solitary Fibrous Tumor of Kidney: Case Report and Review of Literature

    PubMed Central

    Cheung, Felix; Talanki, Varun R.; Liu, Jingxuan; Davis, James E.; Waltzer, Wayne C.; Corcoran, Anthony T.

    2015-01-01

    Solitary fibrous tumors are well described in the pleura, but rare extra-pleural neoplasms have been reported. We describe a patient with a solitary left renal fibrous tumor who after undergoing a nephrectomy, presented 8 years later with a contralateral metachronous solitary fibrous tumor. Malignant metastatic extra-pleural solitary fibrous tumors are extremely rare, and to our knowledge, this is the first case of contralateral recurrence of solitary renal fibrous tumor. The patient underwent a robotic assisted partial nephrectomy of the right renal mass. Both tumors showed overlapping histopathology. PMID:26793578

  12. Solitary, multiple, benign, atypical, or malignant: the "Granular Cell Tumor" puzzle.

    PubMed

    Machado, Isidro; Cruz, Julia; Lavernia, Javier; Llombart-Bosch, Antonio

    2016-05-01

    The clinical evolution and biology of granular cell tumors (GCT) are poorly understood and treatment remains an issue of discussion. The majority of GCT are benign, although some display malignant behavior. The distinction between benign, atypical, and malignant GCT is controversial due to morphological and immunohistochemical overlap and lack of consistent histological and phenotypic criteria that predict behavior. Although histological criteria may indicate increased risk of malignant evolution, some GCT with evident benign appearance exceptionally progress towards metastatic disease. In this review, we discuss current knowledge on GCT, including histologic, immunophenotypic, and molecular characteristics and differential diagnosis. We focus on the following problematic items in GCT: (1) evolution of classification, (2) neural versus non-neural GCT, (3) neoplastic versus reactive disease, (4) malignant transformation of benign GCT, and (5) multiple versus metastatic GCT. We conclude that although a Ki-67 index >10 % and the presence of mitoses and/or of necrosis are frequently associated with malignant behavior, metastasis remains the only unequivocal sign of malignancy in GCT. An infiltrative growth pattern and vascular and/or perineural invasion are not indicative of malignancy. GCT with atypical/uncertain features almost never metastasize, and many of these tumors either behave in a benign fashion or only recur locally (similar to incompletely excised benign tumors). We therefore propose that classical and atypical histological variants form a single group of GCT. GCT with various unfavorable histological features might be labeled as "GCT with increased risk of metastasis" rather than malignant GCT. PMID:26637199

  13. Lymphedema-related angiogenic tumors and other malignancies.

    PubMed

    Lee, Robert; Saardi, Karl M; Schwartz, Robert A

    2014-01-01

    Chronic lymphedema has a permissive effect with certain types of malignancies, particularly angiosarcomas, in what is known as Stewart-Treves syndrome. The presumed mechanism of this effect is an immunocompromised district of the affected area. Most other cutaneous malignancies have also been described in lymphedematous areas, including basal cell carcinoma, squamous cell carcinoma, melanoma, Kaposi sarcoma, Merkel cell carcinoma, and several cutaneous lymphomas. The occurrence of such malignancies suggests a more general immunosuppression within the skin. The formation of collateral lymphatic and vascular vessels in response to lymphedema produces an environment rich in growth factors, which may also play a role. In addition to infection and other general skin care issues, regions affected by lymphedema should be monitored for malignant changes not limited to angiosarcomas. PMID:25160102

  14. Aggressive solitary intracranial metastatic malignant melanoma from a primary mediastinal tumour.

    PubMed

    Sivaraju, Laxminadh; Aryan, Saritha; Hegde, Vinay S; Ghosal, Nandita; Hegde, Alangar S

    2016-08-01

    Malignant melanoma is the third most common tumour to cause cerebral metastases, following breast and lung cancer. Central nervous system metastases occur in 10-40% of patients with melanoma. Intracranial metastasis from a primary malignant melanoma of the anterior mediastinum is uncommon. We report a case of solitary intracranial metastatic melanoma arising from a primary mediastinal tumour. We then discuss the clinico-radiological features and treatment options. PMID:27145991

  15. Marsupialization of unicystic ameloblastoma: a conservative approach for aggressive odontogenic tumors.

    PubMed

    Dolanmaz, Dogan; Etoz, Osman A; Pampu, Alper; Kalayci, Abdullah; Gunhan, Omer

    2011-01-01

    Unicystic ameloblastoma (UA) is known as a distinct entity which has a less aggressive behavior when compared with conventional ameloblastoma. In this report, we have presented two cases of UAs, (of which one case showed a more aggressive behavior with mural invasion into the adjacent tissues and granular cell differentiation), both of which were successfully managed with enucleation following marsupialization. We aim to highlight how this method can be used for the successful management of such cases, rather than following more aggressive approaches. In both the cases, marsupialization was done for the UA lesions initially and follow-ups were maintained. When the tumor size had regressed on radiographic follow up, an enucleation procedure with ostectomy of the margins was carried out. Special importance was also given to the endodontic treatment of the teeth involved in the area of the lesion. The patients were free of the condition and did not show any signs of recurrence on radiographic follow-ups even after 30 months of the final procedure. Granular variant of UA is quite rare and had been considered to be more aggressive. Marsupialization of UA is an alternative treatment option of resection even for more aggressive variants, as long as the histological behavior of the lesion was carefully evaluated and strict radiographic follow-up is maintained. PMID:22406718

  16. Infrared absorption spectra of human malignant tumor tissues

    NASA Astrophysics Data System (ADS)

    Skornyakov, I. V.; Tolstorozhev, G. B.; Butra, V. A.

    2008-05-01

    We used infrared spectroscopy methods to study the molecular structure of tissues from human organs removed during surgery. The IR spectra of the surgical material from breast, thyroid, and lung are compared with data from histological examination. We show that in malignant neoplasms, a change occurs in the hydrogen bonds of protein macromolecules found in the tissue of the studied organs. We identify the spectral signs of malignant pathology.

  17. Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumor aggressiveness.

    PubMed

    Afonso, Julieta; Santos, Lúcio L; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

    2016-02-01

    Monocarboxylate transporters (MCTs) are vital for intracellular pH homeostasis by extruding lactate from highly glycolytic cells. These molecules are key players of the metabolic reprogramming of cancer cells, and evidence indicates a potential contribution in urothelial bladder cancer (UBC) aggressiveness and chemoresistance. However, the specific role of MCTs in the metabolic compartmentalization within bladder tumors, namely their preponderance on the tumor stroma, remains to be elucidated. Thus, we evaluated the immunoexpression of MCTs in the different compartments of UBC tissue samples (n = 111), assessing the correlations among them and with the clinical and prognostic parameters. A significant decrease in positivity for MCT1 and MCT4 occurred from normoxic toward hypoxic regions. Significant associations were found between the expression of MCT4 in hypoxic tumor cells and in the tumor stroma. MCT1 staining in normoxic tumor areas, and MCT4 staining in hypoxic regions, in the tumor stroma and in the blood vessels were significantly associated with UBC aggressiveness. MCT4 concomitant positivity in hypoxic tumor cells and in the tumor stroma, as well as positivity in each of these regions concomitant with MCT1 positivity in normoxic tumor cells, was significantly associated with an unfavourable clinicopathological profile, and predicted lower overall survival rates among patients receiving platinum-based chemotherapy. Our results point to the existence of a multi-compartment metabolic model in UBC, providing evidence of a metabolic coupling between catabolic stromal and cancer cells' compartments, and the anabolic cancer cells. It is urgent to further explore the involvement of this metabolic coupling in UBC progression and chemoresistance. PMID:26636903

  18. Desmoplastic Fibroma of the Pediatric Cranium: An Aggressive Skull Tumor with Local Recurrence

    PubMed Central

    KOISO, Takao; MUROI, Ai; YAMAMOTO, Tetsuya; SAKAMOTO, Noriaki; MATSUMURA, Akira

    2016-01-01

    Cranial desmoplastic fibroma (DF) is extremely rare and only 20 cases, including only 7 pediatric cases, have been reported previously. We describe the first case of a child with cranial DF that increased in size over a short-term and recurred after resection. The aim of this case report was to discuss the clinical, radiological, and histological characteristics and optimal treatment for this rare and aggressive skull tumor. PMID:26804188

  19. Differentiating Benign from Malignant Bone Tumors Using Fluid-Fluid Level Features on Magnetic Resonance Imaging

    PubMed Central

    Yu, Hong; Cui, Sheng-Jie; Sun, Ying-Cai; Cui, Feng-Zhen

    2014-01-01

    Objective To analyze different fluid-fluid level features between benign and malignant bone tumors on magnetic resonance imaging (MRI). Materials and Methods 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 χ2 test. Results 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%. Conclusion 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. PMID:25469087

  20. Ovarian malignant germ cell tumors: cellular classification and clinical and imaging features.

    PubMed

    Shaaban, Akram M; Rezvani, Maryam; Elsayes, Khaled M; Baskin, Henry; Mourad, Amr; Foster, Bryan R; Jarboe, Elke A; Menias, Christine O

    2014-01-01

    Ovarian malignant germ cell tumors (OMGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad. OMGCTs are rare, accounting for about 2.6% of all ovarian malignancies, and typically manifest in adolescence, usually with abdominal pain, a palpable mass, and elevated serum tumor marker levels, which may serve as an adjunct in the initial diagnosis, monitoring during therapy, and posttreatment surveillance. Dysgerminoma, the most common malignant germ cell tumor, usually manifests as a solid mass. Immature teratomas manifest as a solid mass with scattered foci of fat and calcifications. Yolk sac tumors usually manifest as a mixed solid and cystic mass. Capsular rupture or the bright dot sign, a result of increased vascularity and the formation of small vascular aneurysms, may be present. Embryonal carcinomas and polyembryomas rarely manifest in a pure form and are more commonly part of a mixed germ cell tumor. Some OMGCTs have characteristic features that allow a diagnosis to be confidently made, whereas others have nonspecific features, which make them difficult to diagnose. However, imaging features, the patient's age at presentation, and tumor markers may help establish a reasonable differential diagnosis. Malignant ovarian germ cell tumors spread in the same manner as epithelial ovarian neoplasms but are more likely to involve regional lymph nodes. Preoperative imaging may depict local extension, peritoneal disease, and distant metastases. Suspicious areas may be sampled during surgery. Because OMGCTs are almost always unilateral and are chemosensitive, fertility-sparing surgery is the standard of care. PMID:24819795

  1. Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors

    ClinicalTrials.gov

    2016-05-26

    High-grade Salivary Gland Mucoepidermoid Carcinoma; Low-grade Salivary Gland Mucoepidermoid Carcinoma; Recurrent Salivary Gland Cancer; Salivary Gland Acinic Cell Tumor; Salivary Gland Adenocarcinoma; Salivary Gland Adenoid Cystic Carcinoma; Salivary Gland Anaplastic Carcinoma; Salivary Gland Malignant Mixed Cell Type Tumor; Salivary Gland Poorly Differentiated Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IV Salivary Gland Cancer

  2. TLR5 signaling, commensal microbiota and systemic tumor promoting inflammation: the three parcae of malignant progression

    PubMed Central

    Rutkowski, Melanie R; Conejo-Garcia, Jose R

    2015-01-01

    We have reported that TLR5-mediated recognition of commensal microbiota modulates systemic tumor-promoting inflammation and malignant progression of tumors at distal locations. Approximately 7–10% of the general population harbors a deleterious single nucleotide polymorphism in TLR5, implicating a novel role for genetic variation during the initiation and progression of cancer. PMID:26405577

  3. Underexpression of LKB1 tumor suppressor is associated with enhanced Wnt signaling and malignant characteristics of human intrahepatic cholangiocarcinoma

    PubMed Central

    Wang, Jinghan; Zhang, Keqiang; Wang, Jinhui; Wu, Xiwei; Liu, Xiyong; Li, Bin; Zhu, Yan; Yu, Yong; Cheng, Qingbao; Hu, Zhenli; Guo, Chao; Hu, Shuya; Mu, Bing; Tsai, Chun-Hao; Li, Jie; Smith, Lynne; Yang, Lu; Liu, Qi; Chu, Peiguo; Chang, Vincent; Zhang, Baihe; Wu, Mengchao; Jiang, Xiaoqing; Yen, Yun

    2015-01-01

    Intrahepatic cholangiocarcinoma (ICC) is a rare and highly aggressive malignancy. In this study, we identified the presence of gene deletion and missense mutation leading to inactivation or underexpression of liver kinase B1 (LKB1) tumor suppressor and excluded the involvement of LKB1 gene hypermethylation in ICC tissues. Immunohistochemical analysis showed that LKB1 was underexpressed in a portion of 326 ICC tissues compared to their adjacent normal tissues. By statistical analysis underexpression of LKB1 in ICC tissues significantly correlated with poor survival and malignant disease characteristics in ICC patients. Moreover, we showed that knockdown of LKB1 significantly enhanced growth, migration, and invasion of three LKB1-competent ICC cell lines. Global transcriptional profiling analysis identified multiple malignancy-promoting genes, such as HIF-1α, CD24, Talin1, Vinculin, Wnt5, and signaling pathways including Hedgehog, Wnt/β-catenin, and cell adhesion as novel targets of LKB1 underexpression in ICC cells. Furthermore, knockdown of LKB1 gene expression dramatically enhanced Wnt/β-catenin signaling in ICC cells, while an inverse correlation between LKB1 and nuclear β-catenin was observed in ICC tissues. Our findings suggest a novel mechanism for ICC carcinogenesis in which LKB1 underexpression enhances multiple signaling pathways including Wnt/β-catenin to promote disease progression. PMID:26056085

  4. Decreased expression of SLC 39A14 is associated with tumor aggressiveness and biochemical recurrence of human prostate cancer

    PubMed Central

    Xu, Xiao-Ming; Wang, Cheng-Gong; Zhu, Yu-Di; Chen, Wei-Hua; Shao, Si-Liang; Jiang, Fu-Neng; Liao, Qian-De

    2016-01-01

    Objective Solute carrier family 39, member 14 (SLC39A14), has been identified as a potential biomarker for various cancers. However, its roles in prostate cancer (PCa) are still unclear. The aim of this study was to investigate the clinical significance of SLC39A14 in patients with PCa and its functions in malignant phenotypes of PCa cells. Patients and methods Subcellular localization and expression pattern of SLC39A14 protein were examined by immunohistochemistry. Then, the associations of SLC39A14 expression with various clinicopathological features and clinical outcome of patients with PCa were statistically evaluated. Subsequently, the effects of SLC39A14 overexpression and knockdown on PCa cell proliferation and motility were, respectively, examined by Cell Counting Kit-8, transwell, and wound-healing assays. Results The immunoreactive scores of SLC39A14 protein in human PCa tissues were significantly lower than those in normal prostate tissues. Based on the Taylor dataset, SLC39A14 downregulation occurred more frequently in patients with PCa with a higher Gleason score (P<0.001), advanced clinical stage (P=0.008), presence of metastasis (P=0.009), and prostate-specific antigen failure (P=0.006). More interestingly, the survival analysis identified SLC39A14 as an independent factor for predicting the biochemical recurrence-free survival of patients with PCa (P=0.017). Functionally, the enforced expression of SLC39A14 could suppress cell proliferation, invasion, and migration of PCa cell lines in vitro, which could be reversed by the knockdown of SLC39A14. Conclusion Decreased expression of SLC39A14 may lead to malignant phenotypes of PCa cells and aggressive tumor progression in patients with PCa. Importantly, SLC39A14 may function as a tumor suppressor and a biomarker for screening patients with biochemical recurrence following radical prostatectomy. PMID:27471394

  5. [Current surgical and adjuvant therapy concepts of malignant tumors of the facial skin and the pinna].

    PubMed

    Kolk, A; Wermker, K; Bier, H; Götz, C; Eckert, A W

    2015-02-01

    Malignant tumors of the skin had been a rare entity 2 decades ago. Today they are spread rapidly worldwide. Malignant neoplasms of the skin, the largest human organ, may occur from all structures and layers. While previously skin cancer -occurred mainly after the age of 60, the incidence increases now in younger ages. Strong sunburns in the childhood and before the age of 20 are important risk factors for the development of malignancies of the skin. An increased exposure to UV rays is found especially in the facial skin, where basal cell carcinoma, squamous cell carcinoma, malignant melanoma and Merkel cell carcinomas are the most common malignancies. Early diagnosis of malignancies and therapy-oriented mostly surgical approaches are crucial for the prognosis of all skin cancers. Therefore under the aspect of the increasing incidence these topics will be pointed out according to the latest findings including current multimodal therapy concepts and future treatment options. PMID:25658862

  6. Successful Preoperative Chemoembolization in the Treatment of a Giant Malignant Phyllodes Tumor.

    PubMed

    Hashimoto, Kazuki; Mimura, Hidefumi; Arai, Yasunori; Doi, Masatomo; Kojima, Yasuyuki; Tsugawa, Koichiro; Nakajima, Yasuo

    2016-07-01

    The malignant phyllodes tumor is a relatively rare neoplasm and has not previously been a therapeutic target of interventional radiology. Herein, we report a successful case of preoperative chemoembolization of a giant malignant phyllodes tumor. The objective was to achieve sufficient tumor shrinkage before surgery to avoid the requirement for skin grafting after resection. Intra-arterial epirubicin infusion and subsequent embolization with Embosphere Microspheres (BioSphere Medical, Rockland, MA, USA) was undertaken three times over the course of 6 weeks and was well tolerated. The patient underwent surgery without skin grafting. Neither local recurrence nor distant metastasis was observed at 6 months after surgery. PMID:26916453

  7. Congenital renal tumor: metanephric adenoma, nephrogenic rest, or malignancy?

    PubMed

    Yin, Minzhi; Cai, Jiaoyang; Thorner, Paul Scott

    2015-01-01

    We report a renal tumor detected by prenatal ultrasound and resected at 2 months of age. This 9-cm, solid mass was composed of tubular and papillary structures lined by small, uniform epithelial cells. There was local invasion into renal parenchyma and a tumor deposit in a hilar lymph node. The tumor was immunopositive for WT1, pankeratin, and CD10; focally positive for CK7; and negative for EMA and TFE3. Based on morphology and immunophenotype, the favored diagnosis was metanephric adenoma over Wilms tumor, renal cell carcinoma, and nephrogenic rest. However, metanephric adenoma only occasionally occurs in children and has never been reported prenatally. Alternatively, this tumor might be a congenital Wilms tumor that differentiated completely. Although the nature of the tumor remains unconfirmed, resection appears to have been curative; the patient remains disease-free 18 months following surgery alone. PMID:25734608

  8. Biallelic BRCA2 Mutations Shape the Somatic Mutational Landscape of Aggressive Prostate Tumors.

    PubMed

    Decker, Brennan; Karyadi, Danielle M; Davis, Brian W; Karlins, Eric; Tillmans, Lori S; Stanford, Janet L; Thibodeau, Stephen N; Ostrander, Elaine A

    2016-05-01

    To identify clinically important molecular subtypes of prostate cancer (PCa), we characterized the somatic landscape of aggressive tumors via deep, whole-genome sequencing. In our discovery set of ten tumor/normal subject pairs with Gleason scores of 8-10 at diagnosis, coordinated analysis of germline and somatic variants, including single-nucleotide variants, indels, and structural variants, revealed biallelic BRCA2 disruptions in a subset of samples. Compared to the other samples, the PCa BRCA2-deficient tumors exhibited a complex and highly specific mutation signature, featuring a 2.88-fold increased somatic mutation rate, depletion of context-specific C>T substitutions, and an enrichment for deletions, especially those longer than 10 bp. We next performed a BRCA2 deficiency-targeted reanalysis of 150 metastatic PCa tumors, and each of the 18 BRCA2-mutated samples recapitulated the BRCA2 deficiency-associated mutation signature, underscoring the potent influence of these lesions on somatic mutagenesis and tumor evolution. Among all 21 individuals with BRCA2-deficient tumors, only about half carried deleterious germline alleles. Importantly, the somatic mutation signature in tumors with one germline and one somatic risk allele was indistinguishable from those with purely somatic mutations. Our observations clearly demonstrate that BRCA2-disrupted tumors represent a unique and clinically relevant molecular subtype of aggressive PCa, highlighting both the promise and utility of this mutation signature as a prognostic and treatment-selection biomarker. Further, any test designed to leverage BRCA2 status as a biomarker for PCa must consider both germline and somatic mutations and all types of deleterious mutations. PMID:27087322

  9. Localized malignant pleural sarcomatoid mesothelioma misdiagnosed as benign localized fibrous tumor

    PubMed Central

    Vo, Hong-Phuc

    2016-01-01

    Localized malignant pleural mesothelioma (LMPM) is a rare tumor with good prognosis by surgical resection. We report an atypical case of malignant pleural sarcomatoid mesothelioma (SM) in an asymptomatic 65-year-old woman, who had no history of exposure to asbestos. She presented with a small pleural mass without pleural effusion and was misdiagnosed as a benign localized fibrous tumor (BLFT) on pathologic examination through a surgical tumor specimen. However, seven months later, the patient returned with serious cancerous symptoms. A large recurrent tumor mass was found within the chest wall invading at the old surgical resection site. SM, a subtype of LMPM, was confirmed with histopathogy and immunohistochemisty. In conclusion, malignant pleural mesothelioma (MPM) can present with typical radiologic finding similar to a BLFT, and has a wide histopathologic presentation in biopsy specimen. A thorough pathologic investigation should be attempted even when a pleural mass resembles benign, localized, and small on radiologic studies. PMID:27293862

  10. Malignant Peripheral Nerve Sheath Tumor in Neurofibromatosis Type I : Unusual Presentation of Intraabdominal or Intrathoracic Mass

    PubMed Central

    Kim, Jong Gwang; Sung, Woo Jin; Kim, Dong Hwan; Kim, Young Hwan; Lee, Kyu Bo

    2005-01-01

    A malignant peripheral nerve sheath tumor (MPNST) is an extremely rare soft tissue tumor in the general population. On the other hand, there is a higher incidence of MPNST in patients with neurofibromatosis type I (von Recklinghausen's disease). The common sites are the extremities, trunk, head and neck. However, an intraabdominal or intrathoracic manifestation is uncommon. This paper reports two patients, a 31 year-old woman with multiple neurofibromatosis presenting as an intraabdominal malignant peripheral nerve sheath tumor, and a 33 year-old woman with an intrathoracic malignant peripheral nerve sheath tumor. The patients were treated with chemotherapy followed by radiotherapy. However, one patient died as a result of disease progression 21 months after the diagnosis and the other patient is currently being treated with radiotherapy. PMID:15906964

  11. Localized malignant pleural sarcomatoid mesothelioma misdiagnosed as benign localized fibrous tumor.

    PubMed

    Kim, Kwan-Chang; Vo, Hong-Phuc

    2016-06-01

    Localized malignant pleural mesothelioma (LMPM) is a rare tumor with good prognosis by surgical resection. We report an atypical case of malignant pleural sarcomatoid mesothelioma (SM) in an asymptomatic 65-year-old woman, who had no history of exposure to asbestos. She presented with a small pleural mass without pleural effusion and was misdiagnosed as a benign localized fibrous tumor (BLFT) on pathologic examination through a surgical tumor specimen. However, seven months later, the patient returned with serious cancerous symptoms. A large recurrent tumor mass was found within the chest wall invading at the old surgical resection site. SM, a subtype of LMPM, was confirmed with histopathogy and immunohistochemisty. In conclusion, malignant pleural mesothelioma (MPM) can present with typical radiologic finding similar to a BLFT, and has a wide histopathologic presentation in biopsy specimen. A thorough pathologic investigation should be attempted even when a pleural mass resembles benign, localized, and small on radiologic studies. PMID:27293862

  12. DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors

    PubMed Central

    el Din, Amina A. Gamal; Badawi, Manal A.; Aal, Shereen E. Abdel; Ibrahim, Nihad A.; Morsy, Fatma A.; Shaffie, Nermeen M.

    2015-01-01

    BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours. PMID:27275284

  13. Malignant Nerve Sheath Tumor of the Spinal Accessory Nerve: A Unique Presentation of a Rare Tumor

    PubMed Central

    Sheikh, Omair A.; Reaves, Ann; Kralick, Francis A.; Brooks, Ari; Musial, Rachel E.

    2012-01-01

    Background Malignant peripheral nerve sheath tumors (MPNSTs), sarcomas originating from tissues of mesenchymal origin, are rare in patients without a history of neurofibromatosis. Case Report We report a case of an MPNST of the spinal accessory nerve, unassociated with neurofibromatosis, which metastasized to the brain. The tumor, originating in the intrasternomastoid segment of the spinal accessory nerve, was removed. Two years later, the patient presented with focal neurological deficits. Radiographic findings revealed a well-defined 2.2×2.2×2.2 cm, homogeneously enhancing mass in the left parieto-occipital region of the brain surrounded by significant vasogenic edema and mass effect, culminating in a 1-cm midline shift to the right. The mass was surgically removed. The patient had nearly complete recovery of vision, speech, and memory. Conclusions To our knowledge, this is the first documented case of an MPNST arising from an extracranial segment of the spinal accessory nerve and metastasizing to the brain. PMID:22523517

  14. The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors.

    PubMed

    Smith, Myles J; Smith, Henry G; Mahar, Alyson L; Law, Calvin; Ko, Yoo-Joung

    2016-10-15

    A higher incidence of additional malignancies has been described in patients diagnosed with gastrointestinal stromal tumors (GIST). This study aimed to identify risk factors for developing additional malignancies in patients diagnosed with GIST and evaluate the impact on survival. Individuals diagnosed with GIST from 2001 to2009 were identified from the SEER database. Logistic regression was used to identify predictors of additional malignancies and Cox-proportional hazards regression used to identify predictors of survival. In the study period, 1705 cases of GIST were identified, with 181 (10.6%) patients developing additional malignancies. Colorectal cancer was the most common cancer developing within 6 months of GIST diagnosis (30%). The median time to diagnosis of a malignancy after 6 months of GIST diagnosis was 21.9 months. Older age (p < 0.0001) and extraoesophagogastric GIST (p = 0.0027) were significant prognostic factors associated with additional malignancies. The overall 5-year survival was 65%, with the presence of additional malignancies within 6 months of GIST diagnosis associated with poor overall survival (54%, HR 1.55 1.05-2.3 95% CI, p = 0.04). Predictive factors of additional malignancies in patients diagnosed with GIST are increasing age and the primary disease site. Developing additional malignancies within 6 months of GIST diagnosis is associated with poorer overall survival. Targeted surveillance may be warranted in patients diagnosed with GIST that are at high risk of developing additional malignancies. PMID:27299364

  15. LGR5 is associated with tumor aggressiveness in papillary thyroid cancer

    PubMed Central

    Michelotti, Gregory; Jiang, Xiaoyin; Sosa, Julie Ann; Diehl, Anna Mae; Henderson, Brittany Bohinc

    2015-01-01

    PURPOSE Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a cancer stem cell marker and a down-stream target in Wnt/β-catenin signaling. In human papillary thyroid cancer (PTC), over activation of Wnt/β-catenin has been associated with tumor aggressiveness. PATIENTS AND METHODS Using established human cell lines (TPC-1, KTC-1, Nthy-ori-3–1), we report LGR5 and R-spondin (RSPO1–3) overexpression in PTC and manipulate LGR5 and Wnt/β-catenin signaling via both pharmacologic and genetic interventions. We test the association of LGR5 tumor expression with markers of PTC aggressiveness using a Discovery Cohort (n = 26 patients) and a Validation Cohort (n = 157 patients). Lastly, we explore the association between LGR5 and the BRAFV600E mutation (n = 33 patients). RESULTS Our results reveal that LGR5 and its ligand, RSPO, are overexpressed in human PTC, whereby Wnt/β-catenin signaling regulates LGR5 expression and promotes cellular migration. In two separate cohorts of patients, LGR5 and RSPO2 were associated with markers of tumor aggressiveness including: lymph node metastases, vascular invasion, increased tumor size, aggressive histology, advanced AJCC TNM stage, microscopic extra thyroidal extension, capsular invasion, and macroscopic invasion. As a biomarker, LGR5 positivity predicts lymph node metastasis with 95.5% sensitivity (95% CI 88.8%-98.7%) and 61% specificity (95% CI: 48.4%–72.4%) and has a negative predictive value (NPV) of 91.3% (95% CI 79.2%–97.5%) for lymph node metastatic disease. In human PTC, LGR5 is also strongly associated with the BRAFV600E mutation (p = 0.005). CONCLUSION We conclude that overexpression of LGR5 is associated with markers of tumor aggressiveness in human PTC. LGR5 may serve as a future potential biomarker for patient risk stratification and loco regional metastases in PTC. PMID:26416247

  16. Salivary Secretory Immunoglobulin (SIgA) and Lysozyme in Malignant Tumor Patients

    PubMed Central

    Sun, Haiyan; Chen, Yong; Zou, Xuan; Li, Qihong; Li, Huan; Shu, Yao; Li, Xia; Li, Weihong; Han, Li; Ge, Cheng

    2016-01-01

    Background. The purpose of this study is to understand the oral mucosal immune status of cancer patients and to make clear whether antibacterial proteins such as salivary secretory immunoglobulin (SIgA) and lysozyme in saliva were influenced by patients' health status and certain medical treatment therapy. Materials and Methods. This study included 221 patients with malignant tumor receiving antineoplastic treatment and 171 age- and gender-matched healthy controls. Results. The results showed that patients suffering malignant tumor had lower level of SIgA and higher level of lysozyme than healthy subjects (P < 0.05). The SIgA level was significantly different among different cancer tumors, while the lysozyme level showed significant difference only between patients with digestive tract malignant tumor and hematopoietic system tumor. Pretreatment before transplantation for hematopoietic system tumor patients significantly affected the lysozyme level other than SIgA. SIgA level was affected by many factors such as age, therapy factors, and oral hygiene. Conclusion. Malignant tumor and the antineoplaston may weaken the patients' oral mucosal immunity, influence levels of some salivary proteins, and decrease the level of SIgA, resulting in aggregation of oral bacteria and failure of clearing them from the oral cavity. PMID:27294141

  17. Malignant phyllodes tumor of the breast presenting with hypoglycemia: a case report and literature review

    PubMed Central

    Pacioles, Toni; Seth, Rahul; Orellana, Cesar; John, Ivy; Panuganty, Veera; Dhaliwal, Ruban

    2014-01-01

    Phyllodes tumors are rare fibroepithelial neoplasms that account for less than 1% of all breast tumors and are typically found in middle-aged women. Phyllodes tumors that present with hypoglycemia are even rarer. No one morphologic finding is reliable in predicting the clinical behavior of this tumor. Surgery has been the primary mode of treatment to date. However, the extent of resection and the role of adjuvant radiotherapy or chemotherapy are still controversial. Here, we present a challenging case of malignant phyllodes tumor of the breast associated with hypoglycemia, and review the literature regarding clinical findings, pathologic risk factors for recurrence, and treatment recommendations. PMID:25525388

  18. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2015-07-27

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

  19. Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells

    PubMed Central

    2014-01-01

    Introduction Although breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. A malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in phyllodes tumors. Methods Paraffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and their ability to undergo differentiation. Results Immunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+ cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells displayed 12.8-fold greater mammosphere forming ability than ALDH-/GD2- cells. In vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being sufficient for engraftment. Moreover, we

  20. Malignant Transformation of a Dysembryoplastic Neuroepithelial Tumor (DNET) Characterized by Genome-Wide Methylation Analysis.

    PubMed

    Heiland, Dieter Henrik; Staszewski, Ori; Hirsch, Martin; Masalha, Waseem; Franco, Pamela; Grauvogel, Jürgen; Capper, David; Schrimpf, Daniel; Urbach, Horst; Weyerbrock, Astrid

    2016-04-01

    Dysembryoplastic neuroepithelial tumors (DNET) are considered to be rare, benign, and associated with chronic epilepsy. We present the case of a 28-year-old man with a history of epilepsy since age 12. Surgery of an occipital cortical lesion in 2009 revealed a DNET. Five years later, a recurrent tumor at the edge of the resection cavity was removed, and the tissue underwent an intensive diagnostic workup. The first tumor was unequivocally characterized as a DNET, but neuropathological diagnostics of the recurrent tumor revealed a glioblastoma. After 6 months, another recurrent tumor was detected next to the location of the original tumor, and this was also resected. An Illumina 450 K beadchip methylation array was performed to characterize all of the tumors. The methylation profile of these tumors significantly differed from other glioblastoma and epilepsy-associated tumor profiles and revealed a DNET-like methylation profile. Thus, molecular characterization of these recurrent tumors suggests malignant transformation of a previously benign DNET. We found increased copy number changes in the recurrent DNET tumors after malignant transformation. Modern high-throughput analysis adds essential molecular information in addition to standard histopathology for proper identification of rare brain tumors that present with an unusual clinical course. PMID:26921879

  1. Characterization of highly proliferative secondary tumor clusters along host blood vessels in malignant glioma

    PubMed Central

    WANG, TING-CHUNG; CHENG, CHUN-YU; YANG, WEI-HSUN; CHEN, WEN-CHENG; CHANG, PEY-JIUM

    2015-01-01

    The aim of the present study was to investigate the extensive invasion of tumor cells into normal brain tissue, a life-threatening feature of malignant gliomas. How invasive tumor cells migrate into normal brain tissue and form a secondary tumor structure remains to be elucidated. In the present study, the morphological and phenotypic changes of glioma cells during invasion in a C6 glioma model were investigated. C6 glioma cells were stereotactically injected into the right putamen region of adult Sprague-Dawley rats. The brain tissue sections were then subjected to hematoxylin and eosin, immunohistochemical or immunofluorescent staining. High magnification views of the tissue sections revealed that C6 cells formed tumor spheroids following implantation and marked invasion was observed shortly after spheroid formation. In the later stages of invasion, certain tumor cells invaded the perivascular space and formed small tumor clusters. These small tumor clusters exhibited certain common features, including tumor cell multilayers surrounding an arteriole, which occurred up to several millimeters away from the primary tumor mass; a high proliferation rate; and similar gene expression profiles to the primary tumor. In conclusion, the present study revealed that invading tumor cells are capable of forming highly proliferative cell clusters along arterioles near the tumor margin, which may be a possible cause of the recurrence of malignant glioma. PMID:26299849

  2. Correlation of histological and ex-vivo confocal tumor thickness in malignant melanoma.

    PubMed

    Hartmann, Daniela; Krammer, Sebastian; Ruini, Cristel; Ruzicka, Thomas; von Braunmühl, Tanja

    2016-07-01

    The ex-vivo confocal laser scanning microscopy (ex-vivo CLSM) is a novel diagnostic method for fresh tissue examination, which has already shown promising results in the evaluation of healthy skin and different skin tumors. In malignant melanoma, the histological tumor thickness plays an essential role for further treatment strategies. The immediate perioperative measurement of tumor thickness by means of ex-vivo CLSM might accelerate the decision for further operating procedures in malignant melanoma. Ten histologically confirmed malignant melanomas from various donor sites were blindly examined by two investigators via ex-vivo CLSM and conventional light microscopy. The histopathological tumor thickness (HTT) and confocal tumor thickness (CTT) were measured independently and evaluated using correlation curves, Spearman's correlation coefficient, and Bland-Altman plots. Bland-Altman plots for HTT and reflectance-mode CTT, as well as for fluorescence-mode CTT, showed high correlations. Spearman's correlation coefficient of HTT and CTT was 1.00 in FM and RM. The mean difference of RM-CTT and FM-CTT versus HTT was 0.09 ± 0.30 mm and 0.19 ± 0.35 mm. In one case, the HTT was identical to the CTT in both modes. This pilot study shows high conformity of CTT and HTT measured in malignant melanoma underlining the potential of ex-vivo CLSM for perioperative decisions on safety margin excisions of malignant melanoma in the future. PMID:27056706

  3. Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

    SciTech Connect

    Gu Yongpeng; Li Hongzhen; Miki, Jun; Kim, Kee-Hong; Furusato, Bungo; Sesterhenn, Isabell A.; Chu, Wei-Sing; McLeod, David G.; Srivastava, Shiv; Ewing, Charles M.; Isaacs, William B.; Rhim, Johng S. . E-mail: jrhim@cpdr.org

    2006-04-01

    In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents.

  4. Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression

    SciTech Connect

    Katsumi, Yoshiki; Iehara, Tomoko; Miyachi, Mitsuru; Yagyu, Shigeki; Tsubai-Shimizu, Satoko; Kikuchi, Ken; Tamura, Shinichi; Kuwahara, Yasumichi; Tsuchiya, Kunihiko; Kuroda, Hiroshi; Sugimoto, Tohru; Houghton, Peter J.; Hosoi, Hajime

    2011-09-16

    Highlights: {yields} PD 0332991 (PD) could suppress four of five malignant rhabdoid tumor (MRT) cell lines. {yields} The sensitivity of the MRT cell lines to PD was inversely correlated with p16 expression (r = 0.951). {yields} p16 expression in MRT could be used to predict its sensitivity to PD. {yields} PD may be an attractive agent for patients with MRT whose tumors express low levels of p16. -- Abstract: Malignant rhabdoid tumor (MRT) is a rare and highly aggressive neoplasm of young children. MRT is characterized by inactivation of integrase interactor 1 (INI1). Cyclin-dependent kinase 4 (CDK4), which acts downstream of INI1, is required for the proliferation of MRT cells. Here we investigated the effects of PD 0332991 (PD), a potent inhibitor of CDK4, against five human MRT cell lines (MP-MRT-AN, KP-MRT-RY, G401, KP-MRT-NS, KP-MRT-YM). In all of the cell lines except KP-MRT-YM, PD inhibited cell proliferation >50%, (IC{sub 50} values 0.01 to 0.6 {mu}M) by WST-8 assay, and induced G1-phase cell cycle arrest, as shown by flow cytometry and BrdU incorporation assay. The sensitivity of the MRT cell lines to PD was inversely correlated with p16 expression (r = 0.951). KP-MRT-YM cells overexpress p16 and were resistant to the growth inhibitory effect of PD. Small interfering RNA against p16 significantly increased the sensitivity of KP-MRT-YM cells to PD (p < 0.05). These results suggest that p16 expression in MRT could be used to predict its sensitivity to PD. PD may be an attractive agent for patients with MRT whose tumors express low levels of p16.

  5. Multifrequency YAG:Nd laser for diagnosis of malignant tumors

    NASA Astrophysics Data System (ADS)

    Lalayan, Asatur A.; Aydinyan, Lusine; Harutyunyan, Ishkhan G.; Galstian, Hayro M.

    1999-01-01

    The spectral peculiarities of normal and tumor human tissues of different localization after sensitization by sodium fluorescein has been studied with help of multifrequency YAG:Nd laser. Fluorescence spectra of normal human tissue and breast, stomach, intestine, skin cancer at 355, 440 nm laser excitation were registered. The pharmacokinetic behavior of sodium fluorescein in normal and different tumor tissues has been investigated. The optimal time for diagnosis (12 - 18 hours after drug injection) was determined. The intensification of tumor tissue autofluorescence decreasing after sensitization of organisms by tumor seeking dye was observed. The electron excitation energy transfer from NAD(P)H to endogen chromophores or dyes localized in tumor has been discussed as possible reason of the observed phenomenon.

  6. Interleukin-33 Expression Indicates a Favorable Prognosis in Malignant Salivary Gland Tumors.

    PubMed

    Rössle, Matthias; Cathomas, Gieri; Bonapace, Laura; Sachs, Melanie; Dehler, Silvia; Storz, Martina; Huber, Gerhard; Moch, Holger; Junt, Tobias; Mertz, Kirsten D

    2016-08-01

    The cytokine interleukin-33 (IL-33) is abundantly expressed in epithelial barrier tissues such as salivary glands. Here, we characterized nuclear IL-33 protein expression by immunohistochemistry in benign and malignant salivary gland tumors and associated it with disease outcome. Most benign salivary gland tumors expressed IL-33, and all Warthin's tumors showed strong and consistent IL-33 expression in the basally oriented cells of their bilayered epithelium. In the malignant group of neoplasms, nuclear IL-33 expression was limited to specific tumor entities-for example, to epithelial-myopepithelial carcinomas (n = 9/11), acinic cell carcinomas (n = 13/27), and oncocytic carcinomas (n = 2/2). IL-33 expression in the combined group of malignant salivary gland neoplasms was significantly associated with favorable histological parameters, lack of metastasis, and longer overall survival, compared with IL-33-negative tumors. We conclude that IL-33 expression is a novel prognostic marker for malignant salivary gland tumors with potential use in clinical diagnostics. PMID:26912475

  7. Bone Scintigraphy in a Patient With Giant Malignant Solitary Fibrous Tumor of the Pleura.

    PubMed

    Zhao, Long; Liu, JinJun; Li, Qiang; Wang, Huo-Qiang

    2016-06-01

    Chest radiograph performed in a 61-year-old woman to evaluate cough showed a large mass in the right lung. On chest CT images, the mass was measured approximately 8.5 cm. Malignancy was considered, and bone scintigraphy was performed to assess possible osseous metastases. The bone scan images demonstrated increased tracer uptake by the lung mass. The mass was surgically resected, and the pathologic examination confirmed the rare diagnosis of a malignancy solitary fibrous tumors of the pleura. PMID:26914570

  8. A spontaneously occurring malignant ovarian Sertoli cell tumor in a young Sprague Dawley rat

    PubMed Central

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Elmore, Susan A.; Tsubura, Airo

    2015-01-01

    Primary ovarian tumors are generally uncommon in rats used in toxicologic studies. A malignant Sertoli cell tumor was present in the ovary of a 19-week-old female Sprague Dawley rat. Macroscopically, the mass was white and firm, 10 × 13 × 17 mm in size, and located in the right ovary. Histopathologically, the mass was composed of nests of pleomorphic cells, which formed seminiferous-like tubules separated by a thin fibrovascular stroma. The tubules were lined by tumor cells, which had basally located nuclei and abundant eosinophilic and vacuolated cytoplasm. In some areas, the tumor cells were arranged in a retiform growth pattern, mimicking a rete testis/ovarii. Disseminated metastases to the surfaces of the mesentery, spleen and liver were also present. Immunohistochemically, many tumor cells were strongly positive for vimentin, estrogen receptor α and Ki 67. Some tumor cells were positive for pancytokeratin and inhibin α. These findings closely resemble those of an ovarian-derived human malignant Sertoli cell tumor. From our review of the literature, we believe this is the first report of a spontaneous malignant Sertoli cell tumor in the ovary of a young laboratory rat. This case might provide useful historical control information for rat toxicity studies. PMID:26989303

  9. [Prevalence and trend of gastrointestinal malignant tumors in the elderly over 75 years old in China].

    PubMed

    Zheng, Ying; Wu, Chunxiao

    2016-05-25

    Gastrointestinal malignant tumors are the most common malignant neoplasms among the elderly people over 75 years old in China. There are 122.1 thousand new gastric cases and 78.2 thousand new colorectal cancer cases diagnosed each year in China, which accounts for 42.73% and 18.08% respectively of the cases with same age in the world. The gastric cancer accounts for 25.13% and colorectal cancer accounts for 28.86%of all the malignancies in the elderly. The gastric cancer death accounts for 36.38% and colorectal cancer death accounts for 44.68% in those people over 75 years old in China. It was estimated that the risk of developing gastrointestinal malignant tumors of these elderly people was about 5-6 times and the risk of death of gastrointestinal malignant tumors was about 7-8 times of the general population. Compared with the general population and the people of 55-74 years old, the incidence of gastric cancer in the elderly decreased more slowly and the incidence of colorectal cancer increased more quickly over the past 40 years, which brought significant double burden. The survival rate of gastrointestinal malignant tumors in these elderly was lower than that of the general population. We summarized the incidence, mortality, survival and trend of gastrointestinal malignant tumors in the Chinese elderly, in order to provide data for predicting the age distribution and disease burden in the future, to improve the awareness for cancer prevention and control among these elderly, and to call attention to epidemiology, preclinical and clinical medicine for the elderly, especially in the field of study on the influence between comorbidity and cancer treatment, with the aim of improving survival and quality of life among the elderly. PMID:27215509

  10. Hyperspectral imaging system to discern malignant and benign canine mammary tumors

    NASA Astrophysics Data System (ADS)

    Sahu, Amrita; McGoverin, Cushla; Pleshko, Nancy; Sorenmo, Karin; Won, Chang-Hee

    2013-05-01

    Hyperspectral imaging is an emerging technology in the field of biomedical engineering which may be used as a noninvasive modality to characterize tumors. In this paper, a hyperspectral imaging system was used to characterize canine mammary tumors of unknown histopathology (pre-surgery) and correlate these results with the post-surgical histopathology results. The system consisted of a charge coupled device (CCD) camera, a liquid crystal tunable filter in the near infrared range (650-1100 nm) and a controller. Spectral signatures of malignant and benign canine mammary tumors were extracted and analyzed. The reflectance intensities of malignant tumor spectra were generally lower than benign tumor spectra over the entire wavelength range. Previous studies have shown that cancerous tissues have a higher hemoglobin and water content, and lower lipid concentration with respect to benign tissues. The decreased reflectance intensity observed for malignant tumors is likely due to the increased microvasculature and therefore higher blood content of malignant tissue relative to benign tissue. Peaks at 700, 840, 900 and 970 nm were observed in the second derivative absorption spectra, these peaks were attributed to deoxy-hemoglobin, oxy-hemoglobin, lipid and water respectively. A `Tissue Optical Index' was developed that enhances contrast between malignant and benign canine tumors. This index is based on the ratio of the reflectance intensity values corresponding to the wavelengths associated with the four chromophores. Preliminary results from 22 canine mammary tumors showed that the sensitivity and specificity of the proposed method is 85.7% and 94.6% respectively. These results show promise in the non-invasive optical diagnosis of canine mammary cancer.

  11. A Case of Malignant Peripheral Sheath Tumor Arising from Neurofibromatosis Type 1

    PubMed Central

    Kang, Min Ju; Kang, Hoon; Kim, Hyung Ok

    2008-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a term encompassing tumors previously diagnosed as malignant schwannoma, malignant neurilemmoma, neurogenic sarcoma, and neurofibrosarcoma The occurrence rate of MPNST in neurofibromatosis type 1 patients is known to be about 4.6%. Tumors occurring in this particular group have a worse prognosis in that they occur at an earlier age, are more centrally located, tend to be of a larger size and show more metastases and recurrences. We present a typical case of MPNST in a 36-year-old man with NF type 1, which occurred on the left buttock. A PET-CT showed findings of possible inguinal lymph node metastasis and a lymph node biopsy confirmed the diagnosis. The patient was treated with wide surgical resection and is undergoing adjuvant radiation therapy. PMID:27303156

  12. Postoperative Radiotherapy for the Treatment of Solitary Fibrous Tumor With Malignant Transformation of the Pelvic

    PubMed Central

    Gao, Chao; Zhang, Yong; Jing, Ming; Qu, Wei; Li, Jia; Zhao, Xiang-Rong; Yu, Yong-Hua

    2016-01-01

    Abstract Solitary fibrous tumor of the pelvic is an uncommon neoplasm with nonspecific symptoms. Reports of malignant transformation are especially rare. We report a case of solitary fibrous tumor in pelvic. A unique feature of our case compared with previously reported is that this patient relapsed with malignant transformation and had significant response to radiotherapy. The patient was initially treated with surgery, followed by postoperative dimensional conformal intensity modulated radiation therapy (dynamic MLC VRIAN 23EX Linac, inversely optimized by the Eclipse system) to provide a radical cure for residual tumor. In this case, there were no signs of recurrence after six and a half years of further follow-up, indicating that postoperation radiotherapy may be an effective treatment for SFT with malignant transformation in pelvic. PMID:26765426

  13. The Methanol Extract of Angelica sinensis Induces Cell Apoptosis and Suppresses Tumor Growth in Human Malignant Brain Tumors

    PubMed Central

    Lai, Wen-Lin; Harn, Horng-jyh; Hung, Pei-Hsiu; Hsieh, Ming-Chang; Chang, Kai-Fu; Huang, Xiao-Fan; Liao, Kuang-Wen; Lee, Ming-Shih; Tsai, Nu-Man

    2013-01-01

    Glioblastoma multiforme (GBM) is a highly vascularized and invasive neoplasm. The methanol extract of Angelica sinensis (AS-M) is commonly used in traditional Chinese medicine to treat several diseases, such as gastric mucosal damage, hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also displays potency in suppressing the growth of malignant brain tumor cells. The growth suppression of malignant brain tumor cells by AS-M results from cell cycle arrest and apoptosis. AS-M upregulates expression of cyclin kinase inhibitors, including p16, to decrease the phosphorylation of Rb proteins, resulting in arrest at the G0-G1 phase. The expression of the p53 protein is increased by AS-M and correlates with activation of apoptosis-associated proteins. Therefore, the apoptosis of cancer cells induced by AS-M may be triggered through the p53 pathway. In in vivo studies, AS-M not only suppresses the growth of human malignant brain tumors but also significantly prolongs patient survival. In addition, AS-M has potent anticancer effects involving cell cycle arrest, apoptosis, and antiangiogenesis. The in vitro and in vivo anticancer effects of AS-M indicate that this extract warrants further investigation and potential development as a new antibrain tumor agent, providing new hope for the chemotherapy of malignant brain cancer. PMID:24319475

  14. Malignant glioma following radiotherapy for unrelated primary tumors

    SciTech Connect

    Marus, G.; Levin, C.V.; Rutherfoord, G.S.

    1986-08-15

    Four cases are documented where a glioma was histologically verified in the irradiation field of a previously treated malignancy of a different cell line. Radiation-induced neoplasia in the central nervous system now has been established in the induction of meningioma and sarcoma. The association between therapeutic irradiation and glioma in the reported cases lends to the evidence that a causal relation does exist. This incidence is small and does not detract from the overall benefit of irradiation as a therapeutic modality.

  15. Estimation of salivary tumor necrosis factor-alpha in chronic and aggressive periodontitis patients

    PubMed Central

    Varghese, Sheeja S.; Thomas, Hima; Jayakumar, N. D.; Sankari, M.; Lakshmanan, Reema

    2015-01-01

    Introduction: Periodontitis is a chronic bacterial infection characterized by persistent inflammation, connective tissue breakdown and alveolar bone destruction mediated by pro-inflammatory mediators. Tumor necrosis factor-alpha (TNF-α) is an important pro-inflammatory mediator that produced causes destruction of periodontal tissues. Objective: The aim of the study is to estimate the salivary TNF-α in chronic and aggressive periodontitis and control participants and further correlate the levels with clinical parameter such as gingival index (GI), plaque index (PI), probing pocket depth (PPD) and clinical attachment loss. Materials and Methods: The study population consisted of 75 subjects age ranging from 25 to 55 years attending the outpatient section of Department of Periodontics, Saveetha Dental College and Hospital. The study groups included Groups 1, 2, and 3 with participants with healthy periodontium (n = 25), generalized chronic periodontitis (n = 25) and generalized aggressive periodontitis (n = 25), respectively. Salivary samples from the participants were used to assess the TNF-α levels using enzyme-linked immunosorbent assay. Results: GI and PI were found to be significantly higher in chronic and aggressive periodontitis compared to the controls. The mean TNF-α value in chronic periodontitis patients (12.92 ± 17.21 pg/ml) was significantly higher than in control subjects (2.15 ± 3.60 pg/ml). Whereas, in aggressive periodontitis patients the mean TNF-α (7.23 ± 7.67) were not significantly different from chronic periodontitis or healthy subjects. Among periodontitis participants, aggressive periodontitis subjects exhibited a significant positive correlation between the salivary TNF-α and PPD. Conclusion: Salivary TNF-α levels are significantly higher in chronic periodontitis than in healthy subjects, but there was no significant correlation with the clinical parameters. PMID:26604566

  16. CRABP1 provides high malignancy of transformed mesenchymal cells and contributes to the pathogenesis of mesenchymal and neuroendocrine tumors

    PubMed Central

    Kainov, Yaroslav; Favorskaya, Irina; Delektorskaya, Vera; Chemeris, Galina; Komelkov, Andrei; Zhuravskaya, Anna; Trukhanova, Lyubov; Zueva, Elina; Tavitian, Bertrand; Dyakova, Natalya; Zborovskaya, Irina; Tchevkina, Elena

    2014-01-01

    CRABP1 (cellular retinoic acid binding protein 1) belongs to the family of fatty acid binding proteins. Retinoic acid binding is the only known functional activity of this protein. The role of CRABP1 in human carcinogenesis remains poorly understood. Here, for the first time we demonstrated pro-metastatic and pro-tumorigenic activity of CRABP1 in mesenchymal tumors. Further functional analysis revealed that the pro-tumorigenic effect of CRABP1 does not depend on retinoic acid binding activity. These results suggest that CRABP1 could have an alternative intracellular functional activity that contributes to the high malignancy of transformed mesenchymal cells. Microarray analysis detected CRABP1-mediated alterations in the expression of about 100 genes, including those encoding key regulatory proteins. CRABP1 is ubiquitously expressed in monophasic synovial sarcomas, while in biphasic synovial sarcomas it is expressed uniquely by the spindle cells of the aggressive mesenchymal component. High level of CRABP1 expression is associated with lymph node metastasis and poor differentiation/high grade of pancreatic neuroendocrine tumors (pNETs). Presented data suggest CRABP1 as a promising biomarker of pNETs’ clinical behavior. Our results give the first evidence of pro-tumorigenic and pro-metastatic activity of CRABP1 in mesenchymal and neuroendocrine tumors. PMID:24626200

  17. The transducible TAT-RIZ1-PR protein exerts histone methyltransferase activity and tumor-suppressive functions in human malignant meningiomas.

    PubMed

    Ding, Mao-Hua; Wang, Zhen; Jiang, Lei; Fu, Hua-Lin; Gao, Jie; Lin, Xian-Bin; Zhang, Chun-Lei; Liu, Zhen-Yang; Shi, Yi-Fei; Qiu, Guan-Zhong; Ma, Yue; Cui, Da-Xiang; Hu, Guo-Han; Jin, Wei-Lin

    2015-07-01

    Malignant meningiomas are a rare meningioma subtype and tend to have post-surgical recurrence. Significant endeavors have been taken to identify functional therapeutic targets to halt the growth of this aggressive cancer. We have recently discovered that RIZ1 is downregulated in high-grade meningiomas, and RIZ1 overexpression inhibits proliferation while promoting cell apoptosis of the IOMM-Lee malignant meningioma cell line. In this report, we show that the N-terminal PR domain of RIZ1 alone possessed growth-inhibitory activity and anticancer activity in primary human meningioma cells. Interestingly, the effects seem to be dependent on differential RIZ1 protein levels. Transducible TAT-RIZ1-PR protein could also inhibit meningioma tumor growth in nude mice models. We further demonstrate that PR protein exerts histone methyltransferase activity. A microarray analysis of TAT-RIZ1-PR-treated human malignant meningioma cells reveals 969 differentially expressed genes and 848 alternative splicing exons. Moreover, c-Myc and TXNIP, two putative downstream targets of H3K9 methylation, may be involved in regulating RIZ1 tumor-suppressive effects. The reciprocal relationship between RIZ1 and c-Myc was then validated in primary meningioma cells and human tumor samples. These findings provide insights into RIZ1 tumor suppression mechanisms and suggest that TAT-RIZ1-PR protein is a potential new epigenetic therapeutic agent for advanced meningiomas. PMID:25934289

  18. [Malignant metastasizing cystosarcoma phylloides of the breast. Ulm collection of rare tumors: VI].

    PubMed

    Baczako, K; Fischer, H

    1984-12-01

    Malignant cystosarcoma phylloides represents the malignant form of mammary fibroadenoma. In spite of atypical epithelial components, the biological behaviour of the tumour depends on malignant transformation of the dominant mesenchymal stromal tissue in the tumour. The histological appearance, often extremely variable, usually corresponds to a fibrosarcoma. Lipoblastic, chondroid and myxoid structures or areas of ossification may be present, although a completely dedifferentiated cystosarcoma is rare. The epithelial structures which are typically canalicular may reveal hyperplastic and dysplastic changes as well as an apocrine change and occasionally squamous metaplasia. Besides aggressive local infiltration, hematogenous metastasis of the skeletal system and lungs is common. Therapy is dependent on the extent of local tumour growth as well as on the degree of metastasis and usually takes the form of radical mastectomy with lymphadenectomy and postoperative radiotherapy. Local recurrence is found in over 50% of the cases and the 5-year survival rate is in the order of 70%. PMID:6098887

  19. Synchronous perivesical and renal malignant rhabdoid tumor in a 9-year-old boy: a case report and review of literature.

    PubMed

    Szymanski, Konrad M; Tabib, Christian H; Idrees, Muhammad T; Cain, Mark P

    2013-11-01

    Pediatric extrarenal malignant rhabdoid tumors (MRTs) are rare and aggressive (20% 5-year survival). Only 2 cases of bladder MRTs have been published. We report on a 9-year-old boy presenting with gross hematuria, palpable pelvic mass, and an obstructed, nonfunctional kidney. Evaluation was consistent with a 9.7 cm extrarenal MRT invading the bladder and prostate. He underwent a cystoprostatectomy, Indiana pouch continent urinary reservoir creation, and a left nephroureterectomy. A discrete 2.5 cm focus of renal MRT was found. To our knowledge, this is the first case of simultaneous perivesical and renal MRT. We review the current management of pediatric extrarenal MRTs. PMID:23830079

  20. Metastatic Malignant Ovarian Steroid Cell Tumor: A Case Report and Review of the Literature

    PubMed Central

    Lee, Jessica; John, Veena S.; Liang, Sharon X.; D'Agostino, Catherine A.; Menzin, Andrew W.

    2016-01-01

    We report a case of malignant ovarian steroid cell tumor not otherwise specified (NOS) in a 47-year-old female who presented with hirsutism, virilization, and amenorrhea. At the time of laparotomy, the tumor had already spread to the pelvic cul-de-sac. She underwent a total hysterectomy, bilateral salpingo-oophorectomy, and tumor resection with no residual disease. She received three cycles of bleomycin, etoposide, and cisplatin (BEP) and is now free of disease 24 months after surgery. Literature review of ovarian steroid cell tumors NOS including clinicopathological features and clinical management was performed. PMID:27375912

  1. Salivary Heparanase Level Is a Potential Biomarker to Diagnose and Prognose the Malignant Salivary Gland Tumor

    PubMed Central

    Wang, Xin; Liu, Yang; Zhu, Shengrong; Gong, Zhongjian

    2015-01-01

    Background Upregulation of heparanase has been reported in an increasing number of human cancer tissues. However, the level of salivary heparanase and its clinical significance in patients with salivary gland tumors remain unclear. Methods Salivary heparanase levels in patients with salivary gland tumors were detected using enzyme-linked immunosorbent assays (ELISAs) and the clinical significance was evaluated by analyzing the correlations among salivary heparanase levels, clinicopathological parameters, and clinical outcomes. Results The levels of salivary heparanase were significantly higher in patients with malignant salivary gland tumors than in benign tumors and normal controls (P<0.0001). High salivary heparanase levels were positively correlated with increased lymph node metastasis (P = 0.0235) and poorer tumor node metastasis stage (TNM) (P = 0.0183). Survival analyses revealed that high salivary heparanase levels were associated with worse overall survival (P = 0.0023) and disease-free survival (DFS) (P = 0.0025). Conclusions The study shows that salivary heparanase levels, as detected by the ELISAs, can be used to diagnose and provide an accurate prognosis for malignant salivary gland tumors. Salivary heparanase level was an independent predictor in patients with malignant salivary gland tumors. PMID:26569485

  2. Radium-induced malignant tumors of the mastoid and paranasal sinuses.

    PubMed

    Littman, M S; Kirsh, I E; Keane, A T

    1978-11-01

    In the records of 5,058 persons with therapeutic or occupational exposure to radium, 21 patients with carcinoma of the mastoid and 11 with malignant tumors of the paranasal sinuses were identified. Tumor induction times were 21-50 years for mastoid tumors (median, 33) and 19-52 years for paranasal sinus tumors (median, 34). Dosimetric data are given for the patients whose body burdens of radium have been measured. We found a high proportion of mucoepidermoid carcinoma, comprising 38% of the mastoid and 36% of the paranasal sinus tumors. Three patients had antecedent bone sarcoma at 20, 11, and 5 years, respectively, and a bone sarcoma was discovered at autopsy in a fourth patient. Radiographic changes in the mastoid and paranasal sinuses were similar to those seen in nonradium malignant tumors. More than 800 known persons exposed to radium before 1930 and another group of unknown size who received radium water or injections of radium from physicians are still alive and at risk of developing malignant tumors of the mastoid and paranasal sinuses. PMID:101027

  3. Bimodal Multiparameter-Based Approach for Benign-Malignant Classification of Breast Tumors.

    PubMed

    Ara, Sharmin R; Alam, Farzana; Rahman, Md Hadiur; Akhter, Shabnam; Awwal, Rayhana; Hasan, Kamrul

    2015-07-01

    Proposed here is a breast tumor classification technique using conventional ultrasound B-mode imaging and a new elasticity imaging-based bimodal multiparameter index. A set of conventional ultrasound (US) and ultrasound elastography (UE) parameters are studied, and among those, the effective ones whose independent as well as combined performance is found satisfactory are selected. To improve the combined US performance, two new US parameters are proposed: edge diffusivity, which assesses edge blurriness to differentiate malignant from benign lesions, and the shape asymmetry factor, which quantifies tumor shape irregularity by comparing the tumor boundary with an ellipse fitted to the lesion. Then a new bimodal multiparameter characterization index is defined to discriminate 201 pathologically confirmed breast tumors of which 56 are malignant lesions, 79 are fibroadenomas, 42 are cysts and 24 are inflammatory lesions. The weights of the multiparameter bimodal index are optimally computed using a genetic algorithm (GA). To evaluate the performance variation of the index on different data sets, the tumors are categorized into three classes: malignant lesion versus fibroadenoma, malignant lesion versus fibroadenoma and cyst and malignant lesion versus fibroadenoma, cyst and inflammation. The test results reveal that the proposed bimodal index achieves satisfactory quality metrics (e.g., 94.64%-98.21% sensitivity, 97.24%-100.00% specificity and 96.52%-99.44% accuracy) for classification of the aforementioned three classes of breast tumors. Its performance is also observed to be better in totality of the quality metrics sensitivity, specificity, accuracy, positive predictive value and negative predictive value as compared with that of a conventional bimodal index as well as unimodal multiparameter indices based on US or UE. It is suggested that the proposed simple bimodal linear classifier may assist radiologists in better diagnosis of breast tumors and help reduce the

  4. The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival.

    PubMed

    Fogli, Anne; Chautard, Emmanuel; Vaurs-Barrière, Catherine; Pereira, Bruno; Müller-Barthélémy, Mélanie; Court, Franck; Biau, Julian; Pinto, Afonso Almeida; Kémény, Jean-Louis; Khalil, Toufic; Karayan-Tapon, Lucie; Verrelle, Pierre; Costa, Bruno Marques; Arnaud, Philippe

    2016-02-01

    Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ. PMID:26717998

  5. Liquid cooled brassiere and method of diagnosing malignant tumors therewith

    NASA Technical Reports Server (NTRS)

    Elkins, W.; Williams, B. A.; Tickner, E. G. (Inventor)

    1976-01-01

    A device for enhancing the detection of malignant tissue in the breasts of a woman was described. A brassiere-like garment which is fitted with a pair of liquid-perfused cooling panels which completely and compliantly cover the breasts and upper torso was studied. The garment is connected by plastic tubing to a liquid cooling system comprising a fluid pump, a solenoid control valve for controlling the flow of fluid to either the cooling unit or the heating unit, a fluid reservoir, a temperature sensor in the reservoir, and a restrictor valve to control the pressure in the garment inlet cooling line.

  6. MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

    PubMed Central

    Chimal-Ramírez, G. K.; Espinoza-Sánchez, N. A.; Utrera-Barillas, D.; Benítez-Bribiesca, L.; Velázquez, J. R.; Arriaga-Pizano, L. A.; Monroy-García, A.; Reyes-Maldonado, E.; Domínguez-López, M. L.; Piña-Sánchez, Patricia; Fuentes-Pananá, E. M.

    2013-01-01

    Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteases MMP1 and MMP9 and inflammatory COX2 genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets. PMID:23762835

  7. Angiomyolipoma and Malignant PEComa: Discussion of Two Rare Adrenal Tumors

    PubMed Central

    Kwazneski II, Douglas; Merrill, Megan; Young, Jessica; Sell, Harry

    2016-01-01

    Angiomyolipoma and PEComa are rare tumors descending from perivascular epithelial cells (PECs), with distinctive IHC, morphological, and ultrastructural features. The kidney is the most frequent site of origin, but not the only one; however, adrenal gland angiomyolipomas are extremely rare. We describe two cases being found in the adrenal glands. Given the paucity of literature on the subject, more information on this disease is necessary for diagnosis and treatment. Here, we describe two complete case reports, from presentation to treatment and follow-up, along with imaging and microscopic pathology samples, and provide a comprehensive review as to the history and current literature available regarding these extremely rare tumors. PMID:26998374

  8. Characteristics and Patterns of Rare Malignancies Published in Rare Tumors

    PubMed Central

    Habboush, Jacob; Hollant, Laeticia; Smart, Brigit; Single, Megan; Gaines, Katherine; Patel, Ajaykumar; Miller, Robert

    2016-01-01

    Rare Tumors is an international peer-reviewed medical journal established in 2009. The journal is focused on rare cancers and aims to expand upon current knowledge on their presentation, diagnosis, management, and outcomes. We reviewed the 335 case reports published from 2009 to 2015. We found great diversity in both the country of origin as well as specialty of first authors. Outside of the United States (US) and European Union (EU), there were 20 countries with contributions to the journal. Similarly, there was representation from twelve medical specialties with first authorship of reports. Rare Tumors continues to encourage involvement from physicians across the globe and from all medical disciplines. PMID:27441071

  9. Characteristics and Patterns of Rare Malignancies Published in Rare Tumors.

    PubMed

    Habboush, Jacob; Hollant, Laeticia; Smart, Brigit; Single, Megan; Gaines, Katherine; Patel, Ajaykumar; Miller, Robert

    2016-06-28

    Rare Tumors is an international peer-reviewed medical journal established in 2009. The journal is focused on rare cancers and aims to expand upon current knowledge on their presentation, diagnosis, management, and outcomes. We reviewed the 335 case reports published from 2009 to 2015. We found great diversity in both the country of origin as well as specialty of first authors. Outside of the United States (US) and European Union (EU), there were 20 countries with contributions to the journal. Similarly, there was representation from twelve medical specialties with first authorship of reports. Rare Tumors continues to encourage involvement from physicians across the globe and from all medical disciplines. PMID:27441071

  10. Gastric Schwannoma Mimicking Malignant Gastrointestinal Stromal Tumor Exhibiting Increased Fluorodeoxyglucose Uptake

    PubMed Central

    Oh, Sung Jin; Suh, Byoung Jo; Park, Jong Kwon

    2016-01-01

    A schwannoma is a kind of neurogenic tumor that rarely occurs in the gastrointestinal tract. Gastric schwannomas make up 0.2% of all gastric neoplasms. Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors and up to 60–70% of GIST occur in the stomach. Schwannoma and GIST are similar in clinical features, so they are difficult to differentiate preoperatively. Differential diagnosis of these two submucosal tumors is important because of the malignant potential of GIST and the relatively benign course of gastric schwannomas. We report a 49-year-old woman who was diagnosed after operation with a gastric schwannoma, which was suspected a malignant GIST by fluorine-18-fluorodeoxyglucose positron emission computed tomography imaging. PMID:27194983

  11. Large Malignant Phyllodes Tumor of the Breast with Metastases to the Lungs.

    PubMed

    Augustyn, Alexander; Sahoo, Sunati; Wooldridge, Rachel D

    2015-05-01

    Phyllodes tumors of the breast account for less than 0.5% of breast cancers and present most commonly in women 45 to 49 years old. The importance in managing fibroepithelial lesions lies in distinguishing fibroadenomas, which are benign, from phyllodes tumors, which can be malignant and require complete surgical excision. We report the case of a 56-year-old female who presented with a rapidly enlarging mass in her right breast 18 cm in maximum dimension that completely effaced the breast and distorted the nipple. The patient underwent a successful total mastectomy after core biopsy revealed a diagnosis of phyllodes tumor. Surgical resection is the primary treatment modality; neoadjuvant and adjuvant therapies remain controversial. Here, we report the case of a large malignant phyllodes tumor metastatic to the lungs, review the literature, and discuss diagnostic modalities and adjunct nonsurgical therapies. PMID:26266007

  12. Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance

    SciTech Connect

    Hoogsteen, Ilse J.; Marres, Henri A.M.; Hoogen, Franciscus J.A. van den

    2012-11-01

    Purpose: Overexpression of epidermal growth factor receptor (EGFR) and tumor hypoxia have been shown to correlate with worse outcome in several types of cancer including head-and-neck squamous cell carcinoma. Little is known about the combination and possible interactions between the two phenomena. Methods and Materials: In this study, 45 cases of histologically confirmed squamous cell carcinomas of the head and neck were analyzed. All patients received intravenous infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia were examined using immunohistochemistry. Results: Of all biopsies examined, respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A weak but significant association was found between the hypoxic fractions of pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative vascular area. Various degrees of colocalization between hypoxia and EGFR were found, increasing with distance from the vasculature. A high fraction of EGFR was correlated with better disease-free and metastasis-free survival, whereas a high degree of colocalization correlated with poor outcome. Conclusions: Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous cell carcinomas, predominantly at longer distances from vessels. A large amount of colocalization was associated with poor outcome, which points to a survival advantage of hypoxic cells that are also able to express EGFR. This subpopulation of tumor cells might be indicative of tumor aggressiveness and be partly responsible for treatment resistance.

  13. Nuances in the Treatment of Malignant Tumors of the Clival and Petroclival Region

    PubMed Central

    Mohyeldin, Ahmed; Prevedello, Daniel M.; Jamshidi, Ali O.; Filho, Leo F.S. Ditzel; Carrau, Ricardo L.

    2014-01-01

    Introduction Malignancies of the clivus and petroclival region are mainly chordomas and chondrosarcomas. Although a spectrum of malignancies may present in this area, a finite group of commonly encountered malignant pathologies will be the focus of this review, as they are recognized to be formidable pathologies due to adjacent critical neurovascular structures and challenging surgical approaches. Objectives The objective is to review the literature regarding medical and surgical management of malignant tumors of the clival and petroclival region with a focus on clinical presentation, diagnostic identification, and associated adjuvant therapies. We will also discuss our current treatment paradigm using endoscopic, open, and combined approaches to the skull base. Data Synthesis A literature review was conducted, searching for basic science and clinical evidence from PubMed, Medline, and the Cochrane Database. The selection criteria encompassed original articles including data from both basic science and clinical literature, case series, case reports, and review articles on the etiology, diagnosis, treatment, and management of skull base malignancies in the clival and petroclival region. Conclusions The management of petroclival malignancies requires a multidisciplinary team to deliver the most complete surgical resection, with minimal morbidity, followed by appropriate adjuvant therapy. We advocate the combination of endoscopic and open approaches (traditional or minimally invasive) as required by the particular tumor followed by radiation therapy to optimize oncologic outcomes. PMID:25992140

  14. Barriers Prevent Patient Access to Personalized Therapies Identified by Molecular Tumor Profiling of Gynecologic Malignancies

    PubMed Central

    Hillman, R. Tyler; Ward, Kristy; Saenz, Cheryl; McHale, Michael; Plaxe, Steven

    2015-01-01

    Objective. This study was designed to evaluate the ability of commercial molecular tumor profiling to discover actionable mutations and to identify barriers that might prevent patient access to personalized therapies. Methods. We conducted an IRB-approved retrospective review of 26 patients with gynecologic malignancies who underwent commercial tumor profiling at our institution during the first 18 months of test availability. Tumor profiles reported targeted therapies and clinical trials matched to patient-specific mutations. Data analysis consisted of descriptive statistics. Results. Most patients who underwent tumor profiling had serous epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (46%). Patients underwent profiling after undergoing a median of two systemic therapies (range 0 to 13). A median of one targeted therapy was suggested per patient profile. Tumor profiling identified no clinically actionable mutations for seven patients (27%). Six patients sought insurance approval for a targeted therapy and two were declined (33%). One patient (4%) received a targeted therapy and this was discontinued due to tumor progression. Conclusions. There are formidable barriers to targeted therapy for patients with gynecologic malignancies. These barriers include a dearth of FDA-approved targeted agents for gynecologic malignancies, lack of third party insurance coverage and limited geographic availability of clinical trials. PMID:26011384

  15. Malignant granular cell tumor of the lateral femoral cutaneous nerve: report of a case with cytogenetic analysis.

    PubMed

    Di Tommaso, Luca; Magrini, Elisabetta; Consales, Alessandro; Poppi, Massimo; Pasquinelli, Gianandrea; Dorji, Tsering; Benedetti, Giovanni; Baccarini, Paola

    2002-12-01

    Malignant granular cell tumors (MGCTs) are rare neoplasms of uncertain histogenesis. We report a case of MGCT involving a peripheral nerve with peritoneal and omental dissemination in which cytogenetic findings are available. Our results show that MGCTs share some cytogenetic abnormalities with malignant peripheral nerve sheath tumors (MPNSTs), supporting the hypothesis that they may represent histogenetically related lesions. PMID:12514794

  16. A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma

    PubMed Central

    Lai, Jun; Zhou, Zhan; Tang, Xiao-Jing; Gao, Zhi-Bin; Zhou, Jie; Chen, Shu-Qing

    2016-01-01

    Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum. Four somatic base-substitutions in NOTCH2, NSD1, PDE4DIP, and ATP10B and 1 insert frameshift mutation in BAP1 were validated by the Sanger method at the transcriptional level. A 13-amino acids neo-peptide of the truncated Bap1 protein, which was produced as a result of this novel frameshift mutation, was predicted to be presented by this patient’s HLA-B protein. The polyclonal antibody of the synthesized 13-mer neo-peptide was produced in rabbits. Western blotting results showed a good antibody-neoantigen specificity, and Immunohistochemistry (IHC) staining with the antibody of the neo-peptide clearly differentiated neoplastic cells from normal cells. A search of the Catalogue of Somatic Mutations in Cancer (COSMIC) database also revealed that 53.2% of mutations in BAP1 were frameshift indels with neo-peptide formation. An identified tumor-specific neo-antigen could be the potential molecular biomarker for personalized diagnosis to precisely subtype rare malignancies such as MPM. PMID:27187383

  17. A Tumor-Specific Neo-Antigen Caused by a Frameshift Mutation in BAP1 Is a Potential Personalized Biomarker in Malignant Peritoneal Mesothelioma.

    PubMed

    Lai, Jun; Zhou, Zhan; Tang, Xiao-Jing; Gao, Zhi-Bin; Zhou, Jie; Chen, Shu-Qing

    2016-01-01

    Malignant peritoneal mesothelioma (MPM) is an aggressive rare malignancy associated with asbestos exposure. A better understanding of the molecular pathogenesis of MPM will help develop a targeted therapy strategy. Oncogene targeted depth sequencing was performed on a tumor sample and paired peripheral blood DNA from a patient with malignant mesothelioma of the peritoneum. Four somatic base-substitutions in NOTCH2, NSD1, PDE4DIP, and ATP10B and 1 insert frameshift mutation in BAP1 were validated by the Sanger method at the transcriptional level. A 13-amino acids neo-peptide of the truncated Bap1 protein, which was produced as a result of this novel frameshift mutation, was predicted to be presented by this patient's HLA-B protein. The polyclonal antibody of the synthesized 13-mer neo-peptide was produced in rabbits. Western blotting results showed a good antibody-neoantigen specificity, and Immunohistochemistry (IHC) staining with the antibody of the neo-peptide clearly differentiated neoplastic cells from normal cells. A search of the Catalogue of Somatic Mutations in Cancer (COSMIC) database also revealed that 53.2% of mutations in BAP1 were frameshift indels with neo-peptide formation. An identified tumor-specific neo-antigen could be the potential molecular biomarker for personalized diagnosis to precisely subtype rare malignancies such as MPM. PMID:27187383

  18. The Rho guanine nucleotide exchange factor ARHGEF5 promotes tumor malignancy via epithelial-mesenchymal transition.

    PubMed

    Komiya, Y; Onodera, Y; Kuroiwa, M; Nomimura, S; Kubo, Y; Nam, J-M; Kajiwara, K; Nada, S; Oneyama, C; Sabe, H; Okada, M

    2016-01-01

    Epithelial tumor cells often acquire malignant properties, such as invasion/metastasis and uncontrolled cell growth, by undergoing epithelial-mesenchymal transition (EMT). However, the mechanisms by which EMT contributes to malignant progression remain elusive. Here we show that the Rho guanine nucleotide exchange factor (GEF) ARHGEF5 promotes tumor malignancy in a manner dependent on EMT status. We previously identified ARHGEF5, a member of the Dbl family of GEFs, as a multifunctional mediator of Src-induced cell invasion and tumor growth. In the present study, ARHGEF5 was upregulated during tumor growth factor-β-induced EMT in human epithelial MCF10A cells, and promoted cell migration by activating the Rho-ROCK pathway. ARHGEF5 was necessary for the invasive and in vivo metastatic activity of human colorectal cancer HCT116 cells. These findings underscore the crucial role of ARHGEF5 in cell migration and invasion/metastasis. An in vivo tumorigenesis assay revealed that ARHGEF5 had the potential to promote tumor growth via the phosphatidylinositol 3-kinase (PI3K) pathway. However, ARHGEF5 was not required for tumor growth in epithelial-like human colorectal cancer HCT116 and HT29 cells, whereas the growth of mesenchymal-like SW480 and SW620 cells depended on ARHGEF5. Induction of EMT by tumor necrosis factor-α or Slug in HCT116 cells resulted in the dependence of tumor growth on ARHGEF5. In these mesenchymal-like cells, Akt was activated via ARHGEF5 and its activity was required for tumor growth. Analysis of a transcriptome data set revealed that the combination of ARHGEF5 upregulation and E-cadherin downregulation or Snail upregulation was significantly correlated with poor prognosis in patients with colorectal cancers. Taken together, our findings suggest that EMT-induced ARHGEF5 activation contributes to the progression of tumor malignancy. ARHGEF5 may serve as a potential therapeutic target in a subset of malignant tumors that have undergone EMT. PMID

  19. [Secondary malignant lymphedema in head and neck tumors].

    PubMed

    Hammerl, Bernhard; Döller, Walter

    2008-01-01

    The occurrence of edema is a serious problem of patients suffering from cancer and may have various causes. Particularly, the secondary malignant lymphedema poses a special threat to patients. In some cases, it indicates the progression of illness, and in fact also results in mutilating physical changes, which add to the already existing impairments caused by the cancer disease. So far therapeutic interventions are limited. Current management consists of physical therapy and pharmacological interventions. There are few powerful studies concerning the efficiency and hardly any concerning combined or comparative treatment in the literature. Most of them focus on the management of lymphedema in breast cancer patients. Preventive measures and supportive therapy are rarely being discussed. In this case report, we describe the successful use of Selen and Sandostatin in treating a facial edema of a patient with advanced head-neck cancer. PMID:19165449

  20. Fluorescein Sodium-Guided Surgery of Malignant Brain Tumors: History, Current Concepts, and Future Project.

    PubMed

    Schebesch, Karl-Michael; Brawanski, Alexander; Hohenberger, Christoph; Hohne, Julius

    2016-01-01

    Fluorescein sodium (FL)-guided resection has become an important and beneficial treatment method for malignant brain tumors. FL-guided resection improves the rate of gross total resection in high-grade gliomas (HGG) and cerebral metastases (CM). FL sensitively visualizes the disruption of the blood-brain barrier in the area surrounding malignant lesions, similar to contrast-enhanced T1-weighted MR sequences. This review of the current literature summarizes the history of FL in neurosurgery from 1946 until today. We discuss the molecular mechanism of FL accumulation in cerebral malignant tumors and provide an overview of the current practice of using FL and applying a dedicated surgical microscope filter. Additionally, we outline and discuss ongoing trials and future projects. PMID:26956810

  1. Multi-course PDT of malignant tumors: the influence on primary tumor, metastatic spreading and homeostasis of cancer patients

    NASA Astrophysics Data System (ADS)

    Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Filonenko, E. V.; Sukhin, Garry M.; Nemtsova, E. R.; Belous, T. A.; Zharkova, Natalia N.

    1996-12-01

    The first clinical trials of photodynamic therapy (PDT) of cancer with two photosensitizers, PHOTOHEME and PHOTOSENS, were started in P.A. Hertzen Research Oncological Institute (Moscow, Russia) in 1992 and 1994. Up to now, 208 patients with primary, recurrent and metastatic malignant tumors (469) of skin (34 patients/185 tumors), breast cancer (24/101), head and neck (30/31), trachea and bronchus (31/42), esophagus (35/35), stomach (31/32), rectum (4/4), vagina and uterine cervix (7/8) and bladder (12/31) have been treated by PDT. One-hundred-thirty patients were injected with PHOTOHEME, 64 patients were injected with PHOTOSENS, 14 patients were injected with PHOTOHEME and PHOTOSENS. Totally, 302 courses of treatment were performed: 155 patients had one course and 53 patients were subjected to two to nine PDT sources with intervals from 1 to 18 months. A therapeutic effect of a one-course and multi- course PDT of malignant tumors (respiratory, digestive and urogenital systems) was evaluated clinically, histologically, roentgenologically, sonographically and endoscopically. The biochemical, hematological and immunological investigations were performed for all the patients in dynamics. Results of our study showed that a multi-course PDT method seems to be perspective in treatment of malignant tumors of basic localizations.

  2. Photothermal ablation of malignant brain tumors by nanoparticle loaded macrophages

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry; Baek, Seung-Kuk; Kwon, Young Jik; Sun, Chung-Ho; Madsen, Steen J.

    2011-03-01

    Nanoshells are a new class of optically tunable nanoparticles composed of a dielectric core (silica) coated with an ultrathin metallic layer (gold). Since nanoshells are roughly one million times more efficient at converting NIR light into heat than conventional dyes when exposed to NIR light, they can generate sufficient heat to induce cell death. Macrophages are frequently found in and around glioblastomas in both experimental animals and patient biopsies. Inflammatory cells loaded with nanoparticles could therefore be used to target tumors.

  3. Skeletal sequelae of radiation therapy for malignant childhood tumors

    SciTech Connect

    Butler, M.S.; Robertson, W.W. Jr.; Rate, W.; D'Angio, G.J.; Drummond, D.S. )

    1990-02-01

    One hundred forty-three patients who received radiation therapy for childhood tumors, and survived to the age of skeletal maturity, were studied by retrospective review of oncology records and roentgenograms. Diagnoses for the patients were the following: Hodgkin's lymphoma (44), Wilms's tumor (30), acute lymphocytic leukemia (26), non-Hodgkin's lymphoma (18), Ewing's sarcoma (nine), rhabdomyosarcoma (six), neuroblastoma (six), and others (four). Age at the follow-up examination averaged 18 years (range, 14-28 years). Average length of follow-up study was 9.9 years (range, two to 18 years). Asymmetry of the chest and ribs was seen in 51 (36%) of these children. Fifty (35%) had scoliosis; 14 had kyphosis. In two children, the scoliosis was treated with a brace, while one developed significant kyphosing scoliosis after laminectomy and had spinal fusion. Twenty-three (16%) patients complained of significant pain at the radiation sites. Twelve of the patients developed leg-length inequality; eight of those were symptomatic. Three patients developed second primary tumors. Currently, the incidence of significant skeletal sequelae is lower and the manifestations are less severe than reported in the years from 1940 to 1970. The reduction in skeletal complications may be attributed to shielding of growth centers, symmetric field selection, decreased total radiation doses, and sequence changes in chemotherapy.

  4. Molecular characteristics and predictors of survival in patients with malignant neuroendocrine tumors

    PubMed Central

    Arnold, Christian N.; Nagasaka, Takeshi; Goel, Ajay; Scharf, Iris; Grabowski, Patricia; Sosnowski, Andrea; Schmitt-Gräff, Annette; Boland, C. Richard; Arnold, Rudolf; Blum, Hubert E.

    2010-01-01

    To better understand the molecular pathogenesis of neuroendocrine tumors (NET), we investigated the molecular and clinical characteristics of malignant poorly differentiated colorectal NET and compared these findings with sporadic CRC and well-differentiated benign and malignant fore-/midgut NET. Tumors were analyzed and correlated for microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). NET were scored for proliferation using Ki-67. A total of 34 malignant poorly differentiated colorectal NET, 38 well-differentiated benign and malignant fore-/midgut-NET and 150 sporadic colorectal cancers (CRC) with known MSI status were investigated. Among the sporadic CRC, CIMP was significantly correlated with MSI-high (MSI-H) (p < 0.001). Of the 34 colorectal NET, 0/1 of the MSI-H, 3/5 (60%) of the MSI-L and 13/19 (68%) of the MSS tumors were CIMP+ (p = 0.17). Of the fore-/midgut-NET, none was MSI-H. 20/34 (59%) colorectal NET vs. 11/38 (29%) fore-/midgut-NET were CIMP+ (p = 0.01). The Ki-67 index was significantly higher in poorly differentiated colorectal NET compared to the less malignant fore-/midgut-NET (p < 0.0001). Besides the location in the colon, Ki-67 predicted poor outcome in NET (p < 0.0001). CIMP status did not affect survival. In NET, p16 methylation predicted a poor outcome (p = 0.0004). We conclude that molecular pathogenesis in sporadic CRC and poorly differentiated colorectal NET is different despite some similarities. Main differences between malignant well-differentiated and poorly differentiated NET are the Ki-67 proliferation rate and differential methylation in tumor-associated genes. Predictors of a poor outcome in patients with NET are poor differentiation, a high Ki-67 index and p16 methylation. PMID:18646189

  5. Invasion Precedes Tumor Mass Formation in a Malignant Brain Tumor Model of Genetically Modified Neural Stem Cells12

    PubMed Central

    Sampetrean, Oltea; Saga, Isako; Nakanishi, Masaya; Sugihara, Eiji; Fukaya, Raita; Onishi, Nobuyuki; Osuka, Satoru; Akahata, Masaki; Kai, Kazuharu; Sugimoto, Hachiro; Hirao, Atsushi; Saya, Hideyuki

    2011-01-01

    Invasiveness, cellular atypia, and proliferation are hallmarks of malignant gliomas. To effectively target each of these characteristics, it is important to understand their sequence during tumorigenesis. However, because most gliomas are diagnosed at an advanced stage, the chronology of gliomagenesis milestones is not well understood. The aim of the present study was to determine the onset of these characteristics during tumor development. Brain tumor-initiating cells (BTICs) were established by overexpressing H-RasV12 in normal neural stem/progenitor cells isolated from the subventricular zone of adult mice harboring a homozygous deletion of the Ink4a/Arf locus. High-grade malignant brain tumors were then created by orthotopic implantation of 105 BTICs into the forebrain of 6-week-old wild-type mice. Micewere killed every week for 5 weeks, and tumors were assessed for cellular atypia, proliferation, hemorrhage, necrosis, and invasion. All mice developed highly invasive, hypervascular glioblastoma-like tumors. A 100% penetrance rate and a 4-week median survival were achieved. Tumor cell migration along fiber tracts started within days after implantation and was followed by perivascular infiltration of tumor cells with marked recruitment of reactive host cells. Next, cellular atypia became prominent. Finally, mass proliferation and necrosis were observed in the last stage of the disease. Video monitoring of BTICs in live brain slices confirmed the early onset of migration, as well as the main cell migration patterns. Our results showed that perivascular and intraparenchymal tumor cell migration precede tumor mass formation in the adult brain, suggesting the need for an early and sustained anti-invasion therapy. PMID:21969812

  6. Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

    PubMed Central

    Sarin, Hemant; Kanevsky, Ariel S; Wu, Haitao; Brimacombe, Kyle R; Fung, Steve H; Sousa, Alioscka A; Auh, Sungyoung; Wilson, Colin M; Sharma, Kamal; Aronova, Maria A; Leapman, Richard D; Griffiths, Gary L; Hall, Matthew D

    2008-01-01

    Background Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. Methods Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. Results We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. Conclusion The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives. PMID:19094226

  7. Aggressive Locoregional Treatment Improves the Outcome of Liver Metastases from Grade 3 Gastroenteropancreatic Neuroendocrine Tumors.

    PubMed

    Du, Shunda; Ni, Jianjiao; Weng, Linqian; Ma, Fei; Li, Shaohua; Wang, Wenze; Sang, Xinting; Lu, Xin; Zhong, Shouxian; Mao, Yilei

    2015-08-01

    Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are rare, and there is no report specifically dealing with patients of liver metastases from G3 GEP NETs.From January 2004 to January 2014, 36 conservative patients with G3 GEP NET liver metastases were retrospectively identified from 3 hepatobiliary centers in China. The clinical features and treatment outcomes were analyzed.Aggressive locoregional treatments (LT, including cytoreductive surgery, radiofrequency ablation, and liver-directed intra-arterial intervention) and systemic therapy (ST) were introduced separately or combined, with 26 (72%) patients receiving resection of primary tumor and/or hepatic metastases, 12 patients receiving non-surgical locoregional interventions (NSLRIs), and 22 patients receiving certain kind of STs. Median overall survival (OS) was 20.0 months (95% confidence interval [CI]: 8.9-31.1 months) and survival rates were 62.6%, 30.1%, and 19.8%, at 1, 3, and 5 years, respectively. The median OS was 9.0 months (95%CI: 3.3-14.7 months) for patients receiving only STs (n = 6), 19 months (95%CI: 1.3-36.8 months) for patients receiving LT followed by STs (n = 16), and 101 months (95%CI: 0.0-210.2 months) for patients receiving only LT (n = 12). Moreover, compared with those receiving only ST or best supportive care, patients given certain types of LTs had higher rates of symptom alleviation (3/8 versus 20/23). On univariate analysis, positive prognostic factors of survival were pancreatic primary tumor (P = 0.013), normal total bilirubin level (P = 0.035), receiving surgery (P = 0.034), receiving NSLRI (P = 0.014), and sum of diameters of remnant tumor < 5 cm (P = 0.008). On multivariate analyses, pancreatic primary tumor (P = 0.015), normal total bilirubin level (P = 0.002), and sum of diameters of remnant tumor < 5 cm (P = 0.001) remained to be independent prognostic factors.For patients with G3 GEP NET liver

  8. Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST).

    PubMed

    Fujimoto, Takuya; Andoh, Tooru; Sudo, Tamotsu; Fujita, Ikuo; Fukase, Naomasa; Takeuchi, Tamotsu; Sonobe, Hiroshi; Inoue, Masayoshi; Hirose, Tkanori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Kawamoto, Teruya; Fukumori, Yoshinobu; Yamamoto, Satomi; Atagi, Shinji; Sakurai, Yoshinori; Kurosaka, Masahiro; Ono, Koji; Ichikawa, Hideki; Suzuki, Minoru

    2015-12-01

    Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT. PMID:26278348

  9. [Possibilities of boron neutron capture therapy in the treatment of malignant brain tumors].

    PubMed

    Kanygin, V V; Kichigin, A I; Gubanova, N V; Taskaev, S Yu

    2015-01-01

    Boron neutron capture therapy (BNCT) that is of the highest attractiveness due to its selective action directly on malignant tumor cells is a promising approach to treating cancers. Clinical interest in BNCT focuses in neuro-oncology on therapy for gliomas, glioblastoma in particular, and BNCT may be used in brain metastatic involvement. This needs an epithermal neutron source that complies with the requirements for BNCT, as well as a 10B-containing agent that will selectively accumulate in tumor tissue. The introduction of BNCT into clinical practice to treat patients with glial tumors will be able to enhance therapeutic efficiency. PMID:26999933

  10. Early CT findings after interstitial radiation therapy for primary malignant brain tumors

    SciTech Connect

    Tolly, T.L.; Bruckman, J.E.; Czarnecki, D.J.; Frazin, L.J.; Lewis, H.J.; Richards, M.J.; Adamkiewicz, J.J. Jr.

    1988-11-01

    The CT findings after interstitial radiation therapy for brain tumors have not been extensively described. We evaluated retrospectively the CT scans of 13 patients who were treated with brachytherapy for malignant glioma. We found no typical CT appearance that differentiates recurrent tumor from radiation effect. After undergoing brachytherapy, eight of the 13 patients scanned demonstrated enhancement of brain tissue beyond the margins of the original enhancing tumor mass. In most cases, the pattern of enhancement diminished and extended more peripherally from the central necrotic area with time. We also report a new CT finding of focal calcification developing at the site of the radioactive implant.

  11. Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

    NASA Astrophysics Data System (ADS)

    Bastos, Eugenia Maria Chaves De Moraes

    Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced

  12. Current Understanding of Circulating Tumor Cells – Potential Value in Malignancies of the Central Nervous System

    PubMed Central

    Adamczyk, Lukasz A.; Williams, Hannah; Frankow, Aleksandra; Ellis, Hayley Patricia; Haynes, Harry R.; Perks, Claire; Holly, Jeff M. P.; Kurian, Kathreena M.

    2015-01-01

    Detection of circulating tumor cells (CTCs) in the blood via so-called “liquid biopsies” carries enormous clinical potential in malignancies of the central nervous system (CNS) because of the potential to follow disease evolution with a blood test, without the need for repeat neurosurgical procedures with their inherent risk of patient morbidity. To date, studies in non-CNS malignancies, particularly in breast cancer, show increasing reproducibility of detection methods for these rare tumor cells in the circulation. However, no method has yet received full recommendation to use in clinical practice, in part because of lack of a sufficient evidence base regarding clinical utility. In CNS malignancies, one of the main challenges is finding a suitable biomarker for identification of these cells, because automated systems, such as the widely used Cell Search system, are reliant on markers, such as the epithelial cell adhesion molecule, which are not present in CNS tumors. This review examines methods for CTC enrichment and detection, and reviews the progress in non-CNS tumors and the potential for using this technique in human brain tumors. PMID:26322014

  13. Malignant peripheral nerve sheath tumor presenting as orbito temporal lump: Case report and review of literature

    PubMed Central

    Panigrahi, Souvagya; Mishra, Sudhansu S.; Mishra, Sanjib; Das, Srikant

    2016-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. The most common anatomical sites include the upper and lower extremities and trunk and less commonly the head and neck. To our knowledge, few patients with a cranial or facial MPNST have been reported. We report such a lesion in a 35-year-old woman who presented with left sided rapidly progressive proptosis and visual loss due to an orbital lump extending up to the temporal lobe. Cranial imaging showed a huge mass invading the orbital wall and temporal bone. The presumptive diagnosis was a malignant orbital tumor. Preoperative fine needle aspiration cytology of the orbital mass came to be neurofibroma. Near total resection of the tumor was done. Histopathology revealed MPNST which was subsequently confirmed on the basis of immunopositivity for S-100. The patient recovered uneventfully and was discharged 8 days after surgery with an advice to attend cancer institute for possible radiotherapy. PMID:27057226

  14. Prolactinoma ErbB receptor expression and targeted therapy for aggressive tumors.

    PubMed

    Cooper, Odelia; Mamelak, Adam; Bannykh, Serguei; Carmichael, John; Bonert, Vivien; Lim, Stephen; Cook-Wiens, Galen; Ben-Shlomo, Anat

    2014-06-01

    As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors was tested for prolactinoma outcomes and therapy. The objective of this study was to characterize ErbB receptor expression in prolactinomas and then perform a pilot study treating resistant prolactinomas with a targeted tyrosine kinase inhibitor (TKI). Retrospective analysis of prolactinomas and pilot study for dopamine agonist resistant prolactinomas in tertiary referral center. We performed immunofluorescent staining of a tissue array of 29 resected prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical features. Two patients with aggressive resistant prolactinomas enrolled and completed trial. They received lapatinib 1,250 mg daily for 6 months with tumor and hormone assessments. Main outcome measures were positive tumor staining of respective ErbB receptors, therapeutic reduction of prolactin levels and tumor shrinkage. Treated PRL levels and tumor volumes were suppressed in both subjects treated with TKI. EGFR expression was positive in 82 % of adenomas, ErbB2 in 92 %, ErbB3 in 25 %, and ErbB4 in 71 %, with ErbB2 score > EGFR > ErbB4 > ErbB3. Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03), suprasellar extension (p = 0.04), and carotid artery encasement (p = 0.01). Higher DA response rates were observed in tumors with higher ErbB3 expression. Prolactinoma expression of specific ErbB receptors is associated with tumor invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors may be effective therapy in patients with resistant prolactinomas. PMID:24287797

  15. Mechanisms of Cryoablation: Clinical Consequences on Malignant Tumors

    PubMed Central

    Baust, J.G.; Gage, A.A.; Johansen, T.E. Bjerklund; Baust, J.M.

    2014-01-01

    While the destructive actions of a cryoablative freeze cycle are long recognized, more recent evidence has revealed a complex set of molecular responses that provides a path for optimization. The importance of optimization relates to the observation that the cryosurgical treatment of tumors yields success only equivalent to alternative therapies. This is also true of all existing therapies of cancer that, while applied with curative intent; provide only disease suppression for periods ranging from months to years. Recent research has led to an important new understanding of the nature of cancer, which has implications for primary therapies, including cryosurgical treatment. We now recognize that a cancer is a highly organized tissue dependent on other supporting cells for its establishment, growth and invasion. Further, cancer stem cells are now recognized as an origin of disease and prove resistant to many treatment modalities. Growth is dependent on endothelial cells essential to blood vessel formation, fibroblasts production of growth factors, and protective functions of cells of the immune system. This review discusses the biology of cancer, which has profound implications for the diverse therapies of the disease, including cryosurgery. We also describe the cryosurgical treatment of diverse cancers, citing results, types of adjunctive therapy intended to improve clinical outcomes, and comment briefly on other energy-based ablative therapies. With an expanded view of tumor complexity, we identify those elements key to effective cryoablation and strategies designed to optimize cancer cell mortality with a consideration of the now recognized hallmarks of cancer. PMID:24239684

  16. Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update

    PubMed Central

    Gurzu, Simona; Turdean, Sabin; Kovecsi, Attila; Contac, Anca Otilia; Jung, Ioan

    2015-01-01

    Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET). Although much research work has already been done in these fields, the specific molecular pathways of EMT, relating to the tumor type and tumor localization, are yet to be elucidated. In this paper, based on the literature and personal experience of the authors, an update in the field of EMT vs MET in epithelial and mesenchymal tumors is presented. The authors tried to present the latest data about the particularities of these processes, and also of the so-called endothelial-to-mesenchymal transition, based on tumor location. The EMT-angiogenesis link is discussed as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management. The paper begins with presentation of the basic aspects of EMT, its classification and assessment possibilities, and concludes with prognostic and therapeutic perspectives. The particularities of EMT and MET in gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and cholangiocarcinomas, and lung, breast and prostate cancers, respectively in sarcomas and gastrointestinal stromal tumors are presented in detail. PMID:25984514

  17. Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update.

    PubMed

    Gurzu, Simona; Turdean, Sabin; Kovecsi, Attila; Contac, Anca Otilia; Jung, Ioan

    2015-05-16

    Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET). Although much research work has already been done in these fields, the specific molecular pathways of EMT, relating to the tumor type and tumor localization, are yet to be elucidated. In this paper, based on the literature and personal experience of the authors, an update in the field of EMT vs MET in epithelial and mesenchymal tumors is presented. The authors tried to present the latest data about the particularities of these processes, and also of the so-called endothelial-to-mesenchymal transition, based on tumor location. The EMT-angiogenesis link is discussed as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management. The paper begins with presentation of the basic aspects of EMT, its classification and assessment possibilities, and concludes with prognostic and therapeutic perspectives. The particularities of EMT and MET in gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and cholangiocarcinomas, and lung, breast and prostate cancers, respectively in sarcomas and gastrointestinal stromal tumors are presented in detail. PMID:25984514

  18. Tumor interstitial fluid promotes malignant phenotypes of lung cancer independently of angiogenesis.

    PubMed

    Li, Hong; Li, Ganggang; Liu, Linxin; Guo, Zhenzhen; Ma, Xiaofang; Cao, Ning; Lin, Haihong; Han, Guang; Duan, Yongjian; Du, Gangjun

    2015-11-01

    Angiogenesis is necessary for cancer progression, but antiangiogenic therapy actually promotes tumor recurrence, progression, and metastasis. This study focused on the contribution of the tumor interstitial fluid (TIF) to lung cancer progression. TIF was isolated and quantified for 10 μg protein/mL. Malignant driver characteristics of TIF were examined by tumor-initiating cells (TIC), self-renewal, epithelial-mesenchymal transition (EMT), autophagy, and apoptosis in vitro. In vivo tumor model was used to investigate the mechanistic roles of TIF in lung cancer progression. In vitro, TIF exhibited distinct malignant driver characteristics, which led to increased numbers of TICs, increased self-renewal and EMT, as well as to decreased autophagy and apoptosis under cell starvation conditions. In vivo, the contribution of TIF was similar, as judged by increased TICs indicated by the cancer stem cell marker Nanog, the proliferation marker proliferating cell nuclear antigen, and the EMT marker N-cadherin; TIF also increased the formation of pulmonary tumors. Interestingly, the blockers of inflammation, Na-K-ATPase, and aldosterone receptor decreased TIF-induced tumor progression but increased angiogenesis. Further, we found that the water content of the tissue was positively correlated with the levels of plasma 5-hydroxyindoleacetic acid or tissue aquaporin-1 but not with CD31. However, vadimezan reduced angiogenesis but promoted TIF-induced tumor progression. Our results suggested that TIF could provide better nutrition to the tumor than angiogenesis and that it could promote the development of malignant phenotypes of lung cancer independently of angiogenesis. PMID:26342025

  19. A Case of Malignant Peripheral Nerve Sheath Tumor of the Hypoglossal Nerve after Stereotactic Radiosurgery Treatment

    PubMed Central

    Yang, Tong; Juric-Sekhar, Gordana; Born, Donald; Sekhar, Laligam N.

    2014-01-01

    Objectives Hypoglossal schwannomas are rare. Surgical resection has been the standard treatment modality. Radiosurgery has been increasingly used for treatment. Radiation-associated secondary malignancy/malignant transformation has not been documented in the literature for the treatment of nonvestibular schwannomas. Setting The patient was a 52-year-old man with an enlarging high cervical/skull base lesion 8.5 years after CyberKnife treatment of a presumed vagal schwannoma. A decision was made for surgical resection, and the tumor was found to originate from the hypoglossal nerve intraoperatively. Final pathology diagnosis was malignant peripheral nerve sheath tumor. Results Patient had a gross total resection. Three months after resection, he received fractionated radiation of 50 Gy in 25 fractions and a boost gamma knife radiosurgery of 10 Gy to the 50% isodose surface. He remained tumor free on repeat magnetic resonance imaging 9 months after the resection. Conclusion Although extremely rare, radiation treatment of nonvestibular schwannomas can potentially cause malignant transformation. PMID:25083387

  20. [Advanced malignant soft tissue tumors: plastic reconstructive options for palliative treatment].

    PubMed

    Vogt, P M; Jokuszies, A

    2010-12-01

    Plastic and reconstructive procedures for the oncological treatment of malignant tumors in the head and neck region, trunk and extremities are primarily curative. Less is known about the treatment options of plastic surgery in patients with locally advanced or incurable tumors. Therefore superficial, mostly exulcerated and superinfected tumors are treated with a palliative approach. A plethora of symptoms drastically restricts the quality of life in patients with advanced cancer. Pain, oozing of blood and bacterial superinfection with fetidness compromise the patient's general condition, self-esteem and activity. Many patients suffer from increasing isolation. A stage-adapted and plastic-reconstructive approach aiming at reducing the tumor mass and closing ulcerating wounds provides a considerable benefit especially in these patients. In this article a variety of treatment options regarding palliative resections and plastic reconstructive procedures and the disease alleviating benefits for patients with incurable tumors are presented. PMID:19949764

  1. Towards the use of HIFU, in Conjunction with Surgery, in the Treatment of Malignant Brain Tumors

    NASA Astrophysics Data System (ADS)

    Dahl, Elizabeth; Nguyen, Lisa T.; Sparks, Rachel E.; Brayman, Andy A.; Olios, Ryan J.; Silbergeld, Daniel L.; Vaezy, Sarah; Mourad, Pierre D.

    2006-05-01

    The first medical response to the presence of a brain tumor is often its resection, both to alleviate mass effect, and to obtain tissue for diagnosis, itself necessary for guiding adjunctive therapy. Malignant brain tumors typically recur at the tumor resection margin. Most current chemotherapy and radiotherapy strategies target local recurrence with limited success. Here we review a new strategy for delivering chemotherapeutics for brain tumor recurrence. It uses intra-operative high-intensity focused ultrasound (HIFU) to transiently open the blood-brain barrier (BBB) over a significantly large volume of brain at and near the resection margin to enhance the subsequent delivery of systemically delivered chemotherapeutic agents into the region of tumor recurrence.

  2. Over-expression of tetraspanin 8 in malignant glioma regulates tumor cell progression

    SciTech Connect

    Pan, Si-Jian; Wu, Yue-Bing; Cai, Shang; Pan, Yi-Xin; Liu, Wei; Bian, Liu-Guan; Sun, Bomin; Sun, Qing-Fang

    2015-03-13

    Tumor cell invasion and proliferation remain the overwhelming causes of death for malignant glioma patients. To establish effective therapeutic methods, new targets implied in these processes have to be identified. Tetraspanin 8 (Tspn8) forms complexes with a large variety of trans-membrane and/or cytosolic proteins to regulate several important cellular functions. In the current study, we found that Tspn8 was over-expressed in multiple clinical malignant glioma tissues, and its expression level correlated with the grade of tumors. Tspn8 expression in malignant glioma cells (U251MG and U87MG lines) is important for cell proliferation and migration. siRNA-mediated knockdown of Tspn8 markedly reduced in vitro proliferation and migration of U251MG and U87MG cells. Meanwhile, Tspn8 silencing also increased the sensitivity of temozolomide (TMZ), and significantly increased U251MG or U87MG cell death and apoptosis by TMZ were achieved with Tspn8 knockdown. We observed that Tspn8 formed a complex with activated focal adhesion kinase (FAK) in both human malignant glioma tissues and in above glioma cells. This complexation appeared required for FAK activation, since Tspn8 knockdown inhibited FAK activation in U251MG and U87MG cells. These results provide evidence that Tspn8 contributes to the pathogenesis of glioblastoma probably by promoting proliferation, migration and TMZ-resistance of glioma cells. Therefore, targeting Tspn8 may provide a potential therapeutic intervention for malignant glioma. - Highlights: • Tspn8 is over-expressed in multiple clinical malignant glioma tissues. • Tspn8 expression is correlated with the grade of malignant gliomas. • Tspn8 knockdown suppresses U251MG/U87MG proliferation and in vitro migration. • Tspn8 knockdown significantly increases TMZ sensitivity in U251MG/U87MG cells. • Tspn8 forms a complex with FAK, required for FAK activation.

  3. Kallikrein 4 and matrix metalloproteinase-20 immunoexpression in malignant, benign and infiltrative odontogenic tumors

    PubMed Central

    Crivelini, Marcelo Macedo; Oliveira, Denise Tostes; de Mesquita, Ricardo Alves; de Sousa, Suzana Cantanhede Orsini Machado; Loyola, Adriano Motta

    2016-01-01

    Context: Matrix metalloproteinase-20 (MMP20) (enamelysin) and kallikrein 4 (KLK4) are enzymes secreted by ameloblasts that play an important role in enamel matrix degradation during amelogenesis. However, studies have shown that neoplastic cells can produce such enzymes, which may affect the tumor infiltrative and metastatic behaviors. Aims: The aim of this study is to assess the biological role of MMP20 and KLK4 in odontogenic tumors. Materials and Methods: The enzymes were analyzed immunohistochemically in ameloblastoma, adenomatoid odontogenic tumor (AOT), calcifying epithelial odontogenic tumor, keratocystic odontogenic tumor with or without recurrence and odontogenic carcinoma. Statistical Analysis Used: Clinicopathological parameters were statistically correlated with protein expression using the Fisher's exact test. Kruskal–Wallis and Wilcoxon-independent methods were used to evaluate the differences in median values. Results: Positive Immunoexpression was detected in all benign lesions, with a prevalence of 75–100% immunolabeled cells. Patients were predominantly young, Caucasian, female, with slow-growing tumors located in the mandible causing asymptomatic swelling. No KLK4 expression was seen in carcinomas, and the amount of MMP20-positive cells varied between 20% and 80%. Rapid evolution, recurrence and age >60 years characterized the malignant nature of these lesions. Conclusions: Data showed that KLK4 and MMP20 enzymes may not be crucial to tumoral infiltrative capacity, especially in malignant tumors, considering the diversity and peculiarity of these lesions. The significant immunoexpression in benign lesions, remarkably in AOT, is likely associated with differentiated tumor cells that can produce and degrade enamel matrix-like substances. This would be expected since the histogenesis of odontogenic tumors commonly comes from epithelium that recently performed a secretory activity in tooth formation. PMID:27601817

  4. MicroRNA142-3p promotes tumor-initiating and radioresistant properties in malignant pediatric brain tumors.

    PubMed

    Lee, Yi-Yen; Yang, Yi-Ping; Huang, Ming-Chao; Wang, Mong-Lien; Yen, Sang-Hue; Huang, Pin-I; Chen, Yi-Wei; Chiou, Shih-Hwa; Lan, Yuan-Tzu; Ma, Hsin-I; Shih, Yang-Hsin; Chen, Ming-Teh

    2014-01-01

    Primary central nervous system (CNS) atypical teratoid/rhabdoid tumor (ATRT) is an extremely malignant pediatric brain tumor observed in infancy and childhood. It has been reported that a subpopulation of CD133(+) cells isolated from ATRT tumors present with cancer stem-like and radioresistant properties. However, the exact biomolecular mechanisms of ATRT or CD133-positive ATRT (ATRT-CD133(+)) cells are still unclear. We have previously shown that ATRT-CD133(+) cells have pluripotent differentiation ability and the capability of malignant cells to be highly resistant to ionizing radiation (IR). By using microRNA array and quantitative RT-PCR in this study, we showed that expression of miR142-3p was lower in ATRT-CD133(+) cells than in ATRT-CD133(-) cells. miR142-3p overexpression significantly inhibited the self-renewal and tumorigenicity of ATRT-CD133(+) cells. On the contrary, silencing of endogenous miR142-3p dramatically increased the tumor-initiating and stem-like cell capacities in ATRT cells or ATRT-CD133(-) cells and further promoted the mesenchymal transitional and radioresistant properties of ATRT cells. Most importantly, therapeutic delivery of miR142-3p in ATRT cells effectively reduced its lethality by blocking tumor growth, repressing invasiveness, increasing radiosensitivity, and prolonging survival time in orthotropic-transplanted immunocompromised mice. These results demonstrate the prospect of developing novel miRNA-based strategies to block the stem-like and radioresistant properties of malignant pediatric brain cancer stem cells. PMID:24816458

  5. Intratumoral CD3+ T-Lymphocytes Immunoexpression and Its Association with c-Kit, Angiogenesis, and Overall Survival in Malignant Canine Mammary Tumors

    PubMed Central

    Carvalho, Maria Isabel; Pires, Isabel; Dias, Marlene; Prada, Justina; Gregório, Hugo; Lobo, Luis; Queiroga, Felisbina

    2015-01-01

    In this study 80 malignant CMT were submitted to immunohistochemical detection of CD3, c-kit, VEGF, and CD31, together with clinicopathological parameters of tumor aggressiveness. CD3+ T-cells and c-kit overexpression revealed a positive correlation with VEGF (r = 0.503, P < 0.0001; r = 0.284, P = 0.023 for CD3 and c-kit, resp.) and CD31 (r = 0.654, P < 0.0001; r = 0.365, P = 0.003 for CD3 and c-kit, resp.). A significant association (P = 0.039) and a positive correlation (r = 0.263, P = 0.039) between CD3 and c-kit were also observed. High CD3/VEGF, c-kit/VEGF, and CD3/c-kit tumors were associated with elevated grade of malignancy (P < 0.0001 for all groups), presence of intravascular emboli (P < 0.0001 for CD3/VEGF and CD3/c-kit; P = 0.002 for c-kit/VEGF), and presence of lymph node metastasis (P < 0.0001 for all groups). Tumors with high CD3/VEGF (P = 0.006), c-kit/VEGF (P < 0.0001), and CD3/c-kit (P = 0.002) were associated with poor prognosis. Interestingly high c-kit/VEGF tumors retained their significance by multivariate analysis arising as independent prognostic factor. PMID:26346272

  6. Intratumoral CD3+ T-lymphocytes immunoexpression and its association with c-Kit, angiogenesis, and overall survival in malignant canine mammary tumors.

    PubMed

    Carvalho, Maria Isabel; Pires, Isabel; Dias, Marlene; Prada, Justina; Gregório, Hugo; Lobo, Luis; Queiroga, Felisbina

    2015-01-01

    In this study 80 malignant CMT were submitted to immunohistochemical detection of CD3, c-kit, VEGF, and CD31, together with clinicopathological parameters of tumor aggressiveness. CD3+ T-cells and c-kit overexpression revealed a positive correlation with VEGF (r = 0.503, P < 0.0001; r = 0.284, P = 0.023 for CD3 and c-kit, resp.) and CD31 (r = 0.654, P < 0.0001; r = 0.365, P = 0.003 for CD3 and c-kit, resp.). A significant association (P = 0.039) and a positive correlation (r = 0.263, P = 0.039) between CD3 and c-kit were also observed. High CD3/VEGF, c-kit/VEGF, and CD3/c-kit tumors were associated with elevated grade of malignancy (P < 0.0001 for all groups), presence of intravascular emboli (P < 0.0001 for CD3/VEGF and CD3/c-kit; P = 0.002 for c-kit/VEGF), and presence of lymph node metastasis (P < 0.0001 for all groups). Tumors with high CD3/VEGF (P = 0.006), c-kit/VEGF (P < 0.0001), and CD3/c-kit (P = 0.002) were associated with poor prognosis. Interestingly high c-kit/VEGF tumors retained their significance by multivariate analysis arising as independent prognostic factor. PMID:26346272

  7. Desmoid tumor of lung with pleural involvement - the case of unique location of aggressive fibromatosis.

    PubMed

    Tokarek, Tomasz; Szpor, Joanna; Pankowski, Juliusz; Okoń, Krzysztof

    2015-01-01

    Desmoid tumors (DTs) are rare mesenchymal neoplasms with unpredictable natural history. There is a high risk of recurrence despite adequate surgical resection, however DTs do not have the capacity to metastasize. The estimated incidence in general population is 2-4 cases/million/year. They may occur at any age but most commonly in the third and fourth decades. Both sexes may be affected, but there is a slight female predominance. DTs can occur at any body site. The exact etiology remains unclear, but trauma, hormonal disturbances, pregnancy, genetic and hereditary factors are postulated to be in association with its' development. Potential to attain large size, infiltration and destruction of adjacent vital structures and tendency to recur are main management problems and important causes of morbidity and mortality. Wide excision is standard first-line treatment of primary or recurrent symptomatic desmoids. We present case of 33-years-old Caucasian female patient admitted to hospital with 2 months history of squeezing pain in right upper quadrant which appeared after meals. The patient was in general good condition. There were no abnormalities on basic laboratory tests on admission. CT of chest revealed hydrothorax to the level of the apex of the right lung and tumor sized 7 × 13 × 13 cm located in the lower lobe of right lung. Histopathological diagnosis of desmoid tumor of right lung was formulated. We report, to our knowledge for the first time in Poland, case of aggressive fibromatosis of lung with invasion of pleura. PMID:26774632

  8. Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion

    PubMed Central

    Roselli, Séverine; Pundavela, Jay; Demont, Yohann; Faulkner, Sam; Keene, Sheridan; Attia, John; Jiang, Chen Chen; Zhang, Xu Dong; Walker, Marjorie M.; Hondermarck, Hubert

    2015-01-01

    The neuronal membrane protein sortilin has been reported in a few cancer cell lines, but its expression and impact in human tumors is unclear. In this study, sortilin was analyzed by immunohistochemistry in a series of 318 clinically annotated breast cancers and 53 normal breast tissues. Sortilin was detected in epithelial cells, with increased levels in cancers, as compared to normal tissues (p = 0.0088). It was found in 79% of invasive ductal carcinomas and 54% of invasive lobular carcinomas (p < 0.0001). There was an association between sortilin expression and lymph node involvement (p = 0.0093), suggesting a relationship with metastatic potential. In cell culture, sortilin levels were higher in cancer cell lines compared to non-tumorigenic breast epithelial cells and siRNA knockdown of sortilin inhibited cancer cell adhesion, while proliferation and apoptosis were not affected. Breast cancer cell migration and invasion were also inhibited by sortilin knockdown, with a decrease in focal adhesion kinase and SRC phosphorylation. In conclusion, sortilin participates in breast tumor aggressiveness and may constitute a new therapeutic target against tumor cell invasion. PMID:25871389

  9. Hyaluronan in human malignancies

    SciTech Connect

    Sironen, R.K.; Tammi, M.; Tammi, R.; Auvinen, P.K.; Anttila, M.; Kosma, V-M.

    2011-02-15

    Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance.

  10. Hypoxia in Microscopic Tumors

    PubMed Central

    Li, Xiao-Feng; O’Donoghue, Joseph A

    2008-01-01

    Tumor hypoxia has been commonly observed in a broad spectrum of primary solid malignancies. Hypoxia is associated with tumor progression, increased aggressiveness, enhanced metastatic potential and poor prognosis. Hypoxic tumor cells are resistant to radiotherapy and some forms of chemotherapy. Using an animal model, we recently showed that microscopic tumors less than 1 mm diameter were severely hypoxic. In this review, models and techniques for the study of hypoxia in microscopic tumors are discussed. PMID:18384940

  11. The reprogramming of tumor stroma by HSF1 is a potent enabler of malignancy

    PubMed Central

    Scherz-Shouval, Ruth; Santagata, Sandro; Mendillo, Marc L.; Sholl, Lynette M.; Ben-Aharon, Irit; Beck, Andrew H.; Dias-Santagata, Dora; Koeva, Martina; Stemmer, Salomon M.; Whitesell, Luke; Lindquist, Susan

    2014-01-01

    Summary Stromal cells within the tumor microenvironment are essential for tumor progression and metastasis. Surprisingly little is known about the factors that drive the transcriptional reprogramming of stromal cells within tumors. We report that the transcriptional regulator Heat-Shock Factor 1 (HSF1) is frequently activated in cancer-associated fibroblasts (CAFs), where it is a potent enabler of malignancy. HSF1 drives a transcriptional program in CAFs that complements, yet is completely different from, the program it drives in adjacent cancer cells. This CAF program is uniquely structured to support the malignant potential of cancer cells in a non-cell-autonomous way. Two central stromal signaling molecules—TGFβ and stromal-derived factor 1 (SDF1) – play a critical role. In early stage breast and lung cancer, high stromal HSF1 activation is strongly associated with poor patient outcome. Thus, tumors co-opt the ancient survival functions of HSF1 to orchestrate malignancy in both cell-autonomous and non-cell-autonomous ways, with far-reaching therapeutic implications. PMID:25083868

  12. Correlation of CCNA1 promoter methylation with malignant tumors: a meta-analysis introduction.

    PubMed

    Yang, Bin; Miao, Shuai; Zhang, Le-Ning; Sun, Hong-Bin; Xu, Zhe-Nan; Han, Chun-Shan

    2015-01-01

    Epigenetic silencing of tumor suppressor genes by promoter methylation plays vital roles in the process of carcinogenesis. The purpose of this meta-analysis was to determine whether the aberrant methylation of cyclin A1 (CCNA1) may be of great significance to human malignant tumors. By searching both English and Chinese language-based electronic databases carefully, we tabulated and analyzed parameters from each study. All human-associated case-control studies were included providing available data for CCNA1 methylation and reporting the adjusted odds ratios (ORs) and 95% confidence intervals (CI) conducted with the use of Version 12.0 STATA software. A total of 10 case-control studies (619 patients with cancers and 292 healthy controls) were included for the following statistical analysis. Pooled OR values from all articles revealed that the frequency of CCNA1 methylation in cancer tissues was significantly higher than those of normal tissues (P < 0.001). Further ethnicity indicated that the frequency of CCNA1 methylation was correlated with the development of malignant tumors among all those included experimental subgroups (all P < 0.05). These data from results indicated a significant connection of CCNA1 methylation with poor progression in human malignant tumors among both Caucasian and Asian populations. PMID:25654082

  13. Malignant tumors during the first 2 decades of life in the offspring of atomic bomb survivors

    SciTech Connect

    Yoshimoto, Y.; Neel, J.V.; Schull, W.J.; Kato, H.; Soda, M.; Eto, R.; Mabuchi, K. )

    1990-06-01

    The risk of cancer (incidence) prior to age 20 years has been determined for children born to atomic bomb survivors and to a suitable comparison group. Tumor ascertainment was through death certificates and the tumor registries maintained in Hiroshima and Nagasaki. The rationale for the study stemmed from the evidence that a significant proportion of such childhood tumors as retinoblastoma and Wilms tumor arise on the basis of a mutant gene inherited from one parent plus a second somatic cell mutation involving the allele of this gene. Gonadal radiation doses were calculated by the recently established DS86 system, supplemented by an ad hoc system for those children for one or both of whose parents a DS86 dose could not be computed but for whom an ad hoc dose could be developed on the basis of the available information. The total data set consisted of (1) a cohort of 31,150 live-born children one or both of whose parents received greater than 0.01 Sv of radiation at the time of the atomic bombings (average conjoint gonad exposure 0.43 Sv) and (2) two suitable comparison groups totaling 41,066 children. Altogether, 43 malignant tumors were ascertained in the children of exposed parents, and 49 malignant tumors were ascertained in the two control groups. A multiple linear regression analysis revealed no increase in malignancy in the children of exposed parents. However, examination of the data suggested that only 3.0-5.0% of the tumors of childhood that were observed in the comparison groups are associated with an inherited genetic predisposition that would be expected to exhibit an altered frequency if the parental mutation rate were increased. There is thus far no confirmation of the positive findings that Nomura found in a mouse system.

  14. The tumor microenvironment shapes hallmarks of mature B-cell malignancies.

    PubMed

    Shain, K H; Dalton, W S; Tao, J

    2015-09-01

    B-cell tumorigenesis results from a host of known and unknown genetic anomalies, including non-random translocations of genes that normally function as determinants of cell proliferation or cell survival to regions juxtaposed to active immunoglobulin heavy chain enhancer elements, chromosomal aneuploidy, somatic mutations that further affect oncogenic signaling and loss of heterozygosity of tumor-suppressor genes. However, it is critical to recognize that even in the setting of a genetic disease, the B-cell/plasma cell tumor microenvironment (TME) contributes significantly to malignant transformation and pathogenesis. Over a decade ago, we proposed the concept of cell adhesion-mediated drug resistance to delineate a form of TME-mediated drug resistance that protects hematopoietic tumor cells from the initial effect of diverse therapies. In the interim, it has been increasingly appreciated that TME also contributes to tumor initiation and progression through sustained growth/proliferation, self-renewal capacity, immune evasion, migration and invasion as well as resistance to cell death in a host of B-cell malignancies, including mantle cell lymphoma, diffuse large B-cell lymphoma, Waldenstroms macroglobulinemia, chronic lymphocytic leukemia and multiple myeloma. Within this review, we propose that TME and the tumor co-evolve as a consequence of bidirectional signaling networks. As such, TME represents an important target and should be considered integral to tumor progression and drug response. PMID:25639873

  15. Prostatic Stromal Tumor of Uncertain Malignant Potential Which Was Difficult to Diagnose

    PubMed Central

    Matsuyama, Satoko; Nohara, Takahiro; Kawaguchi, Shohei; Seto, Chikashi; Nakanishi, Yuko; Uchiyama, Akio; Ishizawa, Shin

    2015-01-01

    Here, we report a case of stromal tumor of uncertain malignant potential (STUMP) that was difficult to diagnose. A 53-year-old male was found to have a hard nodule on digital rectal examination; magnetic resonance imaging revealed a large nodule on the left side of the prostate, indicating prostate cancer. However, pathological diagnosis of the biopsy specimen was benign prostatic hyperplasia. Although a papillary tumor in the prostatic urethra was also seen on urethrocystoscopy, the tumor specimen obtained from transurethral resection was not malignant. The tumor in the prostatic urethra recurred only 3 months after transurethral resection, and pathological findings revealed benign hyperplasia not only in the stromal tissue but also in the epithelium; therefore, the prostate tumor was suspected to be STUMP. It took many prostate pathologists a long time to reach the final diagnosis of STUMP. STUMP is a rare benign tumor, difficult to diagnose, and sometimes transforms into stromal sarcoma. Thus, we should consider radical resection in such cases. PMID:26839730

  16. Malignant glomus tumor with oncocytic features: an unusual presentation of dysphagia.

    PubMed

    Ugras, Nesrin; Yercİ, Ömer; Yalçınkaya, Ulviye; Gülcü, Barış; Öztürk, Ersin; Yıldırım, Çınar; Çavuşoğlu, İlkin

    2015-07-01

    Glomus tumors in the gastrointestinal tract are unusual, as the previous series in the literature have been mainly limited to the stomach. Less than 10 cases of esophageal glomus tumors have been described in the literature. Oncocytic glomus tumors are a recently identified, rare variant of the glomus tumor. We report a 47-year-old female who presented with an approximately 3-month history of dysphagia and weight loss. Upper gastrointestinal endoscopy showed a black-purple, hypervascular, protruding lesion measuring approximately 65 mm at the 37th cm of the esophagus. The patient underwent an Ivor Lewis operation via open thoracotomy. The resected specimen had a protuberant, ulcerated mass measuring 80 × 35 mm in the posterior wall of the esophagus. Based on the histopathological, immunohistochemical and electron microscope findings, the final diagnosis was a malignant glomus tumor with oncocytic features. To our knowledge, this is the first report of a malignant glomus tumor with oncocytic features in an esophageal location. PMID:25908295

  17. Computed tomography of malignant tumors of the nasal cavity and paranasal sinuses

    SciTech Connect

    Kondo, M.; Horiuchi, M.; Shiga, H.

    1982-07-15

    Staging of malignant tumors of the nasal cavity and paranasal sinuses by computed tomography (CT) was studied in a total of 49 patients, 33 with squamous cell carcinoma and 16 with tumors of other histologic types. Involved sites by the tumor were studied, and clinical staging was made using CT findings alone according to AJC classification for maxillary sinus tumors. Surgical findings for comparison were available for most cases. Of 33 squamous cell carcinomas and of 16 tumors with other histologic types, the maxillary sinus was the site of origin in 29 and eight, respectively. Of these 37 maxillary sinus tumors, 11 were staged T3, 26 T4, and none was staged T1 or T2. None of these tumors were down staged, and one T3 was upstaged after surgical procedures, although all sinuses were not explored in some cases. Sinusitis due to obstruction was indistinguishable from the tumor without bone destruction. And the determination of the site of origin was difficult in some cases. Despite these, CT should be used for pretreatment evaluation of the tumors of these sites.

  18. Malignant melanoma of the nasal septum, a rare tumor, occurring in a 54-year-old patient after hereditary retinoblastoma treatment.

    PubMed

    Djiguimdé, Windinmanégdé Pierre; Diomandé, Ibrahim Abib; Bonnin, Nicolas; Saroul, Nicolas; Touré, Abdoulaye; Sanou, Jérôme; Sankara, Paté; Russier, Marc; Gilain, Laurent; Ahnoux-Zabsonré, Ahgbatouhabéba; Meda, Nonfounikoun; Bacin, Franck

    2016-01-01

    The authors report a case of a malignant melanoma of the nasal cavity that is a rare tumor and very aggressive, constituting 1% of all melanomas. It appeared in a patient 54 years after he was treated for a hereditary retinoblastoma. Its symptoms are nonspecific, and often marked by epistaxis. Its diagnosis is histological, supported by immunohistochemistry. Its prognosis is often unfavorable, and characterized by the occurrence of metastases and recurrences. Because of the risk of secondary cancer that exists in any survivor of hereditary retinoblastoma, we must think of possible mucosal melanoma of the nasal sinus in these patients in cases of chronic epistaxis. The prognosis of this tumor depends on its early diagnosis and surgical treatment. PMID:26929670

  19. Malignant melanoma of the nasal septum, a rare tumor, occurring in a 54-year-old patient after hereditary retinoblastoma treatment

    PubMed Central

    Djiguimdé, Windinmanégdé Pierre; Diomandé, Ibrahim Abib; Bonnin, Nicolas; Saroul, Nicolas; Touré, Abdoulaye; Sanou, Jérôme; Sankara, Paté; Russier, Marc; Gilain, Laurent; Ahnoux-Zabsonré, Ahgbatouhabéba; Meda, Nonfounikoun; Bacin, Franck

    2016-01-01

    The authors report a case of a malignant melanoma of the nasal cavity that is a rare tumor and very aggressive, constituting 1% of all melanomas. It appeared in a patient 54 years after he was treated for a hereditary retinoblastoma. Its symptoms are nonspecific, and often marked by epistaxis. Its diagnosis is histological, supported by immunohistochemistry. Its prognosis is often unfavorable, and characterized by the occurrence of metastases and recurrences. Because of the risk of secondary cancer that exists in any survivor of hereditary retinoblastoma, we must think of possible mucosal melanoma of the nasal sinus in these patients in cases of chronic epistaxis. The prognosis of this tumor depends on its early diagnosis and surgical treatment. PMID:26929670

  20. Fibulin-3 is uniquely upregulated in malignant gliomas and promotes tumor cell motility and invasion.

    PubMed

    Hu, Bin; Thirtamara-Rajamani, Keerthi K; Sim, Hosung; Viapiano, Mariano S

    2009-11-01

    Malignant gliomas are highly invasive tumors with an almost invariably rapid and lethal outcome. Surgery and chemoradiotherapy fail to remove resistant tumor cells that disperse within normal tissue, which are a major cause for disease progression and therapy failure. Infiltration of the neural parenchyma is a distinctive property of malignant gliomas compared with other solid tumors. Thus, glioma cells are thought to produce unique molecular changes that remodel the neural extracellular matrix and form a microenvironment permissive for their motility. Here, we describe the unique expression and proinvasive role of fibulin-3, a mesenchymal matrix protein specifically upregulated in gliomas. Fibulin-3 is downregulated in peripheral tumors and is thought to inhibit tumor growth. However, we found fibulin-3 highly upregulated in gliomas and cultured glioma cells, although the protein was undetectable in normal brain or cultured astrocytes. Overexpression and knockdown experiments revealed that fibulin-3 did not seem to affect glioma cell morphology or proliferation, but enhanced substrate-specific cell adhesion and promoted cell motility and dispersion in organotypic cultures. Moreover, orthotopic implantation of fibulin-3-overexpressing glioma cells resulted in diffuse tumors with increased volume and rostrocaudal extension compared with controls. Tumors and cultured cells overexpressing fibulin-3 also showed elevated expression and activity of matrix metalloproteases, such as MMP-2/MMP-9 and ADAMTS-5. Taken together, our results suggest that fibulin-3 has a unique expression and protumoral role in gliomas, and could be a potential target against tumor progression. Strategies against this glioma-specific matrix component could disrupt invasive mechanisms and restrict the dissemination of these tumors. PMID:19887559

  1. Marked inhibition of tumor growth in a malignant glioma tumor model by a novel synthetic matrix metalloproteinase inhibitor AG3340.

    PubMed

    Price, A; Shi, Q; Morris, D; Wilcox, M E; Brasher, P M; Rewcastle, N B; Shalinsky, D; Zou, H; Appelt, K; Johnston, R N; Yong, V W; Edwards, D; Forsyth, P

    1999-04-01

    Synthetic matrix metalloproteinase (MMP) inhibitors have activity against a variety of tumors in preclinical models but have not been studied in gliomas. We determined the effect of AG3340, a novel synthetic MMP inhibitor with Ki values against gelatinases in the low picomolar range, on the growth of a human malignant glioma cell line (U87) in SCID-NOD mice. Mice were injected s.c. with U87 cells. Tumors were allowed to grow to a size of approximately 0.5 x 0.5 cm (after about 3 weeks), and the mice were randomized to receive either: (a) 100 mg/kg AG3340 in vehicle; or (b) vehicle control (0.5% carboxymethyl cellulose, 0.1% pluronic F68), both given daily i.p. Tumor area was measured twice weekly, and animals were sacrificed when moribund, or earlier if premorbid histology was examined. In vivo inhibition of tumor growth was profound, with AG3340 decreasing tumor size by 78% compared with controls after 31 days (when controls were sacrificed; P < 0.01, Wilcoxon test). Control animals survived 31 days after the i.p. injections began, and AG3340 mice survived 71 days, representing a >2-fold increase in survival associated with tumor growth delay. Histological examination found that AG3340-treated tumors were smaller, had lower rates of proliferation, and significantly less invasion than control-treated tumors. Hepatic or pulmonary metastases were not seen in either group. In a separate experiment, the tumors were smaller and sampled after a shorter duration of treatment; the changes in proliferation were more marked and occurred earlier than differences in tumor invasion between the two groups. Furthermore, in vitro cell growth was not inhibited at AG3340 concentrations of <1 mM. AG3340 plasma concentrations in vivo, 1 h after administration, ranged from 67 to 365 nM. Thus, AG3340 produced a profound inhibition of glioma tumor growth and invasion. AG3340 markedly increased survival in this in vivo glioma model. Treatment with AG3340 may be potentially useful in

  2. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers

    PubMed Central

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-01-01

    Abstract A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414–13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674–18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292–13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097–14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects. GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new

  3. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    PubMed

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  4. Lung and skeleton malignant tumor induction due to high let emitters

    SciTech Connect

    Buldakov, L.A.; Lyubchansky, E.R.; Kalmikova, Z.I.; Buhtoyarova, Z.M.

    1992-06-01

    Experimental studies show that malignant tumor induction is of primary importance in regard to the biological action of transuranium elements on the animal body. Clarification of quantitative relationship between these parameters for low-level radiation is aproblem to be solved by health physics. This report aims at analysis of the dose-response relationship following rat exposure to PU-239, Am-241, and NP-237 over a wide range of doses, and also at comparison between risk fact obtained experimentally and tose recommended by the ICRP. The biological effect of transuranium elements was investigated regarding malignant tumor incidence in rat bone for all the pathways of intake covered and in the lung for intakes of radionuclides into the respiratory system.

  5. Potential use of computer navigation in the treatment of primary benign and malignant tumors in children.

    PubMed

    Saidi, Kevan

    2012-06-01

    The treatment of benign and malignant primary bone tumors has progressed over time from relatively simple practice to complex resection and reconstruction techniques. Recently, computer-assisted orthopaedic surgery (CAOS) has been used to assist surgeons to enhance surgical precision in order to achieve these goals. Initially, software developed for CT-based spinal applications was used to perform simple intraoperative point localization. With advances in technique and software design, oncology surgeons have now performed joint sparing complex multiplanar osteotomies using combined CT and MRI image data with precision and accuracy. The purpose of this paper is to provide a review of the clinical progress to date, the different types of navigation available, methods for error management, and limitations of CAOS in the treatment of pediatric benign and malignant primary bone tumors. PMID:22488037

  6. AT9283, a novel aurora kinase inhibitor, suppresses tumor growth in aggressive B-cell lymphomas.

    PubMed

    Qi, Wenqing; Liu, Xiaobing; Cooke, Laurence S; Persky, Daniel O; Miller, Thomas P; Squires, Matthew; Mahadevan, Daruka

    2012-06-15

    Aurora kinases are oncogenic serine/threonine kinases that play key roles in regulating the mitotic phase of the eukaryotic cell cycle. Auroras are overexpressed in numerous tumors including B-cell non-Hodgkin's lymphomas and are validated oncology targets. AT9283, a pan-aurora inhibitor inhibited growth and survival of multiple solid tumors in vitro and in vivo. In this study, we demonstrated that AT9283 had potent activity against Aurora B in a variety of aggressive B-(non-Hodgkin lymphoma) B-NHL cell lines. Cells treated with AT9283 exhibited endoreduplication confirming the mechanism of action of an Aurora B inhibitor. Also, treatment of B-NHL cell lines with AT9283 induced apoptosis in a dose and time dependent manner and inhibited cell proliferation with an IC(50) < 1 μM. It is well known that inhibition of auroras (A or B) synergistically enhances the effects of microtubule targeting agents such as taxanes and vinca alkaloids to induce antiproliferation and apoptosis. We evaluated whether AT9283 in combination with docetaxel is more efficient in inducing apoptosis than AT9283 or docetaxel alone. At very low doses (5 nM) apoptosis was doubled in the combination (23%) compared to AT9283 or docetaxel alone (10%). A mouse xenograft model of mantle cell lymphoma demonstrated that AT9283 at 15 mg/kg and docetaxel (10 mg/kg) alone had modest anti-tumor activity. However, AT9283 at 20 mg/kg and AT9283 (15 or 20 mg/kg) plus docetaxel (10 mg/kg) demonstrated a statistically significant tumor growth inhibition and enhanced survival. Together, our results suggest that AT9283 plus docetaxel may represent a novel therapeutic strategy in B-cell NHL and warrant early phase clinical trial evaluation. PMID:21796626

  7. Multifrequency solid state YAG:Nd laser for diagnosis of malignant tumors

    NASA Astrophysics Data System (ADS)

    Lalayan, Asatur A.; Aidinian, Lusine E.; Galstian, Hayro M.

    1998-09-01

    The possibility of laser fluorescence diagnosis of malignant tumors with the aid of multifrequency (355, 440, 446, 532, 660, 670 nm) solid state YAG:Nd laser and the rise in accuracy of this method were discussed. Permitted for clinical employment sodium fluorescein has been used as human tumor-localizing dye. The fluorescence spectra of sodium fluorescein containing human normal tissue and breast, stomach, intestine, skin cancer during excitation with the third harmonics of YAG:Nd and with help of multichannel fiber-optic spectrofluorometer were studied. The contrast accumulation of the dye in tumors of different localization was investigated. The fluorescence spectra of chlorine e6, containing animal tissues at different excitation wavelength (355, 532 and 660 nm) were obtained. The pharmacokinetic behavior of chlorine e6, containing different organs and tumor tissues of rats, infected with Sarcoma-45 has been investigated.

  8. Cardiac Autotransplantation for Surgical Resection of a Primary Malignant Left Ventricular Tumor

    PubMed Central

    Reardon, Michael J.; Walkes, Jon-Cecil M.; DeFelice, Clement A.; Wojciechowski, Zbigniew

    2006-01-01

    Primary cardiac sarcomas are rare. In such tumors, surgical resection is sometimes considered necessary to correct obstruction of flow caused by the tumor and to accomplish complete resection. The anatomic difficulties associated with large, primary, intracavitary left-sided sarcomas have led us to use cardiac explantation, ex vivo tumor resection, and cardiac autotransplantation to meet the anatomic challenges of left atrial tumors. We report the case of a patient who had a large, primary, intracavitary, left ventricular sarcoma that was successfully removed by cardiac explantation and ex vivo reconstruction with use of the cardiac autotransplantation technique. This is the 1st report describing the use of cardiac autotransplantation to surgically resect an intracavitary left ventricular malignancy. PMID:17215979

  9. Comparison of percutaneous ablation technologies in the treatment of malignant liver tumors.

    PubMed

    Yu, Hyeon; Burke, Charles T

    2014-06-01

    Tumor ablation is a minimally invasive technique used to deliver chemical, thermal, electrical, or ultrasonic damage to a specific focal tumor in an attempt to achieve substantial tumor destruction or complete eradication. As the technology continues to advance, several image-guided tumor ablations have emerged to effectively manage primary and secondary malignancies in the liver. Percutaneous chemical ablation is one of the oldest and most established techniques for treating small hepatocellular carcinomas. However, this technique has been largely replaced by newer modalities including radiofrequency ablation, microwave ablation, laser-induced interstitial thermotherapy, cryoablation, high-intensity-focused ultrasound ablation, and irreversible electroporation. Because there exist significant differences in underlying technological bases, understanding each mechanism of action is essential for achieving desirable outcomes. In this article, the authors review the current state of each ablation method including technological and clinical considerations. PMID:25071303

  10. Characterization of Ex Vivo Expanded Tumor Infiltrating Lymphocytes from Patients with Malignant Melanoma for Clinical Application

    PubMed Central

    Junker, Niels; thor Straten, Per; Andersen, Mads Hald; Svane, Inge Marie

    2011-01-01

    Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have established a method for expanding TILs to clinical relevant quantities in two steps with in 8 weeks. Further characterization of expanded TILs revealed an oligoclonal composition of T-cells with an effector memory like phenotype. When autologous tumor was available, TILs showed specific activity in all patients tested. TIL cultures contained specificity towards tumor cells as well as peptides derived from tumor-associated antigens (TAAs) during expansion procedures. PMID:21773037

  11. [Changes in the phosphoinositide metabolism in the blood and tissues of benign and malignant uterine tumors].

    PubMed

    Damirov, M M; Sliusar', N N; Kulakov, V I; Bakuleva, I P; Matruk, T A

    1995-01-01

    Measurements of phosphoinositide levels in the blood, immunocompetent cells, and tumors of 105 patients with uterine myomas, 24 patients with cancer of the corpus uteri, and 17 ones with uterine sarcoma showed that the parameters of phosphoinositide metabolism in the blood of patients with tumors of the uterus reliably differed from those in healthy women. The content of phosphatidylinosites and other phosphoinositide fractions in patients with uterine myomas reliably differed from those in patients with malignant tumors of the uterus, this permitting the use of such measurements in the differential diagnosis. Phosphoinositide mechanism of development of tumors of the uterus is discussed, which is related to the "new" phosphoinositides and secondary messengers directly participating in transfer of cell growth signals. PMID:7785738

  12. Comparison of Percutaneous Ablation Technologies in the Treatment of Malignant Liver Tumors

    PubMed Central

    Yu, Hyeon; Burke, Charles T.

    2014-01-01

    Tumor ablation is a minimally invasive technique used to deliver chemical, thermal, electrical, or ultrasonic damage to a specific focal tumor in an attempt to achieve substantial tumor destruction or complete eradication. As the technology continues to advance, several image-guided tumor ablations have emerged to effectively manage primary and secondary malignancies in the liver. Percutaneous chemical ablation is one of the oldest and most established techniques for treating small hepatocellular carcinomas. However, this technique has been largely replaced by newer modalities including radiofrequency ablation, microwave ablation, laser-induced interstitial thermotherapy, cryoablation, high-intensity–focused ultrasound ablation, and irreversible electroporation. Because there exist significant differences in underlying technological bases, understanding each mechanism of action is essential for achieving desirable outcomes. In this article, the authors review the current state of each ablation method including technological and clinical considerations. PMID:25071303

  13. Tumor-induced solid stress activates β-catenin signaling to drive malignant behavior in normal, tumor-adjacent cells

    PubMed Central

    Ou, Guanqing; Weaver, Valerie Marie

    2016-01-01

    Recent work by Fernández-Sánchez and coworkers examining the impact of applied pressure on the malignant phenotype of murine colon tissue in vivo revealed that mechanical perturbations can drive malignant behavior in genetically normal cells. Their findings build upon an existing understanding of how the mechanical cues experienced by cells within a tissue become progressively modified as the tissue transforms. Using magnetically stimulated ultra-magnetic liposomes to mimic tumor growth -induced solid stress, Fernández-Sánchez and coworkers were able to stimulate β-catenin to promote the cancerous behavior of both a normal and genetically modified colon epithelium. In this perspective, we discuss their findings in the context of what is currently known regarding the role of the mechanical landscape in cancer progression and β-catenin as a mechanotransducer. We review data that suggest that mechanically regulated activation of β-catenin fosters development of a malignant phenotype in tissue and predict that mechanical cues may contribute to tumor heterogeneity. PMID:26439949

  14. Prolonged Survival of a Patient With Pelvic Recurrence of Ovarian Malignant Mixed Mullerian Tumor After Chemoradiotherapy

    PubMed Central

    Homaei Shandiz, Fatemeh; Kadkhodayan, Sima; Hsanzade Mofrad, Malihe; Yousefi Roodsari, Zohre; Sharifi Sistani, Noorieh; Nabizadeh Marvast, Majid; Sadeghei, Mahbobe

    2014-01-01

    Introduction: Malignant Mixed Mullerian Tumor (MMMT) is a very rare tumor, accounting for less than 1% of all ovarian cancers. Case Presentation: We present a 64-year-old woman with stage III MMMT of ovary that was treated with platinum-based chemotherapy after optimal cytoreductive surgery. After 25 months of being disease free, she had a pelvic recurrence and a good response to chemoradiotherapy. Conclusions: Optimal cytoreductive surgery and chemotherapy may be the best treatment in MMMT but more discussion and experiences are needed regarding the effectiveness of radiotherapy. PMID:25593719

  15. Spinal Tuberculosis (Pott's disease) Mimicking Paravertebral Malignant Tumor in a Child Presenting with Spinal Cord Compression

    PubMed Central

    Emir, Suna; Erdem, Arzu Y; Demir, Haci A; Kaçar, Ayper; Tunç, Bahattin

    2012-01-01

    Paravertebral tumors may interfere with the radiological and clinical features of spinal tuberculosis. We report a case of a 3-year-old boy with spinal tuberculosis who was initially misdiagnosed as having a paraspinal tumor. The diagnosis of tuberculosis was made on the basis of intraoperative findings and confirmed by histopathology. This case highlights the importance of awareness of the different radiographic features of spinal tuberculosis, which can mimic a spinal malignancy. In order to avoid delayed diagnosis, pediatricians and radiologists must be aware of spinal tuberculosis, which may interfere with other clinical conditions. PMID:23439455

  16. Malignant mesenchymal tumors in two white-tailed jack rabbits (Lepus townsendii).

    PubMed

    Jardine, Claire; Wobeser, Gary A; Simko, Elemir

    2004-10-01

    Two white-tailed jack rabbits (Lepus townsendii) with proliferative lesions in their internal organs were submitted to the Canadian Cooperative Wildlife Health Centre (Saskatoon, Saskatchewan, Canada) for necropsy because of concern that dogs that had contact with the hares might have been exposed to an infectious disease. In both hares, the primary diagnosis was neoplasia. One hare had metastatic leiomyosarcoma and uterine fibroma, the other had metastatic mesenchymal tumors involving the liver and mesentery. These cases represent the only reports of malignant mesenchymal tumors in white-tailed jack rabbits that we have found in the literature. PMID:15650095

  17. Fatal Pulmonary Tumor Embolic Microangiopathy in Young Lady without Known Primary Malignancy

    PubMed Central

    Al-Azem, M. Ali; Hanafy, Ahmed; Nakkar, Talal

    2014-01-01

    Pulmonary embolism (PE) is a common cause of morbidity and mortality in hospitalized patients. Malignancy, prolonged recumbence, and chemotherapy are renowned risk factors for development of clinically significant PE. Cancer exerts a multitude of pathophysiological processes, for example, hypercoagulability and abnormal vessels with sluggish circulation that can lead to PE. One of the peculiar characteristics of tumor cells is their ability to reach the circulation and behave as blood clot—not a metastasis-occluding the pulmonary circulation. We present a case of fatal pulmonary embolism diagnosed histologically to be due to tumor cell embolism. PMID:25478243

  18. Association between tumor size and Breslow's thickness in malignant melanoma: a cross-sectional, multicenter study.

    PubMed

    Moreno-Ramírez, David; Ojeda-Vila, Teresa; Ríos-Martín, Juan J; Nieto-García, Adoración; Ferrándiz, Lara

    2015-10-01

    The aim of this study was to assess the potential role of tumor diameter in explaining variations in tumoral invasion and in the initial prognosis for patients with malignant melanoma (MM). This was a multicenter, cross-sectional study that recruited between 2000 and 2009 patients with primary in-situ MM (Tis) and invasive cutaneous MM. Tis and MMs with a Breslow's thickness less than 1 mm (T1) were grouped (Tis-T1) and tumors with a Breslow's thickness 1 mm or more were also analyzed in combination (T2-T4). The tumor size was measured after routine formalin tissue fixation. Primary outcomes were the correlation between Breslow's thickness and tumor size, and the role of tumor size in explaining variations in Breslow's thickness, as assessed by the Pearson correlation test and logistic binary regression with calculation of the odds ratios. A total of 1610 MM patients were included and analyzed. The Pearson correlation between tumor size and Breslow's thickness was 0.42, with a determination coefficient of R2=0.18 (P>0.01). Correlations between tumor size and thickness were stronger in patients aged 30-60 years (r=0.42, R2=0.1764, P<0.001) and in tumors arising on the upper limbs (r=0.55, R2=0.3025). The odds ratio of identifying a T2-T4 stage MM in patients with tumors larger than 1 cm in size was 2.76 (95% confidence interval 2.25-3.39, P<0.001). Even though a direct, positive, and strong association between tumoral size and Breslow's thickness might be expected in melanoma cases, the strength of this association has been moderate. Tumor size explains a low burden of the variation observed in the Breslow's thickness. PMID:26237766

  19. IgD plasma cell leukemia and uterine malignant mixed Müllerian tumor.

    PubMed

    Berneman, Z N; Mathijs, R; Bultinck, J M; Mahler, C

    1984-01-01

    The case of a 74-year-old female with an IgD kappa plasma cell leukemia is presented. In contrast to the majority of the cases in the literature, this patient responded rather well to melphalan and prednisolone and survived for 20 months after starting treatment. Another remarkable feature was the simultaneous occurrence of a double uterine neoplasm, a malignant mixed Müllerian tumor of the homologous variety (also called carcinosarcoma). PMID:6433634

  20. [Malignant ovarian tumors in childhood and adolescence in Novi Sad (1946-1989)].

    PubMed

    Berić, B; Gebauer, E; Dordević, M; Konstantinidis, N; Stojić, S

    1991-01-01

    In the period from 1946-1989, at the Department of Gynecology and Obstetrics University of Novi Sad, 79 ovarian tumors in children and adolescents were registered. There were 10 (12.6%) malignant tumours. The most common were dysgerminoma and carcinoma (total 6-7.6%). The treatment depended on the extent of the disease at the time of diagnosis (surgery, irradiation, chemotherapy or combination). PMID:1749284

  1. Detection and Identification of Hematologic Malignancies and Solid Tumors by an Electrochemical Technique

    PubMed Central

    Zhang, Bowen; Zhang, Xiaoping; Wang, Xuemei; Cheng, Jian; Chen, Baoan

    2016-01-01

    Purpose Develop and evaluate an electrochemical method to identify healthy individuals, malignant hematopathic patients and solid tumor patients by detecting the leukocytes in whole-blood. Methods A total of 114 individual blood samples obtained from our affiliated hospital in China (June 2015- August 2015) were divided into three groups: healthy individuals (n = 35), hematologic malignancies (n = 41) and solid tumors (n = 38). An electrochemical workstation system was used to measure differential pulse voltammetry due to the different electrochemical behaviors of leukocytes in blood samples. Then, one-way analysis of variance (ANOVA) was applied to analyze the scanning curves and to compare the peak potential and peak current. Results The scanning curve demonstrated the specific electrochemical behaviors of the blank potassium ferricyanide solution and that mixed with blood samples in different groups. Significant differences in mean peak potentials of mixture and shifts (ΔEp (mV)) were observed of the three groups (P< = 0.001). 106.00±9.00 and 3.14±7.48 for Group healthy individuals, 120.90±11.18 and 18.10±8.81 for Group hematologic malignancies, 136.84±11.53 and 32.89±10.50 for Group solid tumors, respectively. In contrast, there were no significant differences in the peak currents and shifts. Conclusions The newly developed method to apply the electrochemical workstation system to identify hematologic malignancies and solid tumors with good sensitivity and specificity might be effective, suggesting a potential utility in clinical application. PMID:27115355

  2. STAT3 in Epithelial Cells Regulates Inflammation and Tumor Progression to Malignant State in Colon1

    PubMed Central

    Nguyen, Andrew V; Wu, Yuan-Yuan; Liu, Qiang; Wang, Donghai; Nguyen, Stephanie; Loh, Ricky; Pang, Joey; Friedman, Kenneth; Orlofsky, Amos; Augenlicht, Leonard; Pollard, Jeffrey W; Lin, Elaine Y

    2013-01-01

    Chronic inflammation is an important risk factor for the development of colorectal cancer; however, the mechanism of tumorigenesis especially tumor progression to malignancy in the inflamed colon is still unclear. Our study shows that epithelial signal transducer and activator of transcription 3 (STAT3), persistently activated in inflamed colon, is not required for inflammation-induced epithelial overproliferation and the development of early-stage tumors; however, it is essential for tumor progression to advanced malignancy. We found that one of the mechanisms that epithelial STAT3 regulates in tumor progression might be to modify leukocytic infiltration in the large intestine. Activation of epithelial STAT3 promotes the infiltration of the CD8+ lymphocyte population but inhibits the recruitment of regulatory T (Treg) lymphocytes. The loss of Stat3 in epithelial cells promoted the expression of cytokines/chemokines including CCL19, CCL28, and RANTES, which are known to be able to recruit Treg lymphocytes. Linked to these changes was the pathway mediated by sphingosine 1-phosphate receptor 1 and sphingosine 1-phosphate kinases, which is activated in colonic epithelial cells in inflamed colon with functional STAT3 but not in epithelial cells deleted of STAT3. Our data suggest that epithelial STAT3 plays a critical role in inflammation-induced tumor progression through regulation of leukocytic recruitment especially the infiltration of Treg cells in the large intestine. PMID:24027425

  3. [De novo malignant tumors following liver transplantation. A single-center experience in Argentina].

    PubMed

    Antinucci, Florencia; Anders, Margarita; Orozco, Federico; Mella, José; Cobos, Manuel; McCormack, Lucas; Mastai, Ricardo

    2015-01-01

    The aim of the present study was to evaluate the incidence and clinical features of de novo tumors in patients undergoing liver transplantation in our center as well as to assess survival. We retrospectively analyzed 168 liver transplantations (159 patients) performed from May 2006 to May 2014. The incidence of de novo tumors was 7.5% (n = 12). The mean age at diagnosis was 63 ± 7 years. The most frequent neoplasms were non melanoma skin tumors and adenocarcinomas. Fifty percent of the tumors developed in the second and third year after transplantation. Type of immunosuppression did not influence tumoral type, although most patients receive tacrolimus in combination with mycofenolate and/or corticoids. The mean duration of follow-up after diagnosis of the tumor was 25 ± 29 months (range 0-76) and the mortality was 41%. The actuarial probability of survival at 1 and 5 years was 83 and 55%, respectively. De novo tumors are frequent after liver transplantation and their clinical course differs from that in the general population. Because their clinical course is more aggressive, regular follow up of these patients is essential for early diagnosis. PMID:25637895

  4. Malignant Drosophila tumors interrupt insulin signaling to induce cachexia-like wasting.

    PubMed

    Figueroa-Clarevega, Alejandra; Bilder, David

    2015-04-01

    Tumors kill patients not only through well-characterized perturbations to their local environment but also through poorly understood pathophysiological interactions with distant tissues. Here, we use a Drosophila tumor model to investigate the elusive mechanisms underlying such long-range interactions. Transplantation of tumors into adults induces robust wasting of adipose, muscle, and gonadal tissues that are distant from the tumor, phenotypes that resemble the cancer cachexia seen in human patients. Notably, malignant, but not benign, tumors induce peripheral wasting. We identify the insulin growth factor binding protein (IGFBP) homolog ImpL2, an antagonist of insulin signaling, as a secreted factor mediating wasting. ImpL2 is sufficient to drive tissue loss, and insulin activity is reduced in peripheral tissues of tumor-bearing hosts. Importantly, knocking down ImpL2, specifically in the tumor, ameliorates wasting phenotypes. We propose that the tumor-secreted IGFBP creates insulin resistance in distant tissues, thus driving a systemic wasting response. PMID:25850672

  5. Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD

    PubMed Central

    Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K.; Miyazaki, Hideki; Michael, Iacovos P.; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

    2016-01-01

    Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis. PMID:26831065

  6. [Preserving ovarian function in the treatment of epithelial and special (other) malignant ovarian tumors].

    PubMed

    Kolstad, P

    1987-10-01

    About 90% of malignant tumors of the ovary in Scandinavia develop from the germinal epithelium. There are great differences in the incidence rates between countries in the Western world and in Africa and Asia. The WHO classification of ovarian malignancies is generally used. The epithelial tumors comprise the serous, mucinous, endometrioid, clear cell, undifferentiated and mixed true carcinomas. In addition, borderline lesions of especially the serous and mucinous types are of interest when the question of preservation of ovarian function comes into notice. Conservative surgery, which means removal of only the afflicted ovary should be restricted to young women of the childbearing age who want to preserve the possibility of becoming pregnant. However, certain prerequisites must be fulfilled. The tumor must be located to one ovary only (Stage Ia) and must be either a borderline lesion or a Grade 1 true carcinoma of either the serous, mucinous or endometrioid type. There must be no ascites and peritoneal washings must be negative for cancer cells. Germ cell tumors are usually found in young women. Only the dysgerminomas are regularly bilateral in 10-15% of the cases. All other germ cell tumors are rarely bilateral. But both in borderline lesions, Grade 1 true carcinomas, and in germ cell tumors, a biopsy of the normal looking contralateral ovary should always be performed. Endodermal sinus tumors and immature teratomas may well be treated conservatively by surgery, but modern triple chemotherapy (VAC, PVB) must be added. Granulosa theca cell tumors are bilateral in only about 5% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2824278

  7. Increased PADI4 expression in blood and tissues of patients with malignant tumors

    PubMed Central

    2009-01-01

    Background Peptidylarginine deiminase type 4 (PAD4/PADI4) post-translationally converts peptidylarginine to citrulline. Recent studies suggest that PADI4 represses expression of p53-regulated genes via citrullination of histones at gene promoters. Methods Expression of PADI4 was investigated in various tumors and non-tumor tissues (n = 1673) as well as in A549, SKOV3 and U937 tumor cell lines by immunohistochemistry, real-time PCR, and western blot. Levels of PADI4 and citrullinated antithrombin (cAT) were investigated in the blood of patients with various tumors by ELISA (n = 1121). Results Immunohistochemistry detected significant PADI4 expression in various malignancies including breast carcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cancer cells, colorectal adenocarcinomas, renal cancer cells, ovarian adenocarcinomas, endometrial carcinomas, uterine adenocarcinomas, bladder carcinomas, chondromas, as well as other metastatic carcinomas. However, PADI4 expression was not observed in benign leiomyomas of stomach, uterine myomas, endometrial hyperplasias, cervical polyps, teratomas, hydatidiform moles, trophoblastic cell hyperplasias, hyroid adenomas, hemangiomas, lymph hyperplasias, schwannomas, neurofibromas, lipomas, and cavernous hemangiomas of the liver. Additionally, PADI4 expression was not detected in non-tumor tissues including cholecystitis, cervicitis and synovitis of osteoarthritis, except in certain acutely inflamed tissues such as in gastritis and appendicitis. Quantitative PCR and western blot analysis showed higher PADI4 expression in gastric adenocarcinomas, lung adenocarcinomas, hepatocellular carcinomas, esophageal squamous cell cancers and breast cancers (n = 5 for each disease) than in the surrounding healthy tissues. Furthermore, western blot analysis detected PADI4 expression in cultured tumor cell lines. ELISA detected increased PADI4 and cAT levels in the blood of patients with various malignant tumors

  8. Downregulation of SUN2, a novel tumor suppressor, mediates miR-221/222-induced malignancy in central nervous system embryonal tumors.

    PubMed

    Hsieh, Tsung-Han; Chien, Chen-Li; Lee, Yu-Hsiu; Lin, Chen-I; Hsieh, Jui-Yu; Chao, Meng-En; Liu, Da-Jung; Chu, Shing-Shiung; Chen, Wan; Lin, Shih-Chieh; Ho, Donald Ming-Tak; Liu, Ren-Shyan; Lin, Chi-Hung; Wong, Tai-Tong; Wang, Hsei-Wei

    2014-10-01

    Embryonal tumors of the central nervous system represent a highly malignant tumor group of medulloblastoma (MB), atypical teratoid/rhabdoid tumor (AT/RT) and primitive neuroectodermal tumor that frequently afflict children. AT/RT is often misdiagnosed as MB/primitive neuroectodermal tumor but with higher recurrence and lower survival rates. Pathogenesis of AT/RT is largely unknown. In this study, we report both the miRNome and transcriptome traits in AT/RT and MB by using small RNA sequencing and gene expression microarray analyses. Our findings demonstrate that the miR-221/222-encoded micro RNAs are abundantly expressed in AT/RT but not in MB, which contribute substantially to the malignancy of embryonal tumors. miR-221/222 targeted SUN2, a newly discovered tumor suppressor, directly to increase cell proliferation and tumor malignancy in vitro and in vivo. Immunohistochemistry against SUN2 in a tissue microarray of 33 AT/RT and 154 MB tumor specimens also detected less SUN2 protein in AT/RT. Collectively, this study uncovers a novel tumor suppressor, SUN2, plays a critical role in miR-221/222-mediated AT/RT malignancy as well as supports miR-221/222 and SUN2 represent new promising targets for more active therapies in AT/RT. In addition, our miRNome and transcriptome data also provide a roadmap for further embryonal tumor research. PMID:24832085

  9. Dynamic holographic endoscopy--ex vivo investigations of malignant tumors in the human stomach.

    PubMed

    Avenhaus, Wolfgang; Kemper, Björn; Knoche, Sabine; Domagk, Dirk; Poremba, Christopher; von Bally, Gert; Domschke, Wolfram

    2005-01-01

    Laser holographic interferometry is based on the superimposition of the holograms of different motional states of an object on a single holographic storing medium. Using a combination of holographic interferometry and endoscopic imaging, we tried to detect areas of focally disturbed tissue elasticity in gastric cancer preparations. By connecting a mobile electronic speckle pattern interferometry (ESPI) camera system (light source: double frequency Nd:YAG laser, lambda = 532 nm) to different types of endoscopes, ex vivo experiments were performed on ten formalin fixed human stomachs, nine containing adenocarcinomas and one with a gastric lymphoma. Linking the endoscopic ESPI camera complex to a fast image processing system, the method of double pulse exposure image subtraction was applied at a video frame rate of 12.5 Hz. Speckle correlation patterns and corresponding phase difference distributions resulting from gastric wall deformation by gentle touch with a guide wire were analyzed. Tumor-free gastric areas showed high-contrast concentric fringes around the point of stimulation. In contrast, fringe patterns and filtered phase difference distributions corresponding to the areas of malignancy in all the cases were characterized by largely parallel lines, indicating that stimulation of rigid tumor tissue primarily led to tilting. Our ex vivo investigations of malignant gastric tumors show that the application of dynamic holographic endoscopy makes it possible to distinguish areas of malignancy from surrounding healthy tissue based on the differences in tissue elasticity. PMID:15726298

  10. Loss of the respiratory enzyme citrate synthase directly links the Warburg effect to tumor malignancy

    PubMed Central

    Lin, Chin-Chih; Cheng, Tsung-Lin; Tsai, Wen-Hui; Tsai, Hui-Ju; Hu, Keng-Hsun; Chang, Hao-Chun; Yeh, Chin-Wei; Chen, Ying-Chou; Liao, Ching-Chun; Chang, Wen-Tsan

    2012-01-01

    To investigate whether altered energy metabolism induces the Warburg effect and results in tumor malignancy, the respiratory enzyme citrate synthase (CS) was examined, silenced, and the effects analyzed. In human cervical carcinoma cells, RNAi-mediated CS knockdown induced morphological changes characteristic of the epithelial-mesenchymal transition (EMT). This switch accelerated cancer cell metastasis and proliferation in in vitro assays and in vivo tumor xenograft models. Notably, CS knockdown cells exhibited severe defects in respiratory activity and marked decreases in ATP production, but great increases in glycolytic metabolism. This malignant progression was due to activation of EMT-related regulators; altered energy metabolism resulted from deregulation of the p53/TIGAR and SCO2 pathways. This phenotypic change was completely reversed by p53 reactivation via treatment with proteasome inhibitor MG132 or co-knockdown of E3 ligase HDM2 and partially suppressed by ATP treatment. This study directly links the Warburg effect to tumor malignancy via induction of the EMT phenotype. PMID:23139858

  11. Percutaneous fiducial marker placement prior to stereotactic body radiotherapy for malignant liver tumors: an initial experience

    PubMed Central

    Ohta, Kengo; Shimohira, Masashi; Murai, Taro; Nishimura, Junichi; Iwata, Hiromitsu; Ogino, Hiroyuki; Hashizume, Takuya; Shibamoto, Yuta

    2016-01-01

    The aim of this study was to describe our initial experience with a gold flexible linear fiducial marker and to evaluate the safety and technical and clinical efficacy of stereotactic body radiotherapy using this marker for malignant liver tumors. Between July 2012 and February 2015, 18 patients underwent percutaneous fiducial marker placement before stereotactic body radiotherapy for malignant liver tumors. We evaluated the technical and clinical success rates of the procedure and the associated complications. Technical success was defined as successful placement of the fiducial marker at the target site, and clinical success was defined as the completion of stereotactic body radiotherapy without the marker dropping out of position. All 18 fiducial markers were placed successfully, so the technical success rate was 100% (18/18). All 18 patients were able to undergo stereotactic body radiotherapy without marker migration. Thus, the clinical success rate was 100% (18/18). Slight pneumothorax occurred as a minor complication in one case. No major complications such as coil migration or bleeding were observed. The examined percutaneous fiducial marker was safely placed in the liver and appeared to be useful for stereotactic body radiotherapy for malignant liver tumors. PMID:26826200

  12. Incidence of malignant skin tumors in 14,140 patients after grenz-ray treatment for benign skin disorders

    SciTech Connect

    Lindeloef, B.E.; Eklund, G.

    1986-12-01

    During the years 1949 to 1975, 14,237 patients received therapeutic doses of grenz rays for the treatment of benign skin disorders such as chronic eczema, psoriasis, and warts. The records of 14,140 of these patients (99.3%) formed the basis for an epidemiologic study of the incidence of skin malignancies in this population. Information about the patients, diagnoses, doses, and sites of treatment was obtained from separate records. The follow-up time was 15 years on the average. We searched the Swedish Cancer Registry, Stockholm, for records reporting the incidence of malignant skin tumors in the study population (incidences of basal cell carcinoma are not registered). The expected number of malignancies was calculated on the basis of age- and sex-standardized incidence data from the Swedish Cancer Registry. In 58 patients, a malignant skin tumor was diagnosed more than five years after grenz-ray therapy had first been administered. Nineteen patients had malignant melanomas, and 39 patients had other malignant skin tumors. The expected number of melanomas was 17.8, and that of other malignant skin tumors was 26.9. None of the patients with melanomas, and only eight of the patients with other malignant skin tumors, had received grenz-ray therapy at the site of the tumor. Six of these eight patients had also been exposed to other known carcinogens. Four hundred eighty-one patients had received an accumulated high dose of grenz rays (greater than or equal to 10 000 rad (greater than or equal to 100 Gy)) on one and the same area. No malignancies were found on those areas. Although we cannot exclude grenz-ray therapy as a risk factor in the development of nonmelanoma skin malignancies, this risk, if any, is small, if recommendations for therapy are followed.

  13. [An analysis of 117 cases of patients who died from tumor recurrence or from the progression of ovarian malignancies].

    PubMed

    Kano, T; Sakakibara, K; Kamiya, N; Mizuno, K; Miyazaki, T; Ohta, M; Tomoda, Y

    1987-10-01

    Out of 403 patients with ovarian with malignancies during 1978 to, 1985, 117 (29.0%) died from the progression of a non-curative cancer (56 cases, 47.9%) or from a cancer recurrence (61 cases, 52.1%). The mean survival rate 117 cases was 13.4 months, of which 103 (88.0%) cases concerned patients who died within 2 years and 114 (97.4%) who died within 3 years. A histological analysis revealed that patients with a serous or an endometrial cancer had a longer survival rate than others. Among 61 recurrent cases, 59 (96.7%) fell into recurrence within 2 years. Regarding the relationship between a recurrent of cancer and its prognosis, patients with a recurrence of an ascitic or a metastatic disease had a poorer prognosis than patients with a pelvic or an abdominal mass. An aggressive operation, such as a resection of a recurrent tumor, even if small in volume, led to a better prognostic result than no therapy. PMID:3694804

  14. Horizontal Transmission of Malignancy: In-Vivo Fusion of Human Lymphomas with Hamster Stroma Produces Tumors Retaining Human Genes and Lymphoid Pathology

    PubMed Central

    Goldenberg, David M.; Gold, David V.; Loo, Meiyu; Liu, Donglin; Chang, Chien-Hsing; Jaffe, Elaine S.

    2013-01-01

    We report the in-vivo fusion of two Hodgkin lymphomas with golden hamster cheek pouch cells, resulting in serially-transplanted (over 5–6 years) GW-532 and GW-584 heterosynkaryon tumor cells displaying both human and hamster DNA (by FISH), lymphoma-like morphology, aggressive metastasis, and retention of 7 human genes (CD74, CXCR4, CD19, CD20, CD71, CD79b, and VIM) out of 24 tested by PCR. The prevalence of B-cell restricted genes (CD19, CD20, and CD79b) suggests that this uniform population may be the clonal initiating (malignant) cells of Hodgkin lymphoma, despite their not showing translation to their respective proteins by immunohistochemical analysis. This is believed to be the first report of in-vivo cell-cell fusion of human lymphoma and rodent host cells, and may be a method to disclose genes regulating both organoid and metastasis signatures, suggesting that the horizontal transfer of tumor DNA to adjacent stromal cells may be implicated in tumor heterogeneity and progression. The B-cell gene signature of the hybrid xenografts suggests that Hodgkin lymphoma, or its initiating cells, is a B-cell malignancy. PMID:23405135

  15. Spatially- and temporally-controlled postnatal p53 knockdown cooperates with embryonic Schwann cell precursor Nf1 gene loss to promote malignant peripheral nerve sheath tumor formation

    PubMed Central

    Hirbe, Angela C.; Dahiya, Sonika; Friedmann-Morvinski, Dinorah; Verma, Inder M.; Clapp, D. Wade; Gutmann, David H.

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive sarcomas that arise sporadically or in association with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. In individuals with NF1, MPNSTs are hypothesized to arise from Nf1-deficient Schwann cell precursor cells following the somatic acquisition of secondary cooperating genetic mutations (e.g., p53 loss). To model this sequential genetic cooperativity, we coupled somatic lentivirus-mediated p53 knockdown in the adult right sciatic nerve with embryonic Schwann cell precursor Nf1 gene inactivation in two different Nf1 conditional knockout mouse strains. Using this approach, ∼60% of mice with Periostin-Cre-mediated Nf1 gene inactivation (Periostin-Cre; Nf1flox/flox mice) developed tumors classified as low-grade MPNSTs following p53 knockdown (mean, 6 months). Similarly, ∼70% of Nf1+/− mice with GFAP-Cre-mediated Nf1 gene inactivation (GFAP-Cre; Nf1flox/null mice) developed low-grade MPNSTs following p53 knockdown (mean, 3 months). In addition, wild-type and Nf1+/− mice with GFAP-Cre-mediated Nf1 loss develop MPNSTs following somatic p53 knockout with different latencies, suggesting potential influences of Nf1+/− stromal cells in MPNST pathogenesis. Collectively, this new MPNST model system permits the analysis of somatically-acquired events as well as tumor microenvironment signals that potentially cooperate with Nf1 loss in the development and progression of this deadly malignancy. PMID:26859681

  16. Outgrowth of drug-resistant carcinomas expressing markers of tumor aggression after long term TβRI/II kinase inhibition with LY2109761

    PubMed Central

    Connolly, Erin C.; Saunier, Elise F.; Quigley, David; Luu, Minh Thu; Sapio, Angela De; Hann, Byron; Yingling, Jonathan M.; Akhurst, Rosemary J.

    2011-01-01

    Transforming Growth Factor β (TGF-β) is produced excessively by many solid tumors and can drive malignant progression through multiple effects on the tumor cell and microenvironment. TGF-β signaling pathway inhibitors have shown efficacy in pre-clinical models of metastatic cancer. Here we investigated the effect of systemic LY2109761, a type I /II receptor (TβRI/TβRII) kinase inhibitor, in both a tumor allograft model and in the mouse skin model of de novo chemically-induced carcinogenesis in vivo. Systemic LY2109761 administration disrupted tumor vascular architecture and reduced myofibroblast differentiation of E4 skin carcinoma cells in a tumor allograft. In the 7,12 dimethyl-benzanthracene plus phorbol-myristate-acetate -induced skin chemical carcinogenesis model, acute dosing of established naïve primary carcinomas with LY2109761 (100mg/Kg) every eight hours for ten days (100mg/kg) diminished P-Smad2 levels and marginally decreased the expression of inflammatory and invasive markers. Sustained exposure to LY2109761 (100mg/kg/day) throughout the tumor outgrowth phase had no effect on carcinoma latency or incidence. However, molecular analysis of resultant carcinomas by microarray gene expression, Western blot and immunohistochemistry suggests that long term LY2109761 exposure leads to the outgrowth of carcinomas with elevated P-Smad2 levels that do not respond to drug. This is the first description of acquired resistance to a small molecule inhibitor of the TGF-βRI/II kinase. Resultant carcinomas were more aggressive and inflammatory in nature, with delocalized E-Cadherin and elevated expression of Il23a, laminin V and MMPs. Therefore, TGF-β inhibitors might be clinically useful for applications requiring acute administration, but chronic patient exposure to such drugs should be undertaken with caution. PMID:21282335

  17. Methylation-based classification of benign and malignant peripheral nerve sheath tumors.

    PubMed

    Röhrich, Manuel; Koelsche, Christian; Schrimpf, Daniel; Capper, David; Sahm, Felix; Kratz, Annekathrin; Reuss, Jana; Hovestadt, Volker; Jones, David T W; Bewerunge-Hudler, Melanie; Becker, Albert; Weis, Joachim; Mawrin, Christian; Mittelbronn, Michel; Perry, Arie; Mautner, Victor-Felix; Mechtersheimer, Gunhild; Hartmann, Christian; Okuducu, Ali Fuat; Arp, Mirko; Seiz-Rosenhagen, Marcel; Hänggi, Daniel; Heim, Stefanie; Paulus, Werner; Schittenhelm, Jens; Ahmadi, Rezvan; Herold-Mende, Christel; Unterberg, Andreas; Pfister, Stefan M; von Deimling, Andreas; Reuss, David E

    2016-06-01

    The vast majority of peripheral nerve sheath tumors derive from the Schwann cell lineage and comprise diverse histological entities ranging from benign schwannomas and neurofibromas to high-grade malignant peripheral nerve sheath tumors (MPNST), each with several variants. There is increasing evidence for methylation profiling being able to delineate biologically relevant tumor groups even within the same cellular lineage. Therefore, we used DNA methylation arrays for methylome- and chromosomal profile-based characterization of 171 peripheral nerve sheath tumors. We analyzed 28 conventional high-grade MPNST, three malignant Triton tumors, six low-grade MPNST, four epithelioid MPNST, 33 neurofibromas (15 dermal, 8 intraneural, 10 plexiform), six atypical neurofibromas, 43 schwannomas (including 5 NF2 and 5 schwannomatosis associated cases), 11 cellular schwannomas, 10 melanotic schwannomas, 7 neurofibroma/schwannoma hybrid tumors, 10 nerve sheath myxomas and 10 ganglioneuromas. Schwannomas formed different epigenomic subgroups including a vestibular schwannoma subgroup. Cellular schwannomas were not distinct from conventional schwannomas. Nerve sheath myxomas and neurofibroma/schwannoma hybrid tumors were most similar to schwannomas. Dermal, intraneural and plexiform neurofibromas as well as ganglioneuromas all showed distinct methylation profiles. Atypical neurofibromas and low-grade MPNST were indistinguishable with a common methylation profile and frequent losses of CDKN2A. Epigenomic analysis finds two groups of conventional high-grade MPNST sharing a frequent loss of neurofibromin. The larger of the two groups shows an additional loss of trimethylation of histone H3 at lysine 27 (H3K27me3). The smaller one retains H3K27me3 and is found in spinal locations. Sporadic MPNST with retained neurofibromin expression did not form an epigenetic group and most cases could be reclassified as cellular schwannomas or soft tissue sarcomas. Widespread immunohistochemical loss

  18. Treatment of locally advanced, high-grade, malignant tumors of major salivary glands

    SciTech Connect

    Reddy, S.P.; Marks, J.E.

    1988-04-01

    A retrospective review of 45 patients with Stage III and IV malignant tumors of the major salivary glands was undertaken to determine tumor control and patient survival after treatment with surgery and conventional ionizing-radiation therapy. Eight of the 23 patients received early postoperative radiotherapy after initial surgical resection, with a local control rate of 75%. Twelve of 23 patients had surgery as definitive treatment and the tumor recurred locally in all; seven of these 12 patients were subsequently salvaged by further surgery plus postoperative radiotherapy or by radiotherapy alone, with 58% ultimate local control. The remaining three patients had unresectable tumors at diagnosis and received radiation alone, with a local tumor control rate of 33%. Patients were also analyzed according to the extent of surgical resection prior to radiation therapy and according to radiation dose. Eighty-eight percent of completely resected, 50% of partially resected, and 44% of unresected tumors were locally controlled for an overall local control rate of 61%. The 5-year survival rate was significantly higher for patients with local tumor control than for patients who failed locally (31% vs. 0%).

  19. [Significance of urokinase and its inhibitors in the invasiveness and metastasing of malignant tumors].

    PubMed

    Halámková, J; Kiss, I; Tomášek, J; Pavlovský, Z; Tuček, S; Penka, M

    2012-02-01

    Fibrinolysis is process, which leads to the degradation of fibrin to fibrin monomers. Fibrinolysis helps to regulate hemostasis and prevents the creation of inappropriately large thrombus, which could reduce blood flow to the bloodstream. The main enzyme involved in fibrinolysis is plasmin. Tissue plasminogen activator (tPA) and urokinase (uPA) are agents converting plasminogen into active plasmin, together with urokinase receptor (uPAR) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) form plasminogen activator system (PAS) which is among others also part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumours. In contrast to tPA that is fundamental in fibrinolysis, uPA plays an essential role in tissue degradation as part of physiological and pathological processes. uPAR is a GPI (glycosylphosphatidylinositol)-anchored protein. The binding of uPA to uPAR results in activation of protein tyrosine kinase, protein kinase C and MAP kinase. At the same time, direct signalling pathway via Jak/STAT cascade utilising signalling transduction of Scr-like protein tyrosine kinase have also been described. uPAR expression is regulated by many growth factors, e.g. EGF, FGF-2 and HGF. It seems that individual PAS factors are involved in the process of rendering malignant tumors invasive. To what degree this influence is essential to specific malignancies, should be answered by further research. In the article the authors present a summary of findings about the interaction of fibrinolysis and tumor process, especially on the effects of urokinase and other activators and their inhibitors in metastasis of malignant tumors. The text contains information on the factors theirs introduction into practice is still the subject of numerous discussions, but in the future, individual PAS factors could play an important role in planning treatment strategies and also could become targets of targeted therapy. PMID

  20. Exploration of paclitaxel (Taxol) as a treatment for malignant tumors in cats: a descriptive case series.

    PubMed

    Kim, Jennifer; Doerr, Mary; Kitchell, Barbara E

    2015-02-01

    Paclitaxel, an effective chemotherapeutic agent in human oncology, has received little evaluation in feline patients. The diluent used to solubilize paclitaxel, polyoxyethylated castor oil (Cremophor EL), causes anaphylactoid reactions in human and dogs, which limits enthusiasm for use of this agent in veterinary oncology. Nine feline patients with measurable malignant tumors were treated with paclitaxel at a dosage of 80 mg/m(2) intravenously every 21 days for up to two doses. Adverse effects, including evidence of toxicity and anaphylactoid reactions, were assessed. Tumor response, progression and patient time to progression (TTP) were also recorded. Adverse effects included grade III and IV thrombocytopenia, grade III gastrointestinal signs (vomiting and constipation) and hypersensitivity reactions, seen in a total of five patients. Anaphylactoid reactions resolved with appropriate management. Stable disease and partial response were observed in 56% of feline patients. Median TTP was 28 days (range 15-45 days). Intravenous paclitaxel is a safe treatment option for feline malignant tumor patients. Future investigation is warranted to explore the effectiveness and appropriate application of this agent for specific tumor types. PMID:24820996

  1. Intraoperative vascular DIVA surgery reveals angiogenic hotspots in tumor zones of malignant gliomas

    PubMed Central

    Eyüpoglu, Ilker Y.; Hore, Nirjhar; Fan, Zheng; Buslei, Rolf; Merkel, Andreas; Buchfelder, Michael; Savaskan, Nicolai E.

    2015-01-01

    Malignant gliomas belong to the most threatening tumor entities and are hallmarked by rapid proliferation, hypervascularization and an invasive growth pattern. The primary obstacle in surgical treatment lies in differentiation between healthy and pathological tissue at the tumor margins, where current visualization methods reach their limits. Here, we report on a novel technique (vascular dual intraoperative visualization approach - vDIVA) enabling visualization of different tumor zones (TZ I–III) on the basis of angiogenic hotspots. We investigated glioblastoma patients who underwent 5-ALA fluorescence-guided surgery with simultaneous intraoperative ICG fluorescence angiography. This vDIVA technique revealed hypervascularized areas which were further histologically investigated. Neuropathological assessments revealed tissue areas at the resection margins corresponding to TZ II, and postoperative CD34- and Map2 immunostaining confirmed these angiogenic hotspots to be occupied by glioma cells. Hence, the vascular architecture in this transitional zone could be well differentiated from both primary tumor bulk and healthy brain parenchyma. These data demonstrate that ICG fluorescence angiography improves state-of-the-art glioma surgery techniques and facilitates the future characterization of polyclonal attributes of malignant gliomas. PMID:25609379

  2. [Malignant peripheral sheath nerve tumor: An exceptional mass of the anterior and middle mediastinum].

    PubMed

    Bacha, S; Chaouch, N; Ayadi, A; Zidi, A; Cheikhrouhou, S; Racil, H; Chabbou, A

    2015-12-01

    Malignant peripheral nerve sheath tumors (MPNST) are rare nervous tumors usually located in the posterior mediastinum in the paravertebral gutters. We report the case of a non-smoking 62-year-old man who was admitted with a 4 months history of cough, hoarseness and shortness of breath. Physical examination noted a superior vena cava syndrome. CT scan of the chest revealed a right anterior and middle mediastinal mass compressing the superior vena cava, the ascending aorta, the right pulmonary artery, invading the superior root of the pulmonary vein and the right auricle. Flexible bronchoscopy showed extrinsic compression of the right main bronchus, the right upper lobe bronchus and intermedius bronchus. The patient underwent surgical biopsy of the mass by mediastinoscopy. Histological examination revealed a malignant peripheral nerve sheath tumor. The patient received a single cycle of chemotherapy (ifosfamid-adriamycin). Clinical course was marked by the fast worsening of the dyspnea and the general state. Patient died three weeks after the cure of the chemotherapy. This case is original by the exceptional clinical presentation of MPSNT with a superior vena cava syndrome and the very rare location of this tumor in the anterior and middle mediastinum. PMID:26190334

  3. [BETA-III TUBULIN AS A POTENTIAL TARGET FOR BLOCKING INVASIVE GROWTH OF MALIGNANT EPITHELIAL TUMORS].

    PubMed

    Portyanko, A S; Akalovich, S T; Doroshenko, T M

    2015-01-01

    Invasive growth is the first step of metastatic cascade in the growth of malignant tumors. The mobility of cells, which is a necessary factor of the invasive growth of malignant tumors, is closely linked to the dynamic structure of cytoskeleton. An important role in cell motility is played by microtubules and actin microfilaments. Microtubules consist of tubulin--a heterodimer comprising α and β subunits, which can be represented by different isotypes. The appearance of beta-III tubulin in a tumor is essential for chemoresistance and prognosis of some tumors in humans. This study focuses on determining the possibility of using beta-III tubulin as a target molecule for the suppression of invasive growth. It is established that blocking of the beta-III tubulin expression in colorectal cancer cells does not affect their viability, but reduces the cell adhesion to the extracellular matrix by 40% for HT-29 (∂ = 0.0044) and by 15% (p = 0.0436) for HCT 116) and produces a four-fold decrease in the invasive activity (p = 0.0000 and 0.0001, respectively). These facts allow considering beta-III tubulin as a target molecule in the development of antitumor drugs. PMID:26591579

  4. An unusually large aggressive adenomatoid odontogenic tumor of maxilla involving the third molar: A clinical case report

    PubMed Central

    Dhupar, Vikas; Akkara, Francis; Khandelwal, Pulkit

    2016-01-01

    Adenomatoid odontogenic tumor (AOT) is a rare tumor comprising only 3% of all odontogenic tumors. It is a benign, encapsulated, noninvasive, nonaggressive, slowly growing odontogenic lesion associated with an impacted tooth. These lesions may go unnoticed for years. The usual treatment is enucleation and curettage, and the lesion does not recur. Here, we present a rare case of an unusually large aggressive AOT of maxilla associated with impacted third molar. The authors also discuss clinical, radiographic, histopathologic, and therapeutic features of the case. Subtotal maxillectomy with simultaneous reconstruction of the surgical defect with temporalis myofascial flap was planned and carried out. PMID:27095910

  5. [The serum copper/serum iron ratio in malignant tumors of the female genitalia].

    PubMed

    Maas, D H; Hinckers, H J

    1975-08-01

    Copper and iron in blood of 83 women with maligne tumors of the genitalia were regulary controled before, during and till 69 weeks after therapy. The relation between the copper/iron-ratio and the expansion and histology of the tumors, the success of the therapy and the incidence of a recurrence was checked for any significancy. Our results show the improtance of the ratio in the diagnosis and differentialdiagnosis of the ovarian-cancer and the corpus-uteri-cancer, and in the success-controll during tumor-therapy. In the group of the patients with collum-uteri-cancer we found a significant difference in the copper/iron-ratio of the patients with and without a recurrence during the controllperiod after therapy, which emphasizes the importance of this copper/iron-ratio. PMID:1175904

  6. Synthesis and evaluation of boron compounds for neutron capture therapy of malignant brain tumors

    SciTech Connect

    Soloway, A.H.; Barth, R.F.

    1990-01-01

    Boron neutron capture therapy offers the potentiality for treating brain tumors currently resistant to treatment. The success of this form of therapy is directly dependent upon the delivery of sufficient numbers of thermal-neutrons to tumor cells which possess high concentrations of B-10. The objective of this project is to develop chemical methodology to synthesize boron-containing compounds with the potential for becoming incorporated into rapidly-dividing malignant brain tumor cells and excluded from normal components of the brain and surrounding tissues, to develope biological methods for assessing the potential of the compound by use of cell culture or intratumoral injection, to develop analytical methodology for measuring boron in cells and tissue using direct current plasma atomic emission spectroscopy (DCP-AES) and alpha track autoradiography, to develop biochemical and HPLC procedures for evaluating compound uptake and tissue half-life, and to develop procedures required to assess both in vitro and vivo efficacy of BNCT with selected compounds.

  7. Emerging therapies targeting tumor vasculature in multiple myeloma and other hematologic and solid malignancies.

    PubMed

    Podar, K; Anderson, K C

    2011-11-01

    Research on the formation of new blood vessels (angiogenesis) in general and vascular endothelial growth factor (VEGF) in particular is a major focus in biomedicine and has led to the clinical approval of the monoclonal anti- VEGF antibody bevazicumab; and the second-generation multitargeted receptor kinase inhibitors (RTKIs) sorafenib, sunitinib, and pazopanib. Although these agents show significant preclinical and clinical anti-cancer activity, they prolong overall survival of cancer patients for only months, followed by a restoration of tumor growth and progression. Therefore, there is a clear need to increase our understanding of tumor angiogenesis and the development of resistance. In this review we discuss up-to-date knowledge on mechanisms of tumor angiogenesis, and summarize preclinical and clinical data on existing and potential future anti-angiogenic agents and treatment strategies for Multiple Myeloma (MM) and other hematologic and solid malignancies. PMID:21933109

  8. HER-2 and EGFR mRNA Expression and Its Relationship with Versican in Malignant Matrix-Producing Tumors of the Canine Mammary Gland

    PubMed Central

    Damasceno, Karine Araújo; Ferreira, Enio; Estrela-Lima, Alessandra; Gamba, Conrado de Oliveira; Miranda, Fernanda Freitas; Alves, Mariana Rezende; Rocha, Rafael Malagoli; de Barros, André Luís Branco; Cassali, Geovanni Dantas

    2016-01-01

    Versican expression promotes tumor growth by destabilizing focal cell contacts, thus impeding cell adhesion and facilitating cell migration. It not only presents or recruits molecules to the cell surface, but also modulates gene expression levels and coordinates complex signal pathways. Previously, we suggested that the interaction between versican and human epidermal growth factor receptors may be directly associated with tumor aggressiveness. Thus, the expression of EGFR and HER-2 in these neoplasms may contribute to a better understanding of the progression mechanisms in malignant mammary tumors. The purpose of this study was to correlate the gene and protein expressions of EGFR and HER2 by RNA In Situ Hybridization (ISH) and immunohistochemistry (IHC), respectively, and their relationship with the versican expression in carcinomas in mixed tumors and carcinosarcomas of the canine mammary gland. The results revealed that EGFR mRNA expression showed a significant difference between in situ and invasive carcinomatous areas in low and high versican expression groups. Identical results were observed in HER-2 mRNA expression. In immunohistochemistry analysis, neoplasms with low versican expression showed greater EGFR immunostaining in the in situ areas than in invasive areas, even as the group presenting high versican expression displayed greater EGFR and HER-2 staining in in situ areas. Significant EGFR and HER-2 mRNA and protein expressions in in situ carcinomatous sites relative to invasive areas suggest that these molecules play a role during the early stages of tumor progression. PMID:27490467

  9. HER-2 and EGFR mRNA Expression and Its Relationship with Versican in Malignant Matrix-Producing Tumors of the Canine Mammary Gland.

    PubMed

    Damasceno, Karine Araújo; Ferreira, Enio; Estrela-Lima, Alessandra; Gamba, Conrado de Oliveira; Miranda, Fernanda Freitas; Alves, Mariana Rezende; Rocha, Rafael Malagoli; de Barros, André Luís Branco; Cassali, Geovanni Dantas

    2016-01-01

    Versican expression promotes tumor growth by destabilizing focal cell contacts, thus impeding cell adhesion and facilitating cell migration. It not only presents or recruits molecules to the cell surface, but also modulates gene expression levels and coordinates complex signal pathways. Previously, we suggested that the interaction between versican and human epidermal growth factor receptors may be directly associated with tumor aggressiveness. Thus, the expression of EGFR and HER-2 in these neoplasms may contribute to a better understanding of the progression mechanisms in malignant mammary tumors. The purpose of this study was to correlate the gene and protein expressions of EGFR and HER2 by RNA In Situ Hybridization (ISH) and immunohistochemistry (IHC), respectively, and their relationship with the versican expression in carcinomas in mixed tumors and carcinosarcomas of the canine mammary gland. The results revealed that EGFR mRNA expression showed a significant difference between in situ and invasive carcinomatous areas in low and high versican expression groups. Identical results were observed in HER-2 mRNA expression. In immunohistochemistry analysis, neoplasms with low versican expression showed greater EGFR immunostaining in the in situ areas than in invasive areas, even as the group presenting high versican expression displayed greater EGFR and HER-2 staining in in situ areas. Significant EGFR and HER-2 mRNA and protein expressions in in situ carcinomatous sites relative to invasive areas suggest that these molecules play a role during the early stages of tumor progression. PMID:27490467

  10. IL12 and IL27 sequential gene therapy via intramuscular electroporation delivery for eliminating distal aggressive tumors1

    PubMed Central

    Zhu, Shiguo; Lee, Dean Anthony; Li, Shulin

    2010-01-01

    Eradication of residual malignancies and metastatic tumors via a systemic approach is the key for successfully treating cancer and increasing the cancer patient survival. Systemic administration of IL12 protein in an acute large dose is effective but toxic. Systemic administration of IL12 gene by persistently expressing a low level of IL12 protein may reduce the systemic toxicity, but only eradicates IL12 sensitive tumors. Here, we discovered that sequential administration of IL12 and IL27 encoding DNA, referred to as sequential IL12-IL27 gene therapy, not only eradicated IL12 sensitive tumors from 100% of mice but also eradicated the highly malignant 4T1 tumors from 33% of treated mice in multiple independent experiments. This IL12-IL27 sequential gene therapy is not only superior to IL12-IL12 sequential gene therapy for eliminating tumors, but also for inducing CTL activity, increasing T cell infiltration into tumors, and yielding a large number of tumor-specific IFNγ positive CD8 T cells. Notably, depletion of either T- or NK-cells during the IL27 treatment phase reverses tumor eradication, suggesting an NK-cell requirement for this sequential gene therapy-mediated tumor eradication. Both reversal of the administration sequence and co-administration of IL12 and IL27 impaired the tumor eradication in 4T1 tumor bearing mice. This IL12-IL27 sequential gene therapy, via sequential administration of IL12 and IL27 encoding plasmid DNA into tumor-bearing mice through intramuscular electroporation, provides a simple but effective approach for eliminating inaccessible residual tumors. PMID:20139275

  11. Brachytherapy of recurrent malignant brain tumors with removable high-activity iodine-125 sources

    SciTech Connect

    Gutin, P.H.; Phillips, T.L.; Wara, W.M.; Leibel, S.A.; Hosobuchi, Y.; Levin, V.A.; Weaver, K.A.; Lamb, S.

    1984-01-01

    Thirty-seven patients harboring recurrent malignant primary or metastatic brain tumors were treated by 40 implantations of high-activity iodine-125 (/sup 125/I) sources. All patients had been treated with irradiation and most had been treated with chemotherapeutic agents, primarily nitrosoureas. Implantations were performed using computerized tomography (CT)-directed stereotaxy; /sup 125/I sources were held in one or more afterloaded catheters that were removed after the desired dose (minimum tumor dose of 3000 to 12,000 rads) had been delivered. Patients were followed with sequential neurological examinations and CT scans. Results of 34 implantation procedures were evaluable: 18 produced documented tumor regression (response) for 4 to 13+ months; five, performed in deteriorating patients, resulted in disease stability for 4 to 12 months. The overall response rate was 68%. In 11 patients, implantation did not halt clinical deterioration. At exploratory craniotomy 5 to 12 months after implantation, focal radiation necrosis was documented in two patients whose tumor had responded initially and then progressed, and in three patients whose disease had progressed initially (four glioblastomas, one anaplastic astrocytoma); histologically identifiable tumor was documented in two of these patients. All improved after resection of the focal necrotic mass and are still alive 10, 15, 19, 24, and 25 months after the initial implantation procedure; only one patient has evidence of tumor regrowth. The median follow-up period after implantation for the malignant glioma (anaplastic astrocytoma and glioblastoma multiforme) group is 9 months, with 48% of patients still surviving. While direct comparison with the results of chemotherapy is difficult, results obtained in this patient group with interstitial brachytherapy are probably superior to results obtained with chemotherapy.

  12. Fibrobronchoscopic cryosurgery for secondary malignant tumors of the trachea and main bronchi

    PubMed Central

    Ma, Qianli; Tian, Yanchu; Liu, Deruo

    2016-01-01

    Abstract Background Patients with secondary malignant tracheal and main bronchial tumors may suffer severe symptoms as a result of major airway obstruction. Curative surgical resection is usually not suitable because of the presence of metastatic disease and poor performance status. In this study, the use of bronchoscopic cryosurgery to reopen the airway is analyzed. Methods The clinical records of 37 patients who experienced secondary maglinancies from December 2001 to January 2013 were retrospectively reviewed. Low temperature cryotherapy (−50°C to −70°C) was delivered to the central part of the tumor by cryoprobe for four to six minutes causing destruction of the tumor mass (Cryo‐melt method). Subsequently, the edge of the tumor was frozen for 30 seconds to two minutes, followed by piecemeal removal of the frozen tumor tissue (Cryo‐resection method). Results The endpoints of the study were degree of symptomatic improvement and survival. The rates of dramatic and partial symptomatic alleviation were 57.1% and 28.6%, respectively, there were no intraoperative deaths, and median survival was 16.0 months. Prolonged survival was significantly correlated to age (under 60 years of age 22.2% vs. over 60 100%, P = 0.011), tumor location (main bronchi 0% vs. trachea 77.8%, P = 0.003), and cryorecanalization times (once 33.3% vs. twice or more 80.0%, P = 0.037). Conclusion Bronchoscopic cryorecanalization is a safe, effective, non‐invasive choice for improving the symptoms of malignant airway obstruction. In addition to achieving local‐regional control, the technique may also contribute to improved survival. PMID:27385989

  13. Transarterial Fiducial Marker Placement for Image-guided Proton Therapy for Malignant Liver Tumors

    SciTech Connect

    Ohta, Kengo Shimohira, Masashi; Sasaki, Shigeru Iwata, Hiromitsu Nishikawa, Hiroko Ogino, Hiroyuki Hara, Masaki; Hashizume, Takuya Shibamoto, Yuta

    2015-10-15

    PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors.

  14. Nano-Scaled Particles of Titanium Dioxide Convert Benign Mouse Fibrosarcoma Cells into Aggressive Tumor Cells

    PubMed Central

    Onuma, Kunishige; Sato, Yu; Ogawara, Satomi; Shirasawa, Nobuyuki; Kobayashi, Masanobu; Yoshitake, Jun; Yoshimura, Tetsuhiko; Iigo, Masaaki; Fujii, Junichi; Okada, Futoshi

    2009-01-01

    Nanoparticles are prevalent in both commercial and medicinal products; however, the contribution of nanomaterials to carcinogenesis remains unclear. We therefore examined the effects of nano-sized titanium dioxide (TiO2) on poorly tumorigenic and nonmetastatic QR-32 fibrosarcoma cells. We found that mice that were cotransplanted subcutaneously with QR-32 cells and nano-sized TiO2, either uncoated (TiO2−1, hydrophilic) or coated with stearic acid (TiO2−2, hydrophobic), did not form tumors. However, QR-32 cells became tumorigenic after injection into sites previously implanted with TiO2−1, but not TiO2−2, and these developing tumors acquired metastatic phenotypes. No differences were observed either histologically or in inflammatory cytokine mRNA expression between TiO2−1 and TiO2−2 treatments. However, TiO2−2, but not TiO2−1, generated high levels of reactive oxygen species (ROS) in cell-free conditions. Although both TiO2−1 and TiO2−2 resulted in intracellular ROS formation, TiO2−2 elicited a stronger response, resulting in cytotoxicity to the QR-32 cells. Moreover, TiO2−2, but not TiO2−1, led to the development of nuclear interstices and multinucleate cells. Cells that survived the TiO2 toxicity acquired a tumorigenic phenotype. TiO2-induced ROS formation and its related cell injury were inhibited by the addition of antioxidant N-acetyl-l-cysteine. These results indicate that nano-sized TiO2 has the potential to convert benign tumor cells into malignant ones through the generation of ROS in the target cells. PMID:19815711

  15. Pazopanib monotherapy in a patient with a malignant granular cell tumor originating from the right orbit: A case report

    PubMed Central

    MORITA, SACHI; HIRAMATSU, MARIKO; SUGISHITA, MIHOKO; GYAWALI, BISHAL; SHIBATA, TAKASHI; SHIMOKATA, TOMOYA; URAKAWA, HIROSHI; MITSUMA, AYAKO; MORITANI, SUZUKO; KUBOTA, TOSHINOBU; ICHIHARA, SHU; ANDO, YUICHI

    2015-01-01

    Granular cell tumors are uncommon, usually benign tumors of Schwann cell origin. The malignant variant is extremely rare, representing <2% of all granular cell tumors. Therefore, standard systemic chemotherapy for this disease does not exist. The present study reports the case of a 40-year-old female with a malignant granular cell tumor that originally arose in the right orbit and subsequently relapsed. The patient was started on pazopanib monotherapy following treatment with two investigational drugs, a smoothened inhibitor and then a phosphatidylinositol 3-kinase inhibitor, as part of a clinical trial. Although additional radiotherapy for local control was necessary, the lung metastases remained stable during the pazopanib monotherapy, which lasted for 7 months, following which a clinically stable disease state was determined. This case suggests that pazopanib can be a treatment option for the stabilization of disease progression in metastatic malignant granular cell tumor. PMID:26622607

  16. Cks1 is required for tumor cell proliferation but not sufficient to induce hematopoietic malignancies.

    PubMed

    Kratzat, Susanne; Nikolova, Viktoriya; Miething, Cornelius; Hoellein, Alexander; Schoeffmann, Stephanie; Gorka, Oliver; Pietschmann, Elke; Illert, Anna-Lena; Ruland, Jürgen; Peschel, Christian; Nilsson, Jonas; Duyster, Justus; Keller, Ulrich

    2012-01-01

    The Cks1 component of the SCF(Skp2) complex is necessary for p27(Kip1) ubiquitylation and degradation. Cks1 expression is elevated in various B cell malignancies including Burkitt lymphoma and multiple myeloma. We have previously shown that loss of Cks1 results in elevated p27(Kip1) levels and delayed tumor development in a mouse model of Myc-induced B cell lymphoma. Surprisingly, loss of Skp2 in the same mouse model also resulted in elevated p27(Kip1) levels but exhibited no impact on tumor onset. This raises the possibility that Cks1 could have other oncogenic activities than suppressing p27(Kip1). To challenge this notion we have targeted overexpression of Cks1 to B cells using a conditional retroviral bone marrow transduction-transplantation system. Despite potent ectopic overexpression, Cks1 was unable to promote B cell hyperproliferation or B cell malignancies, indicating that Cks1 is not oncogenic when overexpressed in B cells. Since Skp2 overexpression can drive T-cell tumorigenesis or other cancers we also widened the quest for oncogenic activity of Cks1 by ubiquitously expressing Cks1 in hematopoetic progenitors. At variance with c-Myc overexpression, which caused acute myeloid leukemia, Cks1 overexpression did not induce myeloproliferation or leukemia. Therefore, despite being associated with a poor prognosis in various malignancies, sole Cks1 expression is insufficient to induce lymphoma or a myeloproliferative disease in vivo. PMID:22624029

  17. Poly (ADP) ribose polymerase inhibition: A potential treatment of malignant peripheral nerve sheath tumor.

    PubMed

    Kivlin, Christine M; Watson, Kelsey L; Al Sannaa, Ghadah A; Belousov, Roman; Ingram, Davis R; Huang, Kai-Lieh; May, Caitlin D; Bolshakov, Svetlana; Landers, Sharon M; Kalam, Azad Abul; Slopis, John M; McCutcheon, Ian E; Pollock, Raphael E; Lev, Dina; Lazar, Alexander J; Torres, Keila E

    2016-01-01

    Poly (ADP) ribose polymerase (PARP) inhibitors, first evaluated nearly a decade ago, are primarily used in malignancies with known defects in DNA repair genes, such as alterations in breast cancer, early onset 1/2 (BRCA1/2). While no specific mutations in BRCA1/2 have been reported in malignant peripheral nerve sheath tumors (MPNSTs), MPNST cells could be effectively targeted with a PARP inhibitor to drive cells to synthetic lethality due to their complex karyotype and high level of inherent genomic instability. In this study, we assessed the expression levels of PARP1 and PARP2 in MPNST patient tumor samples and correlated these findings with overall survival. We also determined the level of PARP activity in MPNST cell lines. In addition, we evaluated the efficacy of the PARP inhibitor AZD2281 (Olaparib) in MPNST cell lines. We observed decreased MPNST cell proliferation and enhanced apoptosis in vitro at doses similar to, or less than, the doses used in cell lines with established defective DNA repair genes. Furthermore, AZD2281 significantly reduced local growth of MPNST xenografts, decreased the development of macroscopic lung metastases, and increased survival of mice with metastatic disease. Our results suggest that AZD2281 could be an effective therapeutic option in MPNST and should be further investigated for its potential clinical use in this malignancy. PMID:26650448

  18. May Sonic Hedgehog proteins be markers for malignancy in uterine smooth muscle tumors?

    PubMed

    Garcia, Natalia; Bozzini, Nilo; Baiocchi, Glauco; da Cunha, Isabela Werneck; Maciel, Gustavo Arantes; Soares Junior, José Maria; Soares, Fernando Augusto; Baracat, Edmund Chada; Carvalho, Katia Candido

    2016-04-01

    Several studies have demonstrated that the Sonic Hedgehog signaling pathway (SHH) plays an important role in tumorigenesis and cellular differentiation. We analyzed the protein expression of SHH pathway components and evaluated whether their profile could be useful for the diagnosis, prognosis, or prediction of the risk of malignancy for uterine smooth muscle tumors (USMTs). A total of 176 samples (20 myometrium, 119 variants of leiomyoma, and 37 leiomyosarcoma) were evaluated for the protein expression of the SHH signaling components, HHIP1 (SHH inhibitor), and BMP4 (SHH target) by immunohistochemistry. Western blot analysis was performed to verify the specificity of the antibodies. We grouped leiomyoma samples into conventional leiomyomas and unusual leiomyomas that comprise atypical, cellular, mitotically active leiomyomas and uterine smooth muscle tumors of uncertain malignant potential. Immunohistochemical analysis showed that SMO, SUFU, GLI1, GLI3, and BMP4 expression gradually increased depending on to the histologic tissue type. The protein expression of SMO, SUFU, and GLI1 was increased in unusual leiomyoma and leiomyosarcoma samples compared to normal myometrium. The inhibitor HHIP1 showed higher expression in myometrium, whereas only negative or basal expression of SMO, SUFU, GLI1, and GLI3 was detected in these samples. Strong expression of SHH was associated with poorer overall survival. Our data suggest that the expression of SHH proteins can be useful for evaluating the potential risk of malignancy for USMTs. Moreover, GLI1 and SMO may serve as future therapeutic targets for women with USMTs. PMID:26997437

  19. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman

    PubMed Central

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels. PMID:25674278

  20. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.

    PubMed

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels. PMID:25674278

  1. Male patients presenting with rapidly progressive puberty associated with malignant tumors

    PubMed Central

    Kim, Soo Jung; Ko, A Ra; Jung, Mo Kyung; Kim, Ki Eun; Chae, Hyun Wook; Kim, Duk Hee; Kim, Ho-Seong

    2016-01-01

    In males, precocious puberty (PP) is defined as the development of secondary sexual characteristics before age 9 years. PP is usually idiopathic; though, organic abnormalities including tumors are more frequently found in male patients with PP. However, advanced puberty in male also can be an important clinical manifestation in tumors. We report 2 cases of rapidly progressive puberty in males, each associated with a germ-cell tumor. First, an 11-year-old boy presented with mild fever and weight loss for 1 month. Physical examination revealed a pubertal stage of G3P3 with 10-mL testes. Investigations revealed advanced bone age (16 years) with elevated basal luteinizing hormone and testosterone levels. An anterior mediastinal tumor was identified by chest radiography and computed tomography, and elevated α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) levels were noted. Histopathologic analysis confirmed a yolk-sac tumor. Second, a 12-year-old boy presented with diplopia, polydipsia, and polyuria for 4 months. Physical examination revealed a pubertal stage of G3P3 with 8-mL testes. Bone age was advanced (16 years) and laboratory tests indicated panhypopituitarism with elevated testosterone level. A mixed germ-cell tumor was diagnosed with elevated AFP and β-hCG levels. Of course, these patients also have other symptoms of suspecting tumors, however, rapidly progressive puberty can be the more earlier screening sign of tumors. Therefore, in male patients with accelerated or advanced puberty, malignancy should be considered, with evaluation of tumor markers. In addition, advanced puberty in male should be recognized more widely as a unique sign of neoplasm. PMID:27104181

  2. Presence of sst5TMD4, a truncated splice variant of the somatostatin receptor subtype 5, is associated to features of increased aggressiveness in pancreatic neuroendocrine tumors

    PubMed Central

    Gahete, Manuel D.; Serrano-Somavilla, Ana; Villa-Osaba, Alicia; Adrados, Magdalena; Ibáñez-Costa, Alejandro; Martín-Pérez, Elena; Culler, Michael D.

    2016-01-01

    Purpose Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors, and their biological behavior is not well known. We studied the presence and potential functional roles of somatostatin receptors (sst1-5), focusing particularly on the truncated variants (sst5TMD4, sst5TMD5) and on their relationships with the angiogenic system (Ang/Tie-2 and VEGF) in human GEP-NETs. Experimental Design We evaluated 42 tumor tissue samples (26 primary/16 metastatic) from 26 patients with GEP-NETs, and 30 non-tumoral tissues (26 from adjacent non-tumor regions and 4 from normal controls) from a single center. Expression of sst1-5, sst5TMD4, sst5TMD5, Ang1-2, Tie-2 and VEGF was analyzed using real-time qPCR, immunofluorescence and immunohistochemistry. Expression levels were associated with tumor characteristics and clinical outcomes. Functional role of sst5TMD4 was analyzed in GEP-NET cell lines. Results sst1 exhibited the highest expression in GEP-NET, whilst sst2 was the most frequently observed sst-subtype (90.2%). Expression levels of sst1, sst2, sst3, sst5TMD4, and sst5TMD5 were significantly higher in tumor tissues compared to their adjacent non-tumoral tissue. Lymph-node metastases expressed higher levels of sst5TMD4 than in its corresponding primary tumor tissue. sst5TMD4 was also significantly higher in intestinal tumor tissues from patients with residual disease of intestinal origin compared to those with non-residual disease. Functional assays demonstrated that the presence of sst5TMD4 was associated to enhanced malignant features in GEP-NET cells. Angiogenic markers correlated positively with sst5TMD4, which was confirmed by immunohistochemical/fluorescence studies. Conclusions sst5TMD4 is overexpressed in GEP-NETs and is associated to enhanced aggressiveness, suggesting its potential value as biomarker and target in GEP-NETs. PMID:26673010

  3. Hypervascular Benign and Malignant Liver Tumors That Require Differentiation from Hepatocellular Carcinoma: Key Points of Imaging Diagnosis

    PubMed Central

    Murakami, Takamichi; Tsurusaki, Masakatsu

    2014-01-01

    Most liver tumors are benign and hypervascular, and it is important to avoid unnecessary interventions for benign lesions. This review describes the typical and atypical imaging features of common hypervascular benign liver tumors and outlines a general approach to distinguishing between benign and malignant hepatic lesions. There are many types of benign liver tumors that need to be differentiated from hepatocellular carcinoma (HCC). Therefore, it is very important to know the imaging characteristics of benign tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging is helpful in diagnosing hypervascular pseudotumors, focal nodular hyperplasia, and nodular lesions associated with alcohol-induced hepatitis. There are also some hypervascular malignant tumors, such as cholangiocarcinoma, cholangiolocellular carcinoma, mixed type tumors, and metastatic liver tumors, which also required differentiation from HCC. PMID:24944999

  4. Computer-Aided Image Analysis and Fractal Synthesis in the Quantitative Evaluation of Tumor Aggressiveness in Prostate Carcinomas

    PubMed Central

    Waliszewski, Przemyslaw

    2016-01-01

    The subjective evaluation of tumor aggressiveness is a cornerstone of the contemporary tumor pathology. A large intra- and interobserver variability is a known limiting factor of this approach. This fundamental weakness influences the statistical deterministic models of progression risk assessment. It is unlikely that the recent modification of tumor grading according to Gleason criteria for prostate carcinoma will cause a qualitative change and improve significantly the accuracy. The Gleason system does not allow the identification of low aggressive carcinomas by some precise criteria. The ontological dichotomy implies the application of an objective, quantitative approach for the evaluation of tumor aggressiveness as an alternative. That novel approach must be developed and validated in a manner that is independent of the results of any subjective evaluation. For example, computer-aided image analysis can provide information about geometry of the spatial distribution of cancer cell nuclei. A series of the interrelated complexity measures characterizes unequivocally the complex tumor images. Using those measures, carcinomas can be classified into the classes of equivalence and compared with each other. Furthermore, those measures define the quantitative criteria for the identification of low- and high-aggressive prostate carcinomas, the information that the subjective approach is not able to provide. The co-application of those complexity measures in cluster analysis leads to the conclusion that either the subjective or objective classification of tumor aggressiveness for prostate carcinomas should comprise maximal three grades (or classes). Finally, this set of the global fractal dimensions enables a look into dynamics of the underlying cellular system of interacting cells and the reconstruction of the temporal-spatial attractor based on the Taken’s embedding theorem. Both computer-aided image analysis and the subsequent fractal synthesis could be performed

  5. Computer-Aided Image Analysis and Fractal Synthesis in the Quantitative Evaluation of Tumor Aggressiveness in Prostate Carcinomas.

    PubMed

    Waliszewski, Przemyslaw

    2016-01-01

    The subjective evaluation of tumor aggressiveness is a cornerstone of the contemporary tumor pathology. A large intra- and interobserver variability is a known limiting factor of this approach. This fundamental weakness influences the statistical deterministic models of progression risk assessment. It is unlikely that the recent modification of tumor grading according to Gleason criteria for prostate carcinoma will cause a qualitative change and improve significantly the accuracy. The Gleason system does not allow the identification of low aggressive carcinomas by some precise criteria. The ontological dichotomy implies the application of an objective, quantitative approach for the evaluation of tumor aggressiveness as an alternative. That novel approach must be developed and validated in a manner that is independent of the results of any subjective evaluation. For example, computer-aided image analysis can provide information about geometry of the spatial distribution of cancer cell nuclei. A series of the interrelated complexity measures characterizes unequivocally the complex tumor images. Using those measures, carcinomas can be classified into the classes of equivalence and compared with each other. Furthermore, those measures define the quantitative criteria for the identification of low- and high-aggressive prostate carcinomas, the information that the subjective approach is not able to provide. The co-application of those complexity measures in cluster analysis leads to the conclusion that either the subjective or objective classification of tumor aggressiveness for prostate carcinomas should comprise maximal three grades (or classes). Finally, this set of the global fractal dimensions enables a look into dynamics of the underlying cellular system of interacting cells and the reconstruction of the temporal-spatial attractor based on the Taken's embedding theorem. Both computer-aided image analysis and the subsequent fractal synthesis could be performed

  6. Tumor apparent diffusion coefficient as an imaging biomarker to predict tumor aggressiveness in patients with estrogen-receptor-positive breast cancer.

    PubMed

    Shin, Hee Jung; Kim, So Hee; Lee, Hee Jin; Gong, Gyungyub; Baek, Seunghee; Chae, Eun Young; Choi, Woo Jung; Cha, Joo Hee; Kim, Hak Hee

    2016-08-01

    The purpose of this retrospective study was to evaluate whether tumor apparent diffusion coefficient (ADC) was correlated with pathologic biomarkers such as tumor cellularity, Ki67, tumor-infiltrating lymphocytes (TILs), and peritumoral lymphocytic infiltrate (PLI) in patients with estrogen receptor (ER)-positive breast cancer. The study was approved by the institutional review board and informed consent was waived. From July 2014 to December 2014, we reviewed 140 ER-positive tumors in 138 consecutive patients (range, 28-77 years; mean, 52 years) who underwent preoperative breast MRI and definitive surgery. All patients underwent diffusion-weighted imaging with a 3T scanner. Two radiologists drew the region of interest of the entire tumor and obtained the mean and pixel-based histogram of ADC. On pathology, two pathologists reviewed tumor cellularity, Ki67, TILs, and PLI. Multiple linear regression analysis was used to determine pathologic variables independently associated with ADC. Tumors with high tumor cellularity and high Ki67 had significantly lower ADCs than those with low tumor cellularity and low Ki67 (P < 0.05 for all). Tumors without PLI had significantly higher standard deviation than those with PLI (0.23 ± 0.08 versus 0.18 ± 0.05; P < 0.001). Median ADC was negatively correlated with tumor cellularity (r = -0.441), and Ki67 (r = -0.382). The standard deviation of ADC was also negatively correlated with the degree of PLI (r = -0.319). On multivariate linear regression analysis, tumor cellularity and Ki67 were independently associated with tumor ADC. Tumor ADC would be an MRI biomarker for the prediction of tumor aggressiveness indicators such as Ki67, tumor cellularity, and PLI in ER-positive breast cancer. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27332719

  7. Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer.

    PubMed

    Yin, Bo; Zhang, Mo; Zeng, Yu; Li, Youqiang; Zhang, Chao; Song, Yongsheng

    2016-04-01

    Paclitaxel frequently serves as the first-line chemotherapeutic agent for castration-resistant prostate cancer (PCa) patients. However, acquired paclitaxel-resistance almost always occurs after initial responses, and the mechanisms by which this occurs remain largely unknown. The goal of the present study was to identify differentially expressed protein(s) associated with paclitaxel-resistance and further explore the potential mechanisms involved in drug resistance. By comparing the nuclear matrix protein (NMP) patterns of DU145-TxR cells, the previously established stable paclitaxel-resistant PCa cells, with that of the parental DU145 cells using two-dimensional electrophoresis, we found that cytokeratin 18 (CK18) is downregulated in DU145-TxR cells. The downregulation of CK18 in DU145-TxR cells at mRNA, NMP and total cellular protein levels was validated by real-time RT-PCR, immunoblotting and immunofluorescence, indicating that the downregulation of CK18 was a global effect in DU145-TxR cells due to paclitaxel-resistance. Furthermore, in vivo assay of xenograft transplantation confirmed the higher tumorigenicity of DU145-TxR cells, suggesting that these paclitaxel-resistant PCa cells possessed potent cancer stem cell (CSC)-like properties and eventually developed paclitaxel-resistance. Moreover, we determined by immunohistochemistry that CK18 expression in PCa tissues was inversely correlated with tumor grade in a statistically significant fashion, indicating a potential association of the downregulation of CK18 with tumor aggressiveness. Therefore, further study to define the potential role of CK18 may lead to novel therapy strategies as well as clinically useful biomarker for PCa patients. PMID:26892177

  8. Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis.

    PubMed

    Karamurzin, Yevgeniy S; Kiyokawa, Takako; Parkash, Vinita; Jotwani, Anjali R; Patel, Prusha; Pike, Malcolm C; Soslow, Robert A; Park, Kay J

    2015-11-01

    Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of 3 institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (1 Li-Fraumeni, 1 Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II to IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least 1 site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 mo); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease-specific survival at 5 years was 42% for GAS versus 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon. PMID:26457350

  9. Case series of cerebral infarction with Trousseau's syndrome associated with malignant gynecological tumors

    PubMed Central

    ISHIKAWA, MASAKO; NAKAYAMA, KENTARO; ISHIBASHI, TOMOKA; SATO, EMI; NAKAMURA, KOHEI; KATAGIRI, HIROSHI; KYO, SATORU

    2016-01-01

    The association between neoplastic disease and thromboembolic disorders was first recognized by Trousseau in 1865. Blood coagulation abnormalities have been reported in the majority of patients with cancer, including those with ovarian carcinoma. However, Trousseau's syndrome (TS) has rarely been reported in women with ovarian carcinoma. We herein report a case series of TS, notably in the brain, in association with gynecological malignant disease, and emphasize the difficulties associated with the management of these thromboembolic effects. The aim of this study was to present our experience with 5 TS patients whose condition was effectively controlled through treatment of the primary malignant disease. Therefore, we suggest that patients with TS may be cured by tumor resection, even if they have severe thromboembolic disease, such as cerebral or pulmonary infarction. PMID:27330786

  10. Metastatic tumor of the hand from malignant cystosarcoma phylloides of the breast. A case report.

    PubMed

    Patel, M R; Anand, V S; Desai, S S

    1985-03-01

    In this case report, a malignant cystosarcoma phylloides of the breast metastasized to the pulp of the little finger in a 47-year-old woman. It initially masqueraded as a whitlow. The diagnosis was helped by radionuclide bone scanning, which showed multiple areas of increased focal uptake including the terminal phalanx of the fifth finger, and the diagnosis was established by a frozen section biopsy of the tumor. The patient underwent a palliative fifth ray resection. She died within six weeks of surgery from extensive pulmonary and osseous metastases. Review of literature revealed only one other case of malignant cystosarcoma phylloides of the breast that metastasized to the hand and was initially misdiagnosed as a whitlow. PMID:3006003

  11. Previously Undiagnosed Malignant Brain Tumor Discovered During Examination of a Patient Seeking Chiropractic Care

    PubMed Central

    Anderson, Brian

    2016-01-01

    Objective This case report describes the diagnosis of a malignant brain tumor in a patient requesting chiropractic care for headaches after a motor vehicle accident. Clinical Features A 30-year-old man presented with numbness and tingling in all extremities, lower extremity muscle weakness, and a recent increase in headaches with the loss of ability to concentrate. He was involved in a high-speed motor vehicle collision approximately 4 months before the onset of symptoms. Examination showed slow gait with a lack of arm swing, bilateral hip flexors and knee extensors were all graded as 4/5 on muscle testing, and cranial nerve examination was unremarkable with the exception of 2 beats of nystagmus on left lateral eye movement. Because of these findings and a family history of multiple sclerosis, the patient was referred for a brain magnetic resonance imaging scan. Intervention and Outcome Imaging showed a craniocervical junction mass centered at the floor of the fourth ventricle with obstruction of foramina and marked impingement on the medulla. A posterior fossa craniotomy and tumor removal procedure was performed by a neurosurgeon, followed by 34 sessions of radiation therapy. The final diagnosis was a grade II glioma with features of ependymoma. Conclusions This report describes the clinical presentation, examination, and medical management of a 30-year-old man presenting to a chiropractic practice with an unsuspected malignant brain tumor. PMID:27069431

  12. Management of bilateral malignant ovarian germ cell tumors: Experience of a single institute

    PubMed Central

    Zhao, Ting; Liu, Yan; Jiang, Hongyuan; Zhang, Hao; Lu, Yuan

    2016-01-01

    Bilateral malignant ovarian germ cell tumors (MOGCTs) are rare. Determination of the optimal treatment modalities is crucial, as these malignancies mainly affect girls and young women who may wish to preserve their fertility. In order to review the prevalence, clinical characteristics, treatment and outcome of bilateral MOGCTs, we performed a retrospective review of patients who were diagnosed with bilateral MOGCTs and underwent primary surgery at the Obstetrics and Gynecology Hospital of Fudan University (Shanghai, China) between January, 2001 and December, 2014. Of the 130 patients investigated, 8 were diagnosed with bilateral disease, most of whom were International Federation of Gynecology and Obstetrics stage I. There was no significant difference in overall and disease-free survival between patients with unilateral and those with bilateral disease. Cases with dysgerminoma, dysgerminoma coexisting with gonadoblastoma, yolk sac tumor and ovarian primary choriocarcinoma were included in this study. Fertility was spared in 2 patients (1 with dysgerminoma and 1 with ovarian primary choriocarcinoma). The patient with ovarian choriocarcinoma experienced relapse and was finally salvaged by radical surgery and adjuvant chemotherapy. According to our results and the published data, patients affected by bilateral MOGCTs have a satisfactory prognosis. The treatment modalities largely depend on the histological type of the tumor. Fertility-sparing surgery may be safe for patients affected by dysgerminoma, but should be considered with caution in patients with ovarian primary choriocarcinoma. PMID:27446585

  13. Intralesional Bleomycin as an Adjunct Therapeutic Modality in Eyelid and Extraocular Malignancies and Tumors

    PubMed Central

    Meyer, David; Gooding, Caroline

    2015-01-01

    To present our recent experience with intralesional bleomycin (IBI) in nonmelanoma extraocular tumors, and present previous experience on periocular capillary hemangiomas and orbital lymphangiomas in a tertiary referral hospital. This was a retrospective descriptive study of patients with eyelid and extraocular malignancies where conventional therapies failed, or surgery was contraindicated or refused and were offered IBI as an alternate therapy. All patients were recruited from the Oculoplastics Clinic at Tygerberg Academic Hospital, Cape Town, South Africa. A solution containing 1 international unit of bleomycin per milliliter saline was injected intralesionally together with 2% lignocaine in a ratio of 4:1. The injected volume was calculated to be equivalent to the estimated volume of the lesion. A multipuncture technique with a 29-gauge needle was used. Patients requiring retreatment were injected every 4–8 weeks until satisfactory clinical endpoints were achieved. Our previous experience with IBI in extensive capillary hemangiomas and orbital lymphangiomas is reviewed. Cases are presented to illustrate that IBI induced significant regression and reduction in tumor size and marked clinical improvement of the eyelid and orbital basal cell carcinomas, Kaposi sarcoma, and mycosis fungoides. The improvements obviated the need for further surgical intervention in most cases. Based on clinical experience we propose that IBI should be considered a treatment modality in select cases of the malignant eyelid and ophthalmic vascular tumors where the conventional standard of care is not possible. IBI is a reasonable alternative or adjunct to consider in such cases. PMID:26692709

  14. Chromosomal imbalances in malignant peripheral nerve sheath tumor detected by metaphase and microarray comparative genomic hybridization.

    PubMed

    Nakagawa, Yasuko; Yoshida, Aki; Numoto, Kunihiko; Kunisada, Toshiyuki; Wai, Daniel; Ohata, Norihide; Takeda, Ken; Kawai, Akira; Ozaki, Toshifumi

    2006-02-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are highly malignant tumors affecting adolescents and adults. There have been a few reports on chromosomal aberrations of MPNSTs; however, the tumor-specific alteration remains unknown. We characterized the genomic alterations in 8 MPNSTs and 8 schwannomas by metaphase comparative genomic hybridization (CGH). In 5 of 8 MPNSTs, microarray CGH was added for more detailed analyses. Frequent gains were identified on 3q13-26, 5p13-14, and 12q11-23 and frequent losses were at 1p31, 10p, 11q24-qter, 16, and 17. Microarray CGH revealed frequent gains of EGFR, DAB2, MSH2, KCNK12, DDX15, CDK6, and LAMA3, and losses of CDH1, GLTSCR2, EGR1, CTSB, GATA3, and SULT2A1. These genes seem to be responsible for developing MPNSTs. The concordance rate between metaphase CGH and microarray CGH was 66%. Metaphase CGH was useful for identifying chromosomal alterations before applying microarray CGH. PMID:16391845

  15. KIT (CD117) Expression in Benign and Malignant Sweat Gland Tumors.

    PubMed

    Nishida, Haruto; Daa, Tsutomu; Kashima, Kenji; Arakane, Motoki; Urabe, Shogo; Yoshikawa, Yasuji; Gamachi, Ayako; Yokoyama, Shigeo

    2015-12-01

    KIT (CD117, c-kit) is a receptor tyrosine kinase involved in the tumorigenesis of several neoplasms. KIT is expressed by the secretory cells of normal sweat glands. We studied the KIT expression and KIT mutational status in various benign and malignant tumors of eccrine and apocrine glands. We included a total of 108 cases comprising 10 benign and 6 malignant sweat gland tumors, and KIT expression was immunohistochemically detected (positive rate): 10 syringomas (0%), 8 poromas (25%), 20 mixed tumors (40%), 21 spiradenomas (43%), 1 cylindroma (0%), 5 hidradenomas (40%), 7 syringocystadenoma papilliferum cases (0%), 1 papillary hidradenoma (100%), 2 tubulopapillary hidradenomas (50%), 8 hidrocystomas (29%), 2 adenoid cystic carcinomas (100%), 5 porocarcinomas (20%), 6 apocrine carcinomas (33%), 10 extramammary Paget diseases (30%), 1 spiradenocarcinoma (100%), and 1 syringocystadenocarcinoma papilliferum (0%). Most KIT-positive cells were luminal cells, arising from glandular structures. We performed polymerase chain reaction-single-strand conformation polymorphism for detecting KIT mutational status. All cases showed no mutations at hot spots for KIT (exons 9, 11, 13, and 17). KIT mutation does not seem to be mechanism for KIT expression, but the expression may be from native sweat glands. PMID:25634571

  16. KIT (CD117) Expression in Benign and Malignant Sweat Gland Tumors

    PubMed Central

    Daa, Tsutomu; Kashima, Kenji; Arakane, Motoki; Urabe, Shogo; Yoshikawa, Yasuji; Gamachi, Ayako; Yokoyama, Shigeo

    2015-01-01

    Abstract: KIT (CD117, c-kit) is a receptor tyrosine kinase involved in the tumorigenesis of several neoplasms. KIT is expressed by the secretory cells of normal sweat glands. We studied the KIT expression and KIT mutational status in various benign and malignant tumors of eccrine and apocrine glands. We included a total of 108 cases comprising 10 benign and 6 malignant sweat gland tumors, and KIT expression was immunohistochemically detected (positive rate): 10 syringomas (0%), 8 poromas (25%), 20 mixed tumors (40%), 21 spiradenomas (43%), 1 cylindroma (0%), 5 hidradenomas (40%), 7 syringocystadenoma papilliferum cases (0%), 1 papillary hidradenoma (100%), 2 tubulopapillary hidradenomas (50%), 8 hidrocystomas (29%), 2 adenoid cystic carcinomas (100%), 5 porocarcinomas (20%), 6 apocrine carcinomas (33%), 10 extramammary Paget diseases (30%), 1 spiradenocarcinoma (100%), and 1 syringocystadenocarcinoma papilliferum (0%). Most KIT-positive cells were luminal cells, arising from glandular structures. We performed polymerase chain reaction–single-strand conformation polymorphism for detecting KIT mutational status. All cases showed no mutations at hot spots for KIT (exons 9, 11, 13, and 17). KIT mutation does not seem to be mechanism for KIT expression, but the expression may be from native sweat glands. PMID:25634571

  17. A case of recurrent malignant triton tumor successfully treated with radiotherapy.

    PubMed

    Yasuda, Makoto; Muto, Yoko; Kuremoto, Toshihiro; Murakami, Kentaro; Onisihi, Toshinori; Koida, Atsuhide; Inui, Takaaki; Hisa, Yasuo

    2016-12-01

    A 15-year-old female was previously admitted to another hospital because of painless swelling of the lateral right nasal ala for 2 months. Magnetic resonance imaging revealed an expansive enhancing lesion in close proximity to the anterior surface of the right maxillary sinus and lateral wall of the right nasal cavity. Tumor extirpation was performed via the supragingival transantral approach under general anesthesia. Histopathological study revealed a malignant triton tumor (MTT) arising from the nasal vestibule. The patient was referred to our department for consultation regarding additional treatment. Because the surgical margin was positive and MTT has high malignant potential, we recommended expansion re-surgical treatment following immediate free-flap reconstruction and postoperative radiotherapy, but family consent was not obtained. Tumor regrowth was noted 1 month after her first visit to our department. The patient and her family accepted radiotherapy instead of surgical treatment. Complete remission was achieved by radiotherapy alone. No local recurrence or distant metastasis was observed for 30 months after radiotherapy. The conventional mode of treatment for MTT is radical excision followed by high-dose radiotherapy. However, this case is remarkable because our patient experienced complete remission by simple radiotherapy. PMID:27146005

  18. Progress in the surgical treatment of malignant liver tumors in children.

    PubMed

    Otte, Jean-Bernard

    2010-06-01

    During the last decade, important progress has been made in the surgical treatment of malignant liver tumors in children. For hepatoblastoma, there is a general consensus for combining surgical resection with neoadjuvant (and adjuvant) chemotherapy. Long-term disease-free survival of around 85-90% can be achieved for resectable HB involving no more than three sections of the liver (PRETEXT I-III). For unresectable HB without extrahepatic invasion (PRETEXT IV with involvement of all four sections and some cases of PRETEXT III with invasion of, or close contact with major venous structures), similar results can be obtained with total hepatectomy and liver transplantation. For hepatocellular carcinoma, most often without underlying liver disease in children of the western world, results of resection with partial hepatectomy remain dismal, due to a high rate of recurrence. In contrast, remarkable survival rates have been obtained during the last decade with liver transplantation. There is no argument, either biological or based on evidence, that the selection of pediatric candidates for transplantation should be based on the same criteria as in adult patients (the Milan criteria). Optimization of results require to concentrate children with a malignant liver tumors in specialized, multidisciplinary pediatric centers with expertise in chemotherapy and in both major liver resections and transplantation. Enrolling these children in prospective trials should be encouraged, as well as prospective registration of transplanted patients in PLUTO (Pediatric Liver Unresectable Tumor Observatory-http://Pluto.cineca.org) in order to clarify issues unresolved by retrospective studies. PMID:20227190

  19. Effects of whole-body irradiation on neonatally thymectomized mice. Incidence of benign and malignant tumors.

    PubMed Central

    Anderson, R. E.; Howarth, J. L.; Troup, G. M.

    1978-01-01

    The individual and combined effects of neonatal thymectomy and whole-body irradiation on the prevalence of benign and malignant tumors in germ-free female mice of the Charles Rivers line were studied to determine if a portion of the tumorigenic effects of irradiation can be attributed to injury of the thymic-dependent component of the immune response. Neonatal thymectomy increased a) the incidence of benign and malignant tumors and b) the prevalence of multiple primary neoplasms in an individual mouse. Whole-body exposure to 700 rad at 6 weeks of age further increased th incidence of tumors, but the relative magnitude of this increase was less pronounced than in sham-operated controls. Thus, the cumulative effects of thymectomy plus irradiation are less pronounced than the sum of the individual effects. One of several possible explanations for this observation is that a portion of the carcinogenic effects of whole-body irradiation is mediated by suppression of the thymic-dependent component of the immune response. PMID:645825

  20. Endoscopic photodynamic therapy with hematoporphyrin derivative in the treatment of malignant tumors: report of 120 cases

    NASA Astrophysics Data System (ADS)

    Tian, Mao-en; Liu, Fa-wen; Qian, Jia-ping; Ji, Qing; Feng, Yun-qiu

    1993-03-01

    One-hundred-twenty cases of malignant tumors treated by endoscopic photodynamic therapy with hematoporphyrin derivative from August 1982 - July 1990 are reported. Of the 120 cases, including 97 males and 23 females ages varying from 39 to 77 years old, 40 cases were primary tumors and 80 cases were local residual or recurrent after surgery or radiotherapy or chemotherapy. All cases were confirmed in pathological biopsy, including 58 squamous cell carcinoma, 28 various adenocarcinoma, and 34 transitional cell carcinoma. Twenty-four, 48 and/or 72 hours after intravenous injection of HpD 2.0 - 3.0 mg/kg, or DHE 1.5 - 2.0 mg/kg, or Y-HpD 5.0 mg/kg, the tumor was irradiated with 630 nm wavelength of argon dye laser via a quartz light fiber inserted through the forceps channel of the endoscope. Of the 120 cases treated, CR was obtained in 38 cases, PR in 25 cases, MR in 52 cases, and NR in 5 cases. Total response rate was 95.8%; significant response rate 52.5%; and tumor eradicated rate 31.7%. The 38 cases included: 14 cases of early esophageal carcinoma, 3 cases of early cardiac carcinoma, 1 case of early lung cancer, 1 case of early gastric carcinoma, 15 cases of superficial bladder carcinoma, 3 cases of local residual recurrent micro lung cancer, and 1 case of cardiac carcinoma. The longest cancer-free survival was over eight years. Endoscopic photodynamic therapy is, therefore, curative effective in the treatment of early and superficial carcinoma, and palliative effective in the treatment of advanced carcinoma. Standardized and controlled trials are required to assess its place in combined treatment of malignant tumors.

  1. Epithelial-mesenchymal transition, the tumor microenvironment, and metastatic behavior of epithelial malignancies

    PubMed Central

    Talbot, Lindsay J; Bhattacharya, Syamal D; Kuo, Paul C

    2012-01-01

    Objective The mechanisms of cancer metastasis have been intensely studied recently and may provide vital therapeutic targets for metastasis prevention. We sought to review the contribution of epithelial-mesenchymal transition and the tumor microenvironment to cancer metastasis. Summary Background Data Epithelial-mesenchymal transition is the process by which epithelial cells lose cell-cell junctions and baso-apical polarity and acquire plasticity, mobility, invasive capacity, stemlike characteristics, and resistance to apoptosis. This cell biology program is active in embryology, wound healing, and pathologically in cancer metastasis, and along with the mechanical and cellular components of the tumor microenvironment, provides critical impetus for epithelial malignancies to acquire metastatic capability. Methods A literature review was performed using PubMed for “epithelial-mesenchymal transition”, “tumor microenvironment”, “TGF-β and cancer”, “Wnt and epithelial-mesenchymal transition”, “Notch and epithelial-mesenchymal transition”, “Hedgehog and epithelial-mesenchymal transition” and “hypoxia and metastasis”. Relevant primary studies and review articles were assessed. Results Major signaling pathways involved in epithelial-mesenchymal transition include TGF-β, Wnt, Notch, Hedgehog, and others. These pathways converge on several transcription factors, including zinc finger proteins Snail and Slug, Twist, ZEB 1/2, and Smads. These factors interact with one another and others to provide crosstalk between the relevant signaling pathways. MicroRNA suppression and epigenetic changes also influence the changes involved in epithelial-mesenchymal transition. Cellular and mechanical components of the tumor microenvironment are also critical in determining metastatic potential. Conclusions While the mechanisms promoting metastasis are extremely wide ranging and still under intense investigation, the epithelial-mesenchymal transition program and

  2. Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells.

    PubMed

    Ruma, I Made Winarsa; Putranto, Endy Widya; Kondo, Eisaku; Watanabe, Risayo; Saito, Ken; Inoue, Yusuke; Yamamoto, Ken-Ichi; Nakata, Susumu; Kaihata, Masaji; Murata, Hitoshi; Sakaguchi, Masakiyo

    2014-07-01

    Angiogenesis is essential for tumor development and metastasis. Among several angiogenic factors, vascular endothelial growth factor receptor (VEGF) is important for tumor-derived angiogenesis and commonly overexpressed in solid tumors. Thus, many antitumor strategies targeting VEGF have been developed to inhibit cancer angiogenesis, offering insights into the successful treatment of solid cancers. However, there are a number of issues such as harmful effects on normal vascularity in clinical trials. Taking this into consideration, we employed Cordyceps militaris as an antitumor approach due to its biological safety in vivo. The herbal medicinal mushroom Cordyceps militaris has been reported to show potential anticancer properties including anti-angiogenic capacity; however, its concrete properties have yet to be fully demonstrated. In this study, we aimed to elucidate the biological role of Cordyceps militaris extract in tumor cells, especially in regulating angiogenesis and tumor growth of a human malignant melanoma cell line. We demonstrated that Cordyceps militaris extract remarkably suppressed tumor growth via induction of apoptotic cell death in culture that links to the abrogation of VEGF production in melanoma cells. This was followed by mitigation of Akt1 and GSK-3β activation, while p38α phosphorylation levels were increased. Extract treatment in mouse model xenografted with human melanoma cells resulted in a dramatic antitumor effect with down-regulation of VEGF expression. The results suggest that suppression of tumor growth by Cordyceps militaris extract is, at least, mediated by its anti-angiogenicity and apoptosis induction capacities. Cordyceps militaris extract may be a potent antitumor herbal drug for solid tumors. PMID:24789042

  3. Coexistence of malignant phyllodes tumor and her2-positive locally advanced breast cancer in distinct breasts: A case report

    PubMed Central

    Sato, Tomoi; Muto, Ichiro; Sakai, Takeshi

    2016-01-01

    Introduction Phyllodes tumor of the breast is a rare biphasic neoplasm, accounting for less than 1% of all breast tumors. Coexistence of phyllodes tumor and breast cancer in distinct breasts is extremely rare. Case presentation A 47-year-old Japanese woman presented with bilateral breast lumps. A HER2-positive, unresectable invasive carcinoma in the right breast and fibroadenoma in the left were diagnosed via core needle biopsy. During chemotherapy with anti-HER2 therapy, the breast cancer shrank quickly, while the left breast lump suddenly enlarged. Under a diagnosis of malignant neoplasm of the breast, left mastectomy was performed. Malignant phyllodes tumor was diagnosed by postoperative histological examination and recurred in multiple areas as early as 2 months after surgery. Discussion Only 10 cases of coexisting phyllodes tumor and breast cancer in distinct breasts have been reported in the English literature. Phyllodes tumor associated with breast cancer in distinct breasts tends to be malignant. This is the first case of phyllodes tumor rapidly enlarging during anti-HER2 chemotherapy for locally advanced HER2-positive breast cancer. Conclusion Even during effective treatment of advanced or recurrent breast cancer, attention should also be paid to the contralateral breast for the possible association of a second malignancy such as phyllodes tumor. PMID:26773878

  4. Diagnostic pitfalls in the preoperative 18F-FDG PET/CT evaluation of a case of giant malignant solitary fibrous tumor of the pleura.

    PubMed

    Lococo, F; Rapicetta, C; Ricchetti, T; Cavazza, A; Filice, A; Treglia, G; Tenconi, S; Paci, M; Sgarbi, G

    2014-01-01

    Solitary fibrous tumor of the pleura (SFTP) is an uncommon entity, generally with an indolent behavior. Nevertheless, some malignant forms have been rarely reported. These, often have an aggressive biological behavior with pathological findings of invasiveness. The preoperative diagnosis and evaluation of the grade of malignancy are extremely challenging. Herein we report a case of a 64-year-old man who presented with a left giant intra-thoracic mass imaged with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG/PET-CT) and sampled via fine-needle aspiration biopsy (FNAB). Imaging and FNAB findings showed suspicion of a benign form of SFTP. Surgical radical resection of the giant mass was performed. The definitive histological diagnosis showed a malignant SFTP. Based on this report, we take the opportunity to briefly discuss the insidious pitfalls concerning the radiological and (18)F-FDG/PET-CT features as well as cyto/histological findings in the pre-operative diagnostic work-up examination of this rare entity. PMID:24079956

  5. Endovascular Therapy for Management of Oral Hemorrhage in Malignant Head and Neck Tumors

    SciTech Connect

    Kakizawa, Hideaki Toyota, Naoyuki; Naito, Akira; Ito, Katsuhide

    2005-12-15

    Purpose. To evaluate the efficacy and safety of endovascular therapy in oral hemorrhage from malignant head and neck tumors. Methods. Ten patients (mean age 56 years) with oral hemorrhage caused by malignant head and neck tumors underwent a total of 13 emergency embolization procedures using gelatin sponge particles, steel and/or platinum coils, or a combination of these embolic materials. Angiographic abnormalities, technical success rate, clinical success rate, recurrence rate, complications, hemostatic period, hospital days, survival days, and patient outcome were all analyzed. Results. Angiographic abnormalities were identified during 85% of procedures (11/13). The technical success rate was 100% (13/13 procedures). The primary and secondary clinical success rates were 77% (10/13 procedures) and 67% (2/3 procedures), respectively. The overall clinical success rate was 92%, and the recurrence rate was 22% (2/9 procedures) in patients whom we were able to observe during the 1-month period after embolization. No major complications occurred. Several patients in whom gelatin sponge particles had been used complained of transient local pain after the procedure. The median hemostatic period was 71 days (range 0-518 days). Median hospital and survival days were 59 days (range 3-209 days) and 141 days (range 4-518 days), respectively. Three patients survived and 7 patients died during the observation period. Only 1 of these 7 patients died from hemorrhage. Conclusion. In conclusion, our findings suggest that endovascular therapy is an effective, safe, and repeatable treatment for oral hemorrhage caused by malignant head and neck tumors.

  6. The role of erythropoietin and erythropoietin receptor in malignant laryngeal tumors.

    PubMed

    Vukelic, Jelena; Dobrila-Dintinjana, Renata; Jonjic, Nives; Dekanic, Andrea; Ilijic, Vjekoslav

    2013-12-01

    Erythropoietin (Epo) is a glycoprotein hormone responsible for erythropoiesis. Its effect is realized by binding erythropoietin receptor (EpoR) expressed on erythroid progenitor cells. Hypoxia is the main stimulus for the secretion of erythropoietin. Anemia is an independent negative prognostic factor for survival in patients with malignant diseases. Synthetic forms of erythropoietin are used in clinical oncology practice to increase the level of hemoglobin. As well as endogenous they can bind to EpoR. Considering the fact that most effects of synthetic Epo are negative, the role of endogenous Epo/EpoR has become an extremely important issue. The authors do not agree on most items related to the effects of exogenous Epo and EpoR in patients with head and neck carcinomas. We are investigating the expression of Epo/EpoR in the tissue of malignant laryngeal carcinoma. Our hypothesis is that less differentiated laryngeal carcinomas will have a higher level of endogenous Epo/EpoR expression. Therefore, in patients with positive Epo/EpoR we expect shorter survival and poorer locoregional disease control. We anticipate that our hypothesis may help to provide the role of endogenous Epo/EpoR in patients with malignant tumors of the larynx. If the assumptions of this study are confirmed, the patients with laryngeal carcinomas whose tumor cells express Epo/EpoR should not be considered for the treatment of anemia with recombinant erythropoietin in any case. We also point out that our research will expand the knowledge of the biology of laryngeal tumor cells and that the results could be utilized as basic knowledge in development of future therapeutic strategies. PMID:24134826

  7. Malignant Rhabdoid Tumor of the Kidney and Spine in an Infant

    PubMed Central

    Park, Sejun; Seo, Jae-Hee; Park, Jun Bum

    2014-01-01

    Rhabdoid tumor of the kidney (RTK) is a rare malignancy in infancy. Central nervous system involvement in RTK is already known. However, solitary spinal metastasis in RTK has been hardly reported. The authors report a case of metastatic RTK to spine causing paraplegia in an 8-month-old girl. Since the patient was young, the diagnosis of spine metastasis was delayed until paraplegia was seen after radical nephrectomy. Thorough neurological examination should be performed for early diagnosis of spinal metastasis in young patients with RTK. If there are any abnormal signs in neurologic examination, magnetic resonance images of brain and spine are recommended. PMID:24570822

  8. Orbital masses: CT and MRI of common vascular lesions, benign tumors, and malignancies

    PubMed Central

    Khan, Sarah N.; Sepahdari, Ali R.

    2012-01-01

    A wide variety of space occupying lesions may be encountered in the orbit. CT and MR imaging frequently help confirm the presence of a mass and define its extent. Characteristic imaging features may help distinguish among lesions that have overlapping clinical presentations. This review focuses on some of the common orbital masses. Common vascular lesions that are reviewed include: capillary (infantile) hemangioma, cavernous hemangioma (solitary encapsulated venous-lymphatic malformation), and lymphangioma (venous-lymphatic malformation). Benign tumors that are reviewed include: optic nerve sheath meningioma, schwannoma, and neurofibroma. Malignancies that are reviewed include: lymphoma, metastasis, rhabdomyosarcoma, and optic glioma. Key imaging features that guide radiological diagnosis are discussed and illustrated. PMID:23961022

  9. Role of diffusion-weighted magnetic resonance imaging in differentiating malignancies from benign ovarian tumors

    PubMed Central

    Fan, Xinhua; Zhang, Hongbin; Meng, Shuang; Zhang, Jing; Zhang, Chuge

    2015-01-01

    Objective: We conducted a case-control study to evaluate the diagnostic values of computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) in differentiating malignancies from benign ovarian tumors and a meta-analysis to further confirm our results on DW-MRI. Methods: Totally 64 patients pathologically confirmed as ovarian cancer were included in this study. CT scan and DWI-MRI were performed and analyzed to get compared with pathological results, thereby assessing their accuracy, sensitivity and specificity. Meta-analysis was conducted by database searching and strict eligibility criteria, using STATA 12.0 (Stata Corp, College Station, TX, USA) software. Results: The accuracy, sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of ovarian cancer in CT were 81.82%, 84.48%, 76.67%, 87.50% and 71.88%, respectively; those in DW-MRI were 89.77%, 93.10%, 83.33%, 91.53% and 86.21%, respectively. The Kappa coefficient of DW-MRI (K = 0.771) compared with pathological results was higher than CT (K = 0.602). The average apparent diffusion coefficient values of DW-MRI in diagnosis of benign and malignant ovarian tumors suggested statistically significant difference (1.325 ± 0.269×10-3 mm2/s vs. 0.878 ± 0.246×10-3 mm2/s, P < 0.001). Meta-analysis results showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of DW-MRI in discriminating benign versus malignant ovarian tumors were 0.93, 0.88, 7.70, 0.08 and 101.24, respectively. The area under the summary receiver operating characteristic curve was 0.95. Conclusions: Both CT and DW-MRI were of great diagnostic value in differentiating malignancies from benign ovarian tumors, while DW-MRI was superior to CT with higher accuracy, sensitivity and specificity. PMID:26884905

  10. Triterpenoid saponin flaccidoside II from Anemone flaccida triggers apoptosis of NF1-associated malignant peripheral nerve sheath tumors via the MAPK-HO-1 pathway.

    PubMed

    Han, Lin-Tao; Fang, Yin; Cao, Yan; Wu, Feng-Hua; Liu, E; Mo, Guo-Yan; Huang, Fang

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue neoplasms that are extremely rare and are frequently associated with neurofibromatosis type 1 patients. MPNSTs are typically fatal, and there is no effective treatment so far. In our previous study, we showed that flaccidoside II, one of the triterpenoid saponins isolated from Anemone flaccida Fr. Schmidt, has antitumor potential by inducing apoptosis. In the present study, we found that flaccidoside II inhibits proliferation and facilitates apoptosis in MPNST cell lines ST88-14 and S462. Furthermore, this study provides a mechanism by which the downregulation of heme oxygenase-1 via extracellular signal-regulated kinase-1/2 and p38 mitogen-activated protein kinase pathways is involved in the apoptotic role of flaccidoside II. This study suggested the potential of flaccidoside II as a novel pharmacotherapeutic approach for MPNSTs. PMID:27103823

  11. Triterpenoid saponin flaccidoside II from Anemone flaccida triggers apoptosis of NF1-associated malignant peripheral nerve sheath tumors via the MAPK-HO-1 pathway

    PubMed Central

    Han, Lin-tao; Fang, Yin; Cao, Yan; Wu, Feng-hua; Liu, E; Mo, Guo-yan; Huang, Fang

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue neoplasms that are extremely rare and are frequently associated with neurofibromatosis type 1 patients. MPNSTs are typically fatal, and there is no effective treatment so far. In our previous study, we showed that flaccidoside II, one of the triterpenoid saponins isolated from Anemone flaccida Fr. Schmidt, has antitumor potential by inducing apoptosis. In the present study, we found that flaccidoside II inhibits proliferation and facilitates apoptosis in MPNST cell lines ST88-14 and S462. Furthermore, this study provides a mechanism by which the downregulation of heme oxygenase-1 via extracellular signal-regulated kinase-1/2 and p38 mitogen-activated protein kinase pathways is involved in the apoptotic role of flaccidoside II. This study suggested the potential of flaccidoside II as a novel pharmacotherapeutic approach for MPNSTs. PMID:27103823

  12. Malignant Peripheral Nerve Sheath Tumor Invasion Requires Aberrantly Expressed Epidermal Growth Factor (EGF) Receptors and is Variably Enhanced by Multiple EGF Family Ligands

    PubMed Central

    Byer, Stephanie J.; Brossier, Nicole M.; Peavler, Lafe T.; Eckert, Jenell M.; Watkins, Stacey; Roth, Kevin A.; Carroll, Steven L.

    2013-01-01

    Aberrant epidermal growth factor receptor (EGFR) expression promotes the pathogenesis of malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy associated with neurofibromatosis type 1, but the mechanisms by which EGFR expression promotes MPNST pathogenesis are poorly understood. We hypothesized that inappropriately expressed EGFRs promote MPNST invasion and found that these kinases are concentrated in MPNST invadopodia in vitro. EGFR knockdown inhibited the migration of unstimulated MPNST cells in vitro and exogenous EGF further enhanced MPNST migration in a substrate-specific manner, promoting migration on laminin and, to a lesser extent, collagen. Thus, in this setting, EGF acts as a chemotactic factor. We also found that the 7 known EGFR ligands (EGF, betacellulin, epiregulin, heparin-binding EGF, transforming growth factor α [TGFα], amphiregulin, and epigen) variably enhanced MPNST migration in a concentration-dependent manner, with TGFα being particularly potent. With the exception of epigen, these factors similarly promoted the migration of non-neoplastic Schwann cells. Although transcripts encoding all 7 EGFR ligands were detected in human MPNST cells and tumor tissues, only TGFα was consistently overexpressed and was found to colocalize with EGFR in situ. These data indicate that constitutive EGFR activation, potentially driven by autocrine or paracrine TGFα signaling, promotes the aggressive invasive behavior characteristic of MPNSTs. PMID:23399900

  13. P08: Somatostatin analogs plus prednisone in aggressive histotype and advanced stage of thymic epithelial tumors

    PubMed Central

    Ottaviano, Margaret; Damiano, Vincenzo; Nappi, Lucia; Rescigno, Pasquale; Marino, Mirella; Del Vecchio, Silvana; Tucci, Irene; von Arx, Claudia; Palumbo, Giuliano; Palmieri, Giovannella

    2015-01-01

    Background Thymic epithelial tumors (TETs) are rare neoplasms characterized by histological variability and different expression at the molecular level. Several biological agents have been evaluated in TETs in small phase II trials. Efficacy of octreotide/lanreotide with or without prednisone in TETs OctreoScan positive has been widely demonstrated in thymoma, but no clearly in thymic carcinoma. Methods Twelve patients (five men, seven women; median age 47 years; range, 27–70 years) with advanced stage disease according to the Masaoka-Koga staging system (seven with IVa stage; five with IVb stage), and aggressive histotype according to WHO classification, revised by central review (two B2/B3; five B3; one B3/thymic carcinoma; four thymic carcinoma) were enrolled in this monocentric referral study. All the patients showed a progressive disease according to RECIST 1.1 criteria to previous conventional chemotherapeutic regimens platinum or not platinum-based. All the patients performed OctreoScan. The schedule includes administration of long-acting analog octreotide (30 mg/every 28 days intramuscularly) plus prednisone 0.2 mg/kg/day until progression of disease was documented. Overall response rate and toxicity were evaluated. Results The median time to progression was 6 months (range, 3–24 months), the overall response rate was 74.9%, particularly three patients (25%) obtained stable disease; four patients (33.3%) partial response; two patients (16.6%) complete response; three patients (25%) progression disease. One patient with Good Syndrome interrupted treatment after 6 months for infection disease. One patient has been lost to follow-up after 24 months of treatment. One patient died after progression disease for PRCA. Treatment was generally well tolerated with acceptable toxicity: no symptomatic cholelithiasis (one patient), grade 1 diarrhea (two patients) hyperglycemia (one patient). One patient with thymic carcinoma and IVB stage had PS improvement from 2

  14. Intracranial malignant triton tumor in a patient with neurofibromatosis type 1: case report and review of the literature.

    PubMed

    Smith, Ross E; Kebriaei, Meysam A; Gard, Andrew P; McComb, Rodney D; Bridge, Julia A; Lennarson, Peter J

    2014-04-01

    We report the fourth case of an intracranial malignant triton tumor not associated with a cranial nerve in a 26-year-old male with a clinical history of neurofibromatosis type 1. The patient was found unresponsive and displayed confusion, lethargy, hyperreflexia, and dysconjugate eye movements upon arrival at the emergency room. MRI revealed a large bifrontal mass. Biopsy demonstrated a high-grade spindle cell tumor with focal areas of rhabdomyoblasts that stained positive for desmin, myogenin, and muscle-specific actin. Electron microscopy showed skeletal muscle differentiation. Based on the clinical history of NF1 and the pathologic results, a diagnosis of malignant triton tumor was made. The differential diagnosis, immunohistochemistry, molecular genetics, and treatment of malignant triton tumor are reviewed. PMID:23633163

  15. Malignant perivascular epithelioid cell tumor (PEComa) of cervix with TFE3 gene rearrangement: a case report

    PubMed Central

    Liu, Feifei; Zhang, Renya; Wang, Zi-Yu; Xia, Qiuyuan; Shen, Qin; Shi, Shanshan; Tu, Pin; Shi, Qunli; Zhou, Xiaojun; Rao, Qiu

    2014-01-01

    In this study, we reported the first PEComa arising within the cervix with TFE3 gene rearrangement and aggressive biological behavior. Morphologically, the tumor showed infiltrative growth into the surrounding parenchyma. The majority of tumor cells were arrayed in sheets, alveolar structures, or nests separated by delicate fibrovascular septa. There was marked intratumoral hemorrhage, necrosis, and stromal calcifications. The tumor cells had abundant clear cytoplasm, focally containing finely granular dark brown pigment, morphologically considered to be melanin. Immunohistochemically, the tumor cells demonstrated moderately (2+) or strongly (3+) positive staining for TFE3, HMB45, and Melan A but negative for CKpan, SMA, S100, PAX8, and PAX2. The presence of Ki-67 protein demonstrated a moderate proliferation rate, with a few Ki-67-positive nuclei. Using a recently developed TFE3 split FISH assay, the presence of TFE3 rearrangement was demonstrated. All these clinicopathologic features are suggestive of TFE3-rearranged PEComas of the cervix. Our results both expand the known characteristics of primary cervix PEComas and add to the data regarding TFE3 rearrangement-associated PEComas. PMID:25337301

  16. Surveillance imaging in children with malignant CNS tumors: low yield of spine MRI.

    PubMed

    Perreault, Sébastien; Lober, Robert M; Carret, Anne-Sophie; Zhang, Guohua; Hershon, Linda; Décarie, Jean-Claude; Vogel, Hannes; Yeom, Kristen W; Fisher, Paul G; Partap, Sonia

    2014-02-01

    Magnetic resonance imaging (MRI) is routinely obtained in patients with central nervous system (CNS) tumors, but few studies have been conducted to evaluate this practice. We assessed the benefits of surveillance MRI and more specifically spine MRI in a contemporary cohort. We evaluated MRI results of children diagnosed with CNS tumors from January 2000 to December 2011. Children with at least one surveillance MRI following the diagnosis of medulloblastoma (MB), atypical teratoid rhabdoid tumor (ATRT), pineoblastoma (PB), supratentorial primitive neuroectodermal tumor, supratentorial high-grade glioma (World Health Organization grade III-IV), CNS germ cell tumors or ependymoma were included. A total of 2,707 brain and 1,280 spine MRI scans were obtained in 258 patients. 97% of all relapses occurred in the brain and 3% were isolated to the spine. Relapse was identified in 226 (8%) brain and 48 (4%) spine MRI scans. The overall rate of detecting isolated spinal relapse was 9/1,000 and 7/1,000 for MB patients. MRI performed for PB showed the highest rate for detecting isolated spinal recurrence with 49/1,000. No initial isolated spinal relapse was identified in patients with glioma, supratentorial primitive neuroectodermal tumor and ATRT. Isolated spinal recurrences are infrequent in children with malignant CNS tumors and the yield of spine MRI is very low. Tailoring surveillance spine MRI to patients with higher spinal relapse risk such as PB, MB with metastatic disease and within 3 years of diagnosis could improve allocation of resources without compromising patient care. PMID:24401959

  17. Malignant peripheral nerve sheath tumor in a cat with nodal and pulmonary metastases.

    PubMed

    Buza, Elizabeth L; Menzies, Robert A; Goldschmidt, Michael H; Durham, Amy C

    2012-07-01

    Peripheral nerve sheath tumors in domestic cats are infrequently reported and are often locally invasive. An 11-year-old Domestic Shorthair cat was originally diagnosed with a right maxillary benign peripheral nerve sheath tumor at incisional biopsy. At necropsy, the neoplasm had features of malignancy including metastases to the regional lymph nodes and lung. Histologically, the neoplasm contained 2 distinct regions: spindle cells arranged in dense interwoven bundles with Antoni A areas and Verocay bodies and Antoni B regions with loosely arranged spindle cells separated by a mucinous matrix. Immunohistochemically, the neoplastic cells in the primary mass and right mandibular lymph node were strongly positive for vimentin, S-100, and glial fibrillar acidic protein. The neoplastic cells within the lung were strongly positive for vimentin and weakly positive for S-100 and glial fibrillar acidic protein. PMID:22604770

  18. Four cases of cell cannibalism in highly malignant feline and canine tumors.

    PubMed

    Ferreira, Fernando Costa; Soares, Maria João; Carvalho, Sandra; Borralho, Liliana; Vicente, Gonçalo; Branco, Sandra; Correia, Jorge; Peleteiro, Maria Conceição

    2015-01-01

    Four cases of tumors in which cell internalization was frequently visualized are reported: one feline mammary carcinoma, one feline cutaneous squamous cell carcinoma, one canine pulmonary squamous cell carcinoma and one canine pleural mesothelioma. Cell internalization was observed by cytology in two of these cases (the feline mammary tumour and the pleural effusion in the canine mesothelioma) and by histopathology in all but the canine mesothelioma. Immunohistochemical staining for pancytokeratin was positive for both internalized and host cells, while E-cadherin expression was frequently absent, although internalized cells occasionally stained positive. This cell-to-cell interaction seems to be associated with tumors displaying a strong epithelial-mesenchymal transitional phenotype, in which cancer cells become engulfed by other cancer cells. Such event could be regarded as an important hallmark of very high malignancy. PMID:26525147

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

    PubMed Central

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

    2009-01-01

    SUMMARY Multiple angiogenesis inhibitors have been therapeutically validated in preclinical cancer models, and several in clinical trials. Here we report that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and distant metastasis. Increased invasiveness is also seen by genetic ablation of the Vegf-A gene in both models, substantiating the results of the pharmacological inhibitors. The realization that potent angiogenesis inhibition can alter the natural history of tumors by increasing invasion and metastasis warrants clinical investigation, as the prospect has important implications for the development of enduring antiangiogenic therapies. PMID:19249680

  20. Phase I study of recombinant human tumor necrosis factor-alpha in patients with advanced malignancies.

    PubMed

    Bartsch, H H; Nagel, G A; Mull, R; Flener, R; Pfizenmaier, K

    1988-01-01

    A clinical phase I trial with recombinant human tumor necrosis factor-alpha (rTNF-alpha) was performed in 30 patients with advanced malignancies. The maximal tolerated dose (MTD) by 3 times weekly intramuscular (i.m.) application was 150 micrograms m-2. Main subjective toxicities including chills, fever, hypotension, fatigue, and anorexia were dose-related. In addition, transient changes in hematologic parameters and lipid metabolism were noted. Two out of 25 evaluated patients showed a minor tumor response after eight weeks of therapy. There was evidence for an improvement of in vivo immuneresponsiveness as revealed from positive delayed type hypersensitivity (DTH) skin tests of 3 out of 6 pretherapeutically anergic patients. We conclude from this phase I trial that rTNF-alpha can be safely administered at doses up to 150 micrograms m-2 i.m., 3 times weekly, without evidence of cumulative toxicity in long-term treatment. PMID:3267369

  1. Is There a Role for PET/CT Parameters to Characterize Benign, Malignant, and Metastatic Parotid Tumors?

    PubMed Central

    Kendi, Ayse Tuba Karagulle; Magliocca, Kelly R.; Corey, Amanda; Galt, James R.; Switchenko, Jeffrey; Wadsworth, J. Trad; El-Deiry, Mark W.; Schuster, David M.; Saba, Nabil F.; Hudgins, Patricia A.

    2016-01-01

    OBJECTIVE Assessment of benign and malignant lesions of the parotid gland, including metastatic lesions, is challenging with current imaging methods. Fluorine-18 FDG PET/CT is a noninvasive imaging modality that provides both anatomic and metabolic information. Semiquantitative data obtained from PET/CT, also known as PET/CT parameters, are maximum, mean, or peak standardized uptake values (SUVs); metabolic tumor volume; total lesion glycolysis; standardized added metabolic activity; and normalized standardized added metabolic activity. Our aim was to determine whether FDG PET/CT parameters can differentiate benign, malignant, and metastatic parotid tumors. MATERIALS AND METHODS Thirty-four patients with parotid neoplasms underwent PET/CT before parotidectomy; maximum SUV, mean SUV, peak SUV, total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity were calculated on a dedicated workstation. Univariate analyses were performed. A ROC analysis was used to determine the ability of PET/CT parameters to predict pathologically proven benign, malignant, and metastatic parotid gland neoplasms. RESULTS Fourteen patients had a benign or malignant primary parotid tumor. Twenty had metastases to the parotid gland. When the specificity was set to at least 85% for each parameter to identify cut points, the corresponding sensitivities ranged from 15% to 40%. Assessment of benign versus malignant lesions of parotid tumors, as well as metastasis from squamous cell carcinoma versus other metastatic causes, revealed that none of the PET/CT parameters has enough power to differentiate among these groups. CONCLUSION PET/CT parameters, including total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity, are not able to differentiate benign from malignant parotid tumors, primary parotid tumors from metastasis, or metastasis

  2. Extending the Convergence of Canonical WNT Signaling and Classic Cancer Pathways for Treatment of Malignant Peripheral Nerve Sheath Tumors

    PubMed Central

    Reilly, Karlyne M.

    2016-01-01

    Summary Malignant peripheral nerve sheath tumors (MPNSTs) are incurable tumors of the Schwann cell lineage that progress unpredictably from benign plexiform neurofibromas (PNFs). In this issue of Cancer Discovery Watson and colleagues (1) use an insertional mutagenesis screen combined with network analysis to identify the canonical Wnt signaling pathway as an important potential biomarker of tumor progression and target for combination therapy in MPNSTs. PMID:23749527

  3. Clinical outcome and prognosis of carbon ion radiotherapy on thoracic malignant tumors

    NASA Astrophysics Data System (ADS)

    Li, Sha

    Objective To evaluate the therapeutic efficacy and side-response of high-LET carbon ion radiotherapy on thoracic malignant tumors. Methods Ten patients with pathological confirmed thoracic malignant tumors received treatment using heavy ion accelerator, which included 6 cases with non-small lung cancer, one case with small lung cancer, 2 cases with metastatic sarcomas and one case with invasive thymoma. The applied regimen included fractioned dose (5.5-6.8GyE/Fraction), one faction/day, and 7 fractions/week. The total dose ranged from 55 to 70 GyE. Results The short-term results showed that the response rate (the complete response (CR) rate +the partial response (PR) rate) was 10% at the first month, 40% at the third month and 90% at the sixth month. The overall response rate was 90% and the rate of stable disease was 10%. There was no relation between the response rate and tumor pathology (P>0.05) while significance between the response rate and the tumor volume.At median follow-up of 27 months (range, 6 to 36 months), the local control rate and free-disease rate were respectively 100% an 90% at the first year, 90% and 80% at the secondary year, 80% and 70% at the third year. The death rate due to disease progression was 20% and the non-specific death rate was 10%. Side and toxicity effects: Grade I skin effect occurred in three cases and Grade I lung effect occurred in two cases. The blood counts didn’t reach significance among pre-radiation course, peri-radiation course and post-radiation course (P>0.05). The subgoups of T cells detected in humoral immunity and cytoimmunity didn’t change between pre-radiation and post radiation(P>0.05). Conclusions Carbon ion radiotherapy is effective and safe in the management of patients with thoracic malignant tumors. There were no obvious side effects. The long term of clinical outcome and the late effect need to be further observed.

  4. Sub-100nm gold nanomatryoshkas improve photo-thermal therapy efficacy in large and highly aggressive triple negative breast tumors.

    PubMed

    Ayala-Orozco, Ciceron; Urban, Cordula; Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-10-10

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or necrotic regions. We report the performance advantages obtained by sub 100nm gold nanomatryushkas, comprising concentric gold-silica-gold layers compared to conventional ~150nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000mm(3)) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5× accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  5. Sub-100 nm Gold Nanomatryoshkas Improve Photo-thermal Therapy Efficacy in Large and Highly Aggressive Triple Negative Breast Tumors

    PubMed Central

    Bishnoi, Sandra; Urban, Alexander; Charron, Heather; Mitchell, Tamika; Shea, Martin; Nanda, Sarmistha; Schiff, Rachel; Halas, Naomi; Joshi, Amit

    2014-01-01

    There is an unmet need for efficient near-infrared photothermal transducers for the treatment of highly aggressive cancers and large tumors where the penetration of light can be substantially reduced, and the intra-tumoral nanoparticle transport is restricted due to the presence of hypoxic or nectrotic regions. We report the performance advantages obtained by sub 100 nm gold nanomatryushkas, comprising of concentric gold-silica-gold layers compared to conventional ~150 nm silica core gold nanoshells for photothermal therapy of triple negative breast cancer. We demonstrate that a 33% reduction in silica-core-gold-shell nanoparticle size, while retaining near-infrared plasmon resonance, and keeping the nanoparticle surface charge constant, results in a four to five fold tumor accumulation of nanoparticles following equal dose of injected gold for both sizes. The survival time of mice bearing large (>1000 mm3) and highly aggressive triple negative breast tumors is doubled for the nanomatryushka treatment group under identical photo-thermal therapy conditions. The higher absorption cross-section of a nanomatryoshka results in a higher efficiency of photonic to thermal energy conversion and coupled with 4-5X accumulation within large tumors results in superior therapy efficacy. PMID:25051221

  6. Tristetraprolin is a tumor suppressor that impairs Myc-induced lymphoma and abolishes the malignant state

    PubMed Central

    Rounbehler, Robert J.; Fallahi, Mohammad; Yang, Chunying; Steeves, Meredith A.; Li, Weimin; Doherty, Joanne R.; Schaub, Franz X.; Sanduja, Sandhya; Dixon, Dan A.; Blackshear, Perry J.; Cleveland, John L.

    2012-01-01

    SUMMARY Myc oncoproteins directly regulate transcription by binding to target genes, yet this only explains a fraction of the genes affected by Myc. mRNA turnover is controlled via AU-binding proteins (AUBPs) that recognize AU-rich elements (AREs) found within many transcripts. Analyses of precancerous and malignant Myc-expressing B cells revealed that Myc regulates hundreds of ARE-containing (ARED) genes and select AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP/ZFP36), an mRNA-destabilizing AUBP, and this circuit is also operational during B lymphopoiesis and IL7 signaling. Importantly, TTP suppression is a hallmark of cancers with MYC involvement, and restoring TTP impairs Myc-induced lymphomagenesis and abolishes maintenance of the malignant state. Further, there is a selection for TTP loss in malignancy; thus, TTP functions as a tumor suppressor. Finally, Myc/TTP-directed control of select cancer-associated ARED genes is disabled during lymphomagenesis. Thus, Myc targets AUBPs to regulate ARED genes that control tumorigenesis. PMID:22863009

  7. [Phase II study of recombinant leukocyte A interferon (Ro 22-8181) in skin malignant tumors].

    PubMed

    1985-04-01

    A clinical phase II study of recombinant human leukocyte interferon A (rIFN-alpha A, Ro 22-8181) for various skin malignant tumors was jointly conducted at nine medical institutes across the country in order to study its clinical effect and side effects. Patients received Ro 22-8181 alone in doses ranging from 3 X 10(6) U/day to 50 X 10(6) U/day either by intramuscular injection or by local injection. Good response was obtained in one (4.8%) of 21 patients treated by intramuscular injection and in 26 (72.2%) of 36 patients treated by local injection. The percentage of good responses achieved by local injection for individual diseases was 55.6% (5/9) for metastatic malignant skin melanoma, 100% (11/11) for cutaneous malignant lymphoma, 100% (5/5) for extramammary Paget's disease, 75% (3/4) for intraepidermal cancer and 50% (2/4) for metastatic skin cancer. Main side effects were fever, anorexia, general fatigue, chills, nausea and vomiting. Abnormal laboratory data included leukopenia, and elevation of GOT and GPT, although their incidence was lower with local injection than with intramuscular injection. Side effects were mostly improved by reduction of the dose or discontinuation of the treatment. PMID:2985007

  8. Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion.

    PubMed

    McNeel, Douglas G; Eickhoff, Jens; Lee, Fred T; King, David M; Alberti, Dona; Thomas, James P; Friedl, Andreas; Kolesar, Jill; Marnocha, Rebecca; Volkman, Jennifer; Zhang, Jianliang; Hammershaimb, Luz; Zwiebel, James A; Wilding, George

    2005-11-01

    At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the alpha(v)beta(3) integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the alpha(v)beta(3) integrin can affect tumor vasculature and block tumor formation and metastasis. These findings suggest that antibodies directed at alpha(v)beta(3) could be investigated in the treatment of human malignancies. The current phase I dose escalation study evaluated the safety of MEDI-522, a monoclonal antibody specific for the alpha(v)beta(3) integrin, in patients with advanced malignancies. Twenty-five patients with a variety of metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly; pharmacokinetic studies were done; and radiographic staging was done every 8 weeks. In addition, dynamic computed tomography imaging was done at baseline and at 8 weeks in patients with suitable target lesions amenable to analysis, to potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was well tolerated, and a maximum tolerated dose was not identified by traditional dose-limiting toxicities. The major adverse events observed were grade 1 and 2 infusion-related reactions (fever, rigors, flushing, injection site reactions, and tachycardia), low-grade constitutional and gastrointestinal symptoms (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic computed tomography imaging suggested a possible effect on tumor perfusion with an increase in contrast mean transit time from baseline to the 8-week evaluation with increasing doses of MEDI-522. No complete or partial responses were observed. Three patients with metastatic renal cell cancer experienced prolonged stable disease (34 weeks, >1 and >2 years) on

  9. Malignant hair follicle tumors of the periorbital region: A review of literature and suggestion of a management guideline.

    PubMed

    Sia, Paul Ikgan; Figueira, Edwin; Allende, Alexandra; Selva, Dinesh

    2016-06-01

    Malignant hair follicle tumors are rare skin adnexal malignancies that have a predilection for the head and neck region. They can be categorized into a number of different subtypes. Histologically, they are distinct from their benign counterpart. To the best of our knowledge, there is no extensive review of these malignancies, especially in the periorbital region. We aim to provide a literature review and a guideline for management of these malignant tumors in the periorbital region. Database from Medline, PubMed, Embase, and Google Scholar were consulted. A total of 16 cases from the literature on hair follicle malignancies in the periorbital region were included in this review. The clinical presentations, diagnostic patterns, investigations used, and best management approach of these tumors are discussed. The American Joint Committee on Cancer (AJCC) 7(th) edition carcinoma of the eyelid staging system was used to describe their behaviors. We recommend wide excision surgery and a close follow-up for these tumors. Tumors presenting with a late stage require work-up for distant metastasis and consideration for exenteration procedures. The role of radiotherapy and chemotherapy in this context is still uncertain. PMID:27171562

  10. miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A.

    PubMed

    Chang, Xiao; Zhang, Haiping; Lian, Shi; Zhu, Wei

    2016-07-01

    As an oncogene, aurora kinase A (AURKA) is overexpressed in various types of human cancers. However, the expression and roles of AURKA in malignant melanoma are largely unknown. In this study, a miR-137-AURKA axis was revealed to regulate melanoma growth. We found a significant increase in levels of AURKA in melanoma. Both genetic knockdown and pharmacologic inhibition of AURKA decreased tumor cell growth in vitro and in vivo. Further found that miR-137 reduced AURKA expression through interaction with its 3' untranslated region (3'UTR) and that miR-137 was negatively correlated with AURKA expression in melanoma specimens. Overexpression of miR-137 decreased cell proliferation and colony formation in vitro. Notably, re-expression of AURKA significantly rescued miR-137-mediated suppression of cell growth and clonality. In summary, these results reveal that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. PMID:27233613

  11. Targeting MCM2 function as a novel strategy for the treatment of highly malignant breast tumors

    PubMed Central

    Abe, Shinya; Yamamoto, Kouhei; Kurata, Morito; Abe-Suzuki, Shiho; Horii, Rie; Akiyama, Futoshi; Kitagawa, Masanobu

    2015-01-01

    Highly malignant tumors express high levels of the minichromosome maintenance 2 (MCM2) protein, which is associated with advanced tumor grade, advanced stage, and poor prognosis. In a previous study, we showed that Friend leukemia virus (FLV) envelope protein gp70 bound MCM2, impaired its nuclear translocation, and enhanced DNA-damage-induced apoptosis in FLV-infected hematopoietic cells when the cells expressed high levels of MCM2. Here, we show that MCM2 is highly expressed in clinical samples of invasive carcinoma of the breast, especially triple-negative breast cancer (TNBC), and in cancer stem cell (CSC) marker-positive breast cancer cells. To generate a cancer therapy model using gp70, we introduced the gp70 protein into the cytoplasm of murine breast cancer cells that express high levels of MCM2 by conjugating the protein transduction domain (PTD) of Hph-1 to gp70 (Hph- 1-gp70). Hph-1-gp70 was successfully transduced into the cytoplasm of breast cancer cells. The transduced protein enhanced the DNA damage-induced apoptosis of cancer cells in vitro and in vivo. Therefore, an MCM2-targeted strategy using Hph-1-gp70 treatment to induce DNA damage might be a successful therapy for highly malignant breast cancers such as TNBC and for the eradication of CSC-like cells from breast cancer tissue. PMID:26430873

  12. 5′-AMP-activated Protein Kinase (AMPK) Supports the Growth of Aggressive Experimental Human Breast Cancer Tumors*

    PubMed Central

    Laderoute, Keith R.; Calaoagan, Joy M.; Chao, Wan-ru; Dinh, Dominc; Denko, Nicholas; Duellman, Sarah; Kalra, Jessica; Liu, Xiaohe; Papandreou, Ioanna; Sambucetti, Lidia; Boros, Laszlo G.

    2014-01-01

    Rapid tumor growth can establish metabolically stressed microenvironments that activate 5′-AMP-activated protein kinase (AMPK), a ubiquitous regulator of ATP homeostasis. Previously, we investigated the importance of AMPK for the growth of experimental tumors prepared from HRAS-transformed mouse embryo fibroblasts and for primary brain tumor development in a rat model of neurocarcinogenesis. Here, we used triple-negative human breast cancer cells in which AMPK activity had been knocked down to investigate the contribution of AMPK to experimental tumor growth and core glucose metabolism. We found that AMPK supports the growth of fast-growing orthotopic tumors prepared from MDA-MB-231 and DU4475 breast cancer cells but had no effect on the proliferation or survival of these cells in culture. We used in vitro and in vivo metabolic profiling with [13C]glucose tracers to investigate the contribution of AMPK to core glucose metabolism in MDA-MB-231 cells, which have a Warburg metabolic phenotype; these experiments indicated that AMPK supports tumor glucose metabolism in part through positive regulation of glycolysis and the nonoxidative pentose phosphate cycle. We also found that AMPK activity in the MDA-MB-231 tumors could systemically perturb glucose homeostasis in sensitive normal tissues (liver and pancreas). Overall, our findings suggest that the contribution of AMPK to the growth of aggressive experimental tumors has a critical microenvironmental component that involves specific regulation of core glucose metabolism. PMID:24993821

  13. Role of the tumor microenvironment in mature B-cell lymphoid malignancies

    PubMed Central

    Fowler, Nathan H.; Cheah, Chan Yoon; Gascoyne, Randy D.; Gribben, John; Neelapu, Sattva S.; Ghia, Paolo; Bollard, Catherine; Ansell, Stephen; Curran, Michael; Wilson, Wyndham H.; O’Brien, Susan; Grant, Cliona; Little, Richard; Zenz, Thorsten; Nastoupil, Loretta J.; Dunleavy, Kieron

    2016-01-01

    The tumor microenvironment is the cellular and molecular environment in which the tumor exists and with which it continuously interacts. In B-cell lymphomas, this microenvironment is intriguing in that it plays critical roles in the regulation of tumor cell survival and proliferation, fostering immune escape as well as the development of treatment resistance. The purpose of this review is to summarize the proceedings of the Second Annual Summit on the Immune Microenvironment in Hematologic Malignancies that took place on September 11–12, 2014 in Dublin, Ireland. We provide a timely overview of the composition and biological relevance of the cellular and molecular microenvironment interface and discuss the role of interactions between the microenvironment and neoplastic cells in a variety of B-cell lymphomas. In addition, we focus on various novel therapeutic strategies that target the tumor microenvironment, including agents that modulate B-cell receptor pathways and immune-checkpoints, chimeric antigen receptor T cells and immunomodulatory agents. PMID:27132279

  14. Papillary Thyroid Carcinoma: A Malignant Tumor with Increased Antioxidant Defense Capacity.

    PubMed

    Rovcanin, Branislav R; Gopcevic, Kristina R; Kekic, Dusan Lj; Zivaljevic, Vladan R; Diklic, Aleksandar Dj; Paunovic, Ivan R

    2016-01-01

    Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy worldwide for which the radiation exposure is the most influential risk factor. The levels of oxidative stress in PTC are not well characterized on the tissue level. The objective of this study was to evaluate total oxidant status (TOS) and total antioxidant status (TAS) in PTC and benign goiter (BG) tissues and to examine their association with clinicopathological characteristics. Tumor and normal thyroid tissue samples were collected from 59 PTC patients, and goiter tissues were collected from 50 BG patients. TOS and TAS were quantified in the tissue homogenates by spectrophotometric assays. TOS values in tumor tissues did not differ significantly from normal and goiter tissues; however, PTC tissues have significantly higher TAS values than normal and goiter tissues. TOS values correlated with retrosternal growth in BG patients. The significant correlations were found between TOS and TAS values and thyroid function parameters. In 17 PTC patients with multiple tumor foci (multicentric phenotype), TAS values were significantly lower, compared to 42 patients with unicentric PTC. TAS and TOS are the most useful predictors of thyroid capsular invasion by PTC. The age, sex, body mass index, smoking, familial history of thyroid disease and nodule size did not influence TOS and TAS in PTC or BG patients. In conclusion, we show the profiles of TOS and TAS in PTC and BG tissues. Importantly, PTC tissues possess increased antioxidant capacity. The redox status influences the parameters of the thyroid function and tumor's biological behavior. PMID:27615359

  15. Malignant peripheral nerve sheath tumor as a cause of chronic cardiac insufficiency in cattle

    PubMed Central

    2013-01-01

    Chronic cardiac insufficiency was associated with a malignant peripheral nerve sheath tumor in a cow. An eight-year-old cow developed a progressive condition (over a period of three months) characterized by an enhanced abdominal volume, reluctance to move, a positive jugular pulse, watery diarrhea and death. At necropsy, moderate subcutaneous edema and an enhanced hepatic lobular pattern were observed. A 23x20x11 cm firm, grayish-white mass adhered to and infiltrated the right atrium. Multiple firm, yellowish-white nodules of 0.5 to 12 cm in diameter were diffusely scattered in the epicardium and parietal pericardium. Histologically, the tumor was poorly circumscribed with foci of infiltration of the myocardium. The neoplastic cells had two major histologic patterns, Antoni types A and B. Within occasional foci, pleomorphic cells with an epithelioid appearance were present in addition to multinucleated cells with periodic acid Schiff (PAS)-positive cytoplasmic globules. Foci of cartilaginous and granular differentiations were interspersed among the neoplastic cells. Multiple vessels presented wall hyalinization and tumoral embolus. Large necrotic foci with mineralization and cholesterol clefts were also observed. Immunohistochemically, the tumor was positive for S100 protein, vimentin and neuron-specific enolase labeling. PMID:23369465

  16. Warburg effect's manifestation in aggressive pheochromocytomas and paragangliomas: insights from a mouse cell model applied to human tumor tissue.

    PubMed

    Fliedner, Stephanie M J; Kaludercic, Nina; Jiang, Xiao-Sheng; Hansikova, Hana; Hajkova, Zuzana; Sladkova, Jana; Limpuangthip, Andrea; Backlund, Peter S; Wesley, Robert; Martiniova, Lucia; Jochmanova, Ivana; Lendvai, Nikoletta K; Breza, Jan; Yergey, Alfred L; Paolocci, Nazareno; Tischler, Arthur S; Zeman, Jiri; Porter, Forbes D; Lehnert, Hendrik; Pacak, Karel

    2012-01-01

    A glycolytic profile unifies a group of pheochromocytomas and paragangliomas (PHEOs/PGLs) with distinct underlying gene defects, including von Hippel-Lindau (VHL) and succinate dehydrogenase B (SDHB) mutations. Nevertheless, their tumor aggressiveness is distinct: PHEOs/PGLs metastasize rarely in VHL-, but frequently in SDHB-patients. To date, the molecular mechanisms causing the more aggressive phenotype in SDHB-PHEOs/PGLs remain largely unknown. Recently, however, an excellent model to study aggressive PHEOs (mouse tumor tissue (MTT) cells) has been developed from mouse PHEO cells (MPC). We employed this model for a proteomics based approach to identify changes characteristic for tumor aggressiveness, which we then explored in a homogeneous set of human SDHB- and VHL-PHEOs/PGLs. The increase of glucose transporter 1 in VHL, and of hexokinase 2 in VHL and SDHB, confirmed their glycolytic profile. In agreement with the cell model and in support of decoupling of glycolysis, the Krebs cycle and oxidative phosphorylation (OXPHOS), SDHB tumors showed increased lactate dehydrogenase levels. In SDHB-PGLs OXPHOS complex activity was increased at complex III and, as expected, decreased at complex II. Moreover, protein and mRNA expression of all tested OXPHOS-related genes were higher in SDHB- than in VHL-derived tumors. Although there was no direct evidence for increased reactive oxygen species production, elevated superoxide dismutase 2 expression may reflect elevated oxidative stress in SDHB-derived PHEOs/PGLs. For the first time, we show that despite dysfunction in complex II and evidence for a glycolytic phenotype, the Warburg effect does not seem to fully apply to SDHB-PHEOs/PGLs with respect to decreased OXPHOS. In addition, we present evidence for increased LDHA and SOD2 expression in SDHB-PHEOs/PGLs, proteins that have been proposed as promising therapeutic targets in other cancers. This study provides new insight into pathogenic mechanisms in aggressive human

  17. Resonant Spectra of Malignant Breast Cancer Tumors Using the Three-Dimensional Electromagnetic Fast Multipole Model. Part 1

    NASA Technical Reports Server (NTRS)

    El-Shenawee, Magda

    2003-01-01

    An intensive numerical study for the resonance scattering of malignant breast cancer tumors is presented. The rigorous three-dimensional electromagnetic model, based on the equivalence theorem, is used to obtain the induced electric and magnetic currents on the breast and tumor surfaces. The results show that a non-spherical malignant tumor can be characterized based its spectra regardless of its orientation, the incident polarization, or the incident or scattered directions. The tumor's spectra depend solely on its physical characteristics (i.e., the shape and the electrical properties), however, their locations are not functions of its burial depth. This work provides a useful guidance to select the appropriate frequency range for the tumor's size.

  18. Differentiation of Benign and Malignant Breast Tumors by In-Vivo Three-Dimensional Parallel-Plate Diffuse Optical Tomography

    PubMed Central

    Choe, Regine; Konecky, Soren D.; Corlu, Alper; Lee, Kijoon; Durduran, Turgut; Busch, David R.; Pathak, Saurav; Czerniecki, Brian J.; Tchou, Julia; Fraker, Douglas L.; DeMichele, Angela; Chance, Britton; Arridge, Simon R.; Schweiger, Martin; Culver, Joseph P.; Schnall, Mitchell D.; Putt, Mary E.; Rosen, Mark A.; Yodh, Arjun G.

    2009-01-01

    We have developed a novel parallel-plate diffuse optical tomography (DOT) system for three-dimensional in vivo imaging of human breast tumor based on large optical data sets. Images of oxy-, deoxy-, total-hemoglobin concentration, blood oxygen saturation, and tissue scattering were reconstructed. Tumor margins were derived using the optical data with guidance from radiology reports and Magnetic Resonance Imaging. Tumor-to-normal ratios of these endogenous physiological parameters and an optical index were computed for 51 biopsy-proven lesions from 47 subjects. Malignant cancers (N=41) showed statistically significant higher total hemoglobin, oxy-hemoglobin concentration, and scattering compared to normal tissue. Furthermore, malignant lesions exhibited a two-fold average increase in optical index. The influence of core biopsy on DOT results was also explored; the difference between the malignant group measured before core biopsy and the group measured more than one week after core biopsy was not significant. Benign tumors (N=10) did not exhibit statistical significance in the tumor-to-normal ratios of any parameter. Optical index and tumor-to-normal ratios of total hemoglobin, oxy-hemoglobin concentration, and scattering exhibited high area under the receiver operating characteristic curve values from 0.90 to 0.99, suggesting good discriminatory power. The data demonstrate that benign and malignant lesions can be distinguished by quantitative three-dimensional DOT. PMID:19405750

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

    PubMed Central

    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

  20. Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Choe, Regine; Konecky, Soren D.; Corlu, Alper; Lee, Kijoon; Durduran, Turgut; Busch, David R.; Pathak, Saurav; Czerniecki, Brian J.; Tchou, Julia; Fraker, Douglas L.; Demichele, Angela; Chance, Britton; Arridge, Simon R.; Schweiger, Martin; Culver, Joseph P.; Schnall, Mitchell D.; Putt, Mary E.; Rosen, Mark A.; Yodh, Arjun G.

    2009-03-01

    We have developed a novel parallel-plate diffuse optical tomography (DOT) system for three-dimensional in vivo imaging of human breast tumor based on large optical data sets. Images of oxy-, deoxy-, and total hemoglobin concentration as well as blood oxygen saturation and tissue scattering were reconstructed. Tumor margins were derived using the optical data with guidance from radiology reports and magnetic resonance imaging. Tumor-to-normal ratios of these endogenous physiological parameters and an optical index were computed for 51 biopsy-proven lesions from 47 subjects. Malignant cancers (N=41) showed statistically significant higher total hemoglobin, oxy-hemoglobin concentration, and scattering compared to normal tissue. Furthermore, malignant lesions exhibited a twofold average increase in optical index. The influence of core biopsy on DOT results was also explored; the difference between the malignant group measured before core biopsy and the group measured more than 1 week after core biopsy was not significant. Benign tumors (N=10) did not exhibit statistical significance in the tumor-to-normal ratios of any parameter. Optical index and tumor-to-normal ratios of total hemoglobin, oxy-hemoglobin concentration, and scattering exhibited high area under the receiver operating characteristic curve values from 0.90 to 0.99, suggesting good discriminatory power. The data demonstrate that benign and malignant lesions can be distinguished by quantitative three-dimensional DOT.

  1. Multiple cytokeratin-negative malignant tumors composed only of rhabdoid cells in the renal pelvis: a sarcomatoid urothelial carcinoma?

    PubMed Central

    Terada, Tadashi

    2013-01-01

    The author presents a unique case of multiple cytokeratin-negative malignant tumors consisting only of rhabdoid cells in the renal pelvis. A 54-year-old man complained of hematuria. A transurethral endoscopic examination revealed multiple papillary tumors, and transurethral resection of the bladder tumors was performed. Pathologically, they were ordinary papillary urothelial transitional cell carcinomas. Imaging modalities revealed multiple tumors of the right renal pelvis, and nephrectomy was performed. Grossly, three polypoid tumors measuring 2-4 cm were present in the pelvis. Histologically, they were composed only of malignant cells with rhabdoid features. There were no elements of transitional cell carcinoma. Immunohistochemically, the pelvic tumors were positive for vimentin and Ki-67 antigen (labeling=40%). They were negative for pancytokeratins (AE1/3, CAM5.2, KL-1 and polyclonal wide), 34βE12, cytokeratin (CK) 5/6, CK7, CK8, CK14, CK18, CK19, CK20, melanosome, EMA, CEA, desmin, S100 protein, α-smooth muscle actin, myoglobin, myogenin, CD34, p53 protein, p63, CD3, CD20, CD30, CD45, CD45RO, chromograin, synaptophysin, CD56, CD68, and KIT. NSE and PDGFRA were focally present, but this appeared nonspecific. Namely, the pelvic tumors expressed only vimentin. The author speculates that the pelvic multiple malignant “rhabdoid” tumors are not sarcomas but urothelial “rhabdoid” carcinoma with complete loss of CKs. PMID:23573320

  2. High levels of EGFR expression in tumor stroma are associated with aggressive clinical features in epithelial ovarian cancer

    PubMed Central

    Wang, Ke; Li, Dan; Sun, Lu

    2016-01-01

    Purpose The aim of this study was to investigate the clinical significance and biological function of epidermal growth factor receptor (EGFR) expressed in tumor stroma of epithelial ovarian cancer. Methods Immunohistological staining of EGFR was evaluated in 242 patients with epithelial ovarian cancer. The correlations of EGFR expression in tumor stroma with clinicopathological features and with the expression level of Ki-67 were analyzed by SPSS software. Kaplan–Meier analysis and the Cox proportional hazard model were used to analyze the effect of EGFR expression in tumor stroma on the prognosis of patients with epithelial ovarian cancer. Meanwhile, the activities of proliferation and migration of tumor cells were detected when EGFR overexpressed in stroma cells. Results EGFR expression in tumor stroma correlated significantly with clinical stage (χ2=7.002, P=0.008) and distant metastases (χ2=16.59, P<0.001). Furthermore, there was a significantly positive correlation between the level of EGFR expressed in tumor stroma and the level of Ki-67 expressed in tumor cells (χ2=6.120, P=0.013). Patients with high EGFR expression level in tumor stroma showed poor survival (P=0.002). Multivariate analysis showed that high expression of EGFR in tumor stroma was an independent predictor for epithelial ovarian cancer patients (hazard ratio =1.703; 95% confidence interval 1.125–2.578, P=0.012). Furthermore, stroma cells overexpressing EGFR could promote the proliferation and migration of adjacent tumor cells. Conclusion High expression of EGFR in tumor stroma correlates with aggressive clinical features in epithelial ovarian cancer, and is an independent prognostic factor. PMID:26855586

  3. Fructose as a carbon source induces an aggressive phenotype in MDA-MB-468 breast tumor cells

    PubMed Central

    MONZAVI-KARBASSI, BEHJATOLAH; HINE, R. JEAN; STANLEY, JOSEPH S.; RAMANI, VISHNU PRAKASH; CARCEL-TRULLOLS, JAIME; WHITEHEAD, TRACY L.; KELLY, THOMAS; SIEGEL, ERIC R.; ARTAUD, CECILE; SHAAF, SAEID; SAHA, RINKU; JOUSHEGHANY, FARIBA; HENRY-TILLMAN, RONDA; KIEBER-EMMONS, THOMAS

    2012-01-01

    Aberrant glycosylation is a universal feature of cancer cells, and certain glycan structures are well-known markers for tumor progression. Availability and composition of sugars in the microenvironment may affect cell glycosylation. Recent studies of human breast tumor cell lines indicate their ability to take up and utilize fructose. Here we tested the hypothesis that adding fructose to culture as a carbon source induces phenotypic changes in cultured human breast tumor cells that are associated with metastatic disease. MDA-MB-468 cells were adapted to culture media in which fructose was substituted for glucose. Changes in cell surface glycan structures, expression of genes related to glycan assembly, cytoskeleton F-actin, migration, adhesion and invasion were determined. Cells cultured in fructose expressed distinct cell-surface glycans. The addition of fructose affected sialylation and fucosylation patterns. Fructose feeding also increased binding of leukoagglutinating Phaseolus vulgaris isolectin, suggesting a possible rise in expression of branching β-1, 6 GlcNAc structures. Rhodamine-phalloidin staining revealed an altered F-actin cytoskeletal system. Fructose accelerated cellular migration and increased invasion. These data suggest that changing the carbon source of the less aggressive MDA-MB-468 cell line induced characteristics associated with more aggressive phenotypes. These data could be of fundamental importance due to the markedly increased consumption of sweeteners containing free fructose in recent years, as they suggest that the presence of fructose in nutritional micro-environment of tumor cells may negatively affect the outcome for some breast cancer patients. PMID:20664930

  4. Fructose as a carbon source induces an aggressive phenotype in MDA-MB-468 breast tumor cells.

    PubMed

    Monzavi-Karbassi, Behjatolah; Hine, R Jean; Stanley, Joseph S; Ramani, Vishnu Prakash; Carcel-Trullols, Jaime; Whitehead, Tracy L; Kelly, Thomas; Siegel, Eric R; Artaud, Cecile; Shaaf, Saeid; Saha, Rinku; Jousheghany, Fariba; Henry-Tillman, Ronda; Kieber-Emmons, Thomas

    2010-09-01

    Aberrant glycosylation is a universal feature of cancer cells, and certain glycan structures are well-known markers for tumor progression. Availability and composition of sugars in the microenvironment may affect cell glycosylation. Recent studies of human breast tumor cell lines indicate their ability to take up and utilize fructose. Here we tested the hypothesis that adding fructose to culture as a carbon source induces phenotypic changes in cultured human breast tumor cells that are associated with metastatic disease. MDA-MB-468 cells were adapted to culture media in which fructose was substituted for glucose. Changes in cell surface glycan structures, expression of genes related to glycan assembly, cytoskeleton F-actin, migration, adhesion and invasion were determined. Cells cultured in fructose expressed distinct cell-surface glycans. The addition of fructose affected sialylation and fucosylation patterns. Fructose feeding also increased binding of leukoagglutinating Phaseolus vulgaris isolectin, suggesting a possible rise in expression of branching beta-1, 6 GlcNAc structures. Rhodamine-phalloidin staining revealed an altered F-actin cytoskeletal system. Fructose accelerated cellular migration and increased invasion. These data suggest that changing the carbon source of the less aggressive MDA-MB-468 cell line induced characteristics associated with more aggressive phenotypes. These data could be of fundamental importance due to the markedly increased consumption of sweeteners containing free fructose in recent years, as they suggest that the presence of fructose in nutritional microenvironment of tumor cells may negatively affect the outcome for some breast cancer patients. PMID:20664930

  5. Urine Steroid Metabolomics as a Biomarker Tool for Detecting Malignancy in Adrenal Tumors

    PubMed Central

    Biehl, Michael; Taylor, Angela E.; Hahner, Stefanie; Libé, Rossella; Hughes, Beverly A.; Schneider, Petra; Smith, David J.; Stiekema, Han; Krone, Nils; Porfiri, Emilio; Opocher, Giuseppe; Bertherat, Jerôme; Mantero, Franco; Allolio, Bruno; Terzolo, Massimo; Nightingale, Peter; Shackleton, Cedric H. L.; Bertagna, Xavier; Fassnacht, Martin; Stewart, Paul M.

    2011-01-01

    Context: Adrenal tumors have a prevalence of around 2% in the general population. Adrenocortical carcinoma (ACC) is rare but accounts for 2–11% of incidentally discovered adrenal masses. Differentiating ACC from adrenocortical adenoma (ACA) represents a diagnostic challenge in patients with adrenal incidentalomas, with tumor size, imaging, and even histology all providing unsatisfactory predictive values. Objective: Here we developed a novel steroid metabolomic approach, mass spectrometry-based steroid profiling followed by machine learning analysis, and examined its diagnostic value for the detection of adrenal malignancy. Design: Quantification of 32 distinct adrenal derived steroids was carried out by gas chromatography/mass spectrometry in 24-h urine samples from 102 ACA patients (age range 19–84 yr) and 45 ACC patients (20–80 yr). Underlying diagnosis was ascertained by histology and metastasis in ACC and by clinical follow-up [median duration 52 (range 26–201) months] without evidence of metastasis in ACA. Steroid excretion data were subjected to generalized matrix learning vector quantization (GMLVQ) to identify the most discriminative steroids. Results: Steroid profiling revealed a pattern of predominantly immature, early-stage steroidogenesis in ACC. GMLVQ analysis identified a subset of nine steroids that performed best in differentiating ACA from ACC. Receiver-operating characteristics analysis of GMLVQ results demonstrated sensitivity = specificity = 90% (area under the curve = 0.97) employing all 32 steroids and sensitivity = specificity = 88% (area under the curve = 0.96) when using only the nine most differentiating markers. Conclusions: Urine steroid metabolomics is a novel, highly sensitive, and specific biomarker tool for discriminating benign from malignant adrenal tumors, with obvious promise for the diagnostic work-up of patients with adrenal incidentalomas. PMID:21917861

  6. Comparative methylome analysis of benign and malignant peripheral nerve sheath tumors.

    PubMed

    Feber, Andrew; Wilson, Gareth A; Zhang, Lu; Presneau, Nadege; Idowu, Bernadine; Down, Thomas A; Rakyan, Vardhman K; Noon, Luke A; Lloyd, Alison C; Stupka, Elia; Schiza, Vassia; Teschendorff, Andrew E; Schroth, Gary P; Flanagan, Adrienne; Beck, Stephan

    2011-04-01

    Aberrant DNA methylation (DNAm) was first linked to cancer over 25 yr ago. Since then, many studies have associated hypermethylation of tumor suppressor genes and hypomethylation of oncogenes to the tumorigenic process. However, most of these studies have been limited to the analysis of promoters and CpG islands (CGIs). Recently, new technologies for whole-genome DNAm (methylome) analysis have been developed, enabling unbiased analysis of cancer methylomes. By using MeDIP-seq, we report a sequencing-based comparative methylome analysis of malignant peripheral nerve sheath tumors (MPNSTs), benign neurofibromas, and normal Schwann cells. Analysis of these methylomes revealed a complex landscape of DNAm alterations. In contrast to what has been reported for other tumor types, no significant global hypomethylation was observed in MPNSTs using methylome analysis by MeDIP-seq. However, a highly significant (P < 10(-100)) directional difference in DNAm was found in satellite repeats, suggesting these repeats to be the main target for hypomethylation in MPNSTs. Comparative analysis of the MPNST and Schwann cell methylomes identified 101,466 cancer-associated differentially methylated regions (cDMRs). Analysis showed these cDMRs to be significantly enriched for two satellite repeat types (SATR1 and ARLα) and suggests an association between aberrant DNAm of these sequences and transition from healthy cells to malignant disease. Significant enrichment of hypermethylated cDMRs in CGI shores (P < 10(-60)), non-CGI-associated promoters (P < 10(-4)) and hypomethylated cDMRs in SINE repeats (P < 10(-100)) was also identified. Integration of DNAm and gene expression data showed that the expression pattern of genes associated with CGI shore cDMRs was able to discriminate between disease phenotypes. This study establishes MeDIP-seq as an effective method to analyze cancer methylomes. PMID:21324880

  7. Photodynamic therapy of malignant brain tumors: supplementary postoperative light delivery by implanted optical fibers: field fractionation

    NASA Astrophysics Data System (ADS)

    Muller, Paul J.; Wilson, Brian C.

    1991-06-01

    Sixty-three patients with malignant brain tumors were treated with intraoperative photodynamic therapy (PDT) using an argon dye pump laser and preoperatively administered hematoporphyrin derivative or dihematoporphyrin ether. In 13 cases, in addition to cavitary photo-illumination, cylindrical diffusion fibers were used to increase the amount of light energy administered to the tumor tissue intraoperatively. This interstitial photo-illumination was tolerated at light energy densities of less than 450 J/cm. In six recent cases, all of whom had large malignant gliomas and could not be illuminated adequately at a single session, cylindrical diffusion fibers were left in situ after intraoperative cavitary photo-illumination of the tumor residuum. The fibers were protected from fracturing by placing all but the exposed diffusing end in a red rubber catheter of the appropriate diameter. The fibers were externalized through a separate stab wound as would be the case for a ventricular drain. Photo-illumination was continued one or two days post-operatively. The optimal fiber couple to the argon dye pump laser was achieved by assessing the fiber side scatter with a photometer. These six patients received 585-2730 Joules during the post-operative photo-illumination. The patients tolerated the fractionated photo-illumination well. A transient scalp inflammation occurred as the consequence light transmission to skin from the implanted fibers in one case. The median survival for the whole series was 8.5 months (40 weeks) with a 1- and 2-year actuarial survival rate of 33, respectively.

  8. Profound tumor-specific Th2 bias in patients with malignant glioma

    PubMed Central

    2012-01-01

    Background Vaccination against tumor-associated antigens is one promising approach to immunotherapy against malignant gliomas. While previous vaccine efforts have focused exclusively on HLA class I-restricted peptides, class II-restricted peptides are necessary to induce CD4+ helper T cells and sustain effective anti-tumor immunity. In this report we investigated the ability of five candidate peptide epitopes derived from glioma-associated antigens MAGE and IL-13 receptor α2 to detect and characterize CD4+ helper T cell responses in the peripheral blood of patients with malignant gliomas. Methods Primary T cell responses were determined by stimulating freshly isolated PBMCs from patients with primary glioblastoma (GBM) (n = 8), recurrent GBM (n = 5), meningioma (n = 7), and healthy controls (n = 6) with each candidate peptide, as well as anti-CD3 monoclonal antibody (mAb) and an immunodominant peptide epitope derived from myelin basic protein (MBP) serving as positive and negative controls, respectively. ELISA was used to measure IFN-γ and IL-5 levels, and the ratio of IFN-γ/IL-5 was used to determine whether the response had a predominant Th1 or Th2 bias. Results We demonstrate that novel HLA Class-II restricted MAGE-A3 and IL-13Rα2 peptides can detect T cell responses in patients with GBMs as well as in healthy subjects. Stimulation with a variety of peptide antigens over-expressed by gliomas is associated with a profound reduction in the IFN-γ/IL-5 ratio in GBM patients relative to healthy subjects. This bias is more pronounced in patients with recurrent GBMs. Conclusions Therapeutic vaccine strategies to shift tumor antigen-specific T cell response to a more immunostimulatory Th1 bias may be needed for immunotherapeutic trials to be more successful clinically. PMID:23186108

  9. CD30 expression in malignant vascular tumors and its diagnostic and clinical implications: a study of 146 cases.

    PubMed

    Alimchandani, Meghna; Wang, Zeng-Feng; Miettinen, Markku

    2014-01-01

    Angiosarcoma (AS) is a rare malignant vascular tumor, whereas epithelioid hemangioendothelioma (EHE) is a vascular tumor of low-grade malignancy. CD30 is a member of the tumor necrosis factor receptor superfamily, member 8 (TNFRSF8). Although the expression of CD30 is most commonly associated with lymphoid malignancies or germ cell tumors, occasional ASs have been reported as CD30 positive. However, there are limited data to evaluate its role definitively in malignant vascular tumors. In this study, we evaluated 91 ASs, 30 EHEs from various sites, and 25 Kaposi sarcomas. Overall, CD30 was expressed in 31/91 cases (34%) of AS, in 7/30 cases (30%) of EHE, but in none of the Kaposi sarcomas. CD30 was expressed in a membranous staining pattern and positivity in tumor cells varied from focal to diffuse. The positive ASs included vasoformative more differentiated tumors and also solid, undifferentiated, lymphoma-like examples, one of which was classified as lymphoma before the era of immunohistochemistry. The CD30 expression was seen in >50% of tumor cells in a majority of ASs but only in 7% of EHEs. None of the 55 ASs studied were immunohistochemically positive for TIA-1 or Granzyme B, antigens used as more specific markers for anaplastic large-cell lymphoma. Compared with AS, normal vascular endothelia of capillaries and muscular vessels showed variable positivity. Among hemangiomas, cavernous and spindle cell hemangiomas showed most frequent endothelial CD30 positivity, whereas in most other hemangiomas, CD30 positivity was scant. In conclusion, CD30 expression occurs in a significant subset of ASs and EHEs and needs to be included in the differential diagnosis with other CD30-positive malignancies to avoid a diagnostic pitfall. It remains to be determined whether patients with strongly CD30-positive ASs could be candidates for targeted therapy using the recently introduced CD30 antibody drug conjugates. PMID:24805132

  10. Ultrasonographic evaluation of depth-width ratio (D/W) of benign and malignant mammary tumors in dogs.

    PubMed

    Tagawa, Michihito; Kanai, Eiichi; Shimbo, Genya; Kano, Mikiya; Kayanuma, Hideki

    2016-04-01

    Depth-width ratio (D/W) is the only quantitative item in the criteria recommended by the Japanese Ultrasound Society for the evaluation of breast tumors in humans. However, the usefulness of the D/W has not been evaluated in dogs. Eighty-six mammary masses in 34 female dogs underwent ultrasonographic examination to determine the D/W and other characteristics. Results of ultrasonographic and histopathologic examinations were compared. The D/W of malignant tumors was significantly greater than that of benign tumors, and it had a sensitivity of 56.3% and a specificity of 92.9% for the diagnosis of malignancy when the threshold of D/W was 0.7. In addition, irregular margin, polymorphous shape and heterogeneous internal echographic characteristics were correlated with malignancy. PMID:26596466

  11. Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone

    PubMed Central

    Kawabata, Shigeru; Christine Hollander, M; Munasinghe, Jeeva P.; Brinster, Lauren R.; Mercado-Matos, José R.; Li, Jie; Regales, Lucia; Pao, William; Jänne, Pasi A.; Wong, Kwok-Kin; Butman, John A.; Lonser, Russell R.; Hansen, Marlan R.; Gurgel, Richard K.; Vortmeyer, Alexander O.; Dennis, Phillip A.

    2015-01-01

    Adenomatous tumors in the middle ear and temporal bone are rare but highly morbid because they are difficult to detect prior to the development of audiovestibular dysfunction. Complete resection is often disfiguring and difficult because of location and the late stage at diagnosis, so identification of molecular targets and effective therapies is needed. Here, we describe a new mouse model of aggressive papillary ear tumor that was serendipitously discovered during the generation of a mouse model for mutant EGFR-driven lung cancer. Although these mice did not develop lung tumors, 43% developed head tilt and circling behavior. Magnetic resonance imaging (MRI) scans showed bilateral ear tumors located in the tympanic cavity. These tumors expressed mutant EGFR as well as active downstream targets such as Akt, mTOR and ERK1/2. EGFR-directed therapies were highly effective in eradicating the tumors and correcting the vestibular defects, suggesting these tumors are addicted to EGFR. EGFR activation was also observed in human ear neoplasms, which provides clinical relevance for this mouse model and rationale to test EGFR-targeted therapies in these rare neoplasms. PMID:26027747

  12. Ménage à trois: Sustained therapeutic anti-tumor immunity requires multiple partners in malignant glioma.

    PubMed

    Wainwright, Derek A; Lesniak, Maciej S

    2014-01-01

    Glioblastoma is an aggressive primary brain cancer. Given our interest in novel immunotherapies, we have recently shown that inhibiting CTLA-4, PD-L1 and IDO results in a dramatic survival advantage in mice with brain tumors. Our preclinical study supports the rapid translation of this approach into phase I clinical trial. PMID:25057450

  13. Chemotherapy and targeted agents for thymic malignancies.

    PubMed

    Girard, Nicolas

    2012-05-01

    Thymic malignancies are rare epithelial tumors that may be aggressive and difficult to treat. Thymomas are usually localized to the anterior mediastinum and are frequently eligible for upfront surgical resection. However, nearly 30% of patients present with locally advanced tumors at time of diagnosis, and chemotherapy is then used to reduce the tumor burden, possibly allowing subsequent surgery and/or radiotherapy. Metastatic and recurrent thymic malignancies may similarly be treated with chemotherapy. More recently, the molecular characterization of thymoma and thymic carcinoma led to the identification of potentially druggable targets, laying the foundations to implement personalized medicine for patients. PMID:22594902

  14. Liquid biopsies for liquid tumors: emerging potential of circulating free nucleic acid evaluation for the management of hematologic malignancies

    PubMed Central

    Hocking, Jay; Mithraprabhu, Sridurga; Kalff, Anna; Spencer, Andrew

    2016-01-01

    Circulating free nucleic acids; cell free DNA and circulating micro-RNA, are found in the plasma of patients with hematologic and solid malignancies at levels higher than that of healthy individuals. In patients with hematologic malignancy cell free DNA reflects the underlying tumor mutational profile, whilst micro-RNAs reflect genetic interference mechanisms within a tumor and potentially the surrounding microenvironment and immune effector cells. These circulating nucleic acids offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognosis and therapeutic decisions in cancer treatment. PMID:27458529

  15. Luteolin and its inhibitory effect on tumor growth in systemic malignancies

    SciTech Connect

    Kapoor, Shailendra

    2013-04-01

    Lamy et al have provided interesting data in their recent article in your esteemed journal. Luteolin augments apoptosis in a number of systemic malignancies. Luteolin reduces tumor growth in breast carcinomas. Luteolin mediates this effect by up-regulating the expression of Bax and down-regulating the expression of Bcl-xL. EGFR-induced MAPK activation is also attenuated. As a result there is increased G2/ M phase arrest. These effects have been seen both in vivo as well as in vitro. It also reduces ERα expression and causes inhibition of IGF-1 mediated PI3K–Akt pathway. Luteolin also activates p38 resulting in nuclear translocation of the apoptosis-inducing factor. Simultaneously it also activates ERK. As a result there is increased intra-tumoral apoptosis which is caspase dependent as well as caspase independent. - Highlights: ► Luteolin and tumor growth in breast carcinomas. ► Luteolin and pulmonary cancer. ► Luteolin and colon cancer.

  16. Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors

    PubMed Central

    Pilon, Catia; Rebellato, Andrea; Urbanet, Riccardo; Guzzardo, Vincenza; Cappellesso, Rocco; Sasano, Hironobu; Fassina, Ambrogio

    2015-01-01

    We previously showed a decreased expression of vitamin D receptor (VDR) mRNA/protein in a small group of adrenocortical carcinoma (ACC) tissues, suggesting the loss of a protective role of VDR against malignant cell growth in this cancer type. Downregulation of VDR gene expression may result from epigenetics events, that is, methylation of cytosine nucleotide of CpG islands in VDR gene promoter. We analyzed methylation of CpG sites in the VDR gene promoter in normal adrenals and adrenocortical tumor samples. Methylation of CpG-rich 5′ regions was assessed by bisulfite sequencing PCR using bisulfite-treated DNA from archival microdissected paraffin-embedded adrenocortical tissues. Three normal adrenals and 23 various adrenocortical tumor samples (15 adenomas and 8 carcinomas) were studied. Methylation in the promoter region of VDR gene was found in 3/8 ACCs, while no VDR gene methylation was observed in normal adrenals and adrenocortical adenomas. VDR mRNA and protein levels were lower in ACCs than in benign tumors, and VDR immunostaining was weak or negative in ACCs, including all 3 methylated tissue samples. The association between VDR gene promoter methylation and reduced VDR gene expression is not a rare event in ACC, suggesting that VDR epigenetic inactivation may have a role in adrenocortical carcinogenesis. PMID:26843863

  17. Prognosis for canine malignant mammary tumors based on TNM and histologic classification.

    PubMed

    Yamagami, T; Kobayashi, T; Takahashi, K; Sugiyama, M

    1996-11-01

    The 2-year prognosis of malignant mammary tumors seen in 175 bitches in the Tokyo metropolitan area was assessed based on their TNM clinical staging and histological classification. The larger the tumor size became (T category), the poorer was the clinical prognosis. The 2-year survival rates of the animals with regional lymph node metastasis of tumor cells (N1, N2 category) and/or distant metastasis (M1 category) were markedly lower than those of the animals without such involvement. As the grade of TNM staging increased, the prognosis was poorer, however, there were no significant differences in survival rates among subtypes of adenocarcinomas (tubular, papillary and papillary cystic) determined by WHO histological classification. It was also noticed that animals having carcinomas without tubular formation or myoepithelial cell proliferation had a lower survival rate than animals having carcinomas with those characteristics; and invasive carcinomas into adjacent skin or lymphatic/vascular vessels implied a poorer prognosis than non-invasive ones. The results suggest that a combined practice of TNM system and our evaluation on the above-mentioned 4 histologic features could be useful for prognostic determination of canine mammary cancers. PMID:8959655

  18. Epiphyseal Sparing and Reconstruction by Frozen Bone Autograft after Malignant Bone Tumor Resection in Children

    PubMed Central

    Hamed Kassem Abdelaal, Ahmed; Yamamoto, Norio; Hayashi, Katsuhiro; Takeuchi, Akihiko; Miwa, Shinji; Tsuchiya, Hiroyuki

    2015-01-01

    Limb salvage surgery has become the standard treatment for malignant primary bone tumors in the extremities. Limb salvage represents a challenge in skeletally immature patients. Several treatment options are available for limb reconstruction after tumor resection in children. We report our results using the technique of epiphyseal sparing and reconstruction with frozen autograft bone in 18 children. The mean follow-up period for the all patients included in this study is 72 ± 26 m. Eight patients remained disease-free, seven patients lived with no evidence of disease, two were alive but with disease, and one patient died of the disease. Five- and ten-year rates of survival were 94.4%. Graft survival at 5 and 10 years was 94.4%. Functional outcome using the Enneking scale was excellent in 17 patients (94.4%) and poor in one patient (5.5%). Complications include 2 nonunions, 2 fractures, 2 deep infections, 1 soft tissue recurrence, and leg length discrepancy in 7 cases. This technique is a good reconstructive choice in a child with a nonosteolytic primary or secondary bone tumor, responsive to chemotherapy, without involvement of the articular cartilage. It is a straight forward, effective, and biological technique, which affords immediate mobilization of joints and possible cryoimmune effects, with excellent long term functional outcome and less complication. PMID:27034614

  19. Colonic adenocarcinoma and bilateral malignant ovarian sex cord tumor with annular tubules in Peutz-Jeghers syndrome.

    PubMed

    Ayadi-Kaddour, A; Bouraoui, S; Bellil, K; Bellil, S; Kchir, N; Zitouna, M M; Haouet, S

    2004-06-01

    Peutz-Jeghers syndrome is characterized by multiple polyps throughout the gastrointestinal tract in association with mucocutaneous pigmentation. Although Peutz-Jeghers syndrome polyps are hamartomas, frequent association of this syndrome with both gastrointestinal and non-gastrointestinal tumours had led to reassessment of the cancer risk in this hereditary disorder. The most common gynaecological tumors in this syndrome are adenoma malignum of the uterine cervix and ovarian sex cord tumor, particularly sex cord tumor with annular tubules. The question of malignant change in a polyp or of the association of gastro intestinal carcinomas still discuss. The authors report a case of Peutz-Jeghers syndrome in a young patient who developed a colonic adenocarcinoma in a hamartomatous polyp together with an incidentally discovered bilateral malignant sex cord tumours. We discuss its association with certain benign and malignant tumors and the risk of rare complications of these hamartomatous polyps. Although malignant tumors are increasingly reported in association with the Peutz-Jeghers syndrome, to our knowledge, there have been no previous reports of such an association in the literature. PMID:15524052

  20. Primary stage of photodestruction of malignant cells under photodynamic therapy of tumors

    NASA Astrophysics Data System (ADS)

    Mostovnikov, Vasili A.; Mostovnikova, Galina R.; Plavski, Vitali Y.; Tretjakova, Antonina I.

    1996-01-01

    In this work we present the experimental results indicating that under photodynamic therapy the primary stage of the photodestruction of malignant cells is based on the irreversible photodestruction of glycolysis enzymes located, first of all, in mitochondria playing a key role in the energy supply for the tumor cells. It was shown that the formation of complexes between glycolysis enzymes and a sensitizer promotes an effective destruction of the formers. The formation of strong complexes was demonstrated for a number of glycolysis enzymes (glyceraldehyde-2-phosphate dehydrogenase, pyruvate kinase, lactate dehydrogenase) with the use of water-soluble pigments chlorin e6 and tetra(carboxyphenyl)porphyrin (T(CP)P) as sensitizers. The direct correlation was shown between the effectiveness of the photodestruction of enzyme molecules and the enzyme-sensitizer binding constant.

  1. New approach for treatment of advanced malignant tumors: combination of chemotherapy and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wang, Lian-xing; Ju, Hua-lamg; Chem, Zhem-ming

    1995-03-01

    Eighty-three patients suffering from moderate or advanced malignant tumors were treated by combined chemotherapy and photodynamic therapy (PDT) in our hospital. The short term result of such management is very promising, the effectiveness seems to be nearly 100% and the general responsive rate is 79.5% (CR + PR). If compared with another group of 84 similar patients whom were treated with PDT alone, the short term efficacy is 85.7% while the general response rate is 54.7% (P < 0.01), there is a significant statistic. The better result of the combined approach is probably due to the action of the chemotherapeutic agent, potentially blocking the mitosis of the cellular cycle at certain phases of the cancer cells, making the cell membrane become more permeable to the photochemical agent, HPD, and eliciting a better cancerocidal effect.

  2. Beyond pancreatic cancer: irinotecan and gemcitabine in solid tumors and hematologic malignancies.

    PubMed

    Rocha Lima, C M; Urbanic, J J; Lal, A; Kneuper-Hall, R; Brunson, C Y; Green, M R

    2001-06-01

    Non-platinum combinations including gemcitabine and irinotecan (Gemzar; Eli Lilly and Company, Indianapolis, IN) for the management of a variety of malignancies have started to emerge. Gemcitabine and irinotecan are well-tolerated single agents, each with a broad spectrum of antitumor activity. Preclinical data suggests synergy for the two drugs when used in combination. A phase I trial has defined a well-tolerated combination regimen using both drugs on a day-1, -8 schedule every 3 weeks. Phase II data suggest activity for the combination in pancreatic cancer, and a phase III trial of the two-drug combination versus gemcitabine alone is underway in previously untreated pancreatic cancer patients. Other phase II trials evaluating the impact of this combination on a variety of other tumors, such as non-small cell lung, small cell lung, breast, colorectal, and non-Hodgkin's lymphoma, are either forthcoming or in progress. Semin Oncol 28 (suppl 10):34-43. PMID:11510032

  3. Tissue Expander Placement to Prevent the Adverse Intestinal Effects of Radiotherapy in Malignant Pelvic Tumors.

    PubMed

    Uehara, Shuichiro; Oue, Takaharu; Adachi, Kana; Yoshioka, Yasuo; Nakahata, Kengo; Ueno, Takehisa; Okuyama, Hiroomi

    2016-03-01

    We herein report the findings of 3 patients with primary Ewing sarcoma in a pelvic lesion who underwent the placement of a tissue expander (TE) before radiation therapy to prevent the adverse effects of radiotherapy. The simulation study showed that the TE drastically reduced volume of the intestine that was irradiated at all dose levels. All patients could receive the scheduled dose of radiotherapy without any acute and late complications such as diarrhea, melena, the dislodging of the TE, infection, or the formation of fistulae. In the 4-year (minimum) observation period, we did not observe intestinal complications in any of our patients. TE placement is considered to be a safe and effective method for preventing the adverse effects of radiotherapy in pediatric malignant pelvic tumors. PMID:26479989

  4. Giant malignant phyllodes tumor of the breast: A rare case report and literature review

    PubMed Central

    LIU, MIN; YANG, SHUO; LIU, BIN; GUO, LIANG; BAO, XUEYING; LIU, BAILONG; DONG, LIHUA

    2016-01-01

    Malignant phyllodes tumor of the breast (MPTB) is rarely encountered in clinical practice. Preoperative diagnosis is challenging due to nonspecific radiological and histological features, and the prognostic factors and optimal treatment remain controversial. The current report describes the case of a middle-aged female with giant MPTB who underwent multidisciplinary intervention, including surgery, postoperative chemotherapy and radiotherapy. To date, the disease-free survival (DFS) of the patient has reached 18 months. Furthermore, a related literature review summarize the clinicopathological characteristics and treatment progress regarding MPTB is presented, along with an analysis of the indications for therapeutic strategy in the current case. In the future, multi-center clinical trials must be initiated to identify the criteria for diagnosis and optimal treatment consensus for MPTB. In conclusion, the present case highlights that multidisciplinary management may contribute to DFS following the treatment of giant MPTB. PMID:27347111

  5. Successful reconstruction after resection of malignant skin tumor on triangular fossa using anterior auricular bilobed flap.

    PubMed

    Fujioka, Masaki; Hayashida, Kenji; Morooka, Sin; Saijo, Hiroto

    2015-10-01

    Reconstruction of surgical defects is challenging, especially when they are localized in an anterior surface. The authors present two patients with a malignant skin neoplasm localized in the triangular fossa. Each tumor was removed and the cartilage-exposing wound was reconstructed using an anterior auricular bilobed flap. The donor site of the flap was primarily closed. The viability of the flap was favorable without complications and with excellent esthetic results. There are various surgical procedures for reconstruction of the anterior auricle. Among them, an anterior auricular bilobed flap can be performed quickly, has minimal associated morbidity and yields a favorable outcome. We believe that this technique is an effective option, especially for the triangular fossa skin defect resurfacing. PMID:25893369

  6. Cytoplasmic localization of Nrf2 promotes colorectal cancer with more aggressive tumors via upregulation of PSMD4.

    PubMed

    Lin, Po-Lin; Chang, Jinghua Tsai; Wu, De-Wei; Huang, Chi-Chou; Lee, Huei

    2016-06-01

    Differences in subcellular localization of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) have been associated with poor outcomes in human cancers. However, the prognostic value of subcellular localization of Nrf2 in colorectal cancer and the underlying mechanism in tumor invasion remain unknown. We enrolled tumors from colorectal patients to evaluate Nrf2, NQO1, and HO-1 expression by immunohistochemistry. NQO1 and HO-1 positive tumors showed nearly complete expression of Nrf2 in the nucleus and/or showed partial expression in the nucleus/cytoplasm (nNrf2); however, tumors negative for NQO1 and HO-1 showed almost complete expression of Nrf2 in the cytoplasm and/or partial expression in the nucleus/cytoplasm (cNrf2). Kaplan-Meier and Cox regression analysis indicated poorer overall survival in patients with cNrf2 tumors than with nNrf2 tumors. Cell models provided evidence that cNrf2, rather than nNrf2, was responsible for cell invasion and soft agar growth triggered by activation of the NF-κB/AKT/β-catenin cascade. Mechanistically, cNrf2 persistently increased PSMD4 expression by the HIF1α/β-catenin axis, whereas PSMD4 reciprocally enhanced Nrf2 nuclear export by increasing CRM1 expression through p53 degradation. The mechanistic action of the cell model was further confirmed with a nude mouse animal model in which xenograft tumors induced by cNrf2 were nearly completely suppressed by the proteasomal inhibitor carfilzomib or the β-catenin inhibitor XAV939. We therefore suggest that PSMD4 or β-catenin might be potential targets for suppressing tumor aggressiveness, and consequently, improving outcomes in patients whose tumors express cNrf2. PMID:27033953

  7. Round cell pattern of prostatic stromal tumor of uncertain malignant potential: a subtle newly recognized variant.

    PubMed

    Sadimin, Evita T; Epstein, Jonathan I

    2016-06-01

    Prostatic stromal tumor of uncertain malignant potential (STUMP) is a distinct entity which includes several different patterns. Four patterns of STUMP have been described including stroma with (1) degenerative atypia, (2) hypercellular spindle cells, (3) myxoid spindle cells, and (4) phyllodes-like pattern. The current study identified a novel round cell pattern. We searched our database from 1999 to 2015 and identified 7 patients with round cell pattern out of a total number of 98 patients with STUMP. All 7 cases showed mildly increased stromal cellularity with rounded nuclei, diagnosed on core biopsies in 5 cases, transurethral resection in 1 case, and radical prostatectomy in 1 case. Some degree of glandular displacement was observed in 4 cases. In 2 of the cases, STUMP was not recognized histologically by the referring pathologists and was initially diagnosed as benign prostatic hyperplasia. As has been described with other patterns of STUMP, several cases showed associated epithelial proliferations that in some instances masked the neoplastic stromal process. The round cell pattern of STUMP is a new deceptively subtle pattern that may not be recognized as a neoplasm and may be misdiagnosed as benign prostatic hyperplasia. Although there was no direct evidence in our study that the round cell pattern of STUMP has the same behavior as other variants of STUMPs, increased recognition of this entity will hopefully lead to additional studies to further understand its malignant potential. PMID:26980017

  8. Disorder of Endothelia Vessels' Functional State with Malignant Tumors in Patients Exposed Anthropogenic Radiation.

    PubMed

    Pak, Laura; Noso, Yoshihiro; Chaizhunusova, Nailya; Anambaeva, Zukhra; Adylkhanov, Tasbolat; Takeichi, Nobuo; Lzhaev, Sayakhat; Aldyngurov, Daniyar; Tuleutayeva, Raikhan; Argynbekova, Ainur; Tanysheva, Gulyash; Zhazykbayeva, Lashyn; Baissalbayeva, Ainur; Rakhypbekov, Tolebay

    2016-01-01

    The aim of this research is to determine the characteristics of endothelial factors and the hemostatic system conditions with malignant neoplasms patients, which were exposed to ionizing radiation. Total number of examined people is 223, 153 of them are patients with gastrointestinal tract oncopathology. The article presents the results of the analysis of numerical indicators of endothelial condition and platelet hemostasis of patients, who had cancer. They lived in the regions of Kazakhstan, subjected to contamination of radionuclides as a result of nuclear weapons tests, which took place in this region from 1949 to 1989. These results then were compared to cancer patients and healthy individuals with no radiation risk. The study revealed the presence of higher levels of endothelial dysfunction and following trigger of the hemostatic system in patients with malignant tumors of the gastrointestinal tract. In particular, the defined high degree of endothelial dysfunction include endothelium- dependent vasodilation, content desquamated endothelial cells in peripheral blood and von Willebrand factor. These indicators have a clear correlation with the degree of disorder of studied parameters of the hemostasis, which can cause the development of thrombotic complications. PMID:26925646

  9. Pure Laparoscopic Liver Resection for Malignant Liver Tumor: Anatomic Resection Versus Nonanatomic Resection

    PubMed Central

    Chen, Ya-Xi; Xiu, Dian-Rong; Yuan, Chun-Hui; Jiang, Bin; Ma, Zhao-Lai

    2016-01-01

    Background: Laparoscopic liver resection (LLR) has been considered to be safe and feasible. However, few studies focused on the comparison between the anatomic and nonanatomic LLR. Therefore, the purpose of this study was to compare the perioperative factors and outcomes of the anatomic and nonanatomic LLR, especially the area of liver parenchymal transection and blood loss per unit area. Methods: In this study, surgical and oncological data of patients underwent pure LLR procedures for malignant liver tumor were prospectively collected. Blood loss per unit area of liver parenchymal transection was measured and considered as an important parameter. All procedures were conducted by a single surgeon. Results: During nearly 5 years, 84 patients with malignant liver tumor received a pure LLR procedure were included. Among them, 34 patients received anatomic LLR and 50 received nonanatomic LLR, respectively. Patients of the two groups were similar in terms of demographic features and tumor characteristics, despite the tumor size was significantly larger in the anatomic LLR group than that in the nonanatomic LLR group (4.77 ± 2.57 vs. 2.87 ± 2.10 cm, P = 0.001). Patients who underwent anatomic resection had longer operation time (364.09 ± 131.22 vs. 252.00 ± 135.21 min, P < 0.001) but less blood loss per unit area (7.85 ± 7.17 vs. 14.17 ± 10.43 ml/cm2, P = 0.018). Nonanatomic LLR was associated with more blood loss when the area of parenchymal transection was equal to the anatomic LLR. No mortality occurred during the hospital stay and 30 days after the operation. Moreover, there was no difference in the incidence of postoperative complications. The disease-free and overall survival rates showed no significant differences between the anatomic LLR and nonanatomic LLR groups. Conclusions: Both anatomic and nonanatomic pure LLR are safe and feasible. Measuring the area of parenchymal transection is a simple and effective method to estimate the outcomes of the liver

  10. Phase II Study of Aflibercept in Recurrent Malignant Glioma: A North American Brain Tumor Consortium Study

    PubMed Central

    de Groot, John F.; Lamborn, Kathleen R.; Chang, Susan M.; Gilbert, Mark R.; Cloughesy, Timothy F.; Aldape, Kenneth; Yao, Jun; Jackson, Edward F.; Lieberman, Frank; Robins, H. Ian; Mehta, Minesh P.; Lassman, Andrew B.; DeAngelis, Lisa M.; Yung, W.K. Alfred; Chen, Alice; Prados, Michael D.; Wen, Patrick Y.

    2011-01-01

    Purpose Antivascular endothelial growth factor (anti-VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. This single-arm phase II study evaluated the efficacy of aflibercept (VEGF Trap), a recombinantly produced fusion protein that scavenges both VEGF and placental growth factor in patients with recurrent malignant glioma. Patients and Methods Forty-two patients with glioblastoma and 16 patients with anaplastic glioma who had received concurrent radiation and temozolomide and adjuvant temozolomide were enrolled at first relapse. Aflibercept 4 mg/kg was administered intravenously on day 1 of every 2-week cycle. Results The 6-month progression-free survival rate was 7.7% for the glioblastoma cohort and 25% for patients with anaplastic glioma. Overall radiographic response rate was 24% (18% for glioblastoma and 44% for anaplastic glioma). The median progression-free survival was 24 weeks for patients with anaplastic glioma (95% CI, 5 to 31 weeks) and 12 weeks for patients with glioblastoma (95% CI, 8 to 16 weeks). A total of 14 patients (25%) were removed from the study for toxicity, on average less than 2 months from treatment initiation. The main treatment-related National Cancer Institute Common Terminology Criteria grades 3 and 4 adverse events (38 total) included fatigue, hypertension, and lymphopenia. Two grade 4 CNS ischemias and one grade 4 systemic hemorrhage were reported. Aflibercept rapidly decreases permeability on dynamic contrast enhanced magnetic resonance imaging, and molecular analysis of baseline tumor tissue identified tumor-associated markers of response and resistance. Conclusion Aflibercept monotherapy has moderate toxicity and minimal evidence of single-agent activity in unselected patients with recurrent malignant glioma. PMID:21606416

  11. Photodynamic therapy of human malignant tumors: a comparative study between photohem and tetrasulfonated aluminum phthalocyanine

    NASA Astrophysics Data System (ADS)

    Stranadko, Eugeny P.; Skobelkin, Oleg K.; Litvin, Grigory D.; Astrakhankina, Tamara A.

    1996-01-01

    The analysis of the results of photodynamic therapy (PDT) for treating malignant neoplasms of the skin, mammary glands, tongue, oral mucous, lower lip, larynx, lungs, urinary bladder, rectum and other locations has been made. During 1992-1995 543 tumoral foci in 146 patients have been treated with PDT. All patients were previously treated with conventional techniques without effect or they were not treated due to contraindications either because of severe accompanying diseases or because of old age. A part of the patients had PDT because of recurrences or intradermal metastases in 1-2 years after surgical, radial or combined treatment. Two home-made preparations were used as photosensitizers: Photohem (hematoporphyrine derivative) and Photosense (aluminum sulfonated phthalocyanine). Light sources were: the argon pumped dye laser ('Innova-200,' 'Coherent') and home-made laser devices: copper-vapor laser-pumped dye laser ('Yakhroma-2,' Frjazino), gas-discharge unit 'Xenon' (wavelength 630 nm), gold-vapor laser (wavelength 627.8 nm) for Photohem; while for Photosense sessions we used solid-state laser on ittrium aluminate 'Poljus-1' (wavelength 670 mn). Up to now we have follow-up control data within 2 months and 3 years. Positive effect of PDT was seen in 92.4% of patients including complete regression of tumors in 62.3% and partial -- in 30.1%. Currently, this new perspective technique of treating malignant neoplasms is successfully being used in Russia; new photosensitizers and light sources for PDT and fluorescent tumour diagnostics are being developed as well.

  12. Application of t-LASCA and speckle-averaging techniques for diagnostics of malignant tumors on animal models

    NASA Astrophysics Data System (ADS)

    Ulyanov, Sergey; Laskavy, Vladislav; Golova, Alina; Polyanina, Tatyana; Ulianova, Onega; Feodorova, Valentina; Ulyanov, Alexander

    2012-03-01

    Method t-LASCA has been adopted for diagnostics of malignant tissue on animal models. Investigations of tumors on inbred mice (line BALB/c) after the inoculation of syngeneic myeloma cells (line Sp.2/0-Ag.8) have been carried out. The efficiency of application of t-LASCA for tumor investigations has been proven. It has been also found that map of time-averaged speckles is more informative rather than LASCA-image.

  13. Application of t-LASCA and speckle-averaging techniques for diagnostics of malignant tumors on animal models

    NASA Astrophysics Data System (ADS)

    Ulyanov, Sergey; Laskavy, Vladislav; Golova, Alina; Polyanina, Tatyana; Ulianova, Onega; Feodorova, Valentina; Ulyanov, Alexander

    2011-10-01

    Method t-LASCA has been adopted for diagnostics of malignant tissue on animal models. Investigations of tumors on inbred mice (line BALB/c) after the inoculation of syngeneic myeloma cells (line Sp.2/0-Ag.8) have been carried out. The efficiency of application of t-LASCA for tumor investigations has been proven. It has been also found that map of time-averaged speckles is more informative rather than LASCA-image.

  14. Tumor-Recruited Neutrophils and Neutrophil TIMP-Free MMP-9 Regulate Coordinately the Levels of Tumor Angiogenesis and Efficiency of Malignant Cell Intravasation

    PubMed Central

    Bekes, Erin M.; Schweighofer, Bernhard; Kupriyanova, Tatyana A.; Zajac, Ewa; Ardi, Veronica C.; Quigley, James P.; Deryugina, Elena I.

    2011-01-01

    Tumor-associated neutrophils contribute to neovascularization by supplying matrix metalloproteinase-9 (MMP-9), a protease that has been genetically and biochemically linked to induction of angiogenesis. Specific roles of inflammatory neutrophils and their distinct proMMP-9 in the coordinate regulation of tumor angiogenesis and tumor cell dissemination, however, have not been addressed. We demonstrate that the primary tumors formed by highly disseminating variants of human fibrosarcoma and prostate carcinoma recruit elevated levels of infiltrating MMP-9-positive neutrophils and concomitantly exhibit enhanced levels of angiogenesis and intravasation. Specific inhibition of neutrophil influx by interleukin 8 (IL-8) neutralization resulted in the coordinated diminishment of tumor angiogenesis and intravasation, both of which were rescued by purified neutrophil proMMP-9. However, if neutrophil proMMP-9, naturally devoid of tissue inhibitor of metalloproteinases (TIMP), was delivered in complex with TIMP-1 or in a mixture with TIMP-2, the protease failed to rescue the inhibitory effects of anti-IL8 therapy, indicating that the TIMP-free status of proMMP-9 is critical for facilitating tumor angiogenesis and intravasation. Our findings directly link tumor-associated neutrophils and their TIMP-free proMMP-9 with the ability of aggressive tumor cells to induce the formation of new blood vessels that serve as conduits for tumor cell dissemination. Thus, treatment of cancers associated with neutrophil infiltration may benefit from specific targeting of neutrophil MMP-9 at early stages to prevent ensuing tumor angiogenesis and tumor metastasis. PMID:21741942

  15. Genes Associated With Prognosis After Surgery For Malignant Pleural Mesothelioma Promote Tumor Cell Survival In Vitro

    PubMed Central

    2011-01-01

    Background Mesothelioma is an aggressive neoplasm with few effective treatments, one being cytoreductive surgery. We previously described a test, based on differential expression levels of four genes, to predict clinical outcome in prospectively consented mesothelioma patients after surgery. In this study, we determined whether any of these four genes could be linked to a cancer relevant phenotype. Methods We conducted a high-throughput RNA inhibition screen to knockdown gene expression levels of the four genes comprising the test (ARHGDIA, COBLL1, PKM2, TM4SF1) in both a human lung-derived normal and a tumor cell line using three different small inhibitory RNA molecules per gene. Successful knockdown was confirmed using quantitative RT-PCR. Detection of statistically significant changes in apoptosis and mitosis was performed using immunological assays and quantified using video-assisted microscopy at a single time-point. Changes in nuclear shape, size, and numbers were used to provide additional support of initial findings. Each experiment was conducted in triplicate. Specificity was assured by requiring that at least 2 different siRNAs produced the observed change in each cell line/time-point/gene/assay combination. Results Knockdown of ARHGDIA, COBLL1, and TM4SF1 resulted in 2- to 4-fold increased levels of apoptosis in normal cells (ARHGDIA only) and tumor cells (all three genes). No statistically significant changes were observed in apoptosis after knockdown of PKM2 or for mitosis after knockdown of any gene. Conclusions We provide evidence that ARHGDIA, COBLL1, and TM4SF1 are negative regulators of apoptosis in cultured tumor cells. These genes, and their related intracellular signaling pathways, may represent potential therapeutic targets in mesothelioma. PMID:21569526

  16. Malignant peripheral nerve sheath tumor of the third eyelid in a 3-year-old Rhodesian Ridgeback

    PubMed Central

    vom Hagen, Franziska; Romkes, Gwendolyna; Kershaw, Olivia; Eule, J Corinna

    2015-01-01

    Key Clinical Message A 3-year-old Rhodesian Ridgeback was presented with conjunctivitis, enlargement of the third eyelid and a dorsotemporal deviation of the right eye. A mass within the third eyelid was detected and excised. The histopathologic examination showed a malignant peripheral nerve sheath tumor, which most likely is a neurofibrosarcoma based on immunohistochemistry. PMID:25678975

  17. Clinical trials of a new chlorin photosensitizer for photodynamic therapy of malignant tumors

    NASA Astrophysics Data System (ADS)

    Privalov, Valeriy A.; Lappa, Alexander V.; Seliverstov, Oleg V.; Faizrakhmanov, Alexey B.; Yarovoy, Nicolay N.; Kochneva, Elena V.; Evnevich, Michail V.; Anikina, Alla S.; Reshetnicov, Andrey V.; Zalevsky, Igor D.; Kemov, Yuriy V.

    2002-06-01

    Photodynamic therapy (PDT) was performed with a new photosensitizer, a water soluble form of chlorins (Radachlorin, Russia) possessing an absorption peak around 662 nm. As light source there was used the diode laser (ML-662-SP, Russia) with 662 nm wavelength and 2.5 W optical power. The sensitizer had passed broad pre-clinical in vitro and in vivo studies, which showed safety and efficiency of it. PDT was applied to 51 patients with basal cell cancer of the skin (about 60% of all cases), breast cancer, lip cancer, melanoma, cancer of esophagus, stomach, and rectum, cancer and leucoplacia of vulva, malignant ganglioneuroma, sarcoma of soft tissue, cancer and reticular sarcoma of thyroid gland, cancer of ductus choledochus. Most of non-basalioma patients had either forth stage or recurrence of disease. The sensitizer was injected intravenously or applied externally (Radachlorin gel). There were used surface, endoscopic, and interstitial ways of irradiation. Full tumor regression with excellent cosmetic effect was reached in 100% cases of 1-3 stage basal cell cancer patients treated with intravenous Radachlorin injection. In most other (non-basalioma) cases significant regression of tumors and improvement of life quality of patients (recanalization and regain of conductivity) was obtained.

  18. Heterogeneous Appearance of Central Nervous System Involvement in Malignant Mixed Müllerian Tumors.

    PubMed

    Könnecke, Helen K; Rushing, Elisabeth J; Neidert, Marian Christoph; Reimann, Regina; Regli, Luca; Bozinov, Oliver; Burkhardt, Jan-Karl

    2016-09-01

    Involvement of the central nervous system (CNS) is rarely described in malignant mixed Müllerian tumors (MMMTs). Only four intracranial and two spinal cases have been published to date. Here we report two more cases with heterogeneous clinical, radiologic and pathologic features and summarize the available contemporary literature. One patient presented with aphasia due to an intra-axial contrast-enhanced left temporal lesion with marked perifocal edema. After surgical resection, histology showed collections of small uniform tumor cells embedded in a myxoid matrix and compartmentalized by connective tissue septations, consistent with an MMMT. The other patient presented with trigeminal/tongue hypesthesia and double vision accompanied by left radiculopathy and paresis. Magnetic resonance imaging MRI revealed an extraaxial lesion at the petrous tip with mild perifocal edema and multiple small intradural contrast-enhancing lesions of the conus and cauda medullaris. Histologic examination of the intracranial lesion showed a mainly papillary architecture, also consistent with MMMTs. The spinal lesions were not excised, and both patients received adjuvant radiochemotherapy. The first patient died 3 months and the second patient 12 months after surgery. As illustrated by the heterogeneous clinicopathologic features of our two cases as well as the reviewed literature, CNS metastasis of MMMTs is diagnostically challenging, shows a variable outcome, and thus requires individualized treatment. In the present cases and CNS metastases reported to date, a higher histologic ratio of sarcomatous to epithelial components portends a worse outcome. PMID:26216730

  19. [The treatment of malignant tumors on venous leg ulcers. Case presentation and literature review].

    PubMed

    Lehnert, W; Kohl, K; Riebe, H; Jünger, M; Ladwig, A

    2008-11-01

    Malignant changes in persistent venous leg ulcers are a grave complication of chronic impaired wound healing. In our case, a venous leg ulcer had persisted on the right calf for 30 years. Exophytic tumors in the ulcer with frequent bleeding prompted biopsies. A squamous cell carcinoma was found, but only in the second biopsy. The surgical procedure was planned so that in a single session both the tumor and the underlying causes of the chronic venous insufficiency in the leg could be treated appropriately. Extirpation of the enlarged lymph nodes in the groin was combined with crossectomy and removal of the long saphenous vein, followed by circular radial excision of the ulcer scar fascia (fasciotomy). The excised tissue was examined histologically. Muscle biopsies were taken from the site of suspicious adhesions of the fascia to the calf muscle. The large, circular defects on the lower leg were covered with the appropriate dressing to condition the wound bed. After three weeks the well-granulated area was covered with meshed split skin grafts. During the operation and in the post-operative phase, machine-assisted and manual decongestion was performed, an established therapy for lymphedema, chronic venous insufficiency and chronic venous ulcers. PMID:18850078

  20. Medullary metastasis of a malignant peripheral nerve sheath tumor: A case report

    PubMed Central

    Hagi, Tomohito; Nakamura, Tomoki; Yokoji, Ayumu; Matsumine, Akihiko; Sudo, Akihiro

    2016-01-01

    The present study reports a case of medullary metastasis without lung metastasis that occurred as a result of a malignant peripheral nerve sheath tumor (MPNST). An 81-year-old woman presented with a MPNST in the left brachial plexus, arising from the cervical nerve root. The patient underwent carbon ion radiotherapy; however, tumor recurrence was identified in the left shoulder. Subsequently, the patient underwent wide excision. Three weeks subsequent to surgery, imbalance and dysarthria developed suddenly. Dysphagia emerged and left upper limb pain disappeared on the day after symptom development. Magnetic resonance imaging (MRI) revealed that this was due to metastasis to the medulla. Five days subsequent to the onset of dysarthria, the patient succumbed due to respiratory failure. To the best of our knowledge, no previous cases of medullary metastasis arising from a MPNST in the absence of lung metastasis have been reported. MRI is a useful examination tool for the identification of brain metastases; however, the high cost of MRI as a routine examination must be considered due to the rarity of brain metastases. Therefore, methods to detect brain metastasis warrant further investigation.