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Sample records for arsenic-induced malignant transformation

  1. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States)

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  2. Silencing KRAS overexpression in arsenic-transformed prostate epithelial and stem cells partially mitigates malignant phenotype.

    Science.gov (United States)

    Ngalame, Ntube N O; Tokar, Erik J; Person, Rachel J; Waalkes, Michael P

    2014-12-01

    Inorganic arsenic is a human carcinogen that likely targets the prostate. Chronic arsenic exposure malignantly transforms the RWPE-1 human prostate epithelial line to chronic arsenic exposed-prostate epithelial (CAsE-PE) cells, and a derivative normal prostate stem cell (SC) line, WPE-stem to arsenic-cancer SCs (As-CSCs). The KRAS oncogene is highly overexpressed in CAsE-PE cells and activation precedes transformation, inferring mechanistic significance. As-CSCs also highly overexpress KRAS. Thus, we hypothesize KRAS activation is key in causing and maintaining an arsenic-induced malignant phenotype, and hence, KRAS knockdown (KD) may reverse this malignant phenotype. RNA interference using shRNAmirs to obtain KRAS KD was used in CAsE-PE and As-CSC cells. Cells analyzed 2 weeks post transduction showed KRAS protein decreased to 5% of control after KD, confirming stable KD. KRAS KD decreased phosphorylated ERK, indicating inhibition of RAS/ERK signaling, a proliferation/survival pathway activated with arsenic transformation. Secreted metalloproteinase (MMP) activity was increased by arsenic-induced malignant transformation, but KRAS KD from 4 weeks on decreased secreted MMP-9 activity by 50% in As-CSCs. Colony formation, a characteristic of cancer cells, was decreased in both KRAS KD transformants. KRAS KD also decreased the invasive capacity of both cell types. KRAS KD decreased proliferation in As-CSCs, consistent with loss of rapid tumor growth. Genes predicted to impact cell proliferation (eg, Cyclin D1, p16, and p21) changed accordingly in both KD cell types. Thus, KRAS silencing impacts aspects of arsenic-induced malignant phenotype, inducing loss of many typical cancer characteristics particularly in As-CSCs.

  3. Oral potentially malignant disorders: is malignant transformation predictable and preventable?

    NARCIS (Netherlands)

    I. van der Waal

    2014-01-01

    Leukoplakia is the most common potentially malignant disorder of the oral mucosa. The prevalence is approximately 1% while the annual malignant transformation ranges from 2% to 3%. At present, there are no reliable clinicopathological or molecular predicting factors of malignant transformation that

  4. Epidermodysplasia verruciformis: An unusual malignant transformation

    Directory of Open Access Journals (Sweden)

    Prachi G Agrawal

    2013-01-01

    Full Text Available Epidermodysplasia verruciformis (EV is a rare, life-long heritable disease caused due to a unique susceptibility to human papilloma virus. The disseminated verrucous lesions and pityriasis versicolor-like lesions persist from early childhood and can transform into a cutaneous malignancy in a fourth of patients. Malignant transformation into syringoid eccrine carcinoma (SEC has been reported only once so far. SEC is an extremely invasive, rare, locally destructive, slowly growing adnexal tumor. We hereby report the association of EV with SEC in a 29-year-old male.

  5. Malignant transformation of aggressive osteoblastoma to ostesarcoma.

    Science.gov (United States)

    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

  6. Rapid malignant transformation of primary synovial chondromatosis into chondrosarcoma.

    Science.gov (United States)

    Jonckheere, J; Shahabpour, M; Willekens, I; Pouliart, N; Dezillie, M; Vanhoenacker, F; De Mey, J

    2014-01-01

    Chondrosarcoma of the synovium is rare. It may arise de novo from the synovium or pre-existing synovial chondro- matosis may undergo malignant transformation into chondrosarcoma. Diagnosing a malignant transformation of the synovium remains a big challenge. It is based on the correlation of clinical findings, imaging and histology, as illustrated in this case report. PMID:25597214

  7. Malignant transformation of diploid human fibroblasts by transfection of oncogenes

    International Nuclear Information System (INIS)

    This document consist of brief reports prepared by postdoctoral students supported by the project, each describing his accomplishments under the grant. Topics include (1) Malignant Transformation of MSU-1. 1 Cells by Gamma Radiation, (2) Correlation between Levels of ras Expression and Presence of Transformed Phenotypes Including Tumorigenicity, Using a Modulatable Promoter, (3) Relation between Specific rad Oncogene Expression, (4) Correlation of Genetic Changes in Fibroblastic Tumors with Malignancies, (5)Transformation of MSU-1.1 Cells by sis Oncogene, (6) Malignant Transformation of MSU-1.0 Cells, (7) Correlation of Urokinase Plasminogen Activation (mu-PA) with Malignant Phenotype, (8)Two Dimensional Gel Electrophoresis Studies of the Proteins of the Major Cell Strains of the MSU-1 Family of Cells, and (9) Correlation between Proteinase Activity Levels and Malignancy

  8. Malignant transformation of diploid human fibroblasts by transfection of oncogenes

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, J.J.

    1992-01-01

    This document consist of brief reports prepared by postdoctoral students supported by the project, each describing his accomplishments under the grant. Topics include (1) Malignant Transformation of MSU-1. 1 Cells by Gamma Radiation, (2) Correlation between Levels of ras Expression and Presence of Transformed Phenotypes Including Tumorigenicity, Using a Modulatable Promoter, (3) Relation between Specific rad Oncogene Expression, (4) Correlation of Genetic Changes in Fibroblastic Tumors with Malignancies, (5)Transformation of MSU-1.1 Cells by sis Oncogene, (6) Malignant Transformation of MSU-1.0 Cells, (7) Correlation of Urokinase Plasminogen Activation (mu-PA) with Malignant Phenotype, (8)Two Dimensional Gel Electrophoresis Studies of the Proteins of the Major Cell Strains of the MSU-1 Family of Cells, and (9) Correlation between Proteinase Activity Levels and Malignancy.

  9. microRNAs in the Malignant Transformation Process.

    Science.gov (United States)

    Sarver, Anne E; Li, Lihua; Kartha, Reena V; Subramanian, Subbaya

    2015-01-01

    Many cancers originate as benign neoplasms that transform into malignant cancerous tumors in a multistep progression that is regulated, in part, by microRNAs. Benign neoplasms, by definition, lack the ability to invade adjacent tissues or spread to distant sites through metastasis. The benign to malignant transition is a critical intervention stage as tumors diagnosed in subsequent nonlocalized and malignant stages are exponentially more difficult to treat successfully. This chapter explores the critical roles that microRNAs play in the transformation from benign to malignant in four representative cancers: colorectal cancer, pancreatic cancer, malignant peripheral nerve sheath tumor, and prostate cancer. Understanding how these microRNAs control this progression and transformation will lead to new therapeutic targets and diagnostic biomarkers, resulting in improved treatments and patient outcomes.

  10. Malignant melanoma transformation within a nevus of Ito.

    Science.gov (United States)

    Wise, Sean R; Capra, Gregory; Martin, Peter; Wallace, Donna; Miller, Charles

    2010-05-01

    The mongolian spot, nevus of Ota, and nevus of Ito are the most common morphologic forms of the dermal melanocytoses, a group of benign pigmented lesions histologically characterized by the presence of melanocytes within the dermis. Nevus of Ito is clinically distinct, presenting with unilateral, bluish gray, patchy discolorations in the skin within the distributions of the posterior supraclavicular and lateral cutaneous brachial nerves. Although all dermal melanocytoses are generally considered benign, rare cases of malignant transformation associated with nevus of Ota have been described. Only one case of malignant melanoma transformation in association with nevus of Ito has previously been reported. We present the second description of malignant melanoma transformation within a nevus of Ito and provide comment on the malignant potential of the dermal melanocytoses.

  11. Transformation of benign fibroadenoma to malignant phyllodes tumor

    Science.gov (United States)

    Daigle, Megan E; Tortora, Matthew; Panasiti, Ryane

    2015-01-01

    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

  12. Malignant transformation of aneurysmal bone cysts: a case report

    Institute of Scientific and Technical Information of China (English)

    MEI Jiong; GAO You-shui; WANG Shu-qing; CAI Xuan-song

    2009-01-01

    @@ An aneurysmal bone cyst is a non-neoplastic, Adestructive and expansile lesion consisting of a "blood-filled sponge" that is defined to represent a benign reactive vascularity.1-3 Szendroi et al4 suggested that the aneurysmal bone cyst corresponds to a haemodynamic disturbance that is primary or secondary venous malformation of the bones. The association with trauma including fracture has also been noted and 25%-71% of such patients have a history of trauma.57 Conventionally, malignant transformation of aneurysmal bone cysts is perceived as a rare occurrence except those induced by irradiation.8-10~ Both malignant fibrous histiocytoma and osteosarcoma have been reported in the malignant transformation cases.

  13. Giant cardiac myxoma with malignant transformed glandular structures

    Energy Technology Data Exchange (ETDEWEB)

    Eckhardt, Boris P.; Stuckmann, Gerd; Zollikofer, Christoph L. [Institute of Radiology, Cantonal Hospital, Brauerstrasse 15, 8401 Winterthur (Switzerland); Dommann-Scherrer, Corina C. [Insitute of Pathology, Cantonal Hospital, Brauerstrasse 15, 8401 Winterthur (Switzerland); Wentz, Klaus U. [Institute of Radiology, Cantonal Hospital, Brauerstrasse 15, 8401 Winterthur (Switzerland); Medical Faculty, University of Witten/Herdecke, Alfred-Herrhausen-Strasse 50, 58448 Witten (Germany)

    2003-09-01

    A case of a right-sided giant cardiac myxoma with malignant transformation of glandular structures causing systemic metastases is described. Plain chest radiography and computed tomography localized the tumor within the heart. Exact depiction of the origin of the tumor using subtracted 2D-projection MR angiography is documented. Radiologic findings and differential diagnosis of this unique tumor are discussed. (orig.)

  14. Spontaneous malignant transformation of conventional giant cell tumor

    Energy Technology Data Exchange (ETDEWEB)

    Grote, H.J.; Pomjanski, N.; Boecking, A. [Institute of Cytopathology, Heinrich Heine University, Moorenstrasse 5, 40225, Duesseldorf (Germany); Braun, M. [Orthopedic Hospital Volmarstein, University of Witten/Herdecke, Hartmannstrasse 24, 58300, Wetter (Ruhr) (Germany); Kalinski, T.; Roessner, A. [Department of Pathology, Otto von Guericke University, Leipziger Strasse 44, 39120, Magdeburg (Germany); Back, W.; Bleyl, U. [Department of Pathology, Ruprecht Karls University Heidelberg, University Hospital Mannheim, Theodor-Kutzer-Ufer, 68167, Mannheim (Germany)

    2004-03-01

    Spontaneous malignant transformation of conventional giant cell tumor (GCT) of bone is exceedingly rare. We report on a case of GCT of the iliac crest in a 35-year-old woman with malignant change into a high-grade osteosarcoma 10 years after the first appearance of GCT on a radiograph. Since the patient refused therapy for personal reasons the tumor remained untreated until sarcomatous transformation occurred. Image cytometry showed DNA aneuploidy and a suspiciously high 2c deviation index (2cDI) in the primary bone lesion. A thorough review of the world literature revealed only seven fully documented cases of secondary malignant GCT which matched the definition of a ''sarcomatous growth that occurs at the site of a previously documented benign giant cell tumor'' and not treated by radiotherapy. These cases as well as the current one suggest that a spontaneous secondary malignant GCT presents as a frankly sarcomatous tumor in the form of an osteosarcoma or malignant fibrous histiocytoma. It usually appears at sites of typical GCTs - often without any recurrent intermediate state - and is diagnosed 3 or more years after the primary bone lesion. The prognosis is poor. (orig.)

  15. Malignant transformation of ectopic pancreatic cells in the duodenal wall

    Institute of Scientific and Technical Information of China (English)

    Roberto; Bini; Paolo; Voghera; Alberto; Tapparo; Raffaele; Nunziata; Andrea; Demarchi; Matteo; Capocefalo; Renzo; Leli

    2010-01-01

    Ectopic pancreas (EP) is the relatively uncommon presence of pancreatic tissue outside the normal location of the pancreas. This condition is usually asymptomatic and rarely complicated by pancreatitis and malignant transformation. A few cases of neoplastic phenomena that developed from EP into the duodenal wall are described in the literature. Herein we report a case of gastric outlet obstruction due to adenocarcinoma arising from EP of the duodenal wall. The patient underwent a Whipple's procedure and had...

  16. PTEN dosage is essential for neurofibroma development and malignant transformation.

    Science.gov (United States)

    Gregorian, Caroline; Nakashima, Jonathan; Dry, Sarah M; Nghiemphu, P Leia; Smith, Kate Barzan; Ao, Yan; Dang, Julie; Lawson, Gregory; Mellinghoff, Ingo K; Mischel, Paul S; Phelps, Michael; Parada, Luis F; Liu, Xin; Sofroniew, Michael V; Eilber, Fritz C; Wu, Hong

    2009-11-17

    Patients with neurofibromatosis type 1 (NF1) carry approximately a 10% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST). Although the molecular mechanisms underlying NF1 to MPNST malignant transformation remain unclear, alterations of both the RAS/RAF/MAPK and PI3K/AKT/mTOR signaling pathways have been implicated. In a series of genetically engineered murine models, we perturbed RAS/RAF/MAPK or/and PTEN/PI3K/AKT pathway, individually or simultaneously, via conditional activation of K-ras oncogene or deletion of Nf1 or Pten tumor suppressor genes. Only K-Ras activation in combination with a single Pten allele deletion led to 100% penetrable development of NF lesions and subsequent progression to MPNST. Importantly, loss or decrease in PTEN expression was found in all murine MPNSTs and a majority of human NF1-associated MPNST lesions, suggesting that PTEN dosage and its controlled signaling pathways are critical for transformation of NFs to MPNST. Using noninvasive in vivo PET-CT imaging, we demonstrated that FDG can be used to identify the malignant transformation in both murine and human MPNSTs. Our data suggest that combined inhibition of RAS/RAF/MAPK and PTEN/PI3K/AKT pathways may be beneficial for patients with MPNST.

  17. PTEN dosage is essential for neurofibroma development and malignant transformation.

    Science.gov (United States)

    Gregorian, Caroline; Nakashima, Jonathan; Dry, Sarah M; Nghiemphu, P Leia; Smith, Kate Barzan; Ao, Yan; Dang, Julie; Lawson, Gregory; Mellinghoff, Ingo K; Mischel, Paul S; Phelps, Michael; Parada, Luis F; Liu, Xin; Sofroniew, Michael V; Eilber, Fritz C; Wu, Hong

    2009-11-17

    Patients with neurofibromatosis type 1 (NF1) carry approximately a 10% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST). Although the molecular mechanisms underlying NF1 to MPNST malignant transformation remain unclear, alterations of both the RAS/RAF/MAPK and PI3K/AKT/mTOR signaling pathways have been implicated. In a series of genetically engineered murine models, we perturbed RAS/RAF/MAPK or/and PTEN/PI3K/AKT pathway, individually or simultaneously, via conditional activation of K-ras oncogene or deletion of Nf1 or Pten tumor suppressor genes. Only K-Ras activation in combination with a single Pten allele deletion led to 100% penetrable development of NF lesions and subsequent progression to MPNST. Importantly, loss or decrease in PTEN expression was found in all murine MPNSTs and a majority of human NF1-associated MPNST lesions, suggesting that PTEN dosage and its controlled signaling pathways are critical for transformation of NFs to MPNST. Using noninvasive in vivo PET-CT imaging, we demonstrated that FDG can be used to identify the malignant transformation in both murine and human MPNSTs. Our data suggest that combined inhibition of RAS/RAF/MAPK and PTEN/PI3K/AKT pathways may be beneficial for patients with MPNST. PMID:19846776

  18. Late malignant transformation of vestibular schwannoma in the absence of irradiation

    DEFF Research Database (Denmark)

    Bashir, Asma; Poulsgaard, Lars; Broholm, Helle;

    2016-01-01

    Late malignant transformation of vestibular schwannoma (VS) following irradiation has previously been reported 29 times in the literature. Here, the authors report the first late malignant transformation of VS unrelated to neurofibromatosis or radiation exposure. After undergoing a near-total exc...

  19. Genomic dynamics associated with malignant transformation in IDH1 mutated gliomas

    OpenAIRE

    Park, Chul-Kee; Park, Inho; Lee, Seungmook; Sun, Choong-Hyun; Koh, Youngil; Park, Sung-Hye; Kim, Ja Eun; Yun, Hongseok; Lee, Se-Hoon

    2015-01-01

    The genomic mechanism responsible for malignant transformation remains an open question for glioma researchers, where differing conclusions have been drawn based on diverse study conditions. Therefore, it is essential to secure direct evidence using longitudinal samples from the same patient. Moreover, malignant transformation of IDH1-mutated gliomas is of potential interest, as its genomic mechanism under influence of oncometabolite remains unclear, and even higher rate of malignant transfor...

  20. Liver cell adenoma with malignant transformation: A case report

    Institute of Scientific and Technical Information of China (English)

    Masahiro Ito; Makoto Sasaki; Chun-Yang Wen; Masahiro Nakashima; Toshihito Ueki; Hiromi Ishibashi; Michitami Yano; Masayoshi Kage; Masamichi Kojiro

    2003-01-01

    A 57-year-old woman was referred to our hospital because of a liver mass detected by computed tomography. She had taken oral contraceptives for only one month at the age of thirty. Physical examination revealed no abnormalities, and laboratory data, including hepatic function tests, were within the normal range, with the exception of elevated levels of those serum proteins induced by the absence of vitamin K or by raised levels of the antagonist (PIVKA)-Ⅱ (3 502 AU/ml).Abdominal ultrasonography revealed a hyperechoic mass measuring 10x10 cm in the left posterior segment of the liver. Because hepatocellular carcinoma could not be completely excluded, this mass was resected. The tumor consisted of sheets of uniform cells with clear cytoplasm,perinuclear eosinophilic granules and round nuclei. These histological findings were consistent with liver cell adenoma.Background hepatic tissue appeared normal. After resection of the tumor, serum PIVKA-Ⅱ fell to within the normal range.An area of hepatocellular carcinoma (HCC) with a midtrabecular pattern was immunohistochemically found, which was positive for PIVKA-Ⅱ. Sinusoidal endothelial cells were CD34-positive, containing scattered PIVKA-Ⅱ positive cells.This tumor was therefore finally diagnosed as liver cell adenoma with focal malignant transformation to HCC.

  1. Malignant transformation of oral leukoplakia: a retrospective cohort study of 218 Chinese patients

    International Nuclear Information System (INIS)

    Oral leukoplakia (OL) is the best-known potentially malignant disorder. A new binary system to grade dysplasia was proposed by WHO, but the biological significance in predicting malignant transformation risk is unknown. The objective of this study is to estimate the rate of malignant transformation in a long-term follow-up cohort, explore the usefulness of the new binary system of grading dysplasia and identify significant risk factors of OL malignant transformation in China. A total of 218 patients with clinical and histopathologic diagnosis of OL were retrospectively reviewed. They were selected among all archived files at the Department of Oral Mucosal Diseases, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The mean follow-up period was 5.3 years. Among 218 cases, 39 (17.9%) OL patients developed oral cancer, with a mean duration of 5.2 years. Cox regression analysis revealed that dysplasia was an independent risk factor for OL malignant transformation, but age, gender, lesion site, diet habit, smoking and ethanol intake were not risk factors. High-risk dysplastic OL was associated with a 4.57-fold (95% confidence interval, 2.36-8.84; P < 0.001) increased risk of malignant transformation, compared with low-risk dysplasia. Consistent with this result, high-risk dysplastic OL had signicantly higher malignant incidence than low-risk dysplasia, particularly during the first 2-3 years of follow-up, by Kaplan-Meier analysis (Log-rank test, P < 0.001). The new binary system's function in predicting OL malignant transformation risk was investigated in this survey. The utilization of high-risk dysplasia as a significant indicator for evaluating malignant transformation risk in patients with OL was suggested, which may be helpful to guide treatment selection in clinical practice

  2. Predictive Factors of Potential Malignant Transformation in Recurrent Calcifying Cystic Odontogenic Tumor: Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sepideh Mokhtari

    2013-01-01

    Full Text Available Calcifying cystic odontogenic tumor (CCOT demonstrates considerable diversity in histopathology and clinical behavior. Ghost cell odontogenic carcinoma (GCOC is the rare malignant counterpart of CCOT and it frequently arises from malignant transformation of a recurrent CCOT. In this paper, we present a case of CCOT and discuss its distinct histopathologic features in recurrence. Then, we will have a review on clinical, histopathological, and immunohistochemical aspects of GCOC in the literature. Predictive factors of malignant transformation in a benign CCOT will also be discussed.

  3. Malignant transformation of craniopharyngioma with detailed follow-up.

    Science.gov (United States)

    Wang, Wei; Chen, Xiao-Dong; Bai, Hong-Min; Liao, Qiu-Lin; Dai, Xue-Jun; Peng, Da-Yun; Cao, Hui-Xia

    2015-02-01

    A 29-year-old male patient was admitted into hospital with the main complaint of progressive visual disturbance. Both CT SCAN and MRI demonstrated a cystic-solid contrast-enhancing sellar-suprasellar mass with obvious calcification. Histopathological examination of the first resected specimen showed a typical appearance of adamantinomatous craniopharyngioma. The patient received gamma knife therapy after his first operation because of partial tumor removal. He experienced two relapses in the subsequent 2 years, for which only surgical resection was performed. The later histopathology presented malignant appearance with tumor cells moderate to severe pleomorphism, hyperchromasia, increased nuclear cytoplastic ratio, high mitotic activity (30/10 high power fields) and focal coagulative necrosis. The patient died 9 months after identification of histologic malignancy. Clinical and histopathological features, biological behavior of one case of malignant craniopharyngioma were discussed, with a brief review of the relevant literature. PMID:25112406

  4. Abnormalities of chromosome No. 1: significance in malignant transformation

    Energy Technology Data Exchange (ETDEWEB)

    Rowley, J.D.

    1978-01-01

    Studies of human hematologic malignancies have provided sufficient data not only for the identification of nonrandom abnormalities of whole chromosomes, but also for determination of the specific chromosome regions involved. In clonal aberrations leading to an excess of chromosome No. 1, or a partial excess of No. 1, trisomy for bands 1q25 to 1q32 was noted in the myeloid cells obtained from every one of 35 patients who had various disorders, such as acute leukemia, polycythemia vera, or myelofibrosis. Similar chromosome changes were a consistent finding in various solid tumors as well. This rearrangement was not the result of a particularly fragile site in that region of the chromosome, since the break points in reciprocal translocations that involve No. 1 occurred almost exclusively in the short arm. The nonrandom chromosome changes found in neoplastic cells can now be correlated with the gene loci on these chromosomes or chromosome segments as an attempt is made to identify specific genes that might be related to malignancy.

  5. Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multistep reactivation process.

    Science.gov (United States)

    Galvao, Rui Pedro; Kasina, Anita; McNeill, Robert S; Harbin, Jordan E; Foreman, Oded; Verhaak, Roel G W; Nishiyama, Akiko; Miller, C Ryan; Zong, Hui

    2014-10-01

    How malignant gliomas arise in a mature brain remains a mystery, hindering the development of preventive and therapeutic interventions. We previously showed that oligodendrocyte precursor cells (OPCs) can be transformed into glioma when mutations are introduced perinatally. However, adult OPCs rarely proliferate compared with their perinatal counterparts. Whether these relatively quiescent cells have the potential to transform is unknown, which is a critical question considering the late onset of human glioma. Additionally, the premalignant events taking place between initial mutation and a fully developed tumor mass are particularly poorly understood in glioma. Here we used a temporally controllable Cre transgene to delete p53 and NF1 specifically in adult OPCs and demonstrated that these cells consistently give rise to malignant gliomas. To investigate the transforming process of quiescent adult OPCs, we then tracked these cells throughout the premalignant phase, which revealed a dynamic multistep transformation, starting with rapid but transient hyperproliferative reactivation, followed by a long period of dormancy, and then final malignant transformation. Using pharmacological approaches, we discovered that mammalian target of rapamycin signaling is critical for both the initial OPC reactivation step and late-stage tumor cell proliferation and thus might be a potential target for both glioma prevention and treatment. In summary, our results firmly establish the transforming potential of adult OPCs and reveal an actionable multiphasic reactivation process that turns slowly dividing OPCs into malignant gliomas.

  6. The Case of an Elderly Male Patient with Unknown Primary Mucinous Adenocarcinoma within Presacral Teratoma (Teratoma with Malignant Transformation)

    OpenAIRE

    Ozgur Tanriverdi; Ayca Ersen; Suna Cokmert; Emine Koca; Naki Bulut; Suha Gul; Nevin Yilmaz

    2015-01-01

    Teratomas are rarely seen in adults, and presacral region is an area where they rarely settle in. Similarly, only about 1% of teratomas show malignant transformation. Malignant transformation is often associated with the area where teratoma settles in. Malignant transformation of mediastinal teratomas is more frequent than the ones located in retroperitoneal area and gonad. They most commonly show rhabdomyosarcoma, primitive neuroectodermal tumor, enteric adenocarcinoma, and leukemia transfor...

  7. Malignant transformation in a hybrid schwannoma/perineurioma: Addition to the spectrum of a malignant peripheral nerve sheath tumor

    Directory of Open Access Journals (Sweden)

    Bharat Rekhi

    2011-01-01

    Full Text Available Benign nerve sheath tumors include schwannomas, neurofibromas and perineuriomas. The malignant counterpart of a nerve sheath tumor is designated as a malignant peripheral nerve sheath tumor (MPNST. Lately, benign nerve sheath tumors comprising more than one component have been described, including hybrid schwannomas/perineuriomas. However, malignant transformation in a hybrid schwannoma/perineurioma has not been documented so far. Herein, we present a rare case of a young adult male who presented with a soft tissue mass in his right thigh that was excised elsewhere and submitted to us for histopathological review. One of the tissue sections displayed histopathological features of a hybrid schwannoma/perineurioma, including alternate arrangement of benign schwann and perineurial cells, reinforced with S100-P and epithelial membrane antigen positivity, respectively, along with low MIB1 and negative p53 immunostaining. The other two tissue sections showed a spindly sarcomatous tumor that was immunohistochemically positive for S100-P, CD34, p53 and exhibited high MIB1 (30-40%. Diagnosis of a MPNST arising in a hybrid schwannoma/perineurioma was made. This unusual case forms yet another addition to the spectrum of a MPNST.

  8. The potent oncogene NPM-ALK mediates malignant transformation of normal human CD4(+) T lymphocytes.

    Science.gov (United States)

    Zhang, Qian; Wei, Fang; Wang, Hong Yi; Liu, Xiaobin; Roy, Darshan; Xiong, Qun-Bin; Jiang, Shuguang; Medvec, Andrew; Danet-Desnoyers, Gwenn; Watt, Christopher; Tomczak, Ewa; Kalos, Michael; Riley, James L; Wasik, Mariusz A

    2013-12-01

    With this study we have demonstrated that in vitro transduction of normal human CD4(+) T lymphocytes with NPM-ALK results in their malignant transformation. The transformed cells become immortalized and display morphology and immunophenotype characteristic of patient-derived anaplastic large-cell lymphomas. These unique features, which are strictly dependent on NPM-ALK activity and expression, include perpetual cell growth, proliferation, and survival; activation of the key signal transduction pathways STAT3 and mTORC1; and expression of CD30 (the hallmark of anaplastic large-cell lymphoma) and of immunosuppressive cytokine IL-10 and cell-surface protein PD-L1/CD274. Implantation of NPM-ALK-transformed CD4(+) T lymphocytes into immunodeficient mice resulted in formation of tumors indistinguishable from patients' anaplastic large-cell lymphomas. Our findings demonstrate that the key aspects of human carcinogenesis closely recapitulating the features of the native tumors can be faithfully reproduced in vitro when an appropriate oncogene is used to transform its natural target cells; this in turn points to the fundamental role in malignant cell transformation of potent oncogenes expressed in the relevant target cells. Such transformed cells should permit study of the early stages of carcinogenesis, and in particular the initial oncogene-host cell interactions. This experimental design could also be useful for studies of the effects of early therapeutic intervention and likely also the mechanisms of malignant progression.

  9. Malignant transformation of neurofibromas in neurofibromatosis 1 is associated with CDKN2A/p16 inactivation

    DEFF Research Database (Denmark)

    Nielsen, G P; Stemmer-Rachamimov, A O; Ino, Y;

    1999-01-01

    Patients with neurofibromatosis 1 (NF1) are predisposed to develop multiple neurofibromas (NFs) and are at risk for transformation of NFs to malignant peripheral nerve sheath tumors (MPNSTs). Little is known, however, about the biological events involved in the malignant transformation of NFs. We...

  10. Differential effects of arsenic on calcium signaling in primary keratinocytes and malignant (HSC-1) cells.

    Science.gov (United States)

    Hsu, W L; Tsai, M H; Lin, M W; Chiu, Y C; Lu, J H; Chang, C H; Yu, H S; Yoshioka, T

    2012-08-01

    Arsenic is highly toxic to living cells, especially skin, and skin cancer is induced by drinking water containing arsenic. The molecular mechanisms of arsenic-induced cancer, however, are not well understood. To examine the initial processes in the development of arsenic-induced cancer, we analyzed calcium signaling at an early stage of arsenic treatment of human primary cells and compared the effects with those observed with arsenic treatment in carcinoma-derived cells. We found that arsenic inhibited inositol trisphosphate receptor (IP3R) function in the endoplasmic reticulum by inducing phosphorylation, which led to decreased intracellular calcium levels. Blockade of IP3R phosphorylation by the serine/threonine protein kinase Akt inhibitor wortmannin rescued calcium signaling. In contrast, arsenic treatment of cells derived from a carcinoma (human squamous carcinoma; HSC-1) for 1h had no obvious effect. Taken together, these results suggest that arsenic-induced reduction in calcium signaling is one of the initial mechanisms underlying the malignant transformation in the development of skin cancer.

  11. Malignant transformation of diploid human fibroblasts by transfection of oncogenes: Progress report, July 1986--June 1989

    International Nuclear Information System (INIS)

    Although there is good evidence that carcinogen exposure is a major cause of human cancer, it has proven impossible to transform normal human fibroblasts or epithelial cells in culture into malignant cells by treating them with carcinogens. This failure may reflect an inability to identify and isolate cells containing one or more premalignant changes so that these can be expanded and exposed to carcinogens a second time to induce additional required changes. A second serious roadblock to the sequential introduction of changes and expansion of clonally-derived cells containing such premalignant changes in the finite life span of human cells in culture. Using transfection of specific human oncogenes in a series of specially-selected vectors, we have overcome these obstacles and have recently succeeded in generating an infinite life span diploid human cell strain MSU-1.0, which appears to be normal in all other characteristics. From that cell a second cell strain, MSU-1.1, was generated which we have been able to transform into a malignant state not only by transfecting the cells with oncogenes but also by treating them with chemical carcinogens. We now have evidence that there is not just a single linear process which results in malignant transformation. Rather, cells appear to progress to malignancy on a series of parallel, sometimes overlapping tracks. We now propose to carry out detailed studies of the specific mechanisms of malignant cell transformation using the cell strains available in this laboratory to achieve the goal of building relevant quantitative models of carcinogenesis. 29 refs

  12. Malignant transformation of guinea pig cells after exposure to ultraviolet-irradiated guinea pig cytomegalovirus

    International Nuclear Information System (INIS)

    Guinea pig cells were malignantly transformed in vitro by ultraviolet (uv)-irradiated guinea pig cytomegalovirus (GPCMV). When guinea pig hepatocyte monolayers were infected with uv-irradiated GPCMV, three continuous epithelioid cell lines which grew in soft agarose were established. Two independently derived GPCMV-transformed liver cells and a cell line derived from a soft agarose clone of one of these lines induced invasive tumors when inoculated subcutaneously or intraperitoneally into nude mice. The tumors were sarcomas possibly derived from hepatic stroma or sinusoid. Transformed cell lines were also established after infection of guinea pig hepatocyte monolayers with human cytomegalovirus (HCMV) or simian virus 40 (SV40). These cell lines also formed colonies in soft agarose and induced sarcomas in nude mice. It is concluded that (i) GPCMV can malignantly transform guinea pig cells; (ii) cloning of GPCMV-transformed cells in soft agarose produced cells that induced tumors with a shorter latency period but with no alteration in growth rate or final tumor size; and (iii) the tumors produced by GPCMV-and HCMV-transformed guinea pig cells were more similar to each other in growth rate than to those induced by SV40-transformed guinea pig cells

  13. Apigenin suppresses migration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lei; Kuang, Lisha; Hitron, John Andrew; Son, Young-Ok; Wang, Xin; Budhraja, Amit [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Lee, Jeong-Chae [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Institute of Oral Biosciences and BK21 Program, Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Pratheeshkumar, Poyil [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Chen, Gang [Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Zhang, Zhuo [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)

    2013-10-01

    Environmental exposure to arsenic is known to cause various cancers. There are some potential relationships between cell malignant transformation and C-X-C chemokine receptor type 4 (CXCR4) expressions. Metastasis, one of the major characteristics of malignantly transformed cells, contributes to the high mortality of cells. CXCR4 and its natural chemokine ligand C-X-C motif ligand 12 (CXCL12) play a critical role in metastasis. Therefore, identification of nutritional factors which are able to inhibit CXCR4 is important for protection from environmental arsenic-induced carcinogenesis and for abolishing metastasis of malignantly transformed cells. The present study demonstrates that apigenin (4′,5,7-trihydroxyflavone), a natural dietary flavonoid, suppressed CXCR4 expression in arsenic-transformed Beas-2B cells (B-AsT) and several other types of transformed/cancer cells in a dose- and time-dependent manner. Neither proteasome nor lysosome inhibitor had any effect in reducing the apigenin-induced down-regulation of CXCR4, indicating that apigenin-induced down-regulation of CXCR4 is not due to proteolytic degradation. The down-regulation of CXCR4 is mainly due to the inhibition of nuclear factor κB (NF-κB) transcriptional activity. Apigenin also abolished migration and invasion of transformed cells induced by CXCL12. In a xenograft mouse model, apigenin down-regulated CXCR4 expression and suppressed tumor growth. Taken together, our results show that apigenin is a novel inhibitor of CXCR4 expression. This dietary flavonoid has the potential to suppress migration and invasion of transformed cells and prevent environmental arsenic-induced carcinogenesis. - Highlights: • Apigenin has a potential in preventing environmental arsenic induced carcinogenesis. • Apigenin suppresses CXCR4 in malignant transformed cells in vitro and in vivo. • The down-regulation of CXCR4 is mainly due to inhibition of NF-κB activity.

  14. EXPRESSION PATTERN OF LUNG CANCER RELATED GENES IN MALIGNANT TRANSFORMATION OF BEP2D

    Institute of Scientific and Technical Information of China (English)

    范保星; 张开泰; 李刚; 谢玲; 马淑华; 葛世丽; 项小琼; 胡迎春; 王升启; 周平坤; 吴德昌

    2002-01-01

    Objective: To detect the expression difference of 60 lung cancer associated genes in human bronchial epithelial malignant transformation cell model (BEP2D) induced by alpha-particles. Methods: 60 lung cancer associated genes were collected and micro-arrayed onto the microscope slides using Cartesian PixSys5500 cDNA Microarray machine. Total RNA from BEP2D cells and passage 20 (Rl5H-20), passage 35 (R15H-35) cells derived from BEP2D following 1.5 Gy alpha-particles was extracted and labeled by fluorescent dye. The labeled probe was then hybridized with the cDNA. Results: 40, 47, 20 genes were detected in BEP2D, R15H-20 and R15H-35 respectively. The expression level of tumor suppressor genes decreased greatly in the transformed R15H-35. Most oncogenes decreased slightly in R15H-20. Most growth factors expressed only in R15H-20. Conclusion: In human bronchial epithelial malignant transformed cell model generated by alpha-particles, the loss-function of tumor suppressor genes at initiation stage was dominant, some related oncogenes and growth factors promoted the malignant transformation.

  15. Diagnosis of colon cancer with Fourier transform infrared spectroscopy on the malignant colon tissue samples

    Institute of Scientific and Technical Information of China (English)

    XIE Yi-bin; LIU Qian; HE Fei; GUO Chun-guang; WANG Cheng-feng; ZHAO Ping

    2011-01-01

    Background Fourier transform infrared spectroscopy (FT-IR) combined with chemometrics discriminant analysis technology could improve diagnosis. The present study aimed to evaluate the effects of FT-IR on malignant colon tissue samples in diagnosis of colon cancer.Methods Principal component analysis (PCA) and support vector machine classification were used to discriminate FT-IR spectra from malignant and normal tissue. Colon tissues samples from 85 patients were used to demonstrate the procedure.Results For this set of colon spectral data, the sensitivity and specificity of the support vector machine (SVM)classification were found both higher than 90%.Conclusions FT-IR provided important information about cancerous tissue, which could be used to discriminate malignant from normal tissues. The combination of PCA and SVM classification indicated that FT-IR has a potential clinical application in diagnosis of colon cancer.

  16. Malignant transformation of diploid human fibroblasts by transfection of oncogenes. Part 2, Progress report, July 1989--June 1992

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, J.J.

    1992-12-31

    This document consist of brief reports prepared by postdoctoral students supported by the project, each describing his accomplishments under the grant. Topics include (1) Malignant Transformation of MSU-1. 1 Cells by Gamma Radiation, (2) Correlation between Levels of ras Expression and Presence of Transformed Phenotypes Including Tumorigenicity, Using a Modulatable Promoter, (3) Relation between Specific rad Oncogene Expression, (4) Correlation of Genetic Changes in Fibroblastic Tumors with Malignancies, (5)Transformation of MSU-1.1 Cells by sis Oncogene, (6) Malignant Transformation of MSU-1.0 Cells, (7) Correlation of Urokinase Plasminogen Activation (mu-PA) with Malignant Phenotype, (8)Two Dimensional Gel Electrophoresis Studies of the Proteins of the Major Cell Strains of the MSU-1 Family of Cells, and (9) Correlation between Proteinase Activity Levels and Malignancy.

  17. Methionine restriction inhibits chemically-induced malignant transformation in the BALB/c 3T3 cell transformation assay.

    Science.gov (United States)

    Nicken, Petra; Empl, Michael T; Gerhard, Daniel; Hausmann, Julia; Steinberg, Pablo

    2016-09-01

    High consumption of red meat entails a higher risk of developing colorectal cancer. Methionine, which is more frequently a component of animal proteins, and folic acid are members of the one carbon cycle and as such important players in DNA methylation and cancer development. Therefore, dietary modifications involving altered methionine and folic acid content might inhibit colon cancer development. In the present study, the BALB/c 3T3 cell transformation assay was used to investigate whether methionine and folic acid are able to influence the malignant transformation of mouse fibroblasts after treatment with the known tumour initiator 3-methylcholanthrene. Three different methionine concentrations (representing a -40%, a "normal" and a +40% cell culture medium concentration, respectively) and two different folic acid concentrations (6 and 20 μM) were thereby investigated. Methionine restriction led to a decrease of type III foci, while enhancement of both methionine and folic acid did not significantly increase the cell transformation rate. Interestingly, the focus-lowering effect of methionine was only significant in conjunction with an elevated folic acid concentration. In summary, we conclude that the malignant transformation of mouse fibroblasts is influenced by methionine levels and that methionine restriction could be a possible approach to reduce cancer development.

  18. Methionine restriction inhibits chemically-induced malignant transformation in the BALB/c 3T3 cell transformation assay.

    Science.gov (United States)

    Nicken, Petra; Empl, Michael T; Gerhard, Daniel; Hausmann, Julia; Steinberg, Pablo

    2016-09-01

    High consumption of red meat entails a higher risk of developing colorectal cancer. Methionine, which is more frequently a component of animal proteins, and folic acid are members of the one carbon cycle and as such important players in DNA methylation and cancer development. Therefore, dietary modifications involving altered methionine and folic acid content might inhibit colon cancer development. In the present study, the BALB/c 3T3 cell transformation assay was used to investigate whether methionine and folic acid are able to influence the malignant transformation of mouse fibroblasts after treatment with the known tumour initiator 3-methylcholanthrene. Three different methionine concentrations (representing a -40%, a "normal" and a +40% cell culture medium concentration, respectively) and two different folic acid concentrations (6 and 20 μM) were thereby investigated. Methionine restriction led to a decrease of type III foci, while enhancement of both methionine and folic acid did not significantly increase the cell transformation rate. Interestingly, the focus-lowering effect of methionine was only significant in conjunction with an elevated folic acid concentration. In summary, we conclude that the malignant transformation of mouse fibroblasts is influenced by methionine levels and that methionine restriction could be a possible approach to reduce cancer development. PMID:27427305

  19. Alteration of gene expression profiles during mycoplasma-induced malignant cell transformation

    International Nuclear Information System (INIS)

    Mycoplasmas are the smallest microorganisms capable of self-replication. Our previous studies show that some mycoplasmas are able to induce malignant transformation of host mammalian cells. This malignant transformation is a multistage process with the early infection, reversible and irreversible stages, and similar to human tumor development in nature. The purpose of this study is to explore mechanisms for this malignant transformation. To better understand mechanisms for this unique process, we examined gene expression profiles of C3H cells at different stages of the mycoplasma-induced transformation using cDNA microarray technology. A total of 1185 genes involved in oncogenesis, apoptosis, cell growth, cell-cycle regulation, DNA repair, etc. were examined. Differences in the expression of these genes were compared and analyzed using the computer software AtlasImage. Among 1185 genes screened, 135 had aberrant expression at the early infection stage, 252 at the reversible stage and 184 at the irreversible stage. At the early infection stage, genes with increased expression (92 genes) were twice more than those with decreased expression (42 genes). The global gene expression at the reversible stage appeared to be more volatile than that at any other stages but still resembled the profile at the early infection stage. The expression profile at the irreversible stage shows a unique pattern of a wide range of expression levels and an increased number of expressing genes, especially the cancer-related genes. Oncogenes and tumor suppressors are a group of molecules that showed significant changes in expression during the transformation. The majority of these changes occurred in the reversible and irreversible stages. A prolonged infection by mycoplasmas lead to the expression of more cancer related genes at the irreversible stage. The results indicate that the expression profiles correspond with the phenotypic features of the cells in the mycoplasma induced

  20. Malignant Transformation Six Months after Removal of Intracranial Epidermoid Cyst: A Case Report

    Directory of Open Access Journals (Sweden)

    Fayçal Lakhdar

    2011-01-01

    Full Text Available Intracranial epidermoid cysts are uncommon benign tumors of developmental origin; malignant transformation of benign epidermoid cysts is rare, and their prognosis remains poor. We report a case of squamous cell carcinoma arising in the cerebellopontine angle. A 52-year-old man presented with left facial paralysis and cerebellar ataxia. He had undergone total removal of a benign epidermoid cyst six months previously. Postoperative magnetic resonance imaging of the brain revealed a heterogeneous and cystic lesion in the left cerebellopontine angle with hydrocephalus. The cyst wall was enhanced by gadolinium. He underwent ventricle-peritoneal shunt and removal again; the histopathological examination revealed a squamous cell carcinoma possibly arising from an underlying epidermoid cyst. This entity is being reported for its rarity. The presence of contrast enhancement at the site of an epidermoid cyst combined with an acute, progressive neurological deficit should alert the neurosurgeon to the possibility of a malignant transformation.

  1. Rate of recurrence and malignant transformation in 88 cases with inverted papilloma between 1998-2008

    DEFF Research Database (Denmark)

    Nygren, Alexander; Kiss, Katalin; von Buchwald, Christian;

    2016-01-01

    growth, causing bone remodulation and the association with malignant transformation. The introduction of endoscopic sinus surgery and computer aided sinus surgery over the last decades has made this tumour more approachable with less cosmetic and functional damage. The objective of this study......Conclusions The recurrence rate of IP in the current study is comparable to international and national studies. When the primary tumour was located in the frontal or the sphenoid sinus, the tumour seemed more likely to recur. Some recurrences were more than 2 years after primary surgery, suggesting...... continued need for long-term follow-up. The rate of malignant transformation in inverted papilloma cases has not changed in Denmark. Objectives Inverted papillomas are benign tumours located in the nasal cavity and paranasal sinuses. They are known for their tendency to recur after surgery and show invasive...

  2. [Key molecular mechanisms associated with cell malignant transformation in acute myeloid leukemia].

    Science.gov (United States)

    Orlova, N N; Lebedev, T D; Spirin, P V; Prassolov, V S

    2016-01-01

    Cancer, along with cardiovascular disorders, is one of the most important problems of healthcare. Pathologies of the hematopoietic system are the most prevalent in patients under 30 years of age, including acute myeloid leukemia (AML), which is widespread and difficult to treat. The review considers the mechanisms that play a significant role in AML cell malignant transformation and shows the contributions of certain genes to both remission and resistance of AML cells to various treatments.

  3. Oncogenes, hormones, and free-radical processes in malignant transformation in vitro

    International Nuclear Information System (INIS)

    Epidemiologic studies and data from experiments in vivo and in vitro support the notion that cancer is a multi-step process, in that a series of specific events is required to transform a normal cell into a malignant one. The multi-step model of carcinogenesis involves initiation, in which irreversible genetic alterations take place, and promotion, in which the clonal population of initiated cells is expanded and ultimately progresses to a malignancy. Within the past decade we have witnessed changes in understanding of the molecular origins of cancer. Much of this progress stems from the discovery of specific genes, the oncogenes, which are present in the genomes of a variety of tumor cells and are responsible for specifying many of the malignant traits of the cells. A number of oncogenes found in tumor cells or in cells transformed in vivo or in vitro play a central role in carcinogenesis. This paper presents work on cell transformation by radiation and chemicals using in vitro cell cultures

  4. Malignant transformation of perianal and enterocutaneous fistulas is rare: results of 17 years of follow-up from The Netherlands

    NARCIS (Netherlands)

    J.E. Baars; E.J. Kuipers; G. Dijkstra; D.W. Hommes; D.J. de Jong; P.C.F. Stokkers; B. Oldenburg; M. Pierik; P.J. Wahab; A.A. van Bodegraven; C.J. van der Woude

    2011-01-01

    Objective. Malignant transformation of fistulas has been observed, particularly in perianal fistulas in Crohn's disease (CD) patients. The prevalence of adenocarcinoma in enterocutaneous fistulas and non-CD-related fistulas, however, is unknown. We investigated adenocarcinoma originating from perian

  5. Malignant transformation of perianal and enterocutaneous fistulas is rare : results of 17 years of follow-up from The Netherlands

    NARCIS (Netherlands)

    Baars, Judith E.; Kuipers, Ernst J.; Dijkstra, Gerard; Hommes, Daniel W.; de Jong, Dirk J.; Stokkers, Pieter C. F.; Oldenburg, Bas; Pierik, Marieke; Wahab, Peter J.; van Bodegraven, Adriaan A.; van der Woude, Christien J.

    2011-01-01

    Objective. Malignant transformation of fistulas has been observed, particularly in perianal fistulas in Crohn's disease (CD) patients. The prevalence of adenocarcinoma in enterocutaneous fistulas and non-CD-related fistulas, however, is unknown. We investigated adenocarcinoma originating from perian

  6. Malignant transformation of perianal and enterocutaneous fistulas is rare: results of 17 years of follow-up from The Netherlands

    NARCIS (Netherlands)

    Baars, J.E.; Kuipers, E.J.; Dijkstra, G.; Hommes, D.W.; Jong, D.J. de; Stokkers, P.C.; Oldenburg, B.; Pierik, M.; Wahab, P.J.; Bodegraven, A.A. van; Woude, C.J. van der

    2011-01-01

    OBJECTIVE: Malignant transformation of fistulas has been observed, particularly in perianal fistulas in Crohn's disease (CD) patients. The prevalence of adenocarcinoma in enterocutaneous fistulas and non-CD-related fistulas, however, is unknown. We investigated adenocarcinoma originating from perian

  7. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis

    Science.gov (United States)

    Wu, Chin-Han; Tseng, Ya-Shih; Yang, Chao-Chun; Kao, Yu-Ting; Sheu, Hamm-Ming; Liu, Hsiao-Sheng

    2013-11-01

    Arsenic may cause serious environmental pollution and is a serious industrial problem. Depending on the dosage, arsenic may trigger the cells undergoing either proliferation or apoptosis-related cell death. Because of lack of the proper animal model to study arsenic induced tumorigenesis, the accurate risk level of arsenic exposure has not been determined. Arsenic shows genotoxic effect on human beings who uptake water contaminated by arsenic. Chromosome aberration is frequently detected in arsenic exposure-related diseases and is associated with increased oxidative stress and decreased DNA repairing activity, but the underlying mechanism remains elusive. Aurora-A is a mitotic kinase, over-expression of Aurora-A leads to centrosome amplification, chromosomal instability and cell transformation. We revealed that Aurora-A is over-expressed in the skin and bladder cancer patients from blackfoot-disease endemic areas. Our cell line studies reveal that arsenic exposure between 0.5 μM and 1 μM for 2-7 days are able to induce Aurora-A expression and activation based on promoter activity, RNA and protein analysis. Aurora-A overexpression further increases the frequency of unsymmetrical chromosome segregation through centrosome amplification followed by cell population accumulated at S phase in immortalized keratinocyte (HaCaT) and uroepithelial cells (E7). Furthermore, Aurora-A over-expression was sustained for 1-4 weeks by chronic treatment of immortalized bladder and skin cells with NaAsO2. Aurora-A promoter methylation and gene amplification was not detected in the long-term arsenic treated E7 cells. Furthermore, the expression level of E2F1 transcription factor (E2F1) is increased in the presence of arsenic, and arsenic-related Aurora-A over-expression is transcriptionally regulated by E2F1. We further demonstrated that overexpression of Aurora-A and mutant Ha-ras or Aurora-A and mutant p53 may act additively to trigger arsenic-related bladder and skin cancer

  8. Persistent exposure to Mycoplasma induces malignant transformation of human prostate cells.

    Directory of Open Access Journals (Sweden)

    Kazunori Namiki

    Full Text Available Recent epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including those of the prostate. The American Cancer Society, estimates that approximately 20% of all worldwide cancers are caused by infection. Mycoplasma, a genus of bacteria that lack a cell wall, are among the few prokaryotes that can grow in close relationship with mammalian cells, often without any apparent pathology, for extended periods of time. In this study, the capacity of Mycoplasma genitalium, a prevalent sexually transmitted infection, and Mycoplasma hyorhinis, a mycoplasma found at unusually high frequency among patients with AIDS, to induce a malignant phenotype in benign human prostate cells (BPH-1 was evaluated using a series of in vitro and in vivo assays. After 19 weeks of culture, infected BPH-1 cells achieved anchorage-independent growth and increased migration and invasion. Malignant transformation of infected BPH-1 cells was confirmed by the formation of xenograft tumors in athymic mice. Associated with these changes was an increase in karyotypic entropy, evident by the accumulation of chromosomal aberrations and polysomy. This is the first report describing the capacity of M. genitalium or M. hyorhinis infection to lead to the malignant transformation of benign human epithelial cells and may serve as a model to further study the relationship between prostatitis and prostatic carcinogenesis.

  9. Unexpected Malignant Diagnosis in Colonic Biopsies: Malignant Transformation of Ovarian Mature Teratomas—Two Case Reports and Review of the Literature

    OpenAIRE

    Claudia P. Rojas; Parvin Ganjei-Azar; Garcia-Buitrago, Monica T

    2015-01-01

    Colorectal adenocarcinoma is the second cause of cancer-related deaths in the United States. The occurrence of squamous cell carcinoma in the colorectum is extremely unusual. Malignant transformation from mature cystic teratoma of the ovary is a rare event. The most common transformation is squamous cell carcinoma, followed by adenocarcinoma. It occurs more often in elderly patients, who usually present with advance disease. We report two unusual cases of postmenopausal women diagnosed with s...

  10. Upregulated expression of Ezrin and invasive phenotype in malignantly transformed esophageal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Zhong-Ying Shen; Li-Yan Xu; Ming-Hua Chen; En-Min Li; Jin-Tao Li; Xian-Ying Wu; Yi Zeng

    2003-01-01

    AIM: To investigate the correlation between ezrin expression and invasive phenotype formation in malignantly transformed esophageal epithelial cells. METHODS: The experimental cell line employed in the present study was originated form the progressive induction of a human embryonic esophageal epithelial cell line (SHEE)by the E6E7 genes of human papillomavirus (HPV) type 18.The cells at the 35th passage after induction called SHEEIMM were in a state of immortalized phase and used as the control,while that of the 85th passage denominated as SHEEMT represented the status of cells that were malignantly transformed. The expression changes of ezrin and its mRNA in both cell passages were respectively analyzed by RT-PCR and Western blot. Invasive phenotype was assessed in vivo by inoculating these cells into the severe combined immunodeficient (SCID) mice via subcutaneous and intraperitoneal injection, and in vitro by inoculating them on the surface of the amnion membranes, which then was determined by light microscopy and scanning electron microscopy. RESULTS: Upregulated expression of ezrin protein and its mRNA was observed in SHEEMT compared with that in SHEEIMM cells. The SHEEMT cells inoculated in SCID mice were observed forming tumor masses in both visceral organs and soft tissues in a period of 40 days with a special propensity to invading mesentery and pancreas, but did not exhibit hepatic metastases. Pathologically, these tumor cells harboring larger nucleus, nucleolus and less cytoplasm could infiltrate and destroy adjacent tissues. In the in vitro study,the inoculated SHEEMT cells could grow in cluster on the amniotic epithelial surface and intrude into the amniotic stroma. In contrast, unrestricted growth and invasiveness were not found in SHEEIMM cells in both in vivo and in vitroexperiment. CONCLUSION: The upregulated ezrin expression is one of the important factors that are possibly associated with the invasive phenotype formation in malignantly

  11. Malignant transformation of ectopic thyroid tissue in the orbit: A rare case report

    Directory of Open Access Journals (Sweden)

    Tuhin Bhattacharya

    2016-01-01

    Full Text Available Ectopic thyroid tissue refers to the presence of thyroid tissue in locations other than normal anterior neck region. It is the most frequent type of thyroid dysgenesis. Lingual thyroid is the most common type accounting for 90% of the cases. The presence of thyroid tissue in orbit is extremely rare along with malignant transformation and the presence of normal thyroid gland. We report a very rare case of follicular carcinoma arising in the ectopic thyroid tissue in the left orbit along with normal thyroid gland. To the best of our knowledge, it is the first ever reported case of this type.

  12. Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells.

    Science.gov (United States)

    Wang, Lei; Hitron, John Andrew; Wise, James T F; Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Pratheeshkumar, Poyil; Zhang, Zhuo; Xu, Mei; Luo, Jia; Shi, Xianglin

    2015-10-15

    Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-κB pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development.

  13. Unexpected Malignant Diagnosis in Colonic Biopsies: Malignant Transformation of Ovarian Mature Teratomas—Two Case Reports and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Claudia P. Rojas

    2015-01-01

    Full Text Available Colorectal adenocarcinoma is the second cause of cancer-related deaths in the United States. The occurrence of squamous cell carcinoma in the colorectum is extremely unusual. Malignant transformation from mature cystic teratoma of the ovary is a rare event. The most common transformation is squamous cell carcinoma, followed by adenocarcinoma. It occurs more often in elderly patients, who usually present with advance disease. We report two unusual cases of postmenopausal women diagnosed with squamous cell carcinoma in colon biopsies. After surgical resections, the carcinoma was proven to be the result of malignant transformation of ovarian mature cystic teratomas. Since squamous cell carcinoma of the colorectum is extremely rare, the presence of squamous cell carcinoma in a colonic biopsy in a female patient should alert the clinicians to other possible primary sites, as seen in these cases.

  14. MALIGNANT TRANSFORMATION OF MATURE CYSTIC TERATOMA OF THE OVARY IN A 19 YEAR OLD PREGNANT WOMAN: A CASE R EPORT AND REVIEW OF LITERATURE

    OpenAIRE

    Umarani; Hema; Bharathi

    2013-01-01

    ABSTRACT: Mature cystic teratomas (MCT) are common ovarian n eoplasms accounting for 20% of all ovarian tumors. Malignant transformation is reported in 1-2% of mature cystic teratomas of ovary. The most common malignant evolu tion is that of squamous cell carcinoma. Malignancy in mature cystic teratoma occurs rarely during the first two decades of life. We report a case of malignant transformation into squam ous cell carcinoma in mature cystic teratoma of ovar...

  15. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Laura Cartularo

    Full Text Available Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress.

  16. The Malignant Transformation of Retrorectal Cystic Hamartomas With Blood Irregular Antibodies Positive: A Case Report.

    Science.gov (United States)

    Zhao, Xiang-Rong; Gao, Chao; Zhang, Yong; Yu, Yong-Hua

    2015-12-01

    Retrorectal cystic hamartomas are rare congenital presacral lesions and malignancy is extremely rare. Although surgical excision is the essential for treatment, a unique feature of our case compared with previously reported tailgut cysts is that this patient's blood irregular antibodies are positive with higher operational risks.A 44-year-old woman presented to our department complaining of pelvic and perineal pain for 6 months. Computed tomography (CT) scan of the abdomen and pelvis demonstrated a well-demarcated hypodense, multilocular cystic lesion, 10 cm in size, in the presacral region of the right of the midline. We found her blood irregular antibodies were positive in the preoperative examination. So she quitted surgery. Exploratory laparotomy and incision and drainage of pelvic tumor were operated. Postoperative routine pathology showed: (retroperitoneal tumors) moderately differentiated adenocarcinoma. Combined with clinical symptom and imaging, malignant transformation of retrorectal cystic hamartomas (tailgut cysts) was diagnosed. Taking into account that cyst is not sensitive to radiotherapy, so tumor necrosis factor (TNF) and raltitrexed were infused into the cysts and 3 cycles oxaliplatin (130 mg/m) were completed. Now although the lesion is shrink, but yellow, viscous mucus still secrete constantly, 100 ml/w.Given surgical excision is the essential for treatment, complete surgical excision should be implemented as far as possible. But if surgery cannot be carried out like the presented case, systemic chemotherapy and local radiotherapy are also available, which can alleviate the symptoms of oppression and improve the quality of life partly. PMID:26656372

  17. The Malignant Transformation of Retrorectal Cystic Hamartomas With Blood Irregular Antibodies Positive: A Case Report.

    Science.gov (United States)

    Zhao, Xiang-Rong; Gao, Chao; Zhang, Yong; Yu, Yong-Hua

    2015-12-01

    Retrorectal cystic hamartomas are rare congenital presacral lesions and malignancy is extremely rare. Although surgical excision is the essential for treatment, a unique feature of our case compared with previously reported tailgut cysts is that this patient's blood irregular antibodies are positive with higher operational risks.A 44-year-old woman presented to our department complaining of pelvic and perineal pain for 6 months. Computed tomography (CT) scan of the abdomen and pelvis demonstrated a well-demarcated hypodense, multilocular cystic lesion, 10 cm in size, in the presacral region of the right of the midline. We found her blood irregular antibodies were positive in the preoperative examination. So she quitted surgery. Exploratory laparotomy and incision and drainage of pelvic tumor were operated. Postoperative routine pathology showed: (retroperitoneal tumors) moderately differentiated adenocarcinoma. Combined with clinical symptom and imaging, malignant transformation of retrorectal cystic hamartomas (tailgut cysts) was diagnosed. Taking into account that cyst is not sensitive to radiotherapy, so tumor necrosis factor (TNF) and raltitrexed were infused into the cysts and 3 cycles oxaliplatin (130 mg/m) were completed. Now although the lesion is shrink, but yellow, viscous mucus still secrete constantly, 100 ml/w.Given surgical excision is the essential for treatment, complete surgical excision should be implemented as far as possible. But if surgery cannot be carried out like the presented case, systemic chemotherapy and local radiotherapy are also available, which can alleviate the symptoms of oppression and improve the quality of life partly.

  18. Exploring the role of inflammation in the malignant transformation of low-grade gliomas.

    Science.gov (United States)

    Michelson, Nicole; Rincon-Torroella, Jordina; Quiñones-Hinojosa, Alfredo; Greenfield, Jeffrey P

    2016-08-15

    Studies of inflammatory mediators have established the tumor micro-environment as a driver of oncogenesis. This inflammatory milieu often precedes cancer, however recent data also point to the ability of oncogenic changes to induce inflammatory responses that are later harnessed by the tumor to survive and proliferate. In this review, we propose that the IDH1 mutation, present in the majority of low-grade gliomas (LGGs), initiates an inflammatory cascade that is ultimately hijacked by the tumor. Glioma infiltrating macrophages and microglia (GIMs) are polarized to the M2 phenotype, subverting the host's adaptive immune response, and fostering a tumor milieu ripe for angiogenesis, migration, and metastasis. As data continue to expand the role of inflammation in low-grade gliomas, new molecular pathways may emerge as therapeutic targets that offer a window of opportunity to intervene before the malignant transformation (MT) of LGGs occurs. PMID:27397086

  19. Enhancing Solid Component within Mature Ovarian Teratomas on MR: Does it Indicate a Malignant Transformation?

    Energy Technology Data Exchange (ETDEWEB)

    Song, Myung Gyu; Kim, Kyeong Ah; Lee, Chang Hee; Choi, Jae Woong; Lee, Jong Mee; Kim, Yun Hwan; Park, Cheol Min [Korea University Guro Hospital, Seoul (Korea, Republic of)

    2010-03-15

    To evaluate the enhancing solid component within mature ovarian teratomas on pelvic MR examinations. Thirty-two women with surgically proven mature cystic teratomas underwent preoperative pelvic MR examinations. Five cases had an enhancing solid component within mature cystic ovarian teratomas on MR images. The MR images were retrospectively analyzed by two radiologists by consensus, focusing on the enhancing portion of tumor and the tumor itself. The study subjects include 5 patients (15.6%) with enhancing solid components within the mature ovarian cystic teratomas. The mean tumor size was 9.8 cm and they were all unilateral. The enhancing solid components of the tumors had a variable appearance and were located in the peripheral region. No cases were found to have a transmural extension or direct invasion of the neighboring pelvic organ. An enhancing solid component associated with mature ovarian teratomas is not uncommon. This finding does not however, necessarily indicate malignant transformation.

  20. Sequential pathological changes during malignant transformation of a craniopharyngioma: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Tetsuya Negoto

    2015-01-01

    Full Text Available Background: Malignant transformation of craniopharyngiomas is quite rare, and the etiology of transformation remains unclear. The prognosis of malignantly transformed craniopharyngiomas is very poor. Case Description: A 36-year-old male had five craniotomies, five transsphenoidal surgeries, and two radiation treatments until 31 years of age after diagnosis of craniopharyngioma at 12 years of age. All serial pathological findings indicated adamantinomatous craniopharyngioma including those of a surgery performed for tumor regrowth at 31 years of age. However, when the tumor recurred approximately 5 years later, the pathological findings showed squamous metaplasia. The patient received CyberKnife surgery, but the tumor rapidly regrew within 4 months. The tumor was resected with the cavernous sinus via a dual approach: Transcranial and transsphenoidal surgery with an extracranial-intracranial bypass using the radial artery. Pathologic examination of a surgical specimen showed that it consisted primarily of squamous cells; the lamina propria was collapsed, and the tumor cells had enlarged nuclei and clarification of the nucleolus. The tumor was ultimately diagnosed as malignant transformation of craniopharyngioma. After surgery, he received combination chemotherapy (docetaxel, cisplatin, and fluorouracil. The tumor has been well controlled for more than 12 months. Conclusion: Serial pathological changes of the craniopharyngioma and a review of the 20 cases reported in the literature suggest that radiation of the squamous epithelial cell component of the craniopharyngioma led to malignant transformation via squamous metaplasia. We recommend aggressive surgical removal of craniopharyngiomas and avoidance of radiotherapy if possible.

  1. Biological effects of radiation: The induction of malignant transformation and programmed cell death

    International Nuclear Information System (INIS)

    In the Chernobyl explosions and fire, powderized nuclear fuel was released from the reactor core, causing an unexpected fallout. X-ray analysis and scanning electron microscopy showed that the isolated single particles were essentially pure uranium. These uranium aerosols contained all of the nonvolatile fission products, including the b-emitters, 95Zr, 103Ru, 106Ru, 141Ce, and 144Ce. The hot particles are extremely effective in inducing malignant transformation in mouse fibroblast cells in vitro. The major factor responsible for this effect is focus promotion caused by a wound-mediated permanent increase in cell proliferation (mitogenesis associated with mutagenesis). Transformed foci were analysed for the activation of c-abl, c-erb-A, c-erb-B, c-fms, c-fos, c-myb, c-myc, c-Ha-ras, c-Ki-ras, c-sis, and c-raf oncogenes at the transcriptional level. The pattern of oncogene activation was found to vary from focus to focus. Long interspersed repeated DNA (L1 or LINE makes up a class of mobile genetic elements which can amplify in the cell genome by retroposition. This element is spontaneously transcriptionally activated at a critical population density and later amplified in rat chloroleukaemia cells. UV light and ionizing radiation induce this activation prematurely, and the activation is followed by programmed cell death (apoptosis) in a sequence of events identical to that seen in LIRn activation occurring spontaneously

  2. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    International Nuclear Information System (INIS)

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  3. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  4. Non-germ cell tumours arising in germ cell tumours (teratoma with malignant transformation) in men: CT and MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Athanasiou, A. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Institut Curie, Paris (France)], E-mail: alexandra.athanasiou@curie.net; Vanel, D. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Istituti Ortopedici Rizzoli, Bologna (Italy); El Mesbahi, O. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Theodore, C. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Department of Oncology, Hopital Foch, Suresnes (France); Fizazi, K. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France)

    2009-02-15

    Purpose: To describe the imaging findings of germ cell tumours (GCT) containing non-germ cell malignant components (also designated teratoma with malignant transformation or TMT). Patients and methods: The records of 14 male patients with GCT and a non-germ cell histological component TMT were retrospectively reviewed. All patients had computed tomography (CT) and/or magnetic resonance (MR) studies before and after initial surgery and chemotherapy, as well as during follow-up. Imaging findings were correlated with the response to treatment and with overall survival. Pathological evaluation, immunohistochemistry, serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were also taken into consideration. Sarcoma was identified in 10 out of 14 patients, with rhabdomyosarcoma ranking first (n = 4), followed by osteosarcoma (n = 2), fusiform cell sarcoma (n = 1), undifferentiated sarcoma (n = 1), neurosarcoma (n = 1) and myxoid sarcoma (n = 1). Other histological types of malignant transformation included adenocarcinoma (n = 3) and bronchoalveolar carcinoma (n = 1). Overall, 9 patients relapsed at a median time of 84 months (range 60-168). Results: Non-GCT malignant transformation was identified in the retroperitoneum (5), testis (3), mediastinum (3), peritoneum (2) and lungs (1). The CT and MR imaging findings before treatment and after relapse were evaluated with emphasis on imaging features that could possibly imply the presence of malignant transformation (heterogeneously enhancing soft-tissue masses, ossified masses with calcified lymph nodes, diffuse epiploic thickening associated with ascites and peritoneal nodules, pulmonary alveolar infiltration with septal thickening). All but 1 patient with TMT presented with nodal and distant metastases. The prognosis was poor: within a median follow-up of 59 months (range 3-180), 4 out of 14 patients were alive. Conclusion: TMT is rare and associated with poorer survival compared to GCT. Imaging can be useful

  5. Increased expression of fascin associated with malignant transformation of sinonasal inverted papilloma

    Institute of Scientific and Technical Information of China (English)

    WANG An-liu; LIU Hong-gang; ZHANG Yong

    2007-01-01

    Background Fascin, an actin binding protein, usually expressed at a low level in normal epithelium, but is significantly increased in transformed epithelial cells and several common carcinomas. In this study, we examined the expression of fascin by immunohistochemistry in sinonasal epithelium with chronic inflammation (control group), exophytic papilloma(EP), inverted papilloma (IP) with dysplasia and cancerated IP (including carcinoma in situ and invasive squamous cell carcinoma, SCC), and furthermore investigated the relationship between fascin expression and formation of malignant IP.Methods Fascin expression was immunohistochemically detected using monoclonal antibody against fascin in 86paraffin embedded tissues, including 10 cases of sinonasal mucosa with chronic inflammation, 10 of EP, 45 of IP with dysplasia (45 cases were divided into three groups: IP with mild dysplasia, IP with moderate dysplasia, and IP with severe dysplasia, 15 cases each), and 21 of cancerated IP.Results The level of fascin expression was significantly higher in the neoplastic tissue than that in control group. Fascin expression increased gradually with the progression from sinonasal epithelium with chronic inflammation, IP with mild dysplasia, IP with moderate dysplasia, IP with severe dysplasia, to cancerated IP, and significant difference of fascin expression was observed between any two groups of the five.Conclusion Precancerous lesions of IP exhibit elevated levels of fascin that may be associated with carcinogenesis of IP. Fascin may play a role in the formation of IP and EP.

  6. HYPOXIC INFLAMMATION, A DEADLY BRIDGE TO MALIGNANT TRANSFORMATION AND A FERTILE SOIL FOR CANCER PREVENTION

    Directory of Open Access Journals (Sweden)

    Kambiz Afrasiabi

    2013-01-01

    Full Text Available The interplay of the inflammatory microenvironment with its hypoxic niche and the potential mechanism by which they lead to malignant transformation has long been the subject of great controversy and continues to be an area of great interest today. In our previous studies we have examined this subject by using Gia2 knock out mice as the focus of our research. These mice are well known for their tendency to develop chronic inflammation in the sub mucosa of their gut, with gradual worsening and development of colon adenocarcinoma in most as they age. It has also attracted our attention that they develop a significant increase in the number of hypoxic niches in their sub mucosa, proven by EF5 staining.In contradistinction to MSI-high colon adenocarcinomas, we have also shown that histone deacetylation rather than MLH1 promoter methylation is the main mechanism of MLH1 and MSH2 deactivation in these mice. Here we show that hypoxic niches evolve under massive selective pressure of the inflammatory microenvironment as a protective shield offering survival advantage by the up regulation of NFKb and its downstream pathways, which indeed independent of true hypoxia leads to stabilization of HIF as well, securing a dual mechanism for perpetuation and expansion of hypoxic niches. We incorporated western blot and Luciferase assay of cells exposed to hypoxia+/-inflammatory cytokines to acquire data.

  7. Possible mechanisms for arsenic-induced proliferative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A. [Dartmouth College and Medical School, Hanover, NH (United States)] [and others

    1996-12-31

    Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

  8. Abnormal Expression of Eukaryotic Translation Factors in Malignant Transformed Human Bronchial Epithelial Cells Induced by Crystalline Nickel Sulfide

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To study the oncogenic potential of mouse translation initiation factor 3 (TIF3) and elongation factor-1δ (TEF-1δ) in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide (NiS). Methods Abnormal expressions of human TIF3 and TEF-1δ genes in two kinds of NiS-transformed cells and NiS-tumorigenic cell lines were investigated and analyzed by the reverse transcript polymerase chain reaction (RT-PCR) and fluorescent quantitative polymerase chain reaction (FQ-PCR), respectively. Results RT-PCR analysis primarily showed that both human TIF3 and TEF-1δ mRNA expressions in two kinds of NiS-transformed cells and NiS-tumorigenic cell lines were increased as compared with controls. FQ-PCR assay showed that the levels of TIF3 expressions in the transformed cells and tumorigenic cells were 3 and 4 times higher respectively, and the elevated expressions of TEF-1δ cDNA copies were 2.7- to 3.5-fold in transformed cells and 4.1- to 5.2-fold in tumorigenic cells when compared with non-transformed cells, indicating that the over-expressions of human TIF3 and TEF-1δ genes were related to malignant degree of the cells induced by nickel. Conclusions These findings demonstrate that there are markedly abnormal expressions of TIF3 and TEF-1δ genes during malignant transformation of human bronchial epithelial cell lines induced by crystalline NiS. They seem to be the molecular mechanisms potentially responsible for human carcinogensis due to nickel.

  9. Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression

    Directory of Open Access Journals (Sweden)

    Hedin Lars

    2006-11-01

    Full Text Available Abstract Background The involvement of the cyclooxygenases (COX, in particular COX-2, is well documented for many tumours, e.g. colon, breast and prostate cancer, by both experimental and clinical studies. There are epidemiological data from subjects using NSAIDs, and experimental evidence supporting the hypothesis of prostaglandins (PGs as regulators of tumourigenesis in the ovary. One of the end products of PG-synthesis, PGE2, regulates several key-processes, which are characteristic for tumour growth, e.g. angiogenesis, proliferation and apoptosisis. The present study investigated the pathway for PGE2 – synthesis and signalling in ovarian tumourigenesis by analysing specimen from normal ovaries (n = 18, benign (B (n = 8, borderline type (BL (n = 6 and malignant tumours (AC (n = 22. The expression and cell-specific localization of COX-1, COX-2, microsomal prostaglandin E synthase-1 (mPGES-1 and two of the receptors for PGE2, EP1 and EP2, were examined by immunoblotting (IB and immunohistochemistry (IHC. Results The results are in line with earlier studies demonstrating an increase of COX-2 in AC compared to the normal ovary, B and BL tumours. Increased expressions were also observed for COX-1, mPGES-1 and EP-1 which all were significantly (p 1 was increased in stage III while no significant alterations were demonstrated for COX-1, mPGES-1 or EP2 for stage. IHC revealed staining of the tumour cells, but also increase of COX-1, COX-2, mPGES-1 and EP1–2 in the stromal compartment of AC (grades: moderately-, poorly- and undifferentiated. This observation suggests interactions between tumour cells and stromal cells (fibroblasts, immune cells, e.g. paracrine signalling mediated by growth factors, cytokines and possibly PGs. Conclusion The increases of COX-1, COX-2, mPGES-1 and EP1–2 in epithelial ovarian cancer, supports the hypothesis that PGE2-synthesis and signalling are of importance for malignant transformation and progression. The

  10. Paclitaxel-loaded ethosomes®: potential treatment of squamous cell carcinoma, a malignant transformation of actinic keratoses.

    Science.gov (United States)

    Paolino, Donatella; Celia, Christian; Trapasso, Elena; Cilurzo, Felisa; Fresta, Massimo

    2012-05-01

    Topical application of anticancer drugs for the treatment of malignancies represents a new challenge in dermatology, potentially being an alternative therapeutic approach for the efficacious treatment of non-melanoma skin cancer, that is, actinic keratoses, and malignant lesions of the skin caused by ultraviolet radiation. Anti-proliferative and antimitotic drugs, including many of the taxanes, are currently under investigation for the treatment of cutaneous malignant transformation of actinic keratoses, particularly the squamous cell carcinoma. Paclitaxel-loaded ethosomes® are proposed as topical drug delivery systems for the treatment of this pathology due to their suitable physicochemical characteristics and enhanced skin penetration ability for deep dermal delivery. Our in vitro data show that the skin application of paclitaxel-loaded ethosomes® improved the permeation of paclitaxel in a stratum corneum-epidermis membrane model and increased its anti-proliferative activity in a squamous cell carcinoma model as compared to the free drug. The results obtained encouraged the use of the paclitaxel-loaded ethosomes® as the formulation for the potential treatment of squamous cell carcinoma, a malignant transformation of actinic keratoses. PMID:22414731

  11. Paclitaxel-loaded ethosomes®: potential treatment of squamous cell carcinoma, a malignant transformation of actinic keratoses.

    Science.gov (United States)

    Paolino, Donatella; Celia, Christian; Trapasso, Elena; Cilurzo, Felisa; Fresta, Massimo

    2012-05-01

    Topical application of anticancer drugs for the treatment of malignancies represents a new challenge in dermatology, potentially being an alternative therapeutic approach for the efficacious treatment of non-melanoma skin cancer, that is, actinic keratoses, and malignant lesions of the skin caused by ultraviolet radiation. Anti-proliferative and antimitotic drugs, including many of the taxanes, are currently under investigation for the treatment of cutaneous malignant transformation of actinic keratoses, particularly the squamous cell carcinoma. Paclitaxel-loaded ethosomes® are proposed as topical drug delivery systems for the treatment of this pathology due to their suitable physicochemical characteristics and enhanced skin penetration ability for deep dermal delivery. Our in vitro data show that the skin application of paclitaxel-loaded ethosomes® improved the permeation of paclitaxel in a stratum corneum-epidermis membrane model and increased its anti-proliferative activity in a squamous cell carcinoma model as compared to the free drug. The results obtained encouraged the use of the paclitaxel-loaded ethosomes® as the formulation for the potential treatment of squamous cell carcinoma, a malignant transformation of actinic keratoses.

  12. E-cadherin as a potential biomarker of malignant transformation in oral leukoplakia: a retrospective cohort study

    OpenAIRE

    von Zeidler, Sandra Ventorin; de Souza Botelho, Talitha; Mendonça, Elismauro Francisco; Batista, Aline Carvalho

    2014-01-01

    Background Numerous attempts have been made to establish and develop tumor markers that could determine the susceptibility of normal tissues to transform into cancerous ones. To determine whether altered expression patterns of E-cadherin could be an early event in the progression of potentially malignant disorders to oral squamous cell carcinoma, this study aimed to assess the relationship between the immunoexpression of E-cadherin and the different degrees of epithelial dysplasia in oral leu...

  13. Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells.

    Science.gov (United States)

    Zhang, R; Wu, W R; Shi, X D; Xu, L B; Zhu, M S; Zeng, H; Liu, C

    2016-01-01

    Adult hepatic progenitor cells (HPCs) are involved in a wide range of human liver diseases, including hepatocellular carcinoma (HCC). Bmi1 has been reported to have vital roles in stem cell self-renewal and carcinogenesis. We have previously demonstrated that Bmi1 is upregulated in HCC with bile duct tumor thrombi, a subtype of HCC characterized by profuse expression of hepatic stem cell markers. However, the function of Bmi1 in HPCs has not yet been well elucidated. The current study was designed to investigate the effects of Bmi1 on the biological properties of rat HPCs. To accomplish this, Bmi1 was silenced or enhanced in two HPC cell lines (WB-F344 and OC3) by, respectively, using either small interfering RNA against Bmi1 or a forced Bmi1 expression retroviral vector. The biological functions of Bmi1 in HPCs were investigated through cell proliferation assays, colony-formation assays, cell cycle analysis and invasion assays, as well as through xenograft-formation assays. In this study, genetic depletion of Bmi1 repressed cell proliferation, colony formation and invasion in both assessed HPC cell lines relative to controls. Conversely, forced expression of Bmi1 in two HPCs cell lines promoted cell proliferation, colony formation and invasion in vitro. Aldehyde dehydrogenase (ALDH) assay revealed a significant increase in the number of ALDH-positive cells following the forced expression of Bmi1 in HPCs. Most importantly, transplantation of forced Bmi1 expression HPCs into nude mice resulted in the formation of tumors with histological features of poorly differentiated HCC. Taken together, our findings indicate that forced expression of Bmi1 promotes the malignant transformation of HPCs, suggesting Bmi1 might be a potential molecular target for the treatment of HCC. PMID:26926789

  14. DNA aneuploidy as a topographic malignant transformation pattern in a pleomorphic adenoma of long-term evolution: a case report

    Directory of Open Access Journals (Sweden)

    Gallego Lorena

    2011-11-01

    Full Text Available Abstract Introduction We present a case of long-term evolution of a submandibular pleomorphic adenoma. There is little information about topographic malignant transformation patterns of pleomorphic adenomas. Case presentation We extensively analyze a giant submandibular mixed tumor of 25-year evolution in a 57-year-old Caucasian woman. Deoxyribonucleic acid ploidy was evaluated in different superficial and deep areas using flow cytometry analysis and correlated with pathological and immunohistochemical characteristics. Superficial areas exhibited a typical histological pleomorphic adenoma pattern and were deoxyribonucleic acid diploid. Deep samples showed deoxyribonucleic acid aneuploidy, atypical histological benign features and expression of markers involved at an early-stage of malignant transformation, such as tumor protein 53 and antigen Ki67. Conclusion These findings revealed that deep tumor compartments may be involved in the initial stages of malignant transformation. Deoxyribonucleic acid ploidy analysis may provide an additional diagnosis tool and indicate 'uncertain' areas that require careful study to avoid diagnostic errors. Larger studies are needed to confirm our results and to evaluate the usefulness of the technique.

  15. Mature cystic teratoma with malignant transformation of teratomatous urothelial cells: Rare case presentation

    OpenAIRE

    Senjuti Dasgupta; Debdas Bose; Nirmal Kumar Bhattacharyya; Pranab Kumar Biswas

    2015-01-01

    The occurrence of malignancies in somatic elements of mature cystic teratoma of ovary is rare. The malignancies that may be encountered in dermoid cyst include squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, melanoma, sarcoma, carcinoid, and germ cell neoplasms. The development of transitional cell carcinoma (TCC) in dermoid cyst is extremely rare with only four such cases having been reported in literature so far. Here we report the fifth case of such an occurrence in a 50-...

  16. Protective effects of Moringa oleifera Lam. leaves against arsenic-induced toxicity in mice

    Institute of Scientific and Technical Information of China (English)

    Afzal Sheikh; Zahangir Alam Saud; Khaled Hossain; Fouzia Yeasmin; Smita Agarwal; Mashiur Rahman; Khairul Islam; Ekhtear Hossain; Shakhawoat Hossain; Md Rezaul Karim; Farjana Nikkon

    2014-01-01

    Objective: To evaluate the protective role of leaves of Moringa oleifera (M. oleifera) Lam. against arsenic-induced toxicity in mice.Methods:non-treated control group while, the second, third, and fourth groups were treated with M.oleifera leaves (50 mg/kg body weight per day), sodium arsenite (10 mg/kg body weight per day) and sodium arsenite plus M. oleifera leaves, respectively. Serum indices related to cardiac, liver and renal functions were analyzed to evaluate the protective effect of Moringa leaves on arsenic-induced effects in mice.Results:Swiss albino male mice were divided into four groups. The first group was used as induced elevation of triglyceride, glucose, urea and the activities of alkaline phospatase, aspartate aminotransferase and alanine aminotransferase in serum. M. oleifera leaves also prevented the arsenic-induced perturbation of serum butyryl cholinesterase activity, total cholesterol and high density lipoprotein cholesterol.Conclusions:The results indicate that the leaves of M. oleifera may be useful in reducing the It revealed that food supplementation of M. oleifera leaves abrogated the arsenic-effects of arsenic-induced toxicity.

  17. Atypical Proliferating Trichilemmal Cyst with Malignant Breast Skin Transformation: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Marino Antonio Capurso-García

    2016-01-01

    Full Text Available Proliferating trichilemmal tumors (PTTs are benign adnexal skin neoplasms that arise from the outer root sheath of the hair follicle. These tumors are most commonly observed on the scalp and occur, most of the time, in elderly women. Malignant transformation of these neoplasms is a rare event; less than 50 cases have been reported in the English medical literature. We present the case of a 39-year-old Hispanic woman with a tumor located on the skin of one of her breasts that in her third surgical procedure the histologic examination revealed the presence of a malignant proliferating trichilemmal tumor (MPTT. Furthermore, a review of the medical literature and a discussion of the clinical and pathologic features of this rare entity are provided.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-01

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

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

    International Nuclear Information System (INIS)

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

  20. Malignant transformation of mature T cells after gammaretrovirus mediated transfer of nucleophosmin-anaplastic lymphoma kinase oncogene

    Directory of Open Access Journals (Sweden)

    Ashok Kumar

    2015-01-01

    Full Text Available Background: Gene therapy has been in use to cure hereditary and acquired diseases by incorporating the desired gene into the cells with the help of gammaretroviral vectors. Despite the success of this therapy in X-linked severe combined immunodeficiency syndrome, few patients developed leukemia as a major adverse event due to retroviral insertional mutagenesis within stem cells. In experimental animals also, retroviral-mediated gene transfer technique resulted in the development of leukemia. On the other hand, evidence suggests that mature T cells (TC are relatively resistant to transformation even after retroviral-mediated transfer of potent oncogenes Tcl1, ΔTrkA and LMO2 with no reported side effects yet. Aims: To further address the safety issue for TC use in gene therapy, this study investigated susceptibility of mature polyclonal TC to malignant transformation by the retroviral-mediated transfer of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK oncogene. Materials and Methods: Wild-type mature TC, isolated from C57BL/6 donor mice (genetic background Ly5.1 were transduced with gamma-retroviral vectors encoding the potent TC oncogene NPM-ALK or the control vector enhanced green fluorescent protein eGFP. The cells were then transplanted into RAG-1 deficient recipient mice (genetic background Ly5.2. Results: Two out of five mice from NPM-ALK oncogene group developed leukemia/lymphoma after latency periods (153 and 250 days, respectively. None of the mice from the control group developed any malignancy throughout the observational period. Conclusion: Mature polyclonal TC are relatively susceptible to malignant transformation after gamma-retroviral mediated transfer of NPM-ALK oncogene; hence safety of TC use in gene therapy should be further investigated to avoid the possible side-effect of development of leukemia/lymphoma.

  1. NIH 3T3 cells malignantly transformed by mot—2 show inactivation and cytoplasmic sequestration of the p53 protein

    Institute of Scientific and Technical Information of China (English)

    WADHWA; SYUICHITAKANO; 等

    1999-01-01

    In previous studies we have reported that a high level of expression of mot-2 protein results in malignant transformation of NIH 3T3 cells as analyzed by anchorage independent growth and nude mice assays [Kaul et al.,Oncogene,17,907-11,1998].Mot-2 was found to interact with tumor suppressor protein p53.The transient overexpression of mot-2 was inhibitory to transcriptional activation function of p53 [Wadhwa et al.,J.Biol.Chem.,273,2958691,1998].We demonstrate here that mot-2 transfected stable clone of NIH 3T3 that showed malignant properties indeed show inactivation of p53 function as assayed by exogenous p53 dependent reporter.The expression level of p53 in response to UV-irradiation was lower in NIH 3T3/mot-2 as compared to NIH 3T3 cells and also exhibited delay in reachingpeak.Furthermore,upon serum starvation p53 was seen to translocate to the nucleus in NIH 3T3,but not in its mot-3 derivative.The data suggests that mot-2 mediated cytoplasmic sequestration and inactivation of p53 may operate,at least in part,for malignant phenotype of NIH 3T3/mot-2 cells.

  2. Rare Leiomyoma of the Tunica Dartos: A Case Report with Clinical Relevance for Malignant Transformation and HLRCC.

    Science.gov (United States)

    Bell, Robert C; Austin, Evan T; Arnold, Stacy J; Lin, Frank C; Walker, Jonathan R; Larsen, Brandon T

    2016-01-01

    Background. Genital leiomyomas fall under the broader category of cutaneous leiomyomas, which are rare smooth muscle neoplasms accounting for 5% of all leiomyomas. Genital leiomyomas arising from the dartos muscle are exceedingly rare with fewer than 30 cases reported in the literature. They are typically benign and adequately treated with simple surgical excision; however, previously reported cases of malignant transformation and a possible link to the hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome warrant closer follow-up. Case Presentation. We report a case of a 47-year-old male refugee from Rwanda found to have a mobile, pea-sized, mildly painful scrotal lesion near the left penoscrotal junction and 1.5 cm indeterminate vascular mass in the right kidney. Surgical excision of the scrotal nodule was performed and the diagnosis of a dartoic leiomyoma was rendered. The presence of moderate nuclear atypia, rare mitotic activity, and close surgical margins prompted a wide reexcision. We report the surgical approach, pathologic findings, and clinical follow-up related to this scrotal lesion. Conclusion. Scrotal leiomyomas demonstrate a high rate of recurrence and pose a risk for malignant transformation. They may also indicate an underlying autosomal dominant syndrome associated with increased risk for development of an aggressive form of renal cell carcinoma. When discovered, management should include surgical excision, screening for syndromic features, and routine follow-up. PMID:27529047

  3. Slit-Robo signaling induces malignant transformation through Hakai-mediated E-cadherin degradation during colorectal epithelial cell carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Wei-Jie Zhou; Yan-Qing Ding; Jian-Guo Geng; Zhen H Geng; Shan Chi; Wenli Zhang; Xiao-Feng Niu; Shu-Jue Lan; Li Ma; Xuesong Yang; Li-Jing Wang

    2011-01-01

    The Slit family of guidance cues binds to Roundabout (Robo) receptors and modulates cell migration. We report here that ectopic expression of Slit2 and Robol or recombinant Slit2 treatment of Robol-expressing colorectal epithelial carcinoma cells recruited an ubiquitin ligase Hakai for E-cadherin (E-cad) ubiquitination and lysosomal degradation, epithelial-mesenchymal transition (EMT), and tumor growth and liver metastasis, which were rescued by knockdown of Hakai. In contrast, knockdown of endogenous Robol or specific blockade of Slit2 binding to Robol prevented E-cad degradation and reversed EMT, resulting in diminished tumor growth and liver metastasis.Ectopic expression of Robol also triggered a malignant transformation in Siit2-positive human embryonic kidney 293 cells. Importantly, the expression of Slit2 and Robol was significantly associated with an increased metastatic risk and poorer overall survival in colorectal carcinoma patients. We conclude that engagement of Robol by Slit2 induces malignant transformation through Hakai-mediated E-cad ubiquitination and lysosomal degradation during colorectal epithelial cell carcinogenesis.

  4. Triple-phase dynamic MRI: A new clue to predict malignant transformation of giant cell tumor of bone

    International Nuclear Information System (INIS)

    Objective: Our purpose was, through the comparison of the characteristics of time–intensity curve on triple-phase dynamic contrast-enhanced MRI among groups of giant cell tumor of bone (GCTB), recurrent benign giant cell tumor of bone (RBGCTB), and secondary malignant giant cell tumor of bone (SMGCTB), to find clues to predict the malignant transformation of GCTB. Subjects and methods: 21 patients diagnosed as GCTB were included in this study. All cases took recurrence after intralesional curettage. 9 cases were confirmed as SMGCTB and 12 cases were confirmed as RBGCTB. Cases were divided into four groups: group A, GCTB (n = 9); group B, SMGCTB (n = 9); group C, GCTB (n = 12); group D, RBGCTB (n = 12). Enhancement index(EI) of lesions on DCEMRI was calculated using formula: EI(t) = [S(t) − S(0)]/S(0), where S(0) was signal intensity of lesion on non-contrast-enhanced T1-weighted images and S(t) was signal intensity of lesion on DCEMRI (t = 30, 60, 180 s). Enhancement index of each group in each phase was compared using One-Way ANOVA analysis. Slope values of time–intensity curve were compared by the same way. Results: Time–intensity curve of SMGCTB was characterized by a steep upward slope followed by an early and rapid washout phase. Time–intensity curve of GCTB and RBGCTB was characterized by a steep slope followed by a relatively slow washout phase. No significant difference in enhancement index was found in the first phase (p > 0.05). There was significant difference in the second and the third phase (p < 0.05). Enhancement index of group B (SMGCTB) was smaller. There was no difference in rising slope value (p > 0.05). Conclusions: Dynamic contrast-enhanced MRI appears a helpful method to find new clues to predict malignant transformation of GCTB

  5. Towards optimal clinical and epidemiological registration of haematological malignancies: Guidelines for recording progressions, transformations and multiple diagnoses.

    Science.gov (United States)

    Gavin, Anna; Rous, Brian; Marcos-Gragera, Rafael; Middleton, Richard; Steliarova-Foucher, Eva; Maynadie, Marc; Zanetti, Roberto; Visser, Otto

    2015-06-01

    Haematological malignancies (HM) represent over 6% of the total cancer incidence in Europe and affect all ages, ranging between 45% of all cancers in children and 7% in the elderly. Thirty per cent of childhood cancer deaths are due to HM, 8% in the elderly. Their registration presents specific challenges, mainly because HM may transform or progress in the course of the disease into other types of HM. In the context of cancer registration decisions have to be made about classifying subsequent notifications on the same patient as the same tumour (progression), a transformation or a new tumour registration. Allocation of incidence date and method of diagnosis must also be standardised. We developed European Network of Cancer Registries (ENCR) recommendations providing specific advice for cancer registries to use haematology and molecular laboratories as data sources, conserve the original date of incidence in case of change of diagnosis, make provision for recording both the original as well as transformed tumour and to apply precise rules for recording and counting multiple diagnoses. A reference table advising on codes which reflect a potential transformation or a new tumour is included. This work will help to improve comparability of data produced by population-based cancer registries, which are indispensable for aetiological research, health care planning and clinical research, an increasing important area with the application of targeted therapies.

  6. Meta-analysis on clinicopathologic risk factors of leukoplakias undergoing malignant transformation

    Directory of Open Access Journals (Sweden)

    T V Narayan

    2016-01-01

    Conclusion: The carcinogenic transformation of a preexisting lesion (leukoplakia is multifactorial and patient specific. The protocol to delineate a high-risk lesion should include the clinical type and site.

  7. [Malignant transformation of human fibroblasts by neutrons and by gamma radiation: Relationship to mutations induced

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    A brief overview if provided of selected reports presented at the International Symposium on Molecular Mechanisms of Radiation- and Chemical Carcinogen-Induced Cell Transformation held at Mackinac Island, Michigan on September 19-23, 1993.

  8. Mature cystic teratoma with malignant transformation of teratomatous urothelial cells: Rare case presentation

    Directory of Open Access Journals (Sweden)

    Senjuti Dasgupta

    2015-01-01

    Full Text Available The occurrence of malignancies in somatic elements of mature cystic teratoma of ovary is rare. The malignancies that may be encountered in dermoid cyst include squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, melanoma, sarcoma, carcinoid, and germ cell neoplasms. The development of transitional cell carcinoma (TCC in dermoid cyst is extremely rare with only four such cases having been reported in literature so far. Here we report the fifth case of such an occurrence in a 50-year-old postmenopausal multiparous female patient. She presented with pain and gradual swelling of abdomen for 1 month. Abdominal computed tomography revealed a solid space occupying lesion with few cystic components at right pelvis, raising the possibility of an ovarian neoplasm. The level of CA-125 was slightly raised (56∙45 U/ml. Total abdominal hysterectomy and bilateral salpingo-oopherectomy was performed. Microscopic examination showed cyst wall lined by stratified squamous epithelium. Beneath the cyst wall, a tumor mass was present, histological features of which resembled that of high-grade TCC (stage pT1aNXMX. On immunohistochemical analysis, the tumor was found to be positive for CK7 and CK20 and negative for WT-1. These results were consistent with a diagnosis of TCC arising in urothelium of mature cystic teratoma. Reporting of such extremely rare cases is important for the assessment of prognostic factors and treatment protocols.

  9. Struma Ovarii With Malignant Transformation and Germline KIT Mutation: A Case Report With Review of the Literature.

    Science.gov (United States)

    Ma, Deqin; Guseva, Natalya V; Dahmoush, Laila; Robinson, Robert A

    2016-09-01

    Struma ovarii accounts for 5% of ovarian teratomas. Malignant transformation occurs in <0.3%, however, the underlying molecular mechanism is unknown. We report a patient with follicular variant and tall cell variant of papillary thyroid carcinoma (PTC) arising from struma ovarii and coexisting incidental PTC in the thyroid. Mutation analysis by next-generation sequencing identified a novel germline mutation, KIT p.V530I mutation in the tumors and normal ovarian and thyroid tissue. Immunohistochemical staining showed loss of KIT expression in the PTCs. Activating mutations in KIT play an important role in diagnosis and prognosis of multiple malignancies including mastocytosis, gastrointestinal stromal tumors, and a subset of melanoma and acute myeloid leukemia. The p.V530I mutation has only been reported in 3 previous cases: acute myeloid leukemia, aggressive fibromatosis, and adenocarcinoma of the colon. In the case of aggressive fibromatosis, the patient responded well to imatinib treatment. KIT mutations have never been reported in thyroid carcinomas. This is the first case of PTC-harboring KIT mutation. Although more work needs to be done to elucidate the significance of this germline mutation, the response of the fibromatosis patient to imatinib may shed light on targeted therapy in PTC harboring this mutation. PMID:27258816

  10. MALIGNANT TRANSFORMATION IN A MATURE CYSTIC TERATOMA OF THE OVARY: A CASE OF RARITY

    Directory of Open Access Journals (Sweden)

    Lekha

    2014-04-01

    Full Text Available Germ cell tumors account for a majority of all ovarian tumors. Ninety five percent of germ cell tumors are dermoid cysts (Mature cystic teratoma. Carcinomas arising from mature cystic teratoma are quite rare. The most common malignancy being Squamous cell carcinoma (75%. In the present study we report a case of Squamous cell carcinoma arising in a mature cystic teratoma. A 45 year old female presented with mass in abdomen, pain abdomen and dysuria since one month. Total abdominal hysterectomy with bilateral salpingo-opherectomy was done. Histopathology showed well differentiated invasive squamous cell carcinoma arising in the background of mature cystic teratoma (dermoid cyst. Purpose of this report was to create awareness among practitioners to consider this possibility in dermoid cysts of large size in older patients

  11. p53-independent upregulation of p21WAF1 in NIH 3T3 cells malignantly transformed by mot-2

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    ot-2 protein is shown to interact with p53 and inhibit its transcriptional activation function.Mot-2 overexpressing stable clones of NIH 3T3 cells were malignantly transformed,however,they had a high level of expression of a p53 downstream gene,P21waf1.The present study was undertaken to elucidate possible molecular mechanism(s) of such upregulation.An increased level of P21waf1 expression was detected in stable transfectants although an exogenous reporter gene driven by P21waf1 promoter exhibited lower activity in these cells suggesting that some post-transcriptional mechanism contributes to upregulation.Western analyses of transient and stable clones revealed that upregulation of P21waf1 in stable NIH 3T3/mot-2 cells may be mediated by cyclin D1 and cdk-2.

  12. Constitutive phosphorylation of eps8 in tumor cell lines: relevance to malignant transformation

    DEFF Research Database (Denmark)

    Matoskova, B; Wong, W T; Salcini, A E;

    1995-01-01

    eps8, a recently identified tyrosine kinase substrate, has been shown to augment epidermal growth factor (EGF) responsiveness, implicating it in EGF receptor (EGFR)-mediated mitogenic signaling. We investigated the status of eps8 phosphorylation in normal and transformed cells and the role of eps...

  13. Extracellular localization of catalase is associated with the transformed state of malignant cells.

    Science.gov (United States)

    Böhm, Britta; Heinzelmann, Sonja; Motz, Manfred; Bauer, Georg

    2015-12-01

    Oncogenic transformation is dependent on activated membrane-associated NADPH oxidase (NOX). However, the resultant extracellular superoxide anions are also driving the NO/peroxynitrite and the HOCl pathway, which eliminates NOX-expressing transformed cells through selective apoptosis induction. Tumor progression is dependent on dominant interference with intercellular apoptosis-inducing ROS signaling through membrane-associated catalase, which decomposes H2O2 and peroxynitrite and oxidizes NO. Particularly, the decomposition of extracellular peroxynitrite strictly requires membrane-associated catalase. We utilized small interfering RNA (siRNA)-mediated knockdown of catalase and neutralizing antibodies directed against the enzyme in combination with challenging H2O2 or peroxynitrite to determine activity and localization of catalase in cells from three distinct steps of multistage oncogenesis. Nontransformed cells did not generate extracellular superoxide anions and only showed intracellular catalase activity. Transformed cells showed superoxide anion-dependent intercellular apoptosis-inducing ROS signaling in the presence of suboptimal catalase activity in their membrane. Tumor cells exhibited tight control of intercellular apoptosis-inducing ROS signaling through a high local concentration of membrane-associated catalase. These data demonstrate that translocation of catalase to the outside of the cell membrane is already associated with the transformation step. A strong local increase in the concentration of membrane-associated catalase is achieved during tumor progression and is controlled by tumor cell-derived H2O2 and by transglutaminase.

  14. Alcohol metabolism by oral streptococci and interaction with human papillomavirus leads to malignant transformation of oral keratinocytes.

    Science.gov (United States)

    Tao, Lin; Pavlova, Sylvia I; Gasparovich, Stephen R; Jin, Ling; Schwartz, Joel

    2015-01-01

    Poor oral hygiene, ethanol consumption, and human papillomavirus (HPV) are associated with oral and esophageal cancers. However, the mechanism is not fully known. This study examines alcohol metabolism in Streptococcus and its interaction with HPV-16 in the malignant transformation of oral keratinocytes. The acetaldehyde-producing strain Streptococcus gordonii V2016 was analyzed for adh genes and activities of alcohol and aldehyde dehydrogenases. Streptococcus attachment to immortalized HPV-16 infected human oral keratinocytes, HOK (HPV/HOK-16B), human oral buccal keratinocytes, and foreskin keratinocytes was studied. Acetaldehyde, malondialdehyde, DNA damage, and abnormal proliferation among keratinocytes were also quantified. We found that S. gordonii V2016 expressed three primary alcohol dehydrogenases, AdhA, AdhB, and AdhE, which all oxidize ethanol to acetaldehyde, but their preferred substrates were 1-propanol, 1-butanol, and ethanol, respectively. S. gordonii V2016 did not show a detectable aldehyde dehydrogenase. AdhE is the major alcohol dehydrogenase in S. gordonii. Acetaldehyde and malondialdehyde production from permissible Streptococcus species significantly increased the bacterial attachment to keratinocytes, which was associated with an enhanced expression of furin to facilitate HPV infection and several malignant phenotypes including acetaldehyde adduct formation, abnormal proliferation, and enhanced migration through integrin-coated basement membrane by HPV-infected oral keratinocytes. Therefore, expression of multiple alcohol dehydrogenases with no functional aldehyde dehydrogenase contributes to excessive production of acetaldehyde from ethanol by oral streptococci. Oral Streptococcus species and HPV may cooperate to transform oral keratinocytes after ethanol exposure. These results suggest a significant clinical interaction, but further validation is warranted.

  15. Prevention of KLF4-mediated tumor initiation and malignant transformation by UAB30 rexinoid.

    Science.gov (United States)

    Jiang, Wen; Deng, Wentao; Bailey, Sarah K; Nail, Clint D; Frost, Andra R; Brouillette, Wayne J; Muccio, Donald D; Grubbs, Clinton J; Ruppert, J Michael; Lobo-Ruppert, Susan M

    2009-02-01

    The transcription factor KLF4 acts in post-mitotic epithelial cells to promote differentiation and functions in a context-dependent fashion as an oncogene. In the skin KLF4 is co-expressed with the nuclear receptors RARgamma and RXRalpha, and formation of the skin permeability barrier is a shared function of these three proteins. We utilized a KLF4-transgenic mouse model of skin cancer in combination with cultured epithelial cells to examine functional interactions between KLF4 and retinoic acid receptors. In cultured cells, activation of a conditional, KLF4-estrogen receptor fusion protein by 4-hydroxytamoxifen resulted in rapid upregulation of transcripts for nuclear receptors including RARgamma and RXRalpha. We tested retinoids in epithelial cell transformation assays, including an RAR-selective agonist (all-trans RA), an RXR-selective agonist (9-cis UAB30, rexinoid), and a pan agonist (9-cis RA). Unlike for several other genes, transformation by KLF4 was inhibited by each retinoid, implicating distinct nuclear receptor heterodimers as modulators of KLF4 transforming activity. When RXRalpha expression was suppressed by RNAi in cultured cells, transformation was promoted and the inhibitory effect of 9-cis UAB30 was attenuated. Similarly as shown for other mouse models of skin cancer, rexinoid prevented skin tumor initiation resulting from induction of KLF4 in basal keratinocytes. Rexinoid permitted KLF4 expression and KLF4-induced cell cycling, but attenuated the KLF4-induced misexpression of cytokeratin 1 in basal cells. Neoplastic lesions including hyperplasia, dysplasia and squamous cell carcinoma-like lesions were prevented for up to 30 days. Taken together, the results identify retinoid receptors including RXRalpha as ligand-dependent inhibitors of KLF4-mediated transformation or tumorigenesis. PMID:19197145

  16. Malignant transformation in non-recurrent peritoneal cystic mesothelioma Our experience and review of the literature.

    Science.gov (United States)

    Santangelo, Giuseppe; Accardo, Marina; De Vita, Ferdinando; Del Giudice, Santolo; Gallucci, Federica; Fabozzi, Alessio; De Falco, Massimo

    2016-01-29

    Il mesotelioma peritoneale cistico è un tumore raro. Si tratta di un tumore benigno, che tuttavia va incontro a recidive locali post-chirurgiche in oltre il 50% dei casi. È proprio a seguito di recidive ricorrenti che si possono determinare trasformazioni maligne di questa neoplasia, come descritto in Letteratura. Nel Giugno del 2004 un paziente di 73 anni è giunto presso la nostra struttura con una tumefazione addominale causa di dolore gravativo: si trattava di una massa di 16 cm, la cui struttura, agli esami strumentali (ecografia, TC con m.d.c. e RMN), appariva pluricistica. Attraverso una laparotomia mediana si è provveduto alla sua rimozione e il paziente è stato dimesso in VIII giornata post-operatoria senza complicanze. L’esame istologico, corredato da studio immunoistochimico e di microscopia elettronica, ha consentito di porre diagnosi di mesotelioma peritoneale pluricistico in trasformazione maligna. D’accordo con gli oncologi, in considerazione della scarsa efficacia dei trattamenti adiuvanti e della scarsità dei dati riportati in Letteratura sull’argomento, si è deciso di sottoporre il paziente unicamente ad uno stretto follow-up, con esecuzione di ecografia addominale ogni sei mesi e TC addominale ogni anno. Ad oggi, dieci anni dopo il trattamento, il paziente, di 83 anni, gode di un discreto stato di salute e non si sono verificate riprese o recidive di malattia, né locali, né a distanza. Oltre al fatto di essere risultato maligno alla sua prima manifestazione e non dopo ripetute recidive, il caso presenta altre particolarità: il mesotelioma peritoneale cistico, infatti, solitamente colpisce soggetti di sesso femminile (con un rapporto F:M di 4,5:1) ad un’età media di 60 anni, mentre il caso descritto riguarda un soggetto di sesso maschile di 73 anni. La nostra osservazione dimostra la possibilità che il mesotelioma peritoneale vada incontro a trasformazioni maligne già alla sua prima manifestazione e non esclusivamente dopo

  17. Abnormal promoter methylation of multiple genes in the malignant transformed PEP2D cells induced by alpha particles exposure

    Institute of Scientific and Technical Information of China (English)

    LiP; SuiJL

    2002-01-01

    The 5' promoter regions of some genes contain CpG-rich areas,known as CpG islands,Methylation of the cytosine in these dinuleotides has important regulatory effects on gene expression.The functional significance of promoter hypermethylation would play the same roles in carcinogenesis as gene mutations.The promoter methylations p14ARF,p16INK4a,MGMT,GSTP1,BUB3 and DAPK genes were analyzed with methylation specific PCR(MSP) in the transformed human bronchial epithelial cells(BEP2D) induced by α-particles.The results indicated that p14ARF gene was not methylated in BEP2D cells,but was methylated in the malignant transformed BERP35T-1 cells,and the level of its transcription was depressed remarkable in the latter.However p16INK4a gene,which shares two exons with p14ARF gene,was not methylated.MGMT gene was methylated in both BEP2D and BERP35T-1.DAPK gene was partially methylated in BEP2D cells and methylated completely in BERP35T1.GSTP1 was not methylated in BEP2D cells and was methylated partly in BERP35T-1.BUB3 gene was not methylated in BEP2D as well as BERP35T1 cells and was further proved by sequencing analysis.

  18. Abnormal expression of c-Myc in human bronchial epithelial cells malignantly transformed by anti-BPDE

    Institute of Scientific and Technical Information of China (English)

    Juan FU; Yiguo JIANG; Xuemin CHEN

    2008-01-01

    Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a metabolite of benzo[a]pyrene (B[a] P) and acts as a potent mutagen in mammalian systems. However, molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood. Here, we investigated the expression of proto-oncogene c-myc in human bronchial epithelial cells (16H BE-T) transformed by exposure to anti-BPDE. The levels ofmRNA and pro-tein of c-M yc were examined in the 16HBE-T and vehicle-treated control cells (16HBE-N) by using different meth-ods respectively, including reverse transcriptase-polymer-ase chain reaction (RT-PCR), quantitative real-time PCR (Q-PCR), western blot and immunocytochemical meth-ods. The level of c-myc mRNA appeared to be signifi-cantly increased in 16HBE-T, as compared with those of the 16H BE-N. Likewise, the expression of c-Myc protein was significantly enhanced as compared with those of the control cells. Moreover, the localization of c-Myc protein shows mainly nuclear staining in 16HBE-T. In conclu-sion, the abnormal expression of c-Myc was present in anti-BPDE malignantly transformed 16HBE cells, which may be involved in the carcinogenesis molecular mech-anism of anti-BPDE.

  19. Frequent deletions of JARID2 in leukemic transformation of chronic myeloid malignancies.

    Science.gov (United States)

    Puda, Ana; Milosevic, Jelena D; Berg, Tiina; Klampfl, Thorsten; Harutyunyan, Ashot S; Gisslinger, Bettina; Rumi, Elisa; Pietra, Daniela; Malcovati, Luca; Elena, Chiara; Doubek, Michael; Steurer, Michael; Tosic, Natasa; Pavlovic, Sonja; Guglielmelli, Paola; Pieri, Lisa; Vannucchi, Alessandro M; Gisslinger, Heinz; Cazzola, Mario; Kralovics, Robert

    2012-03-01

    Chronic myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) have an inherent tendency to progress to acute myeloid leukemia (AML). Using high-resolution SNP microarrays, we studied a total of 517 MPN and MDS patients in different disease stages, including 77 AML cases with previous history of MPN (N = 46) or MDS (N = 31). Frequent chromosomal deletions of variable sizes were detected, allowing the mapping of putative tumor suppressor genes involved in the leukemic transformation process. We detected frequent deletions on the short arm of chromosome 6 (del6p). The common deleted region on 6p mapped to a 1.1-Mb region and contained only the JARID2 gene--member of the polycomb repressive complex 2 (PRC2). When we compared the frequency of del6p between chronic and leukemic phase, we observed a strong association of del6p with leukemic transformation (P = 0.0033). Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1. Using next generation exome sequencing of 40 patients, we identified only one somatic mutation in the PRC2 complex member SUZ12. As the frequency of point mutations in PRC2 members was found to be low, deletions were the main type of lesions targeting PRC2 complex members. Our study suggests an essential role of the PRC2 complex in the leukemic transformation of chronic myeloid disorders. PMID:22190018

  20. Study of immortalization and malignant transformation of human embryonic esophageal epithelial cells induced by HPV18 E6E7.

    Science.gov (United States)

    Shen, Z; Cen, S; Shen, J; Cai, W; Xu, J; Teng, Z; Hu, Z; Zeng, Y

    2000-10-01

    In order to study the effect of viruses and tumor promoters on the tumorigenicity of the esophagus, human embryonic esophageal epithelial cells were infected with human papilloma virus HPV18 E6E7-AAV in synergy with 12-O-tetradecanoylphorbol 13-acetate (TPA) to observe their malignant transformation. The cultured esophageal epithelial cells incubated with HPV18 E6E7-AAV were divided into two groups: the SHEEC1 group was exposed to TPA (5 ng/ml) for 4 weeks at the 5th passage of the cells; the SHEE group served as the control and was cultured in the same medium without TPA. The morphological phenotype, the DNA content during the cell cycle and the chromosomes were analyzed. The tumorigenicity was assessed by colony formation after cultivation in soft agar and transplanting the cells into nude mice. HPV18 E6E7 DNA was assayed by fluorescent in situ hybridization (FISH) and the polymerase chain reaction (PCR). The SHEE group, at its 20th passage, grew as a monolayer with the cells showing anchorage dependence and contact inhibition. The chromosome analysis showed diploidy, and soft-agar cultivation and injection into nude mice showed the cells to be non-tumorigenic. They were therefore immortalized cells. In contrast, the SHEEC1 group (TPA group) showed increased DNA synthesis and a proliferative index that was higher (45%) than that of the SHEE group (34%). The number of large colonies of dense multilayer cells (positively transformed foci) in soft agar was high in SHEEC1 group (4.0%) but low in the SHEE group (0.1%). Tumors resulting from transplantation were observed in all six nude mice injected subcutaneously with cells of the SHEEC1 group but no tumor developed in mice receiving cells of the SHEE group. In both groups of cells, HPV18 E6E7 DNA was positively detected by FISH and PCR. The malignant transformation of human embryonic epithelial cells was induced in vitro by HPV18 E6E7 in synergy with TPA. This is a good evidence for the close relationship between

  1. Dual Aurora A and JAK2 kinase blockade effectively suppresses malignant transformation

    OpenAIRE

    Hua YANG; Lawrence, Harshani R.; Kazi, Aslamuzzaman; Gevariya, Harsukh; Patel, Ronil; Luo, Yunting; Rix, Uwe; Schonbrunn, Ernst; Lawrence, Nicholas J.; Sebti, Said M.

    2014-01-01

    Aurora A and JAK2 kinases are involved in cell division and tumor cell survival, respectively. Here we demonstrate that ectopic expression of Aurora A and JAK2 together is more effective than each alone at inducing non-transformed cells to grow in an anchorage-independent manner and to invade. Furthermore, siRNA silencing or pharmacological inhibition of Aurora A and JAK2 with Alisertib and Ruxolitinib, respectively, is more effective than blocking each kinase alone at suppressing anchorage-d...

  2. Autophagy mediated by arginine depletion activation of the nutrient sensor GCN2 contributes to interferon-γ-induced malignant transformation of primary bovine mammary epithelial cells

    Science.gov (United States)

    Xia, X-j; Gao, Y-y; Zhang, J; Wang, L; Zhao, S; Che, Y-y; Ao, C-j; Yang, H-j; Wang, J-q; Lei, L-c

    2016-01-01

    Autophagy has been linked to the regulation of both the prevention and progression of cancer. IFN-γ has been shown to induce autophagy in multiple cell lines in vitro. However, whether IFN-γ can induce autophagy and whether autophagy promotes malignant transformation in healthy lactating bovine mammary epithelial cells (BMECs) remain unclear. Here, we provide the first evidence of the correlation between IFN-γ treatment, autophagy and malignant transformation and of the mechanism underlying IFN-γ-induced autophagy and subsequent malignant transformation in primary BMECs. IFN-γ levels were significantly increased in cattle that received normal long-term dietary corn straw (CS) roughage supplementation. In addition, an increase in autophagy was clearly observed in the BMECs from the mammary tissue of cows expressing high levels of IFN-γ. In vitro, autophagy was clearly induced in primary BMECs by IFN-γ within 24 h. This induced autophagy could subsequently promote dramatic primary BMEC transformation. Furthermore, we found that IFN-γ promoted arginine depletion, activated the general control nonderepressible-2 kinase (GCN2) signalling pathway and resulted in an increase in autophagic flux and the amount of autophagy in BMECs. Overall, our findings are the first to demonstrate that arginine depletion and kinase GCN2 expression mediate IFN-γ-induced autophagy that may promote malignant progression and that immunometabolism, autophagy and cancer are strongly correlated. These results suggest new directions and paths for preventing and treating breast cancer in relation to diet. PMID:27551491

  3. Malignant transformation of low grade gliomas into glioblastoma a series of 10 cases and review of the literature

    Directory of Open Access Journals (Sweden)

    D. Rotariu1, S. Gaivas1, Z. Faiyad1, D. Haba2, B. Iliescu1, I. Poeata1

    2010-11-01

    Full Text Available Background: Diffuse infiltrative low-gradegliomas (LGG of the cerebral hemispheresin the adult are tumors with distinctclinical, histological and molecularcharacteristics. WHO (World HealthOrganization classification recognizesgrade II astrocytomas, oligodendrogliomasand oligoastrocytomas. Conventional MRIis used for differential diagnosis, guidingsurgery, planning radiotherapy andmonitoring treatment response.Advanced imaging techniques areincreasing the diagnostic accuracy. Lowgradegliomas have been documented toundergo transformation into high-gradegliomas, and the time interval of thistransformation has been reported togenerally occur within 5 years in about 50%of patients diagnosed with low-gradegliomas.Methods: We have reviewed all adultpatients operated on for hemisphericglioblastoma at N Oblu Hospital in Iasibetween 2006 and 2009 and in particularthose patients with secondary glioblastoma.Results: from the total 110 cases ofglioblastoma, ten of them were secondaryto malignant transformation of anpreviously operated low grade glioma. Ofthe 10 patients with secondaryglioblastoma, the initial histology was: gr IIastocytoma in 6 cases, oligoastocytoma in 2cases and in oligodendroglioma in 2 cases.The mean patient age was 46.1± 0.9 yearsand the most frequent symptom wasrepresented by seizures 70%, the mean timefrom the first symptom to diagnosis was11,2 months. 40% of the cases had subtotalresection and 60% had total resection(defined by the surgeon at the time ofoperation. 5 patients received radiotherapypostoperatively, 2 received both radio andchemotherapy and 3 had no adjuvanttreatment. In our series the median time tomalignant transformation was 32,5 months.Conclusions: Younger age, normalneurological examination andoligodendroglial histology are favorableprognostic factors, total/near total resectioncan improve seizure control, progressionfreeand overall survival, mean whilereducing the risk of malignanttransformation. Early post

  4. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity. PMID:26485141

  5. Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid

    Energy Technology Data Exchange (ETDEWEB)

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C. [Bose Institute, Department of Chemistry, Kolkata, West Bengal (India)

    2008-03-15

    Arsenic, one of the most harmful metalloids, is ubiquitous in the environment. The present study has been carried out to investigate the protective role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced cardiac oxidative damage. In the study, NaAsO{sub 2} was chosen as the source of arsenic. The free radical scavenging activity and the effect of AA on the intracellular antioxidant power were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of NaAsO{sub 2} at a dose of 10 mg/kg body weight for 2 days caused significant accumulation of arsenic in cardiac tissues of the experimental mice in association with the reduction in cardiac antioxidant enzymes activities, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase. Arsenic intoxication also decreased the cardiac glutathione (GSH) and total thiol contents and increased the levels of oxidized glutathione (GSSG), lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20 mg/kg body weight for 4 days prior to NaAsO{sub 2} intoxication protected the cardiac tissue from arsenic-induced oxidative impairment. In addition to oxidative stress, arsenic administration increased total cholesterol level as well as the reduced high-density lipoprotein cholesterol level in the sera of the experimental mice. AA pretreatment, however, could prevent this hyperlipidemia. Histological studies on the ultrastructural changes in cardiac tissue supported the protective activity of AA also. Combining all, results suggest that AA could protect cardiac tissues against arsenic-induced oxidative stress probably due to its antioxidant property. (orig.)

  6. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity.

  7. Early Detection of Malignant Transformation in Resected WHO II Low-Grade Glioma Using Diffusion Tensor-Derived Quantitative Measures

    Science.gov (United States)

    Freitag, Martin T.; Maier-Hein, Klaus H.; Binczyk, Francisczek; Laun, Frederik B.; Weber, Christian; Bonekamp, David; Tarnawski, Rafal; Bobek-Billewicz, Barbara; Polanska, Joanna; Majchrzak, Henryk; Stieltjes, Bram

    2016-01-01

    Objective Here, we retrospectively investigate the value of voxel-wisely plotted diffusion tensor-derived (DTI) axial, radial and mean diffusivity for the early detection of malignant transformation (MT) in WHO II glioma compared to contrast-enhanced images. Materials and Methods Forty-seven patients underwent brain magnetic resonance imaging follow-up between 2006–2014 after gross-tumor resection of intra-axial WHO II glioma. Axial/Mean/Radial diffusivity maps (AD/MD/RD) were generated from DTI data. ADmin/MDmin/RDmin values were quantified within tumor regions-of-interest generated by two independent readers including tumor contrast-to-noise (CNR). Sensitivity/specificity and area-under-the-curve (AUC) were calculated using receiver-operating-characteristic analysis. Inter-reader agreement was assessed (Cohen’s kappa). Results Eighteen patients demonstrated malignant transformation (MT) confirmed in 8/18 by histopathology and in 10/18 through imaging follow-up. Twelve of 18 patients (66.6%) with MT showed diffusion restriction timely coincidental with contrast-enhancement (CE). In the remaining six patients (33.3%), the diffusion restriction preceded the CE. The mean gain in detection time using DTI was (0.8±0.5 years, p = 0.028). Compared to MDmin and RDmin, ROC-analysis showed best diagnostic value for ADmin (sensitivity/specificity 94.94%/89.7%, AUC 0.96; p<0.0001) to detect MT. CNR was highest for AD (1.83±0.14), compared to MD (1.31±0.19; p<0.003) and RD (0.90±0.23; p<0.0001). Cohen’s Kappa was 0.77 for ADmin, 0.71 for MDmin and 0.65 for RDmin (p<0.0001, respectively). Conclusion MT is detectable at the same time point or earlier compared to T1w-CE by diffusion restriction in diffusion-tensor-derived maps. AD demonstrated highest sensitivity/specificity/tumor-contrast compared to radial or mean diffusivity (= apparent diffusion coefficient) to detect MT. PMID:27741525

  8. Role of Pin1 in UVA-induced cell proliferation and malignant transformation in epidermal cells

    International Nuclear Information System (INIS)

    Highlights: → Pin1 expression is enhanced by low energy UVA irradiation in both skin tissues of hairless mice and JB6 C141 epidermal cells. → UVA irradiation increases activator protein-1 activity and cyclin D1 in a Pin1-dependent manner. → UVA potentiates EGF-inducible, anchorage-independent growth of epidermal cells, and this is suppressed by Pin1 inhibition or by anti-oxidant. -- Abstract: Ultraviolet A (UVA) radiation (λ = 320-400 nm) is considered a major cause of human skin cancer. Pin1, a peptidyl prolyl isomerase, is overexpressed in most types of cancer tissues and plays an important role in cell proliferation and transformation. Here, we demonstrated that Pin1 expression was enhanced by low energy UVA (300-900 mJ/cm2) irradiation in both skin tissues of hairless mice and JB6 C141 epidermal cells. Exposure of epidermal cells to UVA radiation increased cell proliferation and cyclin D1 expression, and these changes were blocked by Pin1 inhibition. UVA irradiation also increased activator protein-1 (AP-1) minimal reporter activity and nuclear levels of c-Jun, but not c-Fos, in a Pin1-dependent manner. The increases in Pin1 expression and in AP-1 reporter activity in response to UVA were abolished by N-acetylcysteine (NAC) treatment. Finally, we found that pre-exposure of JB6 C141 cells to UVA potentiated EGF-inducible, anchorage-independent growth, and this effect was significantly suppressed by Pin1inhibition or by NAC.

  9. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity

    Science.gov (United States)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-01-01

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered. PMID:27585557

  10. Arsenic-induced bone marrow toxicity: ultrastructural and electron-probe analysis

    Energy Technology Data Exchange (ETDEWEB)

    Feussner, J.R.; Shelburne, J.D.; Bredehoeft, S.; Cohen, H.J.

    1979-05-01

    A patient with severe arsenic poisoning that resulted in marked peripheral blood and bone marrow abnormalities, including megaloblastic erythropoiesis experienced many of the previously reported hematologic complications of arsenic poisoning: leukopenia, granulocytopenia, absolute eosinophilia, and profound anemia. In this study we report an ultrastructural and electron-proble analysis of the bone marrow. Although megaloblastic anemia associated with arsenic poisoning has been described rarely, the presence of arsenic in the local bone marrow milieu has not been demonstrated previously. The ultrastructural features of arsenic-induced bone marrow toxicity are similar to those described in other dyserythropoietic states and include marked nuclear aberrations involving shape, chromatin distribution, and nuclear envelope. Using the technique of energy-dispersive x-ray analysis (electron probe) we demonstrated arsenic in bone marrow spicules; this supports the contention that arsenic can cause megaloblastic anemia. We suggest that this technique may be a useful tool in further studies that attempt to explore the mechanism of arsenic-induced hematologic toxicity. Finally, we suggest that arsenic has a direct toxic effect on DNA synthesis that results in marked disturbances of nuclear division. We recommend that the most appropriate screening procedure to evaluate possible arsenic poisoning is tissue arsenic measurements (hair and nails) rather than 24-hr urinary measurements.

  11. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity.

    Science.gov (United States)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-09-02

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

  12. Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

    Institute of Scientific and Technical Information of China (English)

    LI Shu Gang; GUO Shu Xia; DING Yu Song; NIU Qiang; XU Shang Zhi; PANG Li Juan; MA Ru Lin; JING Ming Xia; FENG Gang Ling; LIU Jia Ming

    2015-01-01

    Objective To determine the ability of grape seed proanthocyanidin extract (GSPE) in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage: normal saline solution (control); arsenic trioxide (ATO; 4 mg/kg); GSPE (400 mg/kg); ATO+GSPE (100 mg/kg);ATO+GSPE (200 mg/kg) and ATO+GSPE (400 mg/kg). Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase 1 (HO1), glutathione S-transferase (GST), NAD(P)H dehydrogenase, and quinone 1 (NQO1) expression in the testis was detected by real-time PCR. Superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability (T-AOC), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO+GSPE group showed recovery of the measured parameters. Mice treated with ATO+high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NQO1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

  13. Antioxidant and modulatory role of Chlorophytum borivilianum against arsenic induced testicular impairment

    Institute of Scientific and Technical Information of China (English)

    Garima Sharma; Madhu Kumar

    2012-01-01

    Arsenic has a suppressive influence on spermatogenesis and induces impairment in male reproductive system due to oxidative stress.The present study was aimed to test the arsenic induced toxicity and protection by Chlorophytum borivilianum.The effect of sodium arsenite (4 mg/(kg body weight (bw)·day)) via double distilled water without or with C.borivilianum (800 mg/(kg bw·day)) was evaluated in Swiss albino mice for 30 days.The radical scavenging activity of the aqueous C.borivilianum root extract was measured using DPPH (l,l-diphenyl-2-picryl hydrayzyl) radical.Qualitative assessment of various cell types in the testis,sperm count and motility,testicular activity of lipid peroxidation (LPO),reduced glutathione (GSH),acid and alkaline phosphatase,cholesterol and serum testosterone were monitored.Arsenic treatment showed a significant increase in LPO,acid and alkaline phosphatase,cholesterol and decrease in sperm count,sperm motility,GSH and serum testosterone.Combined treatment showed significant decrease in LPO,acid and alkaline phosphatase,cholesterol and elevation in sperm count,sperm motility,GSH and serum testosterone.Testiculat histopathology showed that C.borivilianum had reduced degeneration of germ cell in the seminiferous tubules and loss of sperms induced by arsenic intoxication.The results thus led us to conclude that administration of C.borivilianum root extract is found to be protective against arsenic induced toxicity.

  14. Arsenic-induced bone marrow toxicity: ultrastructural and electron-probe analysis.

    Science.gov (United States)

    Feussner, J R; Shelburne, J D; Bredehoeft, S; Cohen, H J

    1979-05-01

    A patient with severe arsenic poisoning that resulted in marked peripheral blood and bone marrow abnormalities, including megaloblastic erythropoiesis experienced many of the previously reported hematologic complications of arsenic poisoning: leukopenia, granulocytopenia, absolute eosinophilia, and profound anemia. In this study we report an ultrastructural and electron-probe analysis of the bone marrow. Although megaloblastic anemia associated with arsenic poisoning has been described rarely, the presence of arsenic in the local bone marrow milieu has not been demonstrated previously. The ultrastructural features of arsenic-induced bone marrow toxicity are similar to those described in other dyserythropoietic states and include marked nuclear aberrations involving shape, chromatin distribution, and nuclear envelope. Using the technique of energy-dispersive x-ray analysis (electron probe) we demonstrated arsenic in bone marrow spicules; this supports the contention that arsenic can cause megaloblastic anemia. We suggest that this technique may be a useful tool in further studies that attempt to explore the mechanism of arsenic-induced hematologic toxicity. Finally, we suggest that arsenic has a direct toxic effect on DNA synthesis that results in marked disturbances of nuclear division. We recommend that the most appropriate screening procedure to evaluate possible arsenic poisoning is tissue arsenic measurements (hair and nails) rather than 24-hr urinary measurements.

  15. Analysis of the miRNA-mRNA networks in malignant transformation BEAS-2B cells induced by alpha-particles.

    Science.gov (United States)

    Nie, Ji-Hua; Chen, Zhi-Hai; Shao, Chun-Lin; Pei, Wei-Wei; Zhang, Jie; Zhang, Shu-Yu; Jiao, Yang; Tong, Jian

    2016-01-01

    The aim of this study was to determine the toxicity induced by irradiation with alpha-particles on malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) using miRNA-mRNA networks. The expression of BEAS-2B cells was determined by measuring colony formation, mtDNA, mitochondrial membrane potential (MMP), and ROS levels. Changes in BEAS-2B cell gene expression were observed and quantified using microarrays that included an increase in 157 mRNA and 20 miRNA expression and a decrease in 77 mRNA and 48 miRNA. Bioinformatic software was used to analyze these different mRNA and miRNA, which indicated that miR-107 and miR-494 play an important role in alpha-particles-mediated cellular malignant transformation processes. The pathways related to systemic lupus erythematosus, cytokine-cytokine receptor interaction, MAPK signaling pathway, regulation of actin cytoskeleton, and cell adhesion molecules (CAMs) were stimulated, while those of ribosome, transforming growth factor (TGF)-beta signaling pathway, and metabolic pathways were inhibited. Data suggest that miRNA and mRNA play a crucial role in alpha-particles-mediated malignant transformation processes. It is worth noting that three target genes associated with lung cancer were identified and upregulated PEG 10 (paternally expressed gene 10), ARHGAP26, and IRS1. PMID:27267825

  16. Hydroquinone-induced malignant transformation of TK6 cells by facilitating SIRT1-mediated p53 degradation and up-regulating KRAS.

    Science.gov (United States)

    Chen, Yuting; Chen, Jiajia; Yun, Lin; Xu, Longmei; Liu, Jiaxian; Xu, Yongchun; Yang, Hui; Liang, Hairong; Tang, Huanwen

    2016-09-30

    Hydroquinone (HQ), known as one of the metabolic products of benzene, causes a number of hematologic malignancies. The study evaluated the potential mechanism of Sirtuin 1 (SIRT1) in HQ-induced TK6 cell malignant transformation. The data of our study show that short term exposure of TK6 cells to HQ led to a decrease expression of SIRT1. Knockdown of SIRT1 sensitized to the HQ-induced apoptosis in vitro and increased the expression of p53, p21 and γ-H2AX. Furthermore, chronic HQ-treated (20μM once a week for 19 weeks) caused carcinogenic transformation and was confirmed by abnormal cell proliferation, matrix metalloproteinase 9(MMP9) and subcutaneous tumor formation in nude mice. SIRT1 increased KRAS expression, and decreased H3K9 and H3K18 acetylation, inhibited p53 signaling and the level of caspase-3 in HQ-induced transformation cells. Taken together, these data suggest that SIRT1 is involved in HQ-induced malignant transformation associated with suppressing p53 signaling and activation of KRAS. PMID:27515134

  17. Malignant Transformation of a Mature Cystic Ovarian Teratoma into Thyroid Carcinoma, Mucinous Adenocarcinoma, and Strumal Carcinoid: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Hilary D. Hinshaw

    2012-01-01

    Full Text Available Malignant transformation of a mature cystic teratoma (MCT is an infrequent, often asymptomatic event. We report the first example of a struma ovarii with a focus of follicular variant of papillary thyroid carcinoma (a, mucinous adenocarcinoma (b, and strumal carcinoid tumor (c—all three arising in one mature cystic teratoma of the ovary. From our reviews, we found limited data to guide management when these malignant foci occur within an MCT. Consideration should be given to thyroidectomy followed by total-body scanning and serum studies for foci of thyroid carcinoma and adjuvant therapy with thyroidectomy and radioablation if residual disease is identified (a. Additionally, extrapolating from data for mucinous adenocarcinomas, consideration could be given to adjuvant chemotherapy after appropriate staging (b. Strumal carcinoid tumors should be treated as tumors of low malignant potential. Observation is appropriate if after complete staging, no invasive implants are noted (c.

  18. Intracellular heavy metal nanoparticle storage: progressive accumulation within lymph nodes with transformation from chronic inflammation to malignancy

    Directory of Open Access Journals (Sweden)

    Tommaso Iannitti

    2010-11-01

    Full Text Available Tommaso Iannitti1, Stefania Capone2, Antonietta Gatti3, Frederico Capitani4, Cetta Francesco5,6, Beniamino Palmieri21Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK; 2Department of General Surgery and Surgical Specialties, 3Laboratory of Biomaterials, Department of Specialistic Surgeries, Head and Neck Medical School and Surgical Clinic, University of Modena and Reggio Emilia, Italy; 4Laboratory of Nanodiagnostics, San Vito, Modena, Italy 5Department of Surgery, University of Siena, Siena; 6Institute of Geriatrics, Pio Albergo Trivulzio Hospital, Milan, ItalyAbstract: A 25-year-old man had complained of sudden fever spikes for two years and his blood tests were within the normal range. In 1993, a surgical biopsy of swollen left inguinal lymph nodes was negative for malignancy, but showed reactive lymphadenitis and widespread sinus histiocytosis. A concomitant needle biopsy of the periaortic lymph nodes and a bone marrow aspirate were also negative. In 1994, after an emergency hospital admission because of a sport-related thoracic trauma, a right inguinal lymph node biopsy demonstrated Hodgkin’s lymphoma Stage IVB (scleronodular mixed cell subtype. Although it was improved by chemotherapy, the disease suddenly relapsed, and a further lymph node biopsy was performed in 1998 confirming the same diagnosis. Despite further treatment, the patient died of septic shock in 2004, at the age of 38 years. Retrospective analysis of the various specimens showed intracellular heavy metal nanoparticles within lymph node, bone marrow, and liver samples by field emission gun environmental scanning electron microscopy and energy dispersive spectroscopy. Heavy metals from environmental pollution may accumulate in sites far from the entry route and, in genetically conditioned individuals with tissue specificity, may act as cofactors for chronic inflammation or even malignant transformation. The present anecdotal report

  19. p85α promotes nucleolin transcription and subsequently enhances EGFR mRNA stability and EGF-induced malignant cellular transformation.

    Science.gov (United States)

    Xie, Qipeng; Guo, Xirui; Gu, Jiayan; Zhang, Liping; Jin, Honglei; Huang, Haishan; Li, Jingxia; Huang, Chuanshu

    2016-03-29

    p85α is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) that is a key lipid enzyme for generating phosphatidylinositol 3, 4, 5-trisphosphate, and subsequently activates signaling that ultimately regulates cell cycle progression, cell growth, cytoskeletal changes, and cell migration. In addition to form a complex with the p110 catalytic subunit, p85α also exists as a monomeric form due to that there is a greater abundance of p85α than p110 in many cell types. Our previous studies have demonstrated that monomeric p85α exerts a pro-apoptotic role in UV response through induction of TNF-α gene expression in PI3K-independent manner. In current studies, we identified a novel biological function of p85α as a positive regulator of epidermal growth factor receptor (EGFR) expression and cell malignant transformation via nucleolin-dependent mechanism. Our results showed that p85α was crucial for EGFR and nucleolin expression and subsequently resulted in an increase of malignant cellular transformation by using both specific knockdown and deletion of p85α in its normal expressed cells. Mechanistic studies revealed that p85α upregulated EGFR protein expression mainly through stabilizing its mRNA, whereas nucleolin (NCL) was able to bind to egfr mRNA and increase its mRNA stability. Consistently, overexpression of NCL in p85α-/- cells restored EGFR mRNA stabilization, protein expression and cell malignant transformation. Moreover, we discovered that p85α upregulated NCL gene transcription via enhancing C-Jun activation. Collectively, our studies demonstrate a novel function of p85α as a positive regulator of EGFR mRNA stability and cell malignant transformation, providing a significant insight into the understanding of biomedical nature of p85α protein in mammalian cells and further supporting that p85α might be a potential target for cancer prevention and therapy. PMID:26918608

  20. p85α promotes nucleolin transcription and subsequently enhances EGFR mRNA stability and EGF-induced malignant cellular transformation

    Science.gov (United States)

    Gu, Jiayan; Zhang, Liping; Jin, Honglei; Huang, Haishan; Li, Jingxia; Huang, Chuanshu

    2016-01-01

    p85α is a regulatory subunit of phosphatidylinositol 3-kinase (PI3K) that is a key lipid enzyme for generating phosphatidylinositol 3, 4, 5-trisphosphate, and subsequently activates signaling that ultimately regulates cell cycle progression, cell growth, cytoskeletal changes, and cell migration. In addition to form a complex with the p110 catalytic subunit, p85α also exists as a monomeric form due to that there is a greater abundance of p85α than p110 in many cell types. Our previous studies have demonstrated that monomeric p85α exerts a pro-apoptotic role in UV response through induction of TNF-α gene expression in PI3K-independent manner. In current studies, we identified a novel biological function of p85α as a positive regulator of epidermal growth factor receptor (EGFR) expression and cell malignant transformation via nucleolin-dependent mechanism. Our results showed that p85α was crucial for EGFR and nucleolin expression and subsequently resulted in an increase of malignant cellular transformation by using both specific knockdown and deletion of p85α in its normal expressed cells. Mechanistic studies revealed that p85α upregulated EGFR protein expression mainly through stabilizing its mRNA, whereas nucleolin (NCL) was able to bind to egfr mRNA and increase its mRNA stability. Consistently, overexpression of NCL in p85α−/− cells restored EGFR mRNA stabilization, protein expression and cell malignant transformation. Moreover, we discovered that p85α upregulated NCL gene transcription via enhancing C-Jun activation. Collectively, our studies demonstrate a novel function of p85α as a positive regulator of EGFR mRNA stability and cell malignant transformation, providing a significant insight into the understanding of biomedical nature of p85α protein in mammalian cells and further supporting that p85α might be a potential target for cancer prevention and therapy. PMID:26918608

  1. Long-term low-dose α-particle enhanced the potential of malignant transformation in human bronchial epithelial cells through MAPK/Akt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Weili; Xiao, Linlin; Dong, Chen; He, Mingyuan; Pan, Yan; Xie, Yuexia; Tu, Wenzhi; Fu, Jiamei; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

    2014-05-09

    Highlights: • Multi-exposures of 25 mGy α-ray enhanced cell proliferation, adhesion, and invasion. • MAPK/Akt but not JNK/P66 was positively correlated with cell invasive phenotypes. • LDR of α-irradiation triggers cell malignant transformation through MAPK/Akt. - Abstract: Since the wide usage of ionizing radiation, the cancer risk of low dose radiation (LDR) (<0.1 Gy) has become attractive for a long time. However, most results are derived from epidemiologic studies on atomic-bomb survivors and nuclear accidents surrounding population, and the molecular mechanism of this risk is elusive. To explore the potential of a long-term LDR-induced malignant transformation, human bronchial epithelial cells Beas-2B were fractionally irradiated with 0.025 Gy α-particles for 8 times in total and then further cultured for 1–2 months. It was found that the cell proliferation, the abilities of adhesion and invasion, and the protein expressions of p-ERK, p-Akt, especially p-P38 were not only increased in the multiply-irradiated cells but also in their offspring 1–2 months after the final exposure, indicating high potentiality of cell malignant transformation. On opposite, the expressions of p-JNK and p-P66 were diminished in the subcultures of irradiated cells and thus may play a role of negative regulation in canceration. When the cells were transferred with p38 siRNA, the LDR-induced enhancements of cell adhesion and invasion were significantly reduced. These findings suggest that long-term LDR of α-particles could enhance the potential of malignant transformation incidence in human bronchial epithelial cells through MAPK/Akt pathway.

  2. Intervention effect of pinelliae decoction for purging stomach-fire on malignant transformation of bone marrow mesenchymal stem cells in the gastric cancer microenvironment

    Science.gov (United States)

    Liu, Xi-Ping; Ming, Hai-Xia; Li, Pei-Qing

    2016-01-01

    Objective: The study aimed to simulate the microenvironment of gastric cancer to promote the malignant transformation of bone marrow mesenchymal stem cells (BMSCs) and further evaluate the effect of Pinelliae Decoction for Purging Stomach-Fire and its disassembled prescriptions on BMSCs. Methods: Transwell co-culture was performed on the human gastric cancer cell strains BGC-823 and BMSCs to simulate the microenvironment of gastric cancer. The drug-containing serum prepared by Pinelliae Decoction for Purging Stomach-Fire and its disassembled prescriptions was used, and its influence on BMSCs with malignant transformation was observed. Results: BMSCs were harvested successfully from the rat bone marrow, and flow cytometer identification indicated that CD44+/CD34- cells accounted for 70.64%. The co-culture of BGC-823 cells can induce malignant transformation of BMSCs. And the drug-containing serum can induce G2 phase arrest, inhibit cell proliferation, simultaneously inhibit TERT and c-myc expression, lower the cellular ability of chemotactic migration, inhibit the tumor-forming ability of BGC-823 in nude rats and promote the tumor apoptosis. Conclusion: The effective components of Pinelliae Decoction for Purging Stomach-Fire in gastric cancer treatment are pinelliae and dried ginger, and the main acting mechanism is to inhibit tumor cell proliferation and chemotactic migration and promote apoptosis. PMID:27508014

  3. Changes of gene methylation profile in malignant transformation of immortalized human bronchial epithelial cell line induced by alpha-particle irradiation

    International Nuclear Information System (INIS)

    Objective: To identify the changes of DNA methylation profile in the process of malignant transformation of BEP2D cell induced by α particles. Methods: The genomic DNAs were isolated from the malignant transformation BERP35T4 cells and immortalized human bronchial epithelial cell line BEP2D. Genomic DNAs were digested by MseI and ligated of PCR linkers. Methylated DNAs were digested by BstUI and amplified by PCR. The methylated DNA probes were prepared by labeling with Cy3 and Cy5 fluorescence dyes individually and hybridized to the methylation CpG-Island microarray. The hybridization results were scanned and analyzed. Intensity values were quality controlled and normalized. The normalized data were used to identify the differentially expressed genes based on a 1.5 fold difference of the expression level. Results: There were 16 genes which showed changes of methylation level in malignant transformation BERP35T4 cells, 9 of them were hyper methylation and 7 were hypo methylation. These genes were including the SKIP gene, PPP3CC gene, MAP2K6 gene, KIR2DL1 gene, KIR2DL4 gene, KIR3DP1 gene, ZNF493 gene, ZNF100 gene, NKX2-5 gene, TFAP2D gene, DR1 gene, KCNJ16 gene, CCDC18 gene, FNBP1L gene, IRX4 gene, EPB41L3 gene, TCP10 gene and so on. Conclusions: The DNA methylation might have effects on ionizing radiation derived tumorigenesis. (authors)

  4. Involvement of p53 Mutation and Mismatch Repair Proteins Dysregulation in NNK-Induced Malignant Transformation of Human Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Ying Shen

    2014-01-01

    Full Text Available Genome integrity is essential for normal cellular functions and cell survival. Its instability can cause genetic aberrations and is considered as a hallmark of most cancers. To investigate the carcinogenesis process induced by tobacco-specific carcinogen NNK, we studied the dynamic changes of two important protectors of genome integrity, p53 and MMR system, in malignant transformation of human bronchial epithelial cells after NNK exposure. Our results showed that the expression of MLH1, one of the important MMR proteins, was decreased early and maintained the downregulation during the transformation in a histone modification involved and DNA methylation-independent manner. Another MMR protein PMS2 also displayed a declined expression while being in a later stage of transformation. Moreover, we conducted p53 mutation analysis and revealed a mutation at codon 273 which led to the replacement of arginine by histidine. With the mutation, DNA damage-induced activation of p53 was significantly impaired. We further reintroduced the wild-type p53 into the transformed cells, and the malignant proliferation can be abrogated by inducing cell cycle arrest and apoptosis. These findings indicate that p53 and MMR system play an important role in the initiation and progression of NNK-induced transformation, and p53 could be a potential therapeutic target for tobacco-related cancers.

  5. Reactive oxygen species via redox signaling to PI3K/AKT pathway contribute to the malignant growth of 4-hydroxy estradiol-transformed mammary epithelial cells.

    Directory of Open Access Journals (Sweden)

    Victor O Okoh

    Full Text Available The purpose of this study was to investigate the effects of 17-β-estradiol (E2-induced reactive oxygen species (ROS on the induction of mammary tumorigenesis. We found that ROS-induced by repeated exposures to 4-hydroxy-estradiol (4-OH-E2, a predominant catechol metabolite of E2, caused transformation of normal human mammary epithelial MCF-10A cells with malignant growth in nude mice. This was evident from inhibition of estrogen-induced breast tumor formation in the xenograft model by both overexpression of catalase as well as by co-treatment with Ebselen. To understand how 4-OH-E2 induces this malignant phenotype through ROS, we investigated the effects of 4-OH-E2 on redox-sensitive signal transduction pathways. During the malignant transformation process we observed that 4-OH-E2 treatment increased AKT phosphorylation through PI3K activation. The PI3K-mediated phosphorylation of AKT in 4-OH-E2-treated cells was inhibited by ROS modifiers as well as by silencing of AKT expression. RNA interference of AKT markedly inhibited 4-OH-E2-induced in vitro tumor formation. The expression of cell cycle genes, cdc2, PRC1 and PCNA and one of transcription factors that control the expression of these genes - nuclear respiratory factor-1 (NRF-1 was significantly up-regulated during the 4-OH-E2-mediated malignant transformation process. The increased expression of these genes was inhibited by ROS modifiers as well as by silencing of AKT expression. These results indicate that 4-OH-E2-induced cell transformation may be mediated, in part, through redox-sensitive AKT signal transduction pathways by up-regulating the expression of cell cycle genes cdc2, PRC1 and PCNA, and the transcription factor - NRF-1. In summary, our study has demonstrated that: (i 4-OH-E2 is one of the main estrogen metabolites that induce mammary tumorigenesis and (ii ROS-mediated signaling leading to the activation of PI3K/AKT pathway plays an important role in the generation of 4-OH-E2

  6. Arsenic-Induced Genotoxicity and Genetic Susceptibility to Arsenic-Related Pathologies

    Directory of Open Access Journals (Sweden)

    Fabrizio Bianchi

    2013-04-01

    Full Text Available The arsenic (As exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic, mainly through a contamination of groundwaters. Chronic exposure to As is associated with adverse effects on human health such as cancers, cardiovascular diseases, neurological diseases and the rate of morbidity and mortality in populations exposed is alarming. The purpose of this review is to summarize the genotoxic effects of As in the cells as well as to discuss the importance of signaling and repair of arsenic-induced DNA damage. The current knowledge of specific polymorphisms in candidate genes that confer susceptibility to arsenic exposure is also reviewed. We also discuss the perspectives offered by the determination of biological markers of early effect on health, incorporating genetic polymorphisms, with biomarkers for exposure to better evaluate exposure-response clinical relationships as well as to develop novel preventative strategies for arsenic- health effects.

  7. Effects of Echinacea Purpurea on Wound Healing after Arsenic Induced Skin Necrosis

    Directory of Open Access Journals (Sweden)

    Annahita Rezaie

    2013-11-01

    Full Text Available Background: Evaluation of healing effects of Echinacea extract in Arsenic induced dermal necrosis in rat is the objective of this study. Materials and Methods: In this experimental study 20 male Wistar rats were divided to 2 groups. Dermal necrosis was induced by subcutaneously arsenic injection (4mg/kg for 10 days. In group 2, after arsenic receiving, Echinacea were injected intraperitoneally (400mg/kg. After last day of injection, rats were euthanizes and pathologic samples were collected from dermal ulcers.Results: Histopathologic results revealed necrosis of different dermal layers in arsenic group. There were inflammatory exudates instead of impaired structures. In group 2, there were granulation tissue with high cellularity and new vessels.Conclusion: According to this research findings arsenic can induce dermal necrosis which is a good animal model for dermatologic researches and also Echinacea has healing effects and can protect and limit the Arsenic effects.

  8. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  9. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism.

    Science.gov (United States)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark; Stachler, Elyse N; Bibby, Kyle J; Stolz, Donna B; Shiva, Sruti; Wang, Zeneng; Hazen, Stanley L; Barchowsky, Aaron; Stolz, John F

    2015-12-15

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes.

  10. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    International Nuclear Information System (INIS)

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  11. Protective effect of arjunolic acid against arsenic-induced oxidative stress in mouse brain.

    Science.gov (United States)

    Sinha, Mahua; Manna, Prasenjit; Sil, Parames C

    2008-02-01

    Arsenic, a notoriously poisonous metalloid, is ubiquitous in the environment, and it affects nearly all organ systems of animals including humans. The present study was designed to investigate the preventive role of a triterpenoid saponin, arjunolic acid against arsenic-induced oxidative damage in murine brain. Sodium arsenite was selected as a source of arsenic for this study. The free-radical-scavenging activity and the in vivo antioxidant power of arjunolic acid were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of sodium arsenite at a dose of 10 mg/kg body weight for 2 days significantly decreased the activities of antioxidant enzymes, superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase, the level of cellular metabolites, reduced glutathione, total thiols and increased the level of oxidized glutathione. In addition, it enhanced the levels of lipid peroxidation end products and protein carbonyl content. Treatment with arjunolic acid at a dose of 20 mg/kg body weight for 4 days prior to arsenic administration almost normalized above indices. Histological findings due to arsenic intoxication and arjunolic acid treatment supported the other biochemical changes in murine brains. Results of 2,2-diphenyl-1-picryl hydrazyl radical scavenging and ferric reducing/antioxidant power assays clearly showed the in vitro radical scavenging as well as the in vivo antioxidant power of arjunolic acid, respectively. The effect of a well-established antioxidant, vitamin C, has been included in the study as a positive control. Combining all, results suggest that arjunolic acid possessed the ability to ameliorate arsenic-induced oxidative insult in murine brain and is probably due to its antioxidant activity.

  12. Ameliorative efficacy of tetrahydrocurcumin against arsenic induced oxidative damage, dyslipidemia and hepatic mitochondrial toxicity in rats.

    Science.gov (United States)

    Muthumani, M; Miltonprabu, S

    2015-06-25

    Arsenic (As) is a well-known human carcinogen and a potent hepatotoxin. Environmental exposure to arsenic imposes a serious health hazard to humans and other animals worldwide. Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, exhibits many of the same physiological and pharmacological activities as curcumin and in some systems may exert greater antioxidant activity than the curcumin. It has been reported that THC has antioxidant efficacy attributable to the presence of identical β-diketone of 3rd and 5th substitution in heptane moiety. In the present study, rats were orally treated with arsenic alone (5 mg kg(-1) bw/day) with THC (80 mg kg(-1) bw/day) for 28 days. Hepatotoxicity was measured by the increased activities of serum hepatospecific enzymes, namely aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin along with increased elevation of lipid peroxidative markers, thiobarbituric acid reactive substances. And also elevated levels of serum cholesterol, triglycerides, free fatty acids and phospholipids were observed in arsenic intoxicated rats. These effects of arsenic were coupled with enhanced mitochondrial swelling, inhibition of cytochrome c oxidase, Ca(2+)ATPase and a decrease in mitochondrial calcium content. The toxic effect of arsenic was also indicated by significantly decreased activities of enzymatic antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase along with non-enzymatic antioxidant such as reduced glutathione. Administration of THC exhibited significant reversal of arsenic induced toxicity in hepatic tissue. All these changes were supported by the reduction of arsenic concentration and histopathological observations of the liver. These results suggest that THC has a protective effect over arsenic induced toxicity in rat.

  13. Epithelial-mesenchymal transition and cancer stem cells, mediated by a long non-coding RNA, HOTAIR, are involved in cell malignant transformation induced by cigarette smoke extract

    International Nuclear Information System (INIS)

    The incidence of lung diseases, including cancer, caused by cigarette smoke is increasing, but the molecular mechanisms of gene regulation induced by cigarette smoke remain unclear. This report describes a long noncoding RNA (lncRNA) that is induced by cigarette smoke extract (CSE) and experiments utilizing lncRNAs to integrate inflammation with the epithelial-mesenchymal transition (EMT) in human bronchial epithelial (HBE) cells. The present study shows that, induced by CSE, IL-6, a pro-inflammatory cytokine, leads to activation of STAT3, a transcription activator. A ChIP assay determined that the interaction of STAT3 with the promoter regions of HOX transcript antisense RNA (HOTAIR) increased levels of HOTAIR. Blocking of IL-6 with anti-IL-6 antibody, decreasing STAT3, and inhibiting STAT3 activation reduced HOTAIR expression. Moreover, for HBE cells cultured in the presence of HOTAIR siRNA for 24 h, the CSE-induced EMT, formation of cancer stem cells (CSCs), and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates HOTAIR in an autocrine manner, contributes to the EMT and to CSCs induced by CSE. These data define a link between inflammation and EMT, processes involved in the malignant transformation of cells caused by CSE. This link, mediated through lncRNAs, establishes a mechanism for CSE-induced lung carcinogenesis. - Highlights: • STAT3 directly regulates the levels of LncRNA HOTAIR. • LncRNA HOTAIR mediates the link between inflammation and EMT. • LncRNA HOTAIR is involved in the malignant transformation of cells caused by CSE

  14. Downregulation of miR-544 in tissue, but not in serum, is a novel biomarker of malignant transformation in glioma.

    Science.gov (United States)

    Ma, Ruimin; Zhang, Guojun; Wang, Huimin; Lv, Hong; Fang, Fang; Kang, Xixiong

    2012-12-01

    Low-grade glioma is predisposed to progress to anaplastic astrocytoma and eventually secondary glioblastoma. The malignant transformation may involve the accumulation of multiple genetic alterations. The purpose of this study was to explore the role of miR-544 in glioma progression and discuss whether it may be a novel biomarker of malignant transformation. The expression of miR-544 was measured in a series of 198 glioma samples (63 low-grade glioma, 44 anaplastic astrocytoma and 91 glioblastoma tumors) using microarrays. Quantitative real-time reverse transcription PCR (qRT-PCR) was used to validate the expression levels of miR-544 in tissue and serum samples in an independent validated cohort (25 low-grade glioma, 21 anaplastic astrocytoma and 20 glioblastoma tumors). A Pearson correlation analysis was performed to examine the correlation between miR-544 levels of tissue and serum samples. Microarrays revealed that the expression levels of miR-544 decreased significantly in anaplastic gliomas (PmiR-544 exhibited a progression-associated downregulation in glioma tumors. The levels of miR-544 in serum samples tended to be lower in anaplastic and glioblastoma patients compared with low-grade gliomas, but with no significant difference. The Pearson correlation analysis revealed a weakly positive correlation between tissue and serum levels of miR-544. These data support a significant role for miR-544 aberration in the malignant transformation of glioma. The downregulation of miR-544 in tissue may be used as a novel biomarker.

  15. Epithelial-mesenchymal transition and cancer stem cells, mediated by a long non-coding RNA, HOTAIR, are involved in cell malignant transformation induced by cigarette smoke extract

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yi; Luo, Fei; Xu, Yuan; Wang, Bairu; Zhao, Yue; Xu, Wenchao; Shi, Le; Lu, Xiaolin; Liu, Qizhan, E-mail: drqzliu@hotmail.com

    2015-01-01

    The incidence of lung diseases, including cancer, caused by cigarette smoke is increasing, but the molecular mechanisms of gene regulation induced by cigarette smoke remain unclear. This report describes a long noncoding RNA (lncRNA) that is induced by cigarette smoke extract (CSE) and experiments utilizing lncRNAs to integrate inflammation with the epithelial-mesenchymal transition (EMT) in human bronchial epithelial (HBE) cells. The present study shows that, induced by CSE, IL-6, a pro-inflammatory cytokine, leads to activation of STAT3, a transcription activator. A ChIP assay determined that the interaction of STAT3 with the promoter regions of HOX transcript antisense RNA (HOTAIR) increased levels of HOTAIR. Blocking of IL-6 with anti-IL-6 antibody, decreasing STAT3, and inhibiting STAT3 activation reduced HOTAIR expression. Moreover, for HBE cells cultured in the presence of HOTAIR siRNA for 24 h, the CSE-induced EMT, formation of cancer stem cells (CSCs), and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates HOTAIR in an autocrine manner, contributes to the EMT and to CSCs induced by CSE. These data define a link between inflammation and EMT, processes involved in the malignant transformation of cells caused by CSE. This link, mediated through lncRNAs, establishes a mechanism for CSE-induced lung carcinogenesis. - Highlights: • STAT3 directly regulates the levels of LncRNA HOTAIR. • LncRNA HOTAIR mediates the link between inflammation and EMT. • LncRNA HOTAIR is involved in the malignant transformation of cells caused by CSE.

  16. Expression profiling of 519 kinase genes in matched malignant peripheral nerve sheath tumor/plexiform neurofibroma samples is discriminatory and identifies mitotic regulators BUB1B, PBK and NEK2 as overexpressed with transformation.

    Science.gov (United States)

    Stricker, Thomas P; Henriksen, Kammi J; Tonsgard, James H; Montag, Anthony G; Krausz, Thomas N; Pytel, Peter

    2013-07-01

    About 50% of all malignant peripheral nerve sheath tumors (MPNSTs) arise as neurofibromatosis type 1 associated lesions. In those patients malignant peripheral nerve sheath tumors are thought to arise through malignant transformation of a preexisting plexiform neurofibroma. The molecular changes associated with this transformation are still poorly understood. We sought to test the hypothesis that dysregulation of expression of kinases contributes to this malignant transformation. We analyzed expression of all 519 kinase genes in the human genome using the nanostring nCounter system. Twelve cases of malignant peripheral nerve sheath tumor arising in a background of preexisting plexiform neurofibroma were included. Both components were separately sampled. Statistical analysis compared global changes in expression levels as well as changes observed in the pairwise comparison of samples taken from the same surgical specimen. Immunohistochemical studies were performed on tissue array slides to confirm expression of selected proteins. The expression pattern of kinase genes can separate malignant peripheral nerve sheath tumors and preexisting plexiform neurofibromas. The majority of kinase genes is downregulated rather than overexpressed with malignant transformation. The patterns of expression changes are complex without simple recurring alteration. Pathway analysis demonstrates that differentially expressed kinases are enriched for kinases involved in the direct regulation of mitosis, and several of these show increased expression in malignant peripheral nerve sheath tumors. Immunohistochemical studies for the mitotic regulators BUB1B, PBK and NEK2 confirm higher expression levels at the protein level. These results suggest that the malignant transformation of plexiform neurofibroma is associated with distinct changes in the expression of kinase genes. The patterns of these changes are complex and heterogeneous. There is no single unifying alteration. Kinases involved

  17. Biochanin A Ameliorates Arsenic-Induced Hepato- and Hematotoxicity in Rats.

    Science.gov (United States)

    Jalaludeen, Abdulkadhar Mohamed; Ha, Woo Tae; Lee, Ran; Kim, Jin Hoi; Do, Jeong Tae; Park, Chankyu; Heo, Young Tae; Lee, Won Young; Song, Hyuk

    2016-01-09

    Biochanin A (BCA) is a natural organic compound of the phytoestrogenic isoflavone class that has antioxidant and metal chelator properties in the presence of transition metal ions, however, its efficacy in animal models is still obscure. Therefore, the objective of this study was to investigate the protective effects of BCA against arsenic-induced hepatic injury and hematotoxicity in rats. The results suggest that arsenic intoxicated rats showed significantly higher levels of plasma hepatic markers than normal control rats. Furthermore, an increase in lipid peroxidation with depletion of reduced glutathione (GSH) and activities of superoxide dismutase (SOD) and catalase (CAT) occurred in the livers of rats exposed to arsenic. Administration of BCA (20 mg/kg·bw/day) and selenium (3 mg/kg·bw/day) resulted in a significant reversal of hepatic and oxidative stress markers in arsenic-intoxicated rats. A low dose of BCA (10 mg/kg·bw/day) did not show any preventive effect, while a high dose of BCA (40 mg/kg·bw/day) partially prevented all hepatotoxicity events. These biochemical perturbations were supported by histopathological observations of the liver. Our results suggest that administration of BCA (20 mg/kg·bw/day) attenuated the arsenic hepatotoxicity, a property that could contribute to the therapeutic approaches for chronic liver diseases.

  18. Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis

    International Nuclear Information System (INIS)

    Oxidative stress has been suggested to be a major cause of male reproductive failure. Here, we investigated whether arsenic, which impairs male reproductive functions in rodent models, acts by inducing oxidative stress. Male 8-week-old ICR mice were given drinking water containing 20 or 40 mg/l sodium arsenite with or without 0.75 or 1.5 g/l of the antioxidant ascorbic acid for 5 weeks. The arsenic-treated mice showed decreased epididymidal sperm counts and testicular weights compared to untreated mice. These effects were reversed in mice that were co-treated with ascorbic acid. Similarly, arsenic treatment lowered the activities of testicular 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD, which play important roles in steroidogenesis, and this was reversed by co-treatment with ascorbic acid. The testicles of arsenic-treated mice had decreased glutathione (GSH) levels (which correlate inversely with the degree of cellular oxidative stress) and elevated levels of protein carbonyl (a marker of oxidative damage to tissue proteins). Ascorbic acid co-treatment reversed both of these effects. Thus, ascorbic acid blocks both the adverse effects of arsenic on male reproductive functions and the arsenic-induced testicular oxidative changes. These observations support the notion that arsenic impairs male reproductive function by inducing oxidative stress

  19. ARSENIC INDUCES SUSTAINED IMPAIRMENT OF SKELETAL MUSCLE AND MUSCLE PROGENITOR CELL ULTRASTRUCTURE AND BIOENERGETICS

    Science.gov (United States)

    Fabrisia, Ambrosio; Elke, Brown; Donna, Stolz; Ricardo, Ferrari; Bret, Goodpaster; Bridget, Deasy; Giovanna, Distefano; Alexandra, Roperti; Amin, Cheikhi; Yesica, Garciafigueroa; Aaron, Barchowsky

    2014-01-01

    Over 4 million individuals in the US, and over 140 million individuals worldwide, are exposed daily to arsenic-contaminated drinking water. Human exposures can range from below the current limit of 10 µg/L to over 1 mg/L, with 100 µg/L promoting disease in a large portion of those exposed. Although increased attention has recently been paid to myopathy following arsenic exposure, the pathogenic mechanisms underlying clinical symptoms remain poorly understood. This study tested the hypothesis that arsenic induces lasting muscle mitochondrial dysfunction and impairs metabolism. When compared to non-exposed controls, mice exposed to drinking water containing 100µg/L arsenite for 5 weeks demonstrated impaired muscle function, mitochondrial myopathy, and altered oxygen consumption that were concomitant with increased mitochondrial fusion gene transcription. There was no difference in levels of inorganic arsenic or its mononomethyl- and dimethyl- metabolites between controls and exposed muscles, confirming that arsenic does not accumulate in muscle. Nevertheless, muscle progenitor cells isolated from exposed mice recapitulated the aberrant myofiber phenotype and were more resistant to oxidative stress, generated more reactive oxygen species, and displayed autophagic mitochondrial morphology, as compared to cells isolated from non-exposed mice. These pathological changes from a possible maladaptive oxidative stress response provide insight into declines in muscle functioning caused by exposure to this common environmental contaminant. PMID:24960579

  20. Arsenic-induced morphogenic response in roots of arsenic hyperaccumulator fern Pteris vittata.

    Science.gov (United States)

    Forino, Laura Maria Costantina; Ruffini Castiglione, Monica; Bartoli, Giacomo; Balestri, Mirko; Andreucci, Andrea; Tagliasacchi, Anna Maria

    2012-10-15

    On the assumption that arsenic induces stress morphogenetic responses involved in As tolerance and hyperaccumulation in the Pteris vittata fern, we analyzed the root system of young sporophytes grown in 250, 334, and 500 μM As for five days and for 14 days. Anatomical and histological analyses were performed in plants grown for five days to evaluate the number, position, length and differentiation pattern of root hairs. AgNOR staining, employed to study nucleolus behavior in root apices, showed that arsenic influences nucleolar activity (evaluated by nucleolus size, number and absorbance) in the root meristem. In plants treated with 250 and 334 μM As an acropetal shift of root hair development and an increase in hair length and density were observed, linked to an ectopic pattern of differentiation. The opposite trend was recorded in plants treated with 500 μM As. It is worth noting the presence of living border-like cells, not yet observed in ferns, and their increase following As treatments. Analysis and vitality of border-like cells were surveyed after 14 days of treatments. In conclusion As treatments elicited a stress-induced morphogenic response which, by modifying the differentiation pattern, number and length of root hairs, modulating nucleolar activity and interacting with the rhizosphere by inducing border-like cell production, may adjust the rate of root uptake and its metabolic activity.

  1. Effect of vitamin E supplementation on arsenic induced oxidative stress in goats.

    Science.gov (United States)

    Das, T K; Mani, V; Kaur, H; Kewalramani, N; De, S; Hossain, A; Banerjee, D; Datta, B K

    2012-07-01

    The present study was designed to assess whether supplementation of different levels of vitamin E to long-term arsenic exposed goats affords protection against the oxidative stress caused by the metalloid. Twenty-four crossbred lactating goats were distributed randomly into four groups (control, T(1), T(2) and T(3)) of six in each. The animals in T(1), T(2) and T(3) were given 50 mg/kg DM arsenic daily, while in T(2) and T(3), vitamin E @100 IU and 150 IU/kg DM, respectively, was also supplemented additionally for the period of 12 months. Compared to control, significant (p 63 %), plasma total Ig (22 %) and total antioxidant activity (24 %) was observed in only arsenic treated groups and vitamin E supplementation in both doses produced partial mitigation effect against SOD (23 %, 20 %) and CAT (39 %, 48 %) while complete mitigation against total Ig (16 %, 7 %) and antioxidant activity (10 %, 8 %) was found. Average lymphocyte stimulation index at the end of experiment was (p arsenic exposed groups (1.003 ± 0.01) and significant (p arsenic induced oxidative stress and activities of antioxidant enzymes in goats.

  2. Arsenic-induced genotoxicity in Nile tilapia (Orechromis niloticus); the role of Spirulina platensis extract.

    Science.gov (United States)

    Sayed, Alaa El-Din H; Elbaghdady, Heba Allah M; Zahran, Eman

    2015-12-01

    Arsenic (As) is one of the most relevant environmental global single substance toxicants that have long been regarded as a carcinogenic and genotoxic potential. In this respect, we evaluated the cytogenetic effect of arsenic exposure in Nile tilapia (Oreochromis niloticus), in terms of erythrocyte alteration, apoptosis, and induction of micronuclei. Spirulina platensis (SP) is a filamentous cyanobacterium microalgae with potent dietary phytoantioxidant, anti-inflammatory, and anti-cancerous properties supplementation. The protective role of Spirulina as supplementary feeds was studied in Nile tilapia (O. niloticus) against arsenic-induced cytogenotoxicity. Four groups were assigned as control group (no SP or As), As group (exposed to water-born As in the form of NaAsO2 at 7 ppm), SP1 (SP at 7.5% + As at the same level of exposure), and SP2 (SP at 10% + As at the same level of exposure). As-treated group had a significant increase in all cytogenetic analyses including erythrocyte alteration, apoptosis, and induction of micronuclei after 2 weeks with continuous increase in response after 3 weeks. The combined treatment of Spirulina at two different concentrations of 7.5 and 10% had significantly declined the induction of erythrocyte alteration, apoptosis, and micronuclei formation induced by arsenic intoxication.

  3. Prospective validation of microRNA signatures for detecting pancreatic malignant transformation in endoscopic-ultrasound guided fine-needle aspiration biopsies

    Science.gov (United States)

    Frampton, Adam E.; Krell, Jonathan; Prado, Mireia Mato; Gall, Tamara M.H.; Abbassi-Ghadi, Nima; Del Vecchio Blanco, Giovanna; Funel, Niccola; Giovannetti, Elisa; Castellano, Leandro; Basyouny, Mohamed; Habib, Nagy A.; Kaltsidis, Harry; Vlavianos, Panagiotis; Stebbing, Justin; Jiao, Long R.

    2016-01-01

    Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Novel biomarkers are required to aid treatment decisions and improve patient outcomes. MicroRNAs (miRNAs) are potentially ideal diagnostic biomarkers, as they are stable molecules, and tumour and tissue specific. Results Logistic regression analysis revealed an endoscopic-ultrasound fine-needle aspiration (EUS-FNA) 2-miRNA classifier (miR-21 + miR-155) capable of distinguishing benign from malignant pancreatic lesions with a sensitivity of 81.5% and a specificity of 85.7% (AUC 0.930). Validation FNA cohorts confirmed both miRNAs were overexpressed in malignant disease, while circulating miRNAs performed poorly. Methods Fifty-five patients with a suspicious pancreatic lesion on cross-sectional imaging were evaluated by EUS-FNA. At echo-endoscopy, the first part of the FNA was sent for cytological assessment and the second part was used for total RNA extraction. Candidate miRNAs were selected after careful review of the literature and expression was quantified by qRT-PCR. Validation was performed on an independent cohort of EUS-FNAs, as well as formalin-fixed paraffin embedded (FFPE) and plasma samples. Conclusions We provide further evidence for using miRNAs as diagnostic biomarkers for pancreatic malignancy. We demonstrate the feasibility of using fresh EUS-FNAs to establish miRNA-based signatures unique to pancreatic malignant transformation and the potential to enhance risk stratification and selection for surgery. PMID:27086919

  4. Experimental Study onMalignant Transformation of Human Bronchial Epithelial CellsInduced by Glycidyl Methacrylate and Analysis on its Methylation

    Institute of Scientific and Technical Information of China (English)

    WANG An Na; WANG Quan Kai; YANG Min; HU Jie; DONG Lin; andXU Jian Ning

    2014-01-01

    ObjectiveTo establish the model of human bronchial epithelial cells(16HBE) malignant transformation induced by glycidyl methacrylate(GMA)and define the different methylation genes at different stages. MethodsDNA was extracted at different 16HBE malignant phasesandchanges of genes DNA methylation atdifferent stages weredetectedusing Methylation chip of‘NimbleGen HG18 CpG Promoter Microarray Methylation’. Methylation-specific PCR (MSP) was usedto observe the methylation status ofsome genes, and then compared with the control groups. ResultsThe resultshowed that GMA induced 16HBE morphorlogical transformation at the dose of 8µg/mL, and cell exposed to GMA had 1374 genes in protophase, 825 genes inmetaphase, 1149 genes in anaphase, respectively; 30 genes are all methylation in the 3 stages; 318 genes in protophase but not inmetaphase and anaphase; 272 genes in metaphase but not inprotophase and anaphase; 683 genes in anaphase but not inmetaphase and protophase; 73 genes inprotophase andmetaphase but not in anaphase; 67 genes in protophase and anaphase but not inmetaphase; 59 genes inmetaphase and anaphase but not in protophase. ConclusionThe pattern of DNA methylation could change in the process of 16HBEinduced by GMA.

  5. Papillary Thyroid Cancer in Struma Testis with Malignant Transformation in the Lung Associated with Trisomy 17 Successfully Treated with Total Thyroidectomy and Radioiodine Ablation

    Directory of Open Access Journals (Sweden)

    Shadi Barakat

    2014-11-01

    Full Text Available Background: Struma testis is a rare entity, and there are only few reports on the malignant transformation of a testicular teratoma to papillary thyroid carcinoma in the literature. In this report, we describe the malignant transformation of struma testis with distant lung metastasis associated with trisomy 17 and a coexisting papillary microcarcinoma in the thyroid. Case Report: A 56-year-old man presented after a left orchiectomy for an undescended left testicle. Pathologic examination identified a monodermal teratoma composed of thyroid parenchyma and associated with a 1.7-cm papillary thyroid carcinoma. Further evaluation showed a pulmonary mass on a chest CT scan. Total thyroidectomy revealed a 0.5-mm focus of papillary thyroid cancer, and removal of the lung mass confirmed metastatic papillary thyroid cancer. Array-comparative genomic hybridization of both tumors showed trisomy 17 in the struma testes and the lung metastasis. The patient responded well to radioactive iodine ablation and has no evidence of cancer 3 years later. Conclusion: To our knowledge, this is the first case of papillary thyroid cancer in struma testes metastatic to the lung. It highlights the difficulties in treating these patients. Surgery to remove cancer foci, followed by radioactive iodine ablation, resulted in an excellent response in our patient. Interestingly, trisomy 17, which has so far been observed only in noninvasive thyroid nodules, was associated with pulmonary metastasis in our patient.

  6. Clinical trial analyzing the impact of continuous defocused CO2 laser vaporisation on the malignant transformation of erosive oral lichen planus.

    Science.gov (United States)

    Mücke, Thomas; Gentz, Irina; Kanatas, Anastasios; Ritschl, Lucas M; Mitchell, David A; Wolff, Klaus-Dietrich; Deppe, Herbert

    2015-10-01

    The erosive oral lichen planus (OLP) represents a management challenge to the clinician and can have debilitating consequences to patients' quality of life. The aims of this work were to determine the incidence of malignant transformation to squamous cell carcinoma (SCC) in patients undergoing traditional symptomatic treatments (oral salve containing lidocaine hydrochloride or systemic diclofenac) compared to patients that were managed with a defocused continuous CO2 laser beam. A total of 171 patients with histologically confirmed erosive OLP were included into this study. After treatment, patients were assessed until completion of wound healing, at least every 3-6 months for the first 2 years, and every 6-12 months thereafter. The study included 87 women (50.9%) and 84 men (49.1%). A total of 103 patients (60.2%) underwent symptomatic conservative treatment, and 68 patients (39.8%) underwent continuous defocused CO2 laser treatments. SCC developed in 16 patients (9.4%), 2 patients (2.9%) after continuous defocused CO2 laser treatment and 14 patients (13.6%) with symptomatic treatment only. This study provides insight into the potential impact of the CO2 laser in the management of patients with erosive OLP and the influence on the recurrence rate of erosive OLP, as well as malignant transformation to oral SCC.

  7. FOXM1 upregulation is an early event in human squamous cell carcinoma and it is enhanced by nicotine during malignant transformation.

    Directory of Open Access Journals (Sweden)

    Emilios Gemenetzidis

    Full Text Available BACKGROUND: Cancer associated with smoking and drinking remains a serious health problem worldwide. The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC. METHODOLOGY/PRINCIPAL FINDINGS: FOXM1 mRNA and protein expressions were investigated in four independent cohorts (total 75 patients consisting of normal, premalignant and HNSCC tissues and cells using quantitative PCR (qPCR, expression microarray, immunohistochemistry and immunocytochemistry. Effect of putative oral carcinogens on FOXM1 transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblotting and short-hairpin RNA interference. Genome-wide single nucleotide polymorphism (SNP array was used to 'trace' the genomic instability signature pattern in 8 clonal lines of FOXM1-induced malignant human oral keratinocytes. Furthermore, acute FOXM1 upregulation in primary oral keratinocytes directly induced genomic instability. We have shown for the first time that overexpression of FOXM1 precedes HNSCC malignancy. Screening putative carcinogens in human oral keratinocytes surprisingly showed that nicotine, which is not perceived to be a human carcinogen, directly induced FOXM1 mRNA, protein stabilisation and transcriptional activity at concentrations relevant to tobacco chewers. Importantly, nicotine also augmented FOXM1-induced transformation of human oral keratinocytes. A centrosomal protein CEP55 and a DNA helicase/putative stem cell marker HELLS, both located within a consensus loci (10q23, were found to be novel targets of FOXM1 and their expression correlated tightly with HNSCC progression. CONCLUSIONS/SIGNIFICANCE: This study cautions the potential co-carcinogenic effect of nicotine in tobacco replacement therapies. We hypothesise that

  8. Malignant Transformation of Endometrioma in a Woman with a History of Ovulation Induction and In Vitro Fertilization

    Directory of Open Access Journals (Sweden)

    Terri L. Woodard

    2012-01-01

    Full Text Available Our aim is to document a case of endometrioid adenocarcinoma of the ovary found in an endometriotic cyst that was suspected on pelvic ultrasound in a patient with polycystic ovary syndrome, normal Ca125, and a recent history of ovulation induction for IVF. She underwent an exploratory laparotomy with left salpingo-oophorectomy and omental biopsies followed by reexploration, complete staging, and modified radical abdominal hysterectomy and right salpingo-oophorectomy. An endometrioma described as suspicious for malignancy by an experienced ultrasound examiner should prompt immediate referral to a gynecological oncologist irrespective of Ca125 levels especially in women with a history of ovulation induction and endometriosis.

  9. Arsenic induces apoptosis by the lysosomal-mitochondrial pathway in INS-1 cells.

    Science.gov (United States)

    Pan, Xiao; Jiang, Liping; Zhong, Laifu; Geng, Chengyan; Jia, Li; Liu, Shuang; Guan, Huai; Yang, Guang; Yao, Xiaofeng; Piao, Fengyuan; Sun, Xiance

    2016-02-01

    Recently, long term arsenic exposure was considered to be associated with an increased risk of diabetes mellitus. While a relation of cause-and-effect between apoptosis of pancreatic β-cells and arsenic exposure, the precise mechanisms of these events remains unclear. The aim of this study was to explore arsenic-induced pancreatic β-cell apoptosis and the mechanisms of through the possible link between lysosomal and the mitochondrial apoptotic pathway. After exposure to 10 μM of arsenic, the reactive oxygen species (ROS) level was significantly increased at 12 h, while the mitochondrial membrane potential was reduced at 24 h and the lysosomal membrane integrity was disrupted at 48 h. A significant increase in protein expression for cytochrome c was also observed using Western blot analysis after exposure to arsenic for 48 h. To further demonstrate that arsenic reduced the lysosomal membrane integrity, cells pretreated with NH4 Cl and exposed to arsenic harbored a lower fluorescence increase than cells that were only exposed to arsenic. In addition, apoptosis was mesured using Hoechst 33342/PI dual staining by microscopy and annexin V-FITC/propidium iodide dual staining by flow cytometry. The results show an increased uptake of the arsenic dose and the cells changed from dark blue to light blue, karyopyknosis, nuclear chromatin condensation, side set or fracture, and a correlation was found between the number of apoptotic cells and arsenic dose. The result of present study suggest that arsenic may induce pancreatic β-cell apoptosis through activation of the lysosome-mitochondrial pathway.

  10. Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling.

    Science.gov (United States)

    Li, S G; Xu, S Z; Niu, Q; Ding, Y S; Pang, L J; Ma, R L; Jing, M X; Wang, K; Ma, X M; Feng, G L; Liu, J M; Zhang, X F; Xiang, H L; Li, F

    2016-05-01

    This study aims to investigate the mechanisms involved in the action of lutein (LU) alleviating arsenic-induced reproductive toxicity using mice model. Forty male Kunming mice were received following treatments by gavage: normal saline solution (control), arsenic trioxide (ATO; 5 mg/kg/day), LU (40 mg/kg/day), and ATO + LU (5 mg/kg/day + 40 mg/kg/day). At the end, the mice were killed by cervical dislocation and weighed. Pathological examination was done on the testis. The biomedical parameters including superoxide dismutase (SOD), glutathione (GSH), total antioxidative capability, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and reproductive indexes were analyzed. The messenger RNA (mRNA) and protein expression of Nrf2, heme oxygenase 1 (HO-1), glutathione S-transferase (GST), nicotinamide adenine dinucleotide phosphate dehydrogenase, quinone 1 (NQO1) in testis were detected by real-time polymerase chain reaction and Western blot. We found that there was a decrease in sperm count; testis somatic index; the activities of SOD, GSH, total antioxidative capacity (p treated mice, while there was an increase in the levels of sperm abnormalities, MDA, and 8-OHdG than control (p treated with ATO + LU showed recovery of the measured parameters between those of ATO or saline-treated group. The antagonized interaction between ATO and LU was statistically significant (p treated with ATO + LU also showed greater mRNA expression of Nrf2, HO-1, NQO1, and GST than ATO or saline-treated groups. These findings suggest that LU alleviates reproductive toxicity induced by arsenic in male mice via Nrf2 signaling, which implicates a possible mechanism of LU in preventing the reproductive injury, and elucidates that consuming the rich plant sources of LU will alleviate the reproductive toxicity induced by chemicals.

  11. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja; Roy, Ram Vinod; Hitron, John Andrew; Wang, Lei [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Kim, Donghern; Dai, Jin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Asha, Padmaja [National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Cochin (India); Zhang, Zhuo [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Wang, Yitao [State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau (China); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States)

    2014-12-01

    Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5 μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promoter activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. - Highlights: • Luteolin inhibited Cr(VI)-induced oxidative stress. • Luteolin inhibited chronic Cr(VI)-induced malignant transformation.

  12. Interleukin-8 (IL-8) over-production and autocrine cell activation are key factors in monomethylarsonous acid [MMA(III)]-induced malignant transformation of urothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Escudero-Lourdes, C., E-mail: cescuder@uaslp.mx [Centro de Investigación y Estudios de Posgrado (CIEP), Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí (Mexico); Wu, T.; Camarillo, J.M.; Gandolfi, A.J. [Department of Pharmacology and Toxicology College of Pharmacy, University of Arizona. Tucson, AZ (United States)

    2012-01-01

    The association between chronic human exposure to arsenicals and bladder cancer development is well recognized; however, the underlying molecular mechanisms have not been fully determined. We propose that inflammatory responses can play a pathogenic role in arsenic-related bladder carcinogenesis. In previous studies, it was demonstrated that chronic exposure to 50 nM monomethylarsenous acid [MMA(III)] leads to malignant transformation of an immortalized model of urothelial cells (UROtsa), with only 3 mo of exposure necessary to trigger the transformation-related changes. In the three-month window of exposure, the cells over-expressed pro-inflammatory cytokines (IL-1β, IL-6 and IL-8), consistent with the sustained activation of NFKβ and AP1/c-jun, ERK2, and STAT3. IL-8 was over-expressed within hours after exposure to MMA(III), and sustained over-expression was observed during chronic exposure. In this study, we profiled IL-8 expression in UROtsa cells exposed to 50 nM MMA(III) for 1 to 5 mo. IL-8 expression was increased mainly in cells after 3 mo MMA(III) exposure, and its production was also found increased in tumors derived from these cells after heterotransplantation in SCID mice. UROtsa cells do express both receptors, CXCR1 and CXCR2, suggesting that autocrine cell activation could be important in cell transformation. Supporting this observation and consistent with IL-8 over-expression, CXCR1 internalization was significantly increased after three months of exposure to MMA(III). The expression of MMP-9, cyclin D1, bcl-2, and VGEF was significantly increased in cells exposed to MMA(III) for 3 mo, but these mitogen-activated kinases were significantly decreased after IL-8 gene silencing, together with a decrease in cell proliferation rate and in anchorage-independent colony formation. These results suggest a relevant role of IL-8 in MMA(III)-induced UROtsa cell transformation. -- Highlights: ► IL-8 is over-expressed in human MMA(III)-exposed urothelial

  13. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lingzhi; Qiu, Ping; Chen, Bailing; Lu, Yongju; Wu, Kai; Thakur, Chitra; Chang, Qingshan; Sun, Jiaying; Chen, Fei, E-mail: fchen@wayne.edu

    2014-05-01

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H{sub 2}O{sub 2}, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H{sub 2}O{sub 2}. Furthermore, both arsenic and H{sub 2}O{sub 2} were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As{sup 3+}) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As{sup 3+}-induced EZH2 phosphorylation. • As{sup 3+} induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm.

  14. Regulation of the pituitary tumor transforming gene by insulin-like-growth factor-I and insulin differs between malignant and non-neoplastic astrocytes

    International Nuclear Information System (INIS)

    The reasons for overexpression of the oncogene pituitary tumor transforming gene (PTTG) in tumors are still not fully understood. A possible influence of the insulin-like growth factor I (Igf-I) may be of interest, since enhanced Igf-I signalling was reported in various human tumors. We examined the influence of Igf-I and insulin on PTTG expression in human astrocytoma cells in comparison to proliferating non-neoplastic rat embryonal astrocytes. PTTG mRNA expression and protein levels were increased in malignant astrocytes treated with Igf-I or insulin, whereas in rat embryonic astrocytes PTTG expression and protein levels increased only when cells were exposed to Igf-I. Enhanced transcription did not occur after treatment with inhibitors of phosphoinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), blocking the two basic signalling pathways of Igf-I and insulin. In addition to this transcriptional regulation, both kinases directly bind to PTTG, suggesting a second regulatory route by phosphorylation. However, the interaction of endogenous PTTG with MAPK and PI3K, as well as PTTG phosphorylation were independent from Igf-I or insulin. The latter results were also found in human testis, which contains high PTTG levels as well as in nonneoplastic astrocytes. This suggest, that PI3K and MAPK signalling is involved in PTTG regulation not only in malignant astrocytomas but also in non-tumorous cells

  15. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    International Nuclear Information System (INIS)

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited Emax of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  16. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

    2014-10-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  17. Upregulation of miR-27a contributes to the malignant transformation of human bronchial epithelial cells induced by SV40 small T antigen.

    Science.gov (United States)

    Wang, Q; Li, D-C; Li, Z-F; Liu, C-X; Xiao, Y-M; Zhang, B; Li, X-D; Zhao, J; Chen, L-P; Xing, X-M; Tang, S-F; Lin, Y-C; Lai, Y-D; Yang, P; Zeng, J-L; Xiao, Q; Zeng, X-W; Lin, Z-N; Zhuang, Z-X; Zhuang, S-M; Chen, W

    2011-09-01

    The introduction of the Simian virus 40 (SV40) early region, the telomerase catalytic subunit (hTERT) and an oncogenic allele of H-Ras directly transforms primary human cells. SV40 small T antigen (ST), which forms a complex with protein phosphatase 2A (PP2A) and inhibits PP2A activity, is believed to have a critical role in the malignant transformation of human cells. Recent evidence has shown that aberrant microRNA (miRNA) expression patterns are correlated with cancer development. Here, we identified miR-27a as a differentially expressed miRNA in SV40 ST-expressing cells. miR-27a is upregulated in SV40 ST-transformed human bronchial epithelial cells (HBERST). Suppression of miR-27a expression in HBERST cells or lung cancer cell lines (NCI-H226 and SK-MES-1) that exhibited high levels of miR-27a expression lead to cell growth arrested in the G(0)-G(1) phase. In addition, suppression of miR-27a in HBERST cells attenuated the capacity of such cells to grow in an anchorage-independent manner. We also found that suppression of the PP2A B56γ expression resulted in upregulation of miR-27a similar to that achieved by the introduction of ST, indicating that dysregulation of miR-27a expression in ST-expressing cells was mediated by the ST-PP2A interaction. Moreover, we discovered that Fbxw7 gene encoding F-box/WD repeat-containing protein 7 was a potential miR-27a target validated by dual-luciferase reporter system analysis. The inverse correlation between miR-27a expression levels and Fbxw7 protein expression was further confirmed in both cell models and human tumor samples. Fbxw7 regulates cell-cycle progression through the ubiquitin-dependent proteolysis of a set of substrates, including c-Myc, c-Jun, cyclin E1 and Notch 1. Thus, promotion of cell growth arising from the suppression of Fbxw7 by miR-27a overexpression might be responsible for the viral oncoprotein ST-induced malignant transformation. These observations demonstrate that miR-27a functions as an oncogene

  18. Therapeutic effects of Moringa oleifera on arsenic-induced toxicity in rats.

    Science.gov (United States)

    Gupta, Richa; Kannan, Gurusamy M; Sharma, Mamta; S Flora, Swaran J

    2005-11-01

    the seed powder of M. oleifera has significant role in protecting animals from arsenic-induced oxidative stress and in the depletion of arsenic concentration. Further studies thus can be recommended for determining the effect of co-administrating seed powder of M. oleifera during chelation therapy with a thiol chelator. PMID:21783626

  19. EFFECTS OF ADDROGRAPHIS PANICULATA (NEES. ON ARSENIC- INDUCED ALTERED GLUCOSE HOMEOSTASIS AND OXIDATIVE IMPAIRMENT IN PANCREAS OF SWISS MICE

    Directory of Open Access Journals (Sweden)

    MANDAVA V. RAO

    2007-01-01

    Full Text Available The effect of Andrographis paniculata (Nees. on arsenic-induced changes in biochemical and cellular antioxident sytem was studies in adult female mice. Daily oral administration of arsenic trioxide (0.5 and 1.0mg/kg b.w for 30days induced a significant increase in blood glucose level which was associated with impaired glucose tolrence. Arsenic treatment also resulted in elevated level panreatic tissue specific makers such as activities of amylase and lipase in serum indicating pancreatic dysfunction. Interestingly, this biochemical dysfuntion was accompanied by a marked dose related enchancement of lipid peroxidation indicating significant induction of oxidative damage. Additional evidence such as deletion in reduced gluatathione levels and alterations in enzymic antioxidant defences like superoxide dismutase, catalase and glutathione peroxidase in pancreas suggested induction of oxidative stress. Concomitant administration of Adrographis paniculata (50 mg/kg b.w. with arsenic significant restored all these parameters. These results suggest that Adrographis paniculata is capable to reducing arsenic-induce cellular oxidative and inflammatory changes in pancreas.

  20. Feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1 are involved in arsenite-induced cell malignant transformation.

    Directory of Open Access Journals (Sweden)

    Lu Shen

    /c-Jun and the feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1, respectively, are involved in arsenite-induced malignant transformation of HELF cells.

  1. Integration of HPV6 and downregulation of AKR1C3 expression mark malignant transformation in a patient with juvenile-onset laryngeal papillomatosis.

    Science.gov (United States)

    Huebbers, Christian Ulrich; Preuss, Simon Florian; Kolligs, Jutta; Vent, Julia; Stenner, Markus; Wieland, Ulrike; Silling, Steffi; Drebber, Uta; Speel, Ernst-Jan M; Klussmann, Jens Peter

    2013-01-01

    Juvenile-onset recurrent respiratory papillomatosis (RRP) is associated with low risk human papillomavirus (HPV) types 6 and 11. Malignant transformation has been reported solely for HPV11-associated RRP in 2-4% of all RRP-cases, but not for HPV6. The molecular mechanisms in the carcinogenesis of low risk HPV-associated cancers are to date unknown. We report of a female patient, who presented with a laryngeal carcinoma at the age of 24 years. She had a history of juvenile-onset RRP with an onset at the age of three and subsequently several hundred surgical interventions due to multiple recurrences of RRP. Polymerase chain reaction (PCR) or bead-based hybridization followed by direct sequencing identified HPV6 in tissue sections of previous papilloma and the carcinoma. P16(INK4A), p53 and pRb immunostainings were negative in all lesions. HPV6 specific fluorescence in situ hybridization (FISH) revealed nuclear staining suggesting episomal virus in the papilloma and a single integration site in the carcinoma. Integration-specific amplification of papillomavirus oncogene transcripts PCR (APOT-PCR) showed integration in the aldo-keto reductase 1C3 gene (AKR1C3) on chromosome 10p15.1. ArrayCGH detected loss of the other gene copy as part of a deletion at 10p14-p15.2. Western blot analysis and immunohistochemistry of the protein AKR1C3 showed a marked reduction of its expression in the carcinoma. In conclusion, we identified a novel molecular mechanism underlying a first case of HPV6-associated laryngeal carcinoma in juvenile-onset RRP, i.e. that HPV6 integration in the AKR1C3 gene resulted in loss of its expression. Alterations of AKR1C gene expression have previously been implicated in the tumorigenesis of other (HPV-related) malignancies. PMID:23437342

  2. Integration of HPV6 and downregulation of AKR1C3 expression mark malignant transformation in a patient with juvenile-onset laryngeal papillomatosis.

    Directory of Open Access Journals (Sweden)

    Christian Ulrich Huebbers

    Full Text Available Juvenile-onset recurrent respiratory papillomatosis (RRP is associated with low risk human papillomavirus (HPV types 6 and 11. Malignant transformation has been reported solely for HPV11-associated RRP in 2-4% of all RRP-cases, but not for HPV6. The molecular mechanisms in the carcinogenesis of low risk HPV-associated cancers are to date unknown. We report of a female patient, who presented with a laryngeal carcinoma at the age of 24 years. She had a history of juvenile-onset RRP with an onset at the age of three and subsequently several hundred surgical interventions due to multiple recurrences of RRP. Polymerase chain reaction (PCR or bead-based hybridization followed by direct sequencing identified HPV6 in tissue sections of previous papilloma and the carcinoma. P16(INK4A, p53 and pRb immunostainings were negative in all lesions. HPV6 specific fluorescence in situ hybridization (FISH revealed nuclear staining suggesting episomal virus in the papilloma and a single integration site in the carcinoma. Integration-specific amplification of papillomavirus oncogene transcripts PCR (APOT-PCR showed integration in the aldo-keto reductase 1C3 gene (AKR1C3 on chromosome 10p15.1. ArrayCGH detected loss of the other gene copy as part of a deletion at 10p14-p15.2. Western blot analysis and immunohistochemistry of the protein AKR1C3 showed a marked reduction of its expression in the carcinoma. In conclusion, we identified a novel molecular mechanism underlying a first case of HPV6-associated laryngeal carcinoma in juvenile-onset RRP, i.e. that HPV6 integration in the AKR1C3 gene resulted in loss of its expression. Alterations of AKR1C gene expression have previously been implicated in the tumorigenesis of other (HPV-related malignancies.

  3. TRANSFORMATION

    Energy Technology Data Exchange (ETDEWEB)

    LACKS,S.A.

    2003-10-09

    Transformation, which alters the genetic makeup of an individual, is a concept that intrigues the human imagination. In Streptococcus pneumoniae such transformation was first demonstrated. Perhaps our fascination with genetics derived from our ancestors observing their own progeny, with its retention and assortment of parental traits, but such interest must have been accelerated after the dawn of agriculture. It was in pea plants that Gregor Mendel in the late 1800s examined inherited traits and found them to be determined by physical elements, or genes, passed from parents to progeny. In our day, the material basis of these genetic determinants was revealed to be DNA by the lowly bacteria, in particular, the pneumococcus. For this species, transformation by free DNA is a sexual process that enables cells to sport new combinations of genes and traits. Genetic transformation of the type found in S. pneumoniae occurs naturally in many species of bacteria (70), but, initially only a few other transformable species were found, namely, Haemophilus influenzae, Neisseria meningitides, Neisseria gonorrheae, and Bacillus subtilis (96). Natural transformation, which requires a set of genes evolved for the purpose, contrasts with artificial transformation, which is accomplished by shocking cells either electrically, as in electroporation, or by ionic and temperature shifts. Although such artificial treatments can introduce very small amounts of DNA into virtually any type of cell, the amounts introduced by natural transformation are a million-fold greater, and S. pneumoniae can take up as much as 10% of its cellular DNA content (40).

  4. Transformation

    DEFF Research Database (Denmark)

    Peters, Terri

    2011-01-01

    Artiklen diskuterer ordet "transformation" med udgangspunkt i dels hvorledes ordet bruges i arkitektfaglig terminologi og dels med fokus på ordets potentielle indhold og egnethed i samme teminologi.......Artiklen diskuterer ordet "transformation" med udgangspunkt i dels hvorledes ordet bruges i arkitektfaglig terminologi og dels med fokus på ordets potentielle indhold og egnethed i samme teminologi....

  5. Fourier transform infrared microspectroscopy as a diagnostic tool for distinguishing between normal and malignant human gastric tissue

    Indian Academy of Sciences (India)

    Abasalt Hosseinzadeh Colagar; Mohammad Javad Chaichi; Tahereh Khadjvand

    2011-09-01

    Fourier transform infrared (FTIR) microspectroscopy can be considered to be a fast and non-invasive tool for distinguishing between normal and cancerous cells and tissues without the need for laborious and invasive sampling procedures. Gastric samples from four patients (age, 65±2 years) were analysed. Samples were obtained from the organs removed during gastrectomy and then classified as normal or cancerous. Classification was based on histopathological examinations at our institution. Formalin-fixed sections of gastric tissue were analysed by FTIR-microspectroscopy. To characterize differences between sections of normal and cancerous tissue, specific regions of the spectra were analysed to study variations in the levels of metabolites. To distinguish between two conditions (normal and cancerous), changes in the relative intensity of bands in the range 600–4000 cm−1 were analysed. A FTIR spectral map of the bands in the region 2800–3100 cm–1 and 900–1800 cm–1 were created to analyse pathological changes in tissues. The limited data available showed that normal gastric tissue had stronger absorption than cancerous tissue over a wide region in the four patients. There was a significant decrease in total biomolecular components for cancerous tissue compared with normal tissue.

  6. 卵巢成熟性囊性畸胎瘤癌变临床病理分析%Ovarian mature cystic teratoma with malignant transformation: a clinical and pathological study of four cases

    Institute of Scientific and Technical Information of China (English)

    黄家应

    2012-01-01

    目的 探讨卵巢成熟性囊性畸胎瘤癌变的临床病理特征.方法 对4例成熟性囊性畸胎瘤癌变患临床资料、HE切片及免疫组化结果进行观察分析.结果 4例成熟性囊性畸胎瘤癌变成分均为鳞状细胞癌.结论 卵巢成熟性囊性畸胎瘤癌变成分最常见为鳞状细胞癌,病理诊断需与卵巢原发性及继发性鳞状细胞癌、腺癌等进行鉴别.%Objective To investigate the clinicopathologic features of malignant transformation in mature cystic teratomas of o-vary. Methods 4 cases of mature cystic teratomas with malignant transformation were clinically reviewed,the histological and immuno-histochemical results were also analyzed. Results The secondary development of malignancies of 4 cases was all squamous-cell carcinoma. Conclusion Malignant transformation of mature cystic teratomas is rare, with squamous-cell carcinoma being the most common type,and should be considered in the differential diagnosis of primary or secondary squmaous-cell carcinoma,adenocarcinoma,and so on.

  7. TRANSFORMER

    Science.gov (United States)

    Baker, W.R.

    1959-08-25

    Transformers of a type adapted for use with extreme high power vacuum tubes where current requirements may be of the order of 2,000 to 200,000 amperes are described. The transformer casing has the form of a re-entrant section being extended through an opening in one end of the cylinder to form a coaxial terminal arrangement. A toroidal multi-turn primary winding is disposed within the casing in coaxial relationship therein. In a second embodiment, means are provided for forming the casing as a multi-turn secondary. The transformer is characterized by minimized resistance heating, minimized external magnetic flux, and an economical construction.

  8. Arsenic-induced cutaneous hyperplastic lesions are associated with the dysregulation of Yap, a Hippo signaling-related protein

    Energy Technology Data Exchange (ETDEWEB)

    Li, Changzhao; Srivastava, Ritesh K.; Elmets, Craig A.; Afaq, Farrukh; Athar, Mohammad, E-mail: mathar@uab.edu

    2013-09-06

    Highlights: •Arsenic activates canonical Hippo signaling pathway and up-regulates αCatenin in the skin. •Arsenic activates transcriptional activity of Yap by its nuclear translocation. •Yap is involved in the disruption of tight/adherens junctions in arsenic-exposed animals. -- Abstract: Arsenic exposure in humans causes a number of toxic manifestations in the skin including cutaneous neoplasm. However, the mechanism of these alterations remains elusive. Here, we provide novel observations that arsenic induced Hippo signaling pathway in the murine skin. This pathway plays crucial roles in determining organ size during the embryonic development and if aberrantly activated in adults, contributes to the pathogenesis of epithelial neoplasm. Arsenic treatment enhanced phosphorylation-dependent activation of LATS1 kinase and other Hippo signaling regulatory proteins Sav1 and MOB1. Phospho-LATS kinase is known to catalyze the inactivation of a transcriptional co-activator, Yap. However, in arsenic-treated epidermis, we did not observed its inactivation. Thus, as expected, unphosphorylated-Yap was translocated to the nucleus in arsenic-treated epidermis. Yap by binding to the transcription factors TEADs induces transcription of its target genes. Consistently, an up-regulation of Yap-dependent target genes Cyr61, Gli2, Ankrd1 and Ctgf was observed in the skin of arsenic-treated mice. Phosphorylated Yap is important in regulating tight and adherens junctions through its binding to αCatenin. We found disruption of these junctions in the arsenic-treated mouse skin despite an increase in αCatenin. These data provide evidence that arsenic-induced canonical Hippo signaling pathway and Yap-mediated disruption of tight and adherens junctions are independently regulated. These effects together may contribute to the carcinogenic effects of arsenic in the skin.

  9. Activation of Epidermal Growth Factor Receptor/p38/Hypoxia-inducible Factor-1α Is Pivotal for Angiogenesis and Tumorigenesis of Malignantly Transformed Cells Induced by Hexavalent Chromium.

    Science.gov (United States)

    Kim, Donghern; Dai, Jin; Park, Youn-Hee; Fai, Leonard Yenwong; Wang, Lei; Pratheeshkumar, Poyil; Son, Young-Ok; Kondo, Kazuya; Xu, Mei; Luo, Jia; Shi, Xianglin; Zhang, Zhuo

    2016-07-29

    Hexavalent chromium (Cr(VI))-containing compounds are well established environmental carcinogens. Most mechanistic investigations of Cr(VI)-induced carcinogenesis focus on oxidative stress and various cellular responses, leading to malignant cell transformation or the first stage of metal-induced carcinogenesis. The development of malignantly transformed cells into tumors that require angiogenesis is the second stage. This study focuses on the second stage, in particular, the role of EGF receptor (EGFR) signaling in angiogenesis and tumorigenesis of Cr(VI)-transformed cells. Our preliminary studies have shown that EGFR is constitutively activated in Cr(VI)-transformed cells, in lung tissue from Cr(VI)-exposed animals, and in lung tumor tissue from a non-smoking worker occupationally exposed to Cr(VI) for 19 years. Using in vitro and in vivo models, the present study has investigated the role of EGFR in angiogenesis of Cr(VI)-transformed cells. The results show that Cr(VI)-transformed cells are angiogenic. Hypoxia-inducible factor-1α, pro-angiogenic protein matrix metalloproteinase 1, and VEGF are all highly expressed in Cr(VI)-transformed cells, in lung tissue from animals exposed to Cr(VI), and in lung tumor tissue from a non-smoking worker occupationally exposed to Cr(VI) for 19 years. p38 MAPK is also activated in Cr(VI)-transformed cells and in human lung tumor tissue. Inhibition of EGFR reduces p38 MAPK, resulting in decreased expression of hypoxia-inducible factor-1α, metalloproteinase 1, and VEGF, leading to suppressions of angiogenesis and tumorigenesis. Overall, the present study has demonstrated that EGFR plays an important role in angiogenesis and tumorigenesis of Cr(VI)-transformed cells. PMID:27226640

  10. The prognostic significance of indoleamine-2,3-dioxygenase and the receptors for transforming growth factor β and interferon γ in metastatic lymph nodes in malignant melanoma.

    Science.gov (United States)

    Pelak, Maciej J; Śnietura, Mirosław; Lange, Dariusz; Nikiel, Barbara; Pecka, Katarzyna M

    2015-12-01

    We analyzed the prognostic significance of indoleamine-2,3-dioxygenase (IDO) and type 1 receptors for transforming growth factor beta (TGF-βR1) and interferon gamma (IFN-γR1) in resected nodal metastases of 48 malignant melanoma patients. In 32 cases the corresponding skin tumors were available. We used immunohistochemical (IHC) staining which was assessed by pathologists and by a computer-aided algorithm that yielded quantitative results, both absolute and relative. We correlated the results with the patient outcome. We identified absolute computer-assessed IDO levels as positively correlated with increased risk of death in a multivariate model (HR = 1.02; 95% CI: 1.002-1.04; p = 0.03). In univariate analysis, patients with IDO levels below the median had a better overall survival time (30.3 vs. 17.5 months; p = 0.03). TGF-βR1 and IFN-γR1 expression was modestly correlated (R = 0.34; p lt; 0.05) and TGF-βR1 expression was lower in lymph nodes than in matched primary skin tumors (Z = 2.87; p = 0.004). The pathologists' and computer-aided IHC assessment demonstrated high correlation levels (R = 0.61, R = 0.74 and R = 0.88 for IDO, TGF-βR1 and IFN-γR1, respectively). Indoleamine-2,3-dioxygenase is prognostic for the patient outcome in melanoma with nodal involvement and should be investigated prospectively for its predictive significance. IHC assessment by computer-aided methods is recommended as its gives IHC more objectivity and reproducibility. ecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together. PMID:27003769

  11. Arsenite evokes IL-6 secretion, autocrine regulation of STAT3 signaling, and miR-21 expression, processes involved in the EMT and malignant transformation of human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Fei; Xu, Yuan [Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); Ling, Min [Jiangsu Center for Disease Control and Prevention, Nanjing 211166, Jiangsu (China); Zhao, Yue; Xu, Wenchao [Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); Liang, Xiao [Mental Health Center of Xuhui-CDC, Shanghai 200232 (China); Jiang, Rongrong; Wang, Bairu [Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); Bian, Qian [Jiangsu Center for Disease Control and Prevention, Nanjing 211166, Jiangsu (China); Liu, Qizhan, E-mail: drqzliu@hotmail.com [Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China)

    2013-11-15

    Arsenite is an established human carcinogen, and arsenite-induced inflammation contributes to malignant transformation of cells, but the molecular mechanisms by which cancers are produced remain to be established. The present results showed that, evoked by arsenite, secretion of interleukin-6 (IL-6), a pro-inflammatory cytokine, led to the activation of STAT3, a transcription activator, and to increased levels of a microRNA, miR-21. Blocking IL-6 with anti-IL-6 antibody and inhibiting STAT3 activation reduced miR-21 expression. For human bronchial epithelial cells, cultured in the presence of anti-IL-6 antibody for 3 days, the arsenite-induced EMT and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates miR-21in an autocrine manner, contributes to the EMT induced by arsenite. These data define a link from inflammation to EMT in the arsenite-induced malignant transformation of HBE cells. This link, mediated through miRNAs, establishes a mechanism for arsenite-induced lung carcinogenesis. - Highlights: • Arsenite evokes IL-6 secretion. • IL-6 autocrine mediates STAT3 signaling and up-regulates miR-21expression. • Inflammation is involved in arsenite-induced EMT.

  12. Arsenite evokes IL-6 secretion, autocrine regulation of STAT3 signaling, and miR-21 expression, processes involved in the EMT and malignant transformation of human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Arsenite is an established human carcinogen, and arsenite-induced inflammation contributes to malignant transformation of cells, but the molecular mechanisms by which cancers are produced remain to be established. The present results showed that, evoked by arsenite, secretion of interleukin-6 (IL-6), a pro-inflammatory cytokine, led to the activation of STAT3, a transcription activator, and to increased levels of a microRNA, miR-21. Blocking IL-6 with anti-IL-6 antibody and inhibiting STAT3 activation reduced miR-21 expression. For human bronchial epithelial cells, cultured in the presence of anti-IL-6 antibody for 3 days, the arsenite-induced EMT and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates miR-21in an autocrine manner, contributes to the EMT induced by arsenite. These data define a link from inflammation to EMT in the arsenite-induced malignant transformation of HBE cells. This link, mediated through miRNAs, establishes a mechanism for arsenite-induced lung carcinogenesis. - Highlights: • Arsenite evokes IL-6 secretion. • IL-6 autocrine mediates STAT3 signaling and up-regulates miR-21expression. • Inflammation is involved in arsenite-induced EMT

  13. A cross sectional study of anemia and iron deficiency as risk factors for arsenic-induced skin lesions in Bangladeshi women

    OpenAIRE

    Kile, Molly L.; Faraj, Joycelyn M.; Ronnenberg, Alayne G.; Quamruzzaman, Quazi; Rahman, Mahmudar; Mostofa, Golam; Afroz, Sakila; Christiani, David C.

    2016-01-01

    Background In the Ganges Delta, chronic arsenic poisoning is a health concern affecting millions of people who rely on groundwater as their potable water source. The prevalence of anemia is also high in this region, particularly among women. Moreover, arsenic is known to affect heme synthesis and erythrocytes and the risk of arsenic-induced skin lesions appears to differ by sex. Methods We conducted a case-control study in 147 arsenic-exposed Bangladeshi women to assess the association betwee...

  14. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

  15. Arsenic induced toxicity in broiler chicks and its alleviation with ascorbic acid: a toxico-patho-biochemical study

    Science.gov (United States)

    Khan, Ahrar; Sharaf, Rabia; Khan, Muhammad Zargham; Saleemi, Muhammad Kashif; Mahmood, Fazal

    2013-01-01

    To find out toxico-pathological effects of arsenic (As) and ameliorating effect of ascorbic acid (Vit C), broilers birds were administered 50 and 250 mg/kg arsenic and Vit C, respectively alone/in combination. As-treated birds exhibited severe signs of toxicity such as dullness, depression, increased thirst, open mouth breathing and watery diarrhea. All these signs were partially ameliorated with the treatment of Vit C. As-treated birds showed a significant decrease in serum total proteins while serum enzymes, urea and creatinine were significantly increased. Alkaline phosphatase and lactate dehydrogenase completely whereas proteins, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine were partial ameliorated in birds treated with As+Vit C as compared to As-treated and control birds. Pale and hemorrhagic liver and swollen kidneys were observed in As-treated birds. Histopathologically, liver exhibited congestion and cytoplasmic vacuolation while in kidneys, condensation of tubular epithelium nuclei, epithelial necrosis, increased urinary spaces, sloughing of tubules from basement membrane and cast deposition were observed in As-treated birds. Pathological lesions were partially ameliorated with the treatment of Vit C. It can be concluded that arsenic induces biochemical and histopathological alterations in broiler birds; however, these toxic effects can be partially attenuated by Vit C.

  16. Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats.

    Science.gov (United States)

    Jahan, Sarwat; Rehman, Saima; Ullah, Hizb; Munawar, Asma; Ain, Qurat Ul; Iqbal, Tariq

    2016-01-01

    In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage.

  17. Molecular basis for arsenic-induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction.

    Science.gov (United States)

    Kumagai, Yoshito; Pi, Jingbo

    2004-08-01

    Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed.

  18. Phase I study of GC1008 (fresolimumab: a human anti-transforming growth factor-beta (TGFβ monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    John C Morris

    Full Text Available BACKGROUND: In advanced cancers, transforming growth factor-beta (TGFβ promotes tumor growth and metastases and suppresses host antitumor immunity. GC1008 is a human anti-TGFβ monoclonal antibody that neutralizes all isoforms of TGFβ. Here, the safety and activity of GC1008 was evaluated in patients with advanced malignant melanoma and renal cell carcinoma. METHODS: In this multi-center phase I trial, cohorts of patients with previously treated malignant melanoma or renal cell carcinoma received intravenous GC1008 at 0.1, 0.3, 1, 3, 10, or 15 mg/kg on days 0, 28, 42, and 56. Patients achieving at least stable disease were eligible to receive Extended Treatment consisting of 4 doses of GC1008 every 2 weeks for up to 2 additional courses. Pharmacokinetic and exploratory biomarker assessments were performed. RESULTS: Twenty-nine patients, 28 with malignant melanoma and 1 with renal cell carcinoma, were enrolled and treated, 22 in the dose-escalation part and 7 in a safety cohort expansion. No dose-limiting toxicity was observed, and the maximum dose, 15 mg/kg, was determined to be safe. The development of reversible cutaneous keratoacanthomas/squamous-cell carcinomas (4 patients and hyperkeratosis was the major adverse event observed. One malignant melanoma patient achieved a partial response, and six had stable disease with a median progression-free survival of 24 weeks for these 7 patients (range, 16.4-44.4 weeks. CONCLUSIONS: GC1008 had no dose-limiting toxicity up to 15 mg/kg. In patients with advanced malignant melanoma and renal cell carcinoma, multiple doses of GC1008 demonstrated acceptable safety and preliminary evidence of antitumor activity, warranting further studies of single agent and combination treatments. TRIAL REGISTRATION: Clinicaltrials.gov NCT00356460.

  19. Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats.

    Science.gov (United States)

    Jahan, Sarwat; Rehman, Saima; Ullah, Hizb; Munawar, Asma; Ain, Qurat Ul; Iqbal, Tariq

    2016-07-01

    In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180-250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage. PMID:26524343

  20. Selenium ameliorates arsenic induced oxidative stress through modulation of antioxidant enzymes and thiols in rice (Oryza sativa L.).

    Science.gov (United States)

    Kumar, Amit; Singh, Rana Pratap; Singh, Pradyumna Kumar; Awasthi, Surabhi; Chakrabarty, Debasis; Trivedi, Prabodh Kumar; Tripathi, Rudra Deo

    2014-09-01

    Arsenic (As) contamination of rice is a major problem for South-East Asia. In the present study, the effect of selenium (Se) on rice (Oryza sativa L.) plants exposed to As was studied in hydroponic culture. Arsenic accumulation, plant growth, thiolic ligands and antioxidative enzyme activities were assayed after single (As and Se) and simultaneous supplementations (As + Se). The results indicated that the presence of Se (25 µM) decreased As accumulation by threefold in roots and twofold in shoots as compared to single As (25 µM) exposed plants. Arsenic induced oxidative stress in roots and shoots was significantly ameliorated by Se supplementation. The observed positive response was found associated with the increased activities of ascorbate peroxidase (APX; EC 1.11.1.11), catalase (CAT; EC 1.11.1.6) and glutathione peroxidase (GPx; EC 1.11.1.9) and induced levels of non-protein thiols (NPTs), glutathione (GSH) and phytochelatins (PCs) in As + Se exposed plants as compared to single As treatment. Selenium supplementation modulated the thiol metabolism enzymes viz., γ-glutamylcysteine synthetase (γ-ECS; EC 6.3.2.2), glutathione-S-transferase (GST; EC 2.5.1.18) and phytochelatin synthase (PCS; EC 2.3.2.15). Gene expression analysis of several metalloid responsive genes (LOX, SOD and MATE) showed upregulation during As stress, however, significant downregulation during As + Se exposure as compared to single As treatment. Gene expressions of enzymes of antioxidant and GSH and PC biosynthetic systems, such as APX, CAT, GPx, γ-ECS and PCS were found to be significantly positively correlated with their enzyme activities. The findings suggested that Se supplementation could be an effective strategy to reduce As accumulation and toxicity in rice plants.

  1. Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum Album, on arsenic-induced toxicity in mice

    Directory of Open Access Journals (Sweden)

    Guha B

    2003-10-01

    Full Text Available Abstract Background Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols. Methods Mice were divided into different sets of control (both positive and negative and treated series (As-intoxicated, As-intoxicated plus drug-fed. Alanine amino transferase (ALT and aspartate amino transferase (AST activities and reduced glutathione (GSH level in liver and blood were analyzed in the different series of mice at six different fixation intervals. Results Both Arsenicum Album-30 and Arsenicum Album-200 ameliorated arsenic-induced toxicity to a considerable extent as compared to various controls. Conclusions The results lend further support to our earlier views that microdoses of potentized Arsenicum Album are capable of combating arsenic intoxication in mice, and thus are strong candidates for possible use in human subjects in arsenic contaminated areas under medical supervision.

  2. Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance.

    Science.gov (United States)

    McCubrey, James A; Steelman, Linda S; Abrams, Steven L; Lee, John T; Chang, Fumin; Bertrand, Fred E; Navolanic, Patrick M; Terrian, David M; Franklin, Richard A; D'Assoro, Antonio B; Salisbury, Jeffrey L; Mazzarino, Maria Clorinda; Stivala, Franca; Libra, Massimo

    2006-01-01

    The Ras/Raf/MEK/ERK and PI3K/PTEN/AKT signaling cascades play critical roles in the transmission of signals from growth factor receptors to regulate gene expression and prevent apoptosis. Components of these pathways are mutated or aberrantly expressed in human cancer (e.g., Ras, B-Raf, PI3K, PTEN, Akt). Also, mutations occur at genes encoding upstream receptors (e.g., EGFR and Flt-3) and chimeric chromosomal translocations (e.g., BCR-ABL) which transmit their signals through these cascades. These pathways interact with each other to regulate growth and in some cases tumorigenesis. For example, in some cells, PTEN mutation may contribute to suppression of the Raf/MEK/ERK cascade due to the ability of elevated activated Akt levels to phosphorylate and inactivate Raf-1. We have investigated the genetic structures and functional roles of these two signaling pathways in the malignant transformation and drug resistance of hematopoietic, breast and prostate cancer cells. Although both of these pathways are commonly thought to have anti-apoptotic and drug resistance effects on cells, they display different cell-lineage-specific effects. Induced Raf expression can abrogate the cytokine dependence of certain hematopoietic cell lines (FDC-P1 and TF-1), a trait associated with tumorigenesis. In contrast, expression of activated PI3K or Akt does not abrogate the cytokine dependence of these hematopoietic cell lines, but does have positive effects on cell survival. However, activated PI3K and Akt can synergize with activated Raf to abrogate the cytokine dependence of another hematopoietic cell line (FL5.12) which is not transformed by activated Raf expression by itself. Activated Raf and Akt also confer a drug-resistant phenotype to these cells. Raf is more associated with proliferation and the prevention of apoptosis while Akt is more associated with the long-term clonogenicity. In breast cancer cells, activated Raf conferred resistance to the chemotherapeutic drugs

  3. Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages are Prevented by the Combined Action of Folate and Vitamin B12.

    Science.gov (United States)

    Acharyya, Nirmallya; Deb, Bimal; Chattopadhyay, Sandip; Maiti, Smarajit

    2015-11-01

    Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (-CH3) pool. The -CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 μg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.

  4. Pleural malignancies.

    Science.gov (United States)

    Vargas, F S; Teixeira, L R

    1996-07-01

    Carcinoma of the lung, metastatic breast carcinoma, and lymphoma are responsible for approximately 75% of all malignant pleural effusions. The presence of malignant cells in the pleural fluid or in the parietal pleura confirms the diagnosis. Recently, several authors have proposed the combination of morphometric procedures and quantitative analysis of nucleolar organizer regions stained by silver nitrate. Videothoracoscopy is recommended for patients suspected of having a malignant pleural effusion in whom the diagnosis is not established after two cytologic studies of the fluid and one needle biopsy. The standard treatment is the intrapleural instillation of a chemical agent to produce a pleurodesis. The recommended sclerosant is talc, a tetracycline derivative, or Corynebacterium parvum where it is available. When a patient is not an ideal candidate for chemical pleurodesis, the options include symptomatic treatment, serial thoracentesis, implantation of a pleuroperitoneal shunt, and pleurectomy. PMID:9363162

  5. Arsenic-induced intensity oscillations in reflection high-energy electron diffraction measurements. [during MBE of GaAs and InAs

    Science.gov (United States)

    Lewis, B. F.; Fernandez, R.; Grunthaner, F. J.; Madhukar, A.

    1986-01-01

    A technique of arsenic-induced RHEED intensity oscillations has been used to accurately measure arsenic incorporation rates as a function of substrate temperature during the homoepitaxial growths of both GaAs and InAs by molecular beam epitaxy (MBE). Measurements were made at growth temperatures from 350 to 650 C and at arsenic fluxes of 0.1 to 10.0 monolayer/s. The method measures only the arsenic actually incorporated into the growing film and does not include the arsenic lost in splitting the arsenic tetramers or lost by evaporation from the sample.

  6. Malignant Catatonia

    Directory of Open Access Journals (Sweden)

    Ayca Ozkul

    2010-12-01

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

  7. Hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Hoogstraten, B.

    1986-01-01

    The principle aim of this book is to give practical guidelines to the modern treatment of the six important hematologic malignancies. Topics considered include the treatment of the chronic leukemias; acute leukemia in adults; the myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis/agnogenic myeloid metaplasia; Hodgkin's Disease; non-Hodgkin's lymphoma; and Multiple Myeloma.

  8. Malignant melanoma arising in mature cystic teratoma of the ovary

    OpenAIRE

    Heidi E Godoy; Kesterson, Joshua P.; Kasznica, John M.; Lele, Shashikant

    2011-01-01

    ► Teratomas are composed of elements of all three germ layers, all potentially capable of undergoing malignant transformation. ► A case of malignant melanoma arising in a mature teratoma is presented.

  9. 2,3,5,6-Tetramethylpyrazine (TMP) down-regulated arsenic-induced heme oxygenase-1 and ARS2 expression by inhibiting Nrf2, NF-κB, AP-1 and MAPK pathways in human proximal tubular cells.

    Science.gov (United States)

    Gong, Xuezhong; Ivanov, Vladimir N; Hei, Tom K

    2016-09-01

    Our recent study demonstrated that sodium arsenite at a clinically relevant dose induced nephrotoxicity in human renal proximal tubular epithelial cell line HK-2, which could be inhibited by natural product 2,3,5,6-tetramethylpyrazine (TMP) with antioxidant activity. The present study demonstrated that arsenic exposure resulted in protein and enzymatic induction of heme oxygenase-1 (HO-1) in dose- and time-dependent manners in HK-2 cells. Blocking HO-1 enzymatic activity by zinc protoporphyrin (ZnPP) augmented arsenic-induced apoptosis, ROS production and mitochondrial dysfunction, suggesting a critical role for HO-1 as a renal protectant in this procession. On the other hand, TMP, upstream of HO-1, inhibited arsenic-induced ROS production and ROS-dependent HO-1 expression. TMP also prevented mitochondria dysfunction and suppressed activation of the intrinsic apoptotic pathway in HK-2 cells. Our results revealed that the regulation of arsenic-induced HO-1 expression was performed through multiple ROS-dependent signal pathways and the corresponding transcription factors, including p38 MAPK and JNK (but not ERK), AP-1, Nrf2 and NF-κB. TMP inhibited arsenic-induced activations of JNK, p38 MAPK, ERK, AP-1 and Nrf2 and block HO-1 protein expression. The present study, furthermore, demonstrated arsenic-induced expression of arsenic response protein 2 (ARS2) that was regulated by p38 MAPK, ERK and NF-κB. To our knowledge, this is the first report showing that ARS2 involved in arsenic-induced nephrotoxicity, while TMP pretreatment prevented such an up-regulation of ARS2 in HK-2 cells. Given ARS2 and HO-1 sharing the similar regulation mechanism, we speculated that ARS2 might also mediate cell survival in this procession. In summary, our study highlighted a role of HO-1 in the protection against arsenic-induced cytotoxicity downstream from the primary targets of TMP and further indicated that TMP may be used as a potential therapeutic agent in the treatment of arsenic-induced

  10. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Xuefeng, E-mail: xuefengr@buffalo.edu [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Gaile, Daniel P. [Department of Biostatistics, School of Public Health and Health Professions, the State University of New York, Buffalo, NY 14214 (United States); Gong, Zhihong [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Qiu, Wenting [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Ge, Yichen [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Olson, James R. [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Kavanagh, Terrance J. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195 (United States); Wu, Hongmei, E-mail: hongmeiwwu@hotmail.com [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China)

    2015-03-15

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  11. Concomitant administration of Moringa oleifera seed powder in the remediation of arsenic-induced oxidative stress in mouse.

    Science.gov (United States)

    Gupta, Richa; Dubey, D K; Kannan, G M; Flora, S J S

    2007-01-01

    Contamination of ground water by arsenic has become a cause of global public health concern. In West Bengal, India, almost 6 million people are endemically exposed to inorganic arsenic by drinking heavily contaminated groundwater through hand-pumped tube wells. No safe, effective and specific preventive or therapeutic measures for treating arsenic poisoning are available. We recently reported that some of the herbal extracts possess properties effective in reducing arsenic concentration and in restoring some of the toxic effects of arsenic in animal models. Moringa oleifera Lamarack (English: Horseradish-tree, Drumstick-tree, Hindi: Saijan, Sanskrit: Shigru) belongs to the Moringaceae family, is generally known in the developing world as a vegetable, a medicinal plant and a source of vegetable oil. The objective of the present study was to determine whether Moringa oleifera (M. oleifera) seed powder could restore arsenic induced oxidative stress and reduce body arsenic burden. Exposure to arsenic (2.5 mg/kg, intraperitoneally for 6weeks) led to a significant increase in the levels of tissue reactive oxygen species (ROS), metallothionein (MT) and thiobarbituric acid reactive substance (TBARS) which were accompanied by a decrease in the activities in the antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in mice. Arsenic exposed mice also exhibited liver injury as reflected by reduced acid phosphatase (ACP), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities and altered heme synthesis pathway as shown by inhibited blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. Co-administration of M. oleifera seed powder (250 and 500 mg/kg, orally) with arsenic significantly increased the activities of SOD, catalase, GPx with elevation in reduced GSH level in tissues (liver, kidney and brain). These changes were accompanied by approximately 57%, 64% and 17% decrease in blood ROS, liver

  12. Concomitant administration of Moringa oleifera seed powder in the remediation of arsenic-induced oxidative stress in mouse.

    Science.gov (United States)

    Gupta, Richa; Dubey, D K; Kannan, G M; Flora, S J S

    2007-01-01

    Contamination of ground water by arsenic has become a cause of global public health concern. In West Bengal, India, almost 6 million people are endemically exposed to inorganic arsenic by drinking heavily contaminated groundwater through hand-pumped tube wells. No safe, effective and specific preventive or therapeutic measures for treating arsenic poisoning are available. We recently reported that some of the herbal extracts possess properties effective in reducing arsenic concentration and in restoring some of the toxic effects of arsenic in animal models. Moringa oleifera Lamarack (English: Horseradish-tree, Drumstick-tree, Hindi: Saijan, Sanskrit: Shigru) belongs to the Moringaceae family, is generally known in the developing world as a vegetable, a medicinal plant and a source of vegetable oil. The objective of the present study was to determine whether Moringa oleifera (M. oleifera) seed powder could restore arsenic induced oxidative stress and reduce body arsenic burden. Exposure to arsenic (2.5 mg/kg, intraperitoneally for 6weeks) led to a significant increase in the levels of tissue reactive oxygen species (ROS), metallothionein (MT) and thiobarbituric acid reactive substance (TBARS) which were accompanied by a decrease in the activities in the antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in mice. Arsenic exposed mice also exhibited liver injury as reflected by reduced acid phosphatase (ACP), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities and altered heme synthesis pathway as shown by inhibited blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. Co-administration of M. oleifera seed powder (250 and 500 mg/kg, orally) with arsenic significantly increased the activities of SOD, catalase, GPx with elevation in reduced GSH level in tissues (liver, kidney and brain). These changes were accompanied by approximately 57%, 64% and 17% decrease in blood ROS, liver

  13. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    International Nuclear Information System (INIS)

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  14. The contribution of heavy metals in cigarette smoke condensate to malignant transformation of breast epithelial cells and in vivo initiation of neoplasia through induction of a PI3K–AKT–NFκB cascade

    Energy Technology Data Exchange (ETDEWEB)

    Mohapatra, Purusottam; Preet, Ranjan; Das, Dipon; Satapathy, Shakti Ranjan [Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa 751024 (India); Siddharth, Sumit [Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa 751024 (India); Department of Infection Biology, Institute of Life Science, Nalco Square, Bhubaneswar, Orissa 751021 (India); Choudhuri, Tathagata [Department of Infection Biology, Institute of Life Science, Nalco Square, Bhubaneswar, Orissa 751021 (India); Wyatt, Michael D. [Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC (United States); Kundu, Chanakya Nath, E-mail: cnkundu@gmail.com [Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa 751024 (India)

    2014-01-01

    Cigarette smoking is a crucial factor in the development and progression of multiple cancers including breast. Here, we report that repeated exposure to a fixed, low dose of cigarette smoke condensate (CSC) prepared from Indian cigarettes is capable of transforming normal breast epithelial cells, MCF-10A, and delineate the biochemical basis for cellular transformation. CSC transformed cells (MCF-10A-Tr) were capable of anchorage-independent growth, and their anchorage dependent growth and colony forming ability were higher compared to the non-transformed MCF-10A cells. Increased expression of biomarkers representative of oncogenic transformation (NRP-1, Nectin-4), and anti-apoptotic markers (PI3K, AKT, NFκB) were also noted in the MCF-10A-Tr cells. Short tandem repeat (STR) profiling of MCF-10A and MCF-10A-Tr cells revealed that transformed cells acquired allelic variation during transformation, and had become genetically distinct. MCF-10A-Tr cells formed solid tumors when implanted into the mammary fat pads of Balb/c mice. Data revealed that CSC contained approximately 1.011 μg Cd per cigarette equivalent, and Cd (0.0003 μg Cd/1 × 10{sup 7} cells) was also detected in the lysates from MCF-10A cells treated with 25 μg/mL CSC. In similar manner to CSC, CdCl{sub 2} treatment in MCF-10A cells caused anchorage independent colony growth, higher expression of oncogenic proteins and increased PI3K–AKT–NFκB protein expression. An increase in the expression of PI3K–AKT–NFκB was also noted in the mice xenografts. Interestingly, it was noted that CSC and CdCl{sub 2} treatment in MCF-10A cells increased ROS. Collectively, results suggest that heavy metals present in cigarettes of Indian origin may substantially contribute to tumorigenesis by inducing intercellular ROS accumulation and increased expression of PI3K, AKT and NFκB proteins. - Highlights: • Repeated exposure of CSC causes malignant transformation in MCF-10A. • MCF-10A-Tr cells showed a distinct

  15. Adipose tissue-derived stem cells transform malignantly in vitro spontaneously%脂肪组织来源的干细胞体外培养随机恶性转化

    Institute of Scientific and Technical Information of China (English)

    刘桂英; 杨立业; 李文玉; 郑佳坤; 陈辉; 陈强

    2013-01-01

    Objective To study adipose tissue-derived stem cells (ADSCs) whether malignant transformation in vitro. Methods ADSCs were isolated and cultured from adipose tissues of mice, which were observed whether to occur malignant transformation. The tissue-specific markers of transformed cells were detected by immunocytochemistry, and the chromosome structure were analyzed. The transformed cells were transplanted into nude mice to investigate their tumorigenicity. Results A flask of ADSCs were successively cultured for 4 months and a number of cells had transformed and immortalized in vitro. The ADSCs were cultured more than 100 generations and still maintained the original cell proliferation rate. The marker of vimentin, PCNA, Ki67 and VEGF-c were expressed but the pan-CK and p16 were not expressed, which showed the cells were mesenchymal origin. Meanwhile, the chromosome analysis showed all cells were aneuploidy and translocation were very common. Microvilli structure of cell surface could be observed by transmission electron microscopy. There was no clone formation ability of transformed ADSCs in soft agar media. Nude mice subcutaneously transplanted could form tumor tissue that the main component was sarcoma. Conclusion Adipose tissue-derived stem cells could malignantly transformed spontaneously in vitro, and which also could form tumors in nude mice after transplantation.%目的:研究脂肪来源干细胞在体外能否恶性转化。方法从小鼠脂肪组织培养出脂肪组织来源干细胞(ADSCs),观察细胞是否发生恶性转化,应用免疫细胞化学方法检测转化细胞的相关标志物的表达,并对其染色体结构进行分析,并将转化细胞移植到裸鼠皮下以检测其成瘤性。结果1个培养瓶中的细胞在体外培养4个月左右发生了转化,已经永生化,目前体外培养超过100代,细胞仍维持原来的增殖速度。细胞表达中胚层的标志物vimentin,但不表达pan-CK,说明其

  16. 36. Study on p16INK4a and p15INK4b genes of human bronchial epithelial cells malignantly transformed by cyclophosphamide and thiotepa

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Transformed human bronchial epithelial cells BEAS-2B induced by CP and TEPA were used to study abnormity of the tumor suppressor genes p15INK4b and p16INK4a, through which we can provide clues for explanations of the molecular mechanism in carcinogenesis of human bronchial epithelial cells induced by CP and TEPA. Analysis of the genomic DNA from the transformed BEAS-CP, and BEAS-T cells using PCR amplification, singe strand conformation polymorphism(SSCP) and DNA sequencing

  17. Clinical analysis of high-risk factors on malignant transformation of hydatidiform mole%高危因素对葡萄胎后恶变的影响临床分析

    Institute of Scientific and Technical Information of China (English)

    梁哨雅

    2014-01-01

    目的:分析有恶变高危因素的葡萄胎患者的临床特点,为提高妊娠滋养细胞肿瘤(GTN)的诊治手段提供借鉴。方法回顾性分析该院妇产科2007年1月至2013年12月162例在行清宫术后病理检查诊断为葡萄胎患者的临床资料,观察GTN的临床表现、治疗效果等,比较有高危因素与无高危因素葡萄胎后GTN患者的临床特点。结果162例葡萄胎患者中,有46例恶变,其中有高危因素患者36例,无高危因素患者10例。比较两类患者恶变率、临床表现及治疗后效果,早期葡萄胎合并高危因素患者恶变率及临床表现与无合并高危因素患者比较,差异均有统计学意义(P<0.05);葡萄胎后GTN患者治疗效果比较,差异无统计学意义(P>0.05)。结论葡萄胎恶变率与患者发病年龄、子宫大小、卵巢黄素囊肿等高危因素有关。因此,对患者高危因素进行正确评估,对临床早期预测葡萄胎恶变及给予预防性化疗有一定指导意义,也有助于诊治GTN和提高临床疗效。%Objective To analyze the clinical features of hydatidiform mole patients with high-risk factors,in order to provide reference for improving the diagnosis of the gestational trophoblastic tumor (GTN). Methods A retrospective analysis was conducted on clinical data of 162 hydatidiform mole patients ,who were diagnosed after uterine curettage by pathological ex-amination in the Obstetrics Department of the hospital from January 2007 to December 2013. To observe the clinical manifesta-tions of GTN,therapeutic effect and so on,and compare the clinical features of hydatidiform mole patients with and without high-risk factors. Results Amon the 162 patients with hydatidiform mole,46 cases had malignant transformation,including 36 cases with high-risk factors and 10 cases without high-risk factors. The malignant transformation rate,clinical manifestation and thera-peutic effects between the two

  18. Expressions and significances of HGF and c-Met in the malignant transformation of nasal inverted papilloma%HGF、c-Met鼻内翻性乳头瘤恶变中的表达变化及其意义

    Institute of Scientific and Technical Information of China (English)

    段晓辉; 于艳芳; 张艳丽; 王延臣; 裴志萍; 康震; 乔国勇

    2012-01-01

    目的:分析肝细胞生长因子(HGF)与其受体(c-Met)在不同期鼻内翻性乳头瘤中的表达变化,探讨其在鼻内翻性乳头瘤恶变中的作用.方法:选择我院2005年1月至2010年12月间确诊为鼻内翻性乳头状瘤的55例及鼻腔恶性乳头状瘤30例作为实验对象,所有患者均行内镜下切除病变组织,对手术切除组织采用免疫组织化学方法SP法检测HGF、c-Met的表达,并统计其染色得分,比较鼻内翻性乳头瘤组织、癌旁组织与恶性组织的HGF、c-Met表达.分析不同分型的鼻内翻性乳头瘤的HGF、c-Met的表达变化.结果:HGF、c-Met在鼻内翻性乳头瘤组织、癌旁组织与恶性组织中的表达变化一致,均为恶性组织高于鼻内翻性乳头瘤组织与癌旁组织,癌旁组织的表达最低.鼻内翻性乳头瘤的T1期HGF表达明显低于T3期(P<0.05),T4期(P<0.01),c-Met表达T1期明显低于T3、T4期(P<0.01).结论:HGF、c-Met在鼻内翻性乳头瘤中的表达与其不同分期有关,HGF、c-Met可能促进鼻内翻性乳头的恶变.%Objective To analysis the expressions of HGF and c-Met in different stages of intranasal inverted papilloma and try to explore the effects of HGF and c-Met in the malignant transformation of nasal inverted papilloma. Methods 30 cases with confirmed malignant papilloma and 55 cases with nasal inverted papilloma in our hospital from Jan 2005 to Dec 2010 were received as experimental objects. All the patients underwent endoscopic removal of diseased tissue. The expressions of HGF and c-Met in nasal inverted papilloma tissue, adjacent tissues and malignant tissues were determined by immunohistochemical method, and the stain score of each sample was calculated. The expressions of HGF and c-Met in different stages of nasal inverted papilloma were analyzed. Results The staining scores of HGF and c-Met in malignant tissue were higher than those in nasal inverted papilloma tissues and the adjacent tissues, the expressions

  19. Malignant melanoma of nose

    OpenAIRE

    Kundu, I. N.; Haldar, B.; Saha, A. K.

    2001-01-01

    Malignant melanoma (MM) is one of the uncommon malignancies of the nose. We present an unusually big proliferative like MM in the vestibule of the nose. Malignancy of nose constitutes less than 1% of all malignancies (3% of head & neck tumour). MM however contributes only 2% of all malignant neoplasms of the nose (Moore & Martin. 1955).

  20. Malignant transformation of CD4+ T lymphocytes mediated by oncogenic kinase NPM/ALK recapitulates IL-2-induced cell signaling and gene expression reprogramming.

    Science.gov (United States)

    Marzec, Michal; Halasa, Krzysztof; Liu, Xiaobin; Wang, Hong Y; Cheng, Mangeng; Baldwin, Donald; Tobias, John W; Schuster, Stephen J; Woetmann, Anders; Zhang, Qian; Turner, Suzanne D; Ødum, Niels; Wasik, Mariusz A

    2013-12-15

    Anaplastic lymphoma kinase (ALK), physiologically expressed only by nervous system cells, displays a remarkable capacity to transform CD4(+) T lymphocytes and other types of nonneural cells. In this study, we report that activity of nucleophosmin (NPM)/ALK chimeric protein, the dominant form of ALK expressed in T cell lymphomas (TCLs), closely resembles cell activation induced by IL-2, the key cytokine supporting growth and survival of normal CD4(+) T lymphocytes. Direct comparison of gene expression by ALK(+) TCL cells treated with an ALK inhibitor and IL-2-dependent ALK(-) TCL cells stimulated with the cytokine revealed a very similar, albeit inverse, gene-regulation pattern. Depending on the analysis method, up to 67% of the affected genes were modulated in common by NPM/ALK and IL-2. Based on the gene expression patterns, Jak/STAT- and IL-2-signaling pathways topped the list of pathways identified as affected by both IL-2 and NPM/ALK. The expression dependence on NPM/ALK and IL-2 of the five selected genes-CD25 (IL-2Rα), Egr-1, Fosl-1, SOCS3, and Irf-4-was confirmed at the protein level. In both ALK(+) TCL and IL-2-stimulated ALK(-) TCL cells, CD25, SOCS3, and Irf-4 genes were activated predominantly by the STAT5 and STAT3 transcription factors, whereas transcription of Egr-1 and Fosl-1 was induced by the MEK-ERK pathway. Finally, we found that Egr-1, a protein not associated previously with either IL-2 or ALK, contributes to the cell proliferation. These findings indicate that NPM/ALK transforms the target CD4(+) T lymphocytes, at least in part, by using the pre-existing, IL-2-dependent signaling pathways.

  1. Crystalline Nickel Sulfide Induced Malignant Transformation of 16HBE Cells through Autophagic Pathway%结晶型硫化镍通过自噬途径诱导16HBE细胞恶性转化癌变

    Institute of Scientific and Technical Information of China (English)

    张岚; 杨磊; 吕嘉春

    2012-01-01

    Nickel compounds, which widely exist in the environment of human occupation, are the major risk factor for human lung cancer. Our previous studies had confirmed that exposure to toxic,metallic crystalline nickel sulfide (NiS) was an important cause of lung cancer, but the concrete carcinogenic mechanism is still unclear. In this study, we used the previouslyestablished human bronchial epithelial (16HBE-T) cells malignant transformation model, which was induced by crystalline NiS. For the first time, fluorescence intensity and position of the GFP-LC3 protein in malignant transformed (16HBE-T) cells and normal cell (16HBE-N), were real-time monitored with the technique of confocal laser scanning microscopy imaging without damaging the condition. Moreover, we used Western Blotting to detect the intracellular autophagic signal which is expressed by key effective molecule pathway. Confocal experimental results showed that: Compared with that of 16HBE-N-cells, the GFP-LC3 protein punctate aggregation of 16HBE-T cells significantly reduced to the merely 1/3 amount of 16HBE-N-cells, suggesting that autophagy levels declined. At the same time, it was found that the mTOR kinase activity increased, and that Beclin 1 expression decreased. The above research result demonstrated that the mechanism of crystalline NiS induced 16HBE cell malignant transformation was through multiple autophagic pathway and it will provide an important message in the prevention and treatment of lung cancer.%镍化合物广泛存在于人类职业环境中,是人类发生肺癌的主要危险因素.我们前期研究已证实金属毒物结晶型硫化镍(NiS)的暴露是发生肺癌的重要病因,但具体的致癌机制仍未明了.本研究利用前期建立的结晶型NiS恶性转化人支气管上皮细胞的细胞模型,首次采用激光共聚焦扫描显微镜成像技术,在无损伤状态下,实时观测恶性转化细胞(16HBE-T)和正常细胞(16HBE-N)中自噬体标记蛋白GFP-LC3

  2. Malignant transformation of CD4+ T lymphocytes mediated by oncogenic kinase NPM/ALK recapitulates IL-2-induced cell signaling and gene expression reprogramming

    DEFF Research Database (Denmark)

    Marzec, Michal; Halasa, Krzysztof; Liu, Xiaobin;

    2013-01-01

    Anaplastic lymphoma kinase (ALK), physiologically expressed only by nervous system cells, displays a remarkable capacity to transform CD4(+) T lymphocytes and other types of nonneural cells. In this study, we report that activity of nucleophosmin (NPM)/ALK chimeric protein, the dominant form of ALK...... with the cytokine revealed a very similar, albeit inverse, gene-regulation pattern. Depending on the analysis method, up to 67% of the affected genes were modulated in common by NPM/ALK and IL-2. Based on the gene expression patterns, Jak/STAT- and IL-2-signaling pathways topped the list of pathways identified...... as affected by both IL-2 and NPM/ALK. The expression dependence on NPM/ALK and IL-2 of the five selected genes-CD25 (IL-2Rα), Egr-1, Fosl-1, SOCS3, and Irf-4-was confirmed at the protein level. In both ALK(+) TCL and IL-2-stimulated ALK(-) TCL cells, CD25, SOCS3, and Irf-4 genes were activated predominantly...

  3. Malignant lymphoma

    International Nuclear Information System (INIS)

    This paper describes the background and treatment, especially focusing on radiotherapy (RT), of stage I-II malignant lymphoma (ML) occurring in head and neck. For diffuse large B-cell lymphoma, the most frequently occurring ML in Japan (about 40% of all MLs), the current standard protocol involves 3 cycles of chemotherapy (CT) like rituximab to cyclophosphamide/doxorubicin/vincristine/predonisolone (CHOP) regimen followed by RT. Authors use the dose around 30 Gy/15 fr for CR patients after CHOP and 40-50 Gy/20-25 fr for PR ones. Recurrence scarcely occurs in the RT target region. However, significance of RT is still somehow controversial in this ML and addition of CHOP is currently noted. Mucosa-associated lymphoid tissue lymphoma (8.45% of Japanese ML) occurs mainly in glands and orbit and may be related with Chlamydia infection. RT is usually conducted to the whole organ with lesion as the clinical target with fractionated 30 Gy. Nasal NK/T cell lymphoma (2.6%), possibly associated with Epstein-Barr (EB) virus, is usually resistant to CHOP. Recommended is CT after RT with the dose of 50-54 Gy and depending on the target site, advanced RT like intensity-modified one is desirable. Hodgkin lymphoma (about 5%) occurs in lymph node and is derived from B-lymphocyte. Irradiation field involves the region of the disease node or that additionally including its neighbors and doses of about 20 Gy and 30 Gy are given in child and adult patients, respectively. For follicular and other tissue type lymphomas, noted are novel therapies like rituximab-combined CT, immuno-RT with 90Y-ibritumomab and 131I-tositumomab. Recently, positron emission tomography (PET) is essential for treatment assessment of the clinical response of ML in the guideline. (R.T.)

  4. 脂代谢紊乱及脂质过氧化与结肠腺瘤恶变的关系%Lipid disorders and lipid peroxidation associated with the malignant transformation of colorectal adenoma*

    Institute of Scientific and Technical Information of China (English)

    Didi Tao; Zhongyin Zhou; Ximing Xu; Hesheng Luo

    2011-01-01

    Objective: The aim of this study was to investigate lipid disorders and lipid peroxidation associated with the malignant transformation of colorectal adenoma. Methods: Analyses were based on data from 100 subjects with histologically confirmed adenomas (cases) and 50 adenoma-free control subjects, all of whom had colonoscopy. The subjects were divided into two groups: those with no adenoma and those with adenoma. According to subsite of adenomas the subjects with adenoma were divided into group of distal adenoma and group of proximal adenoma. According to histology of adenomas the subjects with adenoma were divided into group of villiform adenoma and group of tubular + tubulo-villous adenoma. Among the groups, the serum levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), Iow density lipoprotein cholesterol (LDL-C), and lipid peroxidation product malondialdehyde (MDA) were compared in all the patients.Results: Plasma total cholesterol and MDA level in group of adenomas were significantly higher than that in group of control subjects, but plasma HDL-C level was Iow in group of adenomas (P < 0.05). Plasma total cholesterol and MDA levels were positively related to distal and villiform adenomas (P < 0.05). Conclusion: The findings suggest that altered lipid metabolism may be differentially associated with colorectal adenomas.

  5. Overexpression of variant PNPLA3 gene at I148M position causes malignant transformation of hepatocytes via IL-6-JAK2/STAT3 pathway in low dose free fatty acid exposure: a laboratory investigation in vitro and in vivo.

    Science.gov (United States)

    Liu, Zhengtao; Chen, Tianchi; Lu, Xiaoxiao; Xie, Haiyang; Zhou, Lin; Zheng, Shusen

    2016-01-01

    Epidemiological survey identified that the variant patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene at I148M position exerts direct effect in promoting hepatocellular carcinoma (HCC) under extraneous oxidative stress by interaction with obesity. However, the mechanism is still unknown. HepG2 cells were overexpressed by transinfection of PNPLA3 with wild-type 148I (PNPLA3(WT)) and mutant 148M (PNPLA3(I148M)), respectively. Variation in metabolic indicators, hepatic steatosis, biological behaviors and signaling molecules related to cancer promotion was measured in hepatocytes using low-dose free fatty acid (FFA) exposure. Effect of PNPLA3(I148M) on xenograft biology and its interaction with dietary obesity were also evaluated in animal study. Cells overexpresssing PNPLA3(I148M) in low-dose FFA incubation showed more proliferation, migration, invasion, and less apoptosis (Pdiet accelerated growth of xenografts derived from PNPLA3(I148M) cells incubated in low-dose FFA. In low oxidative stress, PNPLA3(I148M) initiated the hepatocyte malignant transformation through the activation of inflammation-mediated JAK/STAT pathway. Dietary obesity amplified the growth of tumor from PNPLA3(I148M) cells by interaction with local FFA incubation. Anti-inflammation and weight loss might be potential approaches for preventing HCC in high-risk population carrying PNPLA3 variant. PMID:27186262

  6. Malignant hyperthermia

    Directory of Open Access Journals (Sweden)

    Pollock Neil

    2007-04-01

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

  7. Arsenic Induced Inhibition of δ-aminolevulinate Dehydratase Activity in Rat Blood and its Response To Meso 2,3-dimercaptosuccinic Acid and Monoisoamyl DMSA

    Institute of Scientific and Technical Information of China (English)

    SMRATI BHADAURIA; SWARAN J.S.FLORA

    2004-01-01

    Objective The objective of this study was to investigate arsenic induced changes in blood δ-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination. Methods Rat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (Ⅲ) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1, 0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration. Results In vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (Ⅲ and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (Ⅲ) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (Ⅲ), but at two higher concentrations (0.5and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1, 0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value.Conclusions The results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood

  8. Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings

    Energy Technology Data Exchange (ETDEWEB)

    Samadder, Asmita; Das, Jayeeta; Das, Sreemanti; De, Arnab; Saha, Santu Kumar; Bhattacharyya, Soumya Sundar; Khuda-Bukhsh, Anisur Rahman, E-mail: prof_arkb@yahoo.co.in

    2013-02-15

    Diabetes is a menacing problem, particularly to inhabitants of groundwater arsenic contaminated areas needing new medical approaches. This study examines if PLGA loaded nano-insulin (NIn), administered either intraperitoneally (i.p.) or through oral route, has a greater cost-effective anti-hyperglycemic potential than that of insulin in chronically arsenite-fed hyperglycemic mice. The particle size, morphology and zeta potential of nano-insulin were determined using dynamic light scattering method, scanning electronic and atomic force microscopies. The ability of the nano-insulin (NIn) to cross the blood–brain barrier (BBB) was also checked. Circular dichroic spectroscopic (CD) data of insulin and nano-insulin in presence or absence of arsenic were compared. Several diabetic markers in different groups of experimental and control mice were assessed. The mitochondrial functioning through indices like cytochrome c, pyruvate-kinase, glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cell membrane potential and calcium-ion level was also evaluated. Expressions of the relevant marker proteins and mRNAs like insulin, GLUT2, GLUT4, IRS1, IRS2, UCP2, PI3, PPARγ, CYP1A1, Bcl2, caspase3 and p38 for tracking-down the signaling cascade were also analyzed. Results revealed that i.p.-injected nano-encapsulated-insulin showed better results; NIn, due to its smaller size, faster mobility, site-specific release, could cross BBB and showed positive modulation in mitochondrial signaling cascades and other downstream signaling molecules in reducing arsenic-induced-hyperglycemia. CD data indicated that nano-insulin had less distorted secondary structure as compared with that of insulin in presence of arsenic. Thus, overall analyses revealed that PLGA nano-insulin showed better efficacy in combating arsenite-induced-hyperglycemia than that of insulin and therefore, has greater potentials for use in nano-encapsulated form. - Highlights: ► PLGA encapsulated nano

  9. Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Shafik, Noha M; El Batsh, Maha M

    2016-01-01

    Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p arsenic hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p arsenic toxicity through activation of Nrf2 anti-oxidant pathway.

  10. Research Progress on Molecular Mechanisms of Arsenic- induced Oxidative Stress%砷的氧化应激分子机制研究进展

    Institute of Scientific and Technical Information of China (English)

    白彩军; 刘丹; 李冰

    2012-01-01

    砷暴露能够引起多种疾病和病理损伤.目前氧化应激机制是砷毒性的研究热点.砷通过扰乱氧化/抗氧化平衡,从而引起细胞信号通路和转录因子活性、细胞周期和细胞凋亡、线粒体、抗氧化物酶的活性、抗氧化防御系统等方面的改变.本文将就砷的氧化应激分子机制的研究进展进行综述.%Arsenic exposure can cause a variety of diseases and pathological damages. In recent years, oxidative stress mechanism has been considered to be the research focus of arsenic toxicity. Arsenic alters multiple cellular pathways and transcription factor activities, cell cycle and cell apoptosis, mitochondria, antioxidant enzymes activity, and antioxidant defense system by disturbing the pro/antioxidant balance. This review summarizes the molecular mechanism of arsenic- induced oxidative stress.

  11. 亚砷酸钠对人永生化角质形成细胞株恶性转化的影响%Effect of sodium arsenite on malignant transformation of human immortalized keratinocyte cell lines

    Institute of Scientific and Technical Information of China (English)

    李艳玲; 胡玉贤; 张晓光; 王凌

    2016-01-01

    BACKGROUND:Studies have found that sodium arsenite can cause the malignant transformation and tumorigenicity of HaCaT cels, but whether low concentrations of sodium arsenite can cause the malignant transformation is rarely reported. OBJECTIVE:To study the effect of sodium arsenite on the malignant transformation of human immortalized keratinocyte cel lines. METHODS:HaCaT cels were treated with different concentrations of sodium arsenite. MTT assay was used to determine the effect of sodium arsenite on HaCaT cel morphology and proliferation, flow cytometry used to detect the effect of sodium arsenite on HaCaT cel cycle, and soft agar colony formation experiments assay used to determine the effect of sodium arsenite on HaCaT cel colony formation capacity. RESULTS AND CONCLUSION: HaCaT cels grew wel when the concentration of sodium arsenite was 5 mol/L, but the cel growth was inhibited under intervention with 10 and 50 mol/L sodium arsenite. HaCaT cels treated with 0.1 mol/L sodium arsenite were passaged to the 20th generation, and cel morphology had no notable changes; cels at passage 25 exhibited enlarged size and multiple nucleoli, which had a continued proliferation trend. Compared with the primarily cultured cels, 0.1 mol/L sodium arsenite-treated HaCaT cels at passages 15 and 25 had an increased proportion at S phase and G2/M phase, with strengthened proliferation ability and increased colony-forming efficiency, and moreover, the proliferation ability and colony-forming efficiency of passage 25 cels were higher than those of passage 15 cels. These experimental data show that high concentrations of sodium arsenite reduce HaCaT cel viability, and low concentrations of sodium sulfite have a certain influence on the morphology, cel cycle, proliferation ability and colony-forming efficiency of HaCaT cels, and moreover, the proliferation ability and colony-forming efficiency of human immortalized keratinocytes wil be strengthened with the increase of passage.%背景

  12. Malignant teratoma (image)

    Science.gov (United States)

    A malignant teratoma is a type of cancer consisting of cysts that contain one or more of the three primary embryonic germ layers: ectoderm, mesoderm, and endoderm. Because malignant teratomas have usually spread by the time of diagnosis, ...

  13. Paediatric and adult malignant glioma

    DEFF Research Database (Denmark)

    Jones, Chris; Perryman, Lara; Hargrave, Darren

    2012-01-01

    Gliomas in children differ from their adult counterparts by their distribution of histological grade, site of presentation and rate of malignant transformation. Although rare in the paediatric population, patients with high-grade gliomas have, for the most part, a comparably dismal clinical outcome...... to older patients with morphologically similar lesions. Molecular profiling data have begun to reveal the major genetic alterations underpinning these malignant tumours in children. Indeed, the accumulation of large datasets on adult high-grade glioma has revealed key biological differences between...... the adult and paediatric disease. Furthermore, subclassifications within the childhood age group can be made depending on age at diagnosis and tumour site. However, challenges remain on how to reconcile clinical data from adult patients to tailor novel treatment strategies specifically for paediatric...

  14. Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Shafik, Noha M; El Batsh, Maha M

    2016-01-01

    Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p arsenic hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p treated with both P. granatum and selenium. It was concluded that combined P. granatum and selenium treatment had a synergistic hepatoprotective effect against arsenic toxicity through activation of Nrf2 anti-oxidant pathway.

  15. Segmental neurofibromatosis and malignancy.

    Science.gov (United States)

    Dang, Julie D; Cohen, Philip R

    2010-01-01

    Segmental neurofibromatosis is an uncommon variant of neurofibromatosis type I characterized by neurofibromas and/or café-au-lait macules localized to one sector of the body. Although patients with neurofibromatosis type I have an associated increased risk of certain malignancies, malignancy has only occasionally been reported in patients with segmental neurofibromatosis. The published reports of patients with segmental neurofibromatosis who developed malignancy were reviewed and the characteristics of these patients and their cancers were summarized. Ten individuals (6 women and 4 men) with segmental neurofibromatosis and malignancy have been reported. The malignancies include malignant peripheral nerve sheath tumor (3), malignant melanoma (2), breast cancer (1), colon cancer (1), gastric cancer (1), lung cancer (1), and Hodgkin lymphoma (1). The most common malignancies in patients with segmental neurofibromatosis are derived from neural crest cells: malignant peripheral nerve sheath tumor and malignant melanoma. The incidence of malignancy in patients with segmental neurofibromatosis may approach that of patients with neurofibromatosis type I. PMID:21137621

  16. Malignant colorectal polyps

    Institute of Scientific and Technical Information of China (English)

    Luis; Bujanda; Angel; Cosme; Ines; Gil; Juan; I; Arenas-Mirave

    2010-01-01

    Nowadays, the number of cases in which malignant colorectal polyps are removed is increasing due to colorectal cancer screening programmes. Cancerous polyps are classified into non-invasive high grade neoplasia (NHGN), when the cancer has not reached the muscularis mucosa, and malignant polyps, classed as T1, when they have invaded the submucosa. NHGN is considered cured with polypectomy, while the prognosis for malignant polyps depends on various morphological and histological factors. The prognostic facto...

  17. Response of arsenic-induced oxidative stress, DNA damage, and metal imbalance to combined administration of DMSA and monoisoamyl-DMSA during chronic arsenic poisoning in rats.

    Science.gov (United States)

    Bhadauria, S; Flora, S J S

    2007-03-01

    -exposed rats compared to that of normal animals. These changes were accompanied by a significant elevation in blood and soft-tissue arsenic concentration. Co-administration of DMSA and MiADMSA at lower dose (0.15 mmol/kg) was most effective not only in reducing arsenic-induced oxidative stress but also in depleting arsenic from blood and soft tissues compared to other treatments. This combination was also able to repair DNA damage caused following arsenic exposure. We thus recommend combined administration of DMSA and MiADMSA for achieving optimum effects of chelation therapy.

  18. MALIGNANT CHANGE IN A SOLITARY CYLINDROMA: A RARE CASE REPORT

    Directory of Open Access Journals (Sweden)

    Shivaji D

    2014-06-01

    Full Text Available Cylindroma is a rare tumour which originates from skin appendages. Cylindromas are of two types namely solitary and multiple. Malignant transformation of cylindroma is unusual and is extremely rare in solitary type. They show strong predilection for middle aged and elderly females. We report a case of a 70 year old male patient presented with nodular swelling along with surface ulceration in the right axillary region since six months, which on histopathological examination revealed a case of malignant transformation of benign solitary cylindroma. We report a rare case of malignant cylindroma arising in a patient with solitary cylindroma at an unusual site

  19. MEBO治愈1例下肢慢性溃疡恶变报告%MEBO Curing Malignant Transformation of Chronic Lower Limb Ulcer:A Case Report

    Institute of Scientific and Technical Information of China (English)

    陈方凯; 龚海粟

    2013-01-01

      目的 观察湿润烧伤膏( MEBO)在下肢慢性溃疡恶变中的治疗效果。方法 患者入院后,对创面予以病理活检、微生物培养、摄片等检查后,对创面局部纤维板给予划开清除,逐层削除老化、纤维化肉芽组织,使创面形成相对“新鲜”状态后,采用 MEBO换药治疗(每6 h换药1次),重新培育肉芽组织;全身给予抗感染、改善微循环等治疗。创面肉芽组织成熟后,再次多点活检病理检查,确认创面无明显癌组织后,行“邮票式”植皮手术、周围曲张静脉结扎及分段剥脱术,供皮区使用 MEBO油纱换药治疗;术后5 d,植皮区改用MEBO油纱包扎换药治疗,每日1次,直至创面完全愈合。结果 供皮区创面于术后14 d愈合,植皮区创面于术后30 d痊愈,愈后随访4年,创面轻度瘢痕增生,无新的溃疡创面形成及转移癌发生。结论 MEBO是肉芽组织生长的“培养基”,能促进慢性溃疡创面的愈合,是慢性溃疡创面修复的良好外用药。另外, MEBO可能影响体表肿瘤的生物特性,抑制肿瘤细胞生长。%Objective To observe the efficacy of MEBO in treating malignant transformation of chronic lower limb ulcer. Methods After admission, the wound was examined by pathological biopsy, microbial culture, and imaging. Per-form excision on the local wound fibreboard, excising degenerated and fibrotic granulation tissues layer by layer, exposing the“ fresh” wound surface. Then apply MEBO on the wound and change dressing once every 6 hours, cultivating new granu-lation tissue; systemic anti-infection and microcirculation improvement therapy were performed. When wound granulation tissue matured, multiple site pathological biopsy exam was taken to confirm there was no obvious wound tissue canceration. Then perform“ stamp” skin grafting and peripheral varicose ligation&segmented peeling surgery; the donor site wound was treated

  20. Piwil2基因表达诱导NIH3T3细胞恶性转化%Malignant transformation of HIN3T3 cells induced by expression of Piwil2 genes

    Institute of Scientific and Technical Information of China (English)

    李跃波; 冯定庆; 凌斌; 程敏

    2013-01-01

    目的 通过建立稳定表达外源Piwil2基因的NIH3T3细胞,初步探讨Piwil2基因对NIH3T3细胞生物学特性的调控作用.方法 通过脂质体介导的方法和G418的筛选,建立稳定表达Piwil2基因的NIH3T3细胞株,之后利用细胞集落形成实验、细胞增殖实验、细胞周期分析和裸鼠成瘤实验,观察Piwil2基因表达对NIH3T3细胞的生物学特性的影响.结果 建立了稳定过表达Piwil2基因的NIH3T3细胞株.与对照组空白载体细胞系相比,过表达Piwil2基因的NIH3T3细胞增殖和集落形成能力增强;细胞周期G0/G1期减少、S期明显升高;接种裸鼠后形成的肿瘤体积显著大于对照组.结论 Piwil2基因在NIH3T3细胞中稳定表达具有诱导正常NIH3T3细胞发生恶性转化的重要生物功能.%Objective To establish a mouse fibroblastio cell line stably transfected with Piwil2 gene, and use such cell line to investigate tumor development and progression imposed by the ectopic expression of Piwil2 gene. Methods Eukaryotic expression vector pIRES2-EGFP-Piwil2 was transfected into mouse fibroblast cell line NIH3T3 by lipofectamine. Stable transfect-ants were selected by G418. The integration and expression of Piwil2 gene were analyzed by PCR. And then cell proliferation, cycle and apoptosis in experimental analysis, colony formation and tumor growth experiment were used to observe the impact of Piwil2 gene expression of NIH3T3 on biological characteristics. Results NIH3T3 cell line with stably expression of Piwil2 gene was successfully established and confirmed. Compared with control group, the NIH3T3 cell line with high expression of Piwil2 gene growed quickly and had high capability of colony formation. The S phase and M phase increased significantly. Tumor formation in nude mice was significantly greater than in the control group. Conclusion Expression of Piwil2 gene in NIH3T3 cells can induce malignant transformation of mouse fibroblastic cells both in vitro and in

  1. Familial malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Kopf, A.W.; Hellman, L.J.; Rogers, G.S.; Gross, D.F.; Rigel, D.S.; Friedman, R.J.; Levenstein, M.; Brown, J.; Golomb, F.M.; Roses, D.F.; Gumport, S.L.

    1986-10-10

    Characteristics associated with familial compared with nonfamilial malignant melanoma were assessed. These data were obtained from consecutive prospectively completed questionnaires on 1169 cases of cutaneous malignant melanoma. Of these, 69 patients indicated a positive family history for this cancer. Among the various clinical and histological variables compared, those that significantly correlated with the familial occurrence of malignant melanoma include younger age at first diagnosis, smaller diameter of the lesion, lower Clark level, decreased frequency of nonmelanoma skin cancer, and reduced prevalence of noncutaneous cancer. Increased awareness of malignant melanoma among family members could account for some of these observations. Identification of the familial variety of malignant melanoma has practical implications concerning early detection and prompt intervention.

  2. Malignant tumor formation at the site of previously irradiated acanthomatous epulides in four dogs

    Energy Technology Data Exchange (ETDEWEB)

    Thrall, D.E.; Goldschmidt, M.H.; Biery, D.N.

    1981-01-15

    The radiation response of acanthomatous epulis in 32 dogs was good, with an estimated median survival time of 21 months. Of the 32 patients, 14 have died. In 4 of those 14, malignant tumors developed at the site of the acanthomatous epulis. The tumors were of epithelial origin in 3 patients and of mesenchymal origin in 1 patient. Possibilities explaining the appearance of the malignancies included spontaneous malignant transformation, radiation induction of neoplasms, and radiation induction of malignant transformation. This uncommon complication was not considered contradictory to radiotherapy of acanthomatous epulides, because of their excellent response to irradiation and the long latent period between irradiation and appearance of the malignant tumor.

  3. Stages of Malignant Mesothelioma

    Science.gov (United States)

    ... chest cavity and covers the lungs ) or the peritoneum (the thin layer of tissue that lines the ... to diagnose malignant mesothelioma in the chest or peritoneum: Physical exam and history : An exam of the ...

  4. The Malignant Protein Puzzle.

    Science.gov (United States)

    Walker, Lary C; Jucker, Mathias

    2016-01-01

    When most people hear the words malignant and brain, cancer immediately comes to mind. But our authors argue that proteins can be malignant too, and can spread harmfully through the brain in neurodegenerative diseases that include Alzheimer's, Parkinson's, CTE, and ALS. Studying how proteins such as PrP, amyloid beta, tau, and others aggregate and spread, and kill brain cells, represents a crucial new frontier in neuroscience. PMID:27408676

  5. Sorafenib Tosylate in Treating Patients With Malignant Mesothelioma.

    Science.gov (United States)

    2013-06-04

    Epithelial Mesothelioma; Recurrent Malignant Mesothelioma; Sarcomatous Mesothelioma; Stage IA Malignant Mesothelioma; Stage IB Malignant Mesothelioma; Stage II Malignant Mesothelioma; Stage III Malignant Mesothelioma; Stage IV Malignant Mesothelioma

  6. NPRAP蛋白通过调节小GTP酶活性促进肺癌细胞的恶性转化%NPRAP protein promotes malignant transformation of lung cancer cells by regulating the activity of small GTPases

    Institute of Scientific and Technical Information of China (English)

    张俊毅; 董彩凤; 刘晓辉; 林璐璐; 于佳乐; 刘帅莹

    2013-01-01

    Objective:To explore the influence of NPRAP (neural plakophilin-related armadillo protein) expression on biological behavior of lung cancer cells and its possible mechanism.Methods:The expression level of NPRAP was regulated by plasmid transfection and RNA interference methods in two lung cancer cell lines SK-MES-1 and NCI-H460,respectively.Western blotting was used to detect the expression of NPRAP in cancer cells.Then,the abilities of proliferation and invasion and the morphology of the cancer cells were detected by MTT,Transwell,G-LISA and Pull-Down methods,respectively.The activities of small GTPases (including RhoA,Cdc42,and Rac1) in cancer cells were detected by immunofluorescence assay.At the same time,ML141,an inhibitor of Cdc42 and Rac1 activities,was used to explore whether the change of the activity of small GTPases was involved in the influence of NPRAP on biological behavior of cancer cells or not.Results:Over-expression of NPRAP decreased RhoA activity and increased Cdc42/Rac1 activity,and also promoted the proliferation and invasion abilities of lung cancer cells (P < 0.05),as well as the pseudopodia formation.Conversely,the down-regulation of endogenous NPRAP expression level induced by siRNA (small interference RNA) could increase RhoA activity and decrease Cdc42/Rac1 activity,and also inhibit the proliferation,invasion and pseudopodia formation of lung cancer cells (P < 0.05).In addition,the influence of NPRAP on biological behavior of cancer cells was weakened by using ML1 41 (P < 0.05).Conclusion:NPRAP protein probably results in cytoskeleton reassembly by regulating the activity of small GTPases,and then promotes malignant transformation of lung cancer cells.%目的:探讨NPRAP蛋白表达对肺癌细胞生物学行为的影响及其可能的机制.方法:应用质粒转染和RNA干扰的方法分别调节肺癌细胞株SK-MES-1和NCI-H460中NPRAP的表达水平,蛋白质印迹法检测NPRAP蛋白表达情况后,通过MTT、Transwell、

  7. 食管鳞癌恶性表型相关蛋白的蛋白质组学研究%Proteomic identification of malignant transformation-related proteins in esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    牛保华; 齐义军; 曹世华; 邱政夫; 马远方; 何庆瑜

    2009-01-01

    Objective:To identify differentially expressed proteins related with malignant transformation of esophageal squamous cell carcinoma (ESCC) using proteomic analysis. Methods:Two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization timE-of flight mass spectrometry (MALDI-TOF-MS) in combination with protein database searching were used to determine and identify differentially expressed proteins in esophageal cancer cell lines (EC1, EC18, and EC109) and immortal cell line (NECA-E6E7-hTERT). Western blotting and immunocytochemistry were used to verify the differential expression of annexin 2 in esophageal cancer cell lines and immortal cell line (NECA-E6E7-hTERT). Real-time fluorogentic quantitative PCR(RFQ-PCR) was performed to analyze the expression level of annexin A2 mRNA.Results: A total of 15 differentially expressed proteins were identified with more than 5 folds difference. Among them three proteins were down-regulated and 12 proteins were up-regulated. Western blotting and immunocytochemical analysis verified the down-regulation of annexin A2 protein in ESCC cell lines. However, differential expression pattern of annexin A2 mRNA was not consistant with its protein expression in ESCC cell lines and immortal cell line (NECA-E6E7-hTERT). Conclusion:The findings provide important clues for identifying the candidate biomarkers for high-risk population screening and early diagnosis of ESCC. Post-translative regulation/modification contributes to the down-regulation of annexin A2 protein.%目的:利用蛋白质组学技术探讨与人食管鳞癌细胞(esophageal squamous cell carcinoma, ESCC)恶性表型转化相关的差异表达的蛋白质谱.方法:采用二维双向电泳(two-dimensional electrophoresis, 2-DE)和基质辅助激光解吸电离飞行时间质谱(matrix assisted laser desorption ionisation timE-of-flight mass spectrometry, MALDI-TOF-MS)法鉴定人食管上皮永生化细胞株NECA-E6E7-hTERT和ESCC细胞株EC1

  8. Management of malignant pleural effusions.

    LENUS (Irish Health Repository)

    Uzbeck, Mateen H

    2010-06-01

    Malignant pleural effusions are a common clinical problem in patients with primary thoracic malignancy and metastatic malignancy to the thorax. Symptoms can be debilitating and can impair tolerance of anticancer therapy. This article presents a comprehensive review of pharmaceutical and nonpharmaceutical approaches to the management of malignant pleural effusion, and a novel algorithm for management based on patients\\' performance status.

  9. Activation of NADPH-recycling systems in leaves and roots of Arabidopsis thaliana under arsenic-induced stress conditions is accelerated by knock-out of Nudix hydrolase 19 (AtNUDX19) gene.

    Science.gov (United States)

    Corpas, Francisco J; Aguayo-Trinidad, Simeón; Ogawa, Takahisa; Yoshimura, Kazuya; Shigeoka, Shigeru

    2016-03-15

    NADPH is an important cofactor in cell growth, proliferation and detoxification. Arabidopsis thaliana Nudix hydrolase 19 (AtNUDX19) belongs to a family of proteins defined by the conserved amino-acid sequence GX5-EX7REUXEEXGU which has the capacity to hydrolyze NADPH as a physiological substrate in vivo. Given the importance of NADPH in the cellular redox homeostasis of plants, the present study compares the responses of the main NADPH-recycling systems including NADP-isocitrate dehydrogenase (ICDH), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and NADP-malic enzyme (ME) in the leaves and roots of Arabidopsis wild-type (Wt) and knock-out (KO) AtNUDX19 mutant (Atnudx19) plants under physiological and arsenic-induced stress conditions. Two major features were observed in the behavior of the main NADPH-recycling systems: (i) under optimal conditions in both organs, the levels of these activities were higher in nudx19 mutants than in Wt plants; and, (ii) under 500μM AsV conditions, these activities increase, especially in nudx19 mutant plants. Moreover, G6PDH activity in roots was the most affected enzyme in both Wt and nudx19 mutant plants, with a 4.6-fold and 5.0-fold increase, respectively. In summary, the data reveals a connection between the absence of chloroplastic AtNUDX19 and the rise in all NADP-dehydrogenase activities under physiological and arsenic-induced stress conditions, particularly in roots. This suggests that AtNUDX19 could be a key factor in modulating the NADPH pool in plants and consequently in redox homeostasis. PMID:26878367

  10. Oral verrucous carcinoma arising from lichen planus and esophageal squamous cell carcinoma in a patient with hepatitis C virus-related liver cirrhosis-hyperinsulinemia and malignant transformation: A case report.

    Science.gov (United States)

    Nagao, Yumiko; Sata, Michio

    2013-01-01

    Oral lichen planus (OLP) is a potentially malignant disorder associated with an increased risk of oral cancer. In Japan, the association of OLP with hepatitis C virus (HCV) infection is well documented. In the present study, a case of oral verrucous carcinoma arising from OLP coexisting vulvo-vaginal-gingival syndrome and esophageal squamous cell carcinoma (SCC) in a patient with HCV-related liver cirrhosis is reported. A 71-year old, non-smoking Japanese woman presented with lesions of OLP affecting the bilateral buccal mucosa, tongue, gingival, palate, oral floor and lower lip. Ten years later, an exophytic mass developed in the mandibular alveolar mucosa, the right buccal mucosa and the right lower lip. Pathological diagnosis confirmed the presence of verrucous carcinoma. However, she developed esophageal rather than oral cancer. The oral cancer was resected surgically three times and the patients underwent radiotherapy. The esophageal cancer was removed by endoscopic submucosal dissection. The risk of carcinogenesis increased as hyperinsulinemia continued. The results suggested that it is necessary to monitor for malignant changes in patients with OLP lesions and HCV infection. In addition, treatment requires the cooperation of various medical specialists, as well as an oral surgeon. PMID:24648893

  11. Primary Malignant Tumours of Bone Following Previous Malignancy

    Science.gov (United States)

    Patton, J. T.; Sommerville, S. M. M.; Grimer, R. J.

    2008-01-01

    Destructive bone lesions occurring in patients who have previously had a malignancy are generally assumed to be a metastasis from that malignancy. We reviewed 60 patients with a previous history of malignancy, who presented with a solitary bone lesion that was subsequently found to be a new and different primary sarcoma of bone. These second malignancies occurred in three distinct groups of patients: (1) patients with original tumours well known to be associated with second malignancies (5%); (2) patients whose second malignancies were likely to be due to the previous treatment of their primary malignancy (40%); (3) patients in whom there was no clearly defined association between malignancies (55%). The purpose of this study is to emphasise the necessity for caution in assuming the diagnosis of a metastasis when a solitary bone lesion is identified following a prior malignancy. Inappropriate biopsy and treatment of primary bone sarcomas compromises limb salvage surgery and can affect patient mortality. PMID:18414590

  12. Primary Malignant Tumours of Bone Following Previous Malignancy

    Directory of Open Access Journals (Sweden)

    R. J. Grimer

    2008-04-01

    Full Text Available Destructive bone lesions occurring in patients who have previously had a malignancy are generally assumed to be a metastasis from that malignancy. We reviewed 60 patients with a previous history of malignancy, who presented with a solitary bone lesion that was subsequently found to be a new and different primary sarcoma of bone. These second malignancies occurred in three distinct groups of patients: (1 patients with original tumours well known to be associated with second malignancies (5%; (2 patients whose second malignancies were likely to be due to the previous treatment of their primary malignancy (40%; (3 patients in whom there was no clearly defined association between malignancies (55%. The purpose of this study is to emphasise the necessity for caution in assuming the diagnosis of a metastasis when a solitary bone lesion is identified following a prior malignancy. Inappropriate biopsy and treatment of primary bone sarcomas compromises limb salvage surgery and can affect patient mortality.

  13. 烹调油烟冷凝物诱导永生化人支气管上皮细胞恶性转化的研究%Study for Malignant Transformation of Immortalized Human Bronchial Epithelial (BEP-2D)Cells Induced by Cooking Oil Fumes Condensation

    Institute of Scientific and Technical Information of China (English)

    张诚; 李强; 吴庆琛; 朱茂祥; 杨陟华; 陈丹; 张敏

    2011-01-01

    Objective To find a good method for chronic malignant tranformation of immortalized human bronchial epithelial (BEP-2D) cells induced by cooking oil fumes condensation (COFC ), establish a model of malignant tranformation of BEP-2D cells and discuss the harm of COFC. Methods Cells was divided into control group and experimental group. MTT was used to decide the chronic exposure doses of the COFC. The malignant tendency of transformed BEP-2D cells was identified by anti-blood serum experiment and the malignant features of transformed BEP-2D cells were identified by the method of semisolid agar culture. The capability of COFC inducing differentiation in anti-blood serum experiment and the colony forming frequency of BEP-2D cells in semisolid agar medium in each group were compared. Results The best method for malignant tranformation of BEP-2D cells induced by the COFC was that the BEP-2D cells were treated with COFC at doses of 50 μg/mL respectively. Inoculated to the 20 generations, the cells inoculative efficiency were obviously disparity in the comparison of control group (P < 0.01). Inoculated to the 35th generation, the anchorage independent growth was appeared in the P35 (P < 0.05). The P35 BEP-2DCOFC cells formed tumors in nude mice, and tumors were poorly differentiated to squamous cell carcinoma confirmed by histopathological examination. Conclusion The malignant tranformation of immortalized human bronchial epithelial (BEP-2D) cells could be successfully induced by the COFC at the dose of 50 μg/mL, and the prompt cooking lampblack had the carcinogenicity to the human body.%目的 用烹调油烟冷凝物(COFC)诱导正常永生化人支气管上皮细胞(BEP-2D)慢性恶性转化,构建恶性转化的细胞模型,以探讨COFC的危害.方法 通过MTT法确定诱导物的染毒剂量,以COFC处理细胞,用血清抗性实验和锚着独立生长实验鉴定细胞恶性转化的倾向和恶性特征,比较对照组和实验组抗血清促分化的能力

  14. A Rare Cutaneous Adnexal Tumor: Malignant Proliferating Trichilemmal Tumor

    OpenAIRE

    Omer Alici; Musa Kemal Keles; Alper Kurt

    2015-01-01

    Proliferating trichilemmal tumors (PTTs) are neoplasms derived from the outer root sheath of the hair follicle. These tumors, which commonly affect the scalp of elderly women, rarely demonstrate malignant transformation. Although invasion of the tumors into neighboring tissues and being accompanied with anaplasia and necrosis are accepted as findings of malignancy, histological features may not always be sufficient to identify these tumors. The clinical behavior of the tumor may be incompatib...

  15. Malignant salivary gland tumours

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, S.H. (University of the Witwatersrand, Johannesburg (South Africa). Dept. of Oral Pathology)

    1982-08-01

    The most frequent malignant salivary gland tumours are the mucoepidermoid tumour, adenoid cystic carcinoma and adenocarcinoma. The major salivary glands and the minor glands of the mouth and upper respiratory tract may potentially develop any of these malignant lesions. Malignant lesions most frequently present as a palpable mass and tend to enlarge more rapidly than benign neoplasms. Pain, paresthesia, muscle paralysis and fixation to surrounding tissue are all ominous signs and symptoms. The only reliable means of differential diagnosis of these lesions is biopsy and histologic analysis. Therapy involves surgery or a combination of surgery and radiation therapy. The ultimate prognosis is governed by the intrinsic biologic behaviour of the neoplasms, the extent of disease and adequate clinical therapy.

  16. Surveillance for gastrointestinal malignancies

    Institute of Scientific and Technical Information of China (English)

    Ashish K Tiwari; Heather S Laird-Fick; Ramesh K Wali; Hemant K Roy

    2012-01-01

    Gastrointestinal (GI) malignancies are notorious for frequently progressing to advanced stages even in the absence of serious symptoms,thus leading to delayed diagnoses and dismal prognoses.Secondary prevention of GI malignancies through early detection and treatment of cancer-precursor/premalignant lesions,therefore,is recognized as an effective cancer prevention strategy.In order to efficiently detect these lesions,systemic application of screening tests (surveillance) is needed.However,most of the currently used non-invasive screening tests for GI malignancies (for example,serum markers such as alpha-fetoprotein for hepatocellular carcinoma,and fecal occult blood test,for colon cancer) are only modestly effective necessitating the use of highly invasive endoscopy-based procedures,such as esophagogastroduodenoscopy and colonoscopy for screening purposes.Even for hepatocellular carcinoma where non-invasive imaging (ultrasonography) has become a standard screening tool,the need for repeated liver biopsies of suspicious liver nodules for histopathological confirmation can't be avoided.The invasive nature and high-cost associated with these screening tools hinders implementation of GI cancer screening programs.Moreover,only a small fraction of general population is truly predisposed to developing GI malignancies,and indeed needs surveillance.To spare the average-risk individuals from superfluous invasive procedures and achieve an economically viable model of cancer prevention,it's important to identify cohorts in general population that are at substantially high risk of developing GI malignancies (riskstratification),and select suitable screening tests for surveillance in these cohorts.We herein provide a brief overview of such high-risk cohorts for different GI malignancies,and the screening strategies that have commonly been employed for surveillance purpose in them.

  17. Pleural spill malign

    International Nuclear Information System (INIS)

    The pleural spills are developed because of an alteration in the mechanisms that usually move between 5 and 10 liters of liquid through the space pleural every 24 hours and this is reabsorbed, only leaving 5 to 20 ml present. The causes more common of spill pleural they are: congestive heart failure, bacterial pneumonia, malign neoplasia and pulmonary clot. The causes more common of pleural spill malign in general are: cancer of the lung, cancer of the breast and lymphomas. In the man, cancer of the lung, lymphomas and gastrointestinal cancer. In the woman, cancer of the breast, gynecological cancer and lung cancer. The paper, includes their characteristics, treatments and medicines

  18. Immunotherapy of Genitourinary Malignancies

    Directory of Open Access Journals (Sweden)

    Teruo Inamoto

    2012-01-01

    Full Text Available Most cancer patients are treated with some combination of surgery, radiation, and chemotherapy. Despite recent advances in local therapy with curative intent, chemotherapeutic treatments for metastatic disease often remain unsatisfying due to severe side effects and incomplete long-term remission. Therefore, the evaluation of novel therapeutic options is of great interest. Conventional, along with newer treatment strategies target the immune system that suppresses genitourinary (GU malignancies. Metastatic renal cell carcinoma and non-muscle-invasive bladder caner represent the most immune-responsive types of all human cancer. This review examines the rationale and emerging evidence supporting the anticancer activity of immunotherapy, against GU malignancies.

  19. The Transformations of Transformations.

    Science.gov (United States)

    Lin, Francis Y.

    2000-01-01

    Harris's original idea of transformations has been changed several times in Chomsky's work. This article explicates these transformations, arguing that though their motivations are highly understandable, these transformations are not necessary for understanding the workings of natural languages. (Author/VWL)

  20. Immunotherapy for malignant glioma

    Directory of Open Access Journals (Sweden)

    Carter M Suryadevara

    2015-01-01

    Full Text Available Malignant gliomas (MG are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM, the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM.

  1. The neuroleptic malignant syndrome

    OpenAIRE

    YAZMAN, Yılmaz Niyazi; İYİGÜN, İbrahim

    1998-01-01

    Neuroleptic Malignant Syndrome (NMS) may occur at any time during the course of therapy in as many as 1 percent of persons who take neuroleptics, particulary haloperidol. In this paper, one case with fever (as high as 39 °C), marked rigidity, tachycardia and consciousness is presented, and clinical presentation, treatment and prognosis of NMS is discussed.

  2. AIDS and associated malignancies

    Institute of Scientific and Technical Information of China (English)

    Charles; WOOD; William; HARRINGTON; Jr

    2005-01-01

    AIDS associated malignancies (ARL) is a major complication associated with AIDS patients upon immunosuppression.Chronically immunocompromised patients have a markedly increased risk of developing lymphoproliferative disease. In the era of potent antiretrovirals therapy (ARV), the malignant complications due to HIV- 1 infection have decreased in developed nations where ARV is administered, but still poses a major problem in developing countries where HIV- 1incidence is high and ARV is still not yet widely available. Even in ARV treated individuals there is a concern that the prolonged survival of many HIV- 1 carriers is likely to eventually result in an increased number of malignancies diagnosed.Malignancies that were found to have high incidence in HIV-infected individuals are Kaposi's sarcoma (KS), Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The incidence of NHL has increased nearly 200 fold in HIV-positive patients, and accounts for a greater percentage of AIDS defining illness in the US and Europe since the advent of HAART therapy. These AIDS related lymphomas are distinct from their counterparts seen in HIV- 1 seronegative patients.For example nearly half of all cases of ARL are associated with the presence of a gamma herpesvirus, Epstein Barr virus (EBV) or human herpesvirus-8 (HHV-8)/Kaposi's sarcoma associated herpesvirus (KSHV). The pathogenesis of ARLs is complex. B-cell proliferation driven by chronic antigenemia resulting in the induction of polyclonal and ultimately monoclonal lymphoproliferation may occur in the setting of severe immunosuppression.

  3. Endothelial progenitor cells in hematologic malignancies.

    Science.gov (United States)

    Testa, Ugo; Saulle, Ernestina; Castelli, Germana; Pelosi, Elvira

    2016-01-01

    Studies carried out in the last years have improved the understanding of the cellular and molecular mechanisms controlling angiogenesis during adult life in normal and pathological conditions. Some of these studies have led to the identification of some progenitor cells that sustain angiogenesis through indirect, paracrine mechanisms (hematopoietic angiogenic cells) and through direct mechanisms, i.e., through their capacity to generate a progeny of phenotypically and functionally competent endothelial cells [endothelial colony forming cells (ECFCs)]. The contribution of these progenitors to angiogenetic processes under physiological and pathological conditions is intensively investigated. Angiogenetic mechanisms are stimulated in various hematological malignancies, including chronic myeloid leukemia (CML), acute myeloid leukemia (AML), myelodysplastic syndromes and multiple myeloma, resulting in an increased angiogenesis that contributes to disease progression. In some of these conditions there is preliminary evidence that some endothelial cells could derive from the malignant clone, thus leading to the speculation that the leukemic cell derives from the malignant transformation of a hemangioblastic progenitor, i.e., of a cell capable of differentiation to the hematopoietic and to the endothelial cell lineages. Our understanding of the mechanisms underlying increased angiogenesis in these malignancies not only contributed to a better knowledge of the mechanisms responsible for tumor progression, but also offered the way for the discovery of new therapeutic targets. PMID:27583252

  4. Radiation associated malignant pleural mesothelioma.

    OpenAIRE

    Lerman, Y.; Learman, Y; Schachter, P.; Herceg, E; Lieberman, Y; Yellin, A.

    1991-01-01

    Malignant pleural mesothelioma of epithelial type developed in a 24 year old woman, 20 years after radiotherapy for Hodgkin's disease. This case and a review of published cases indicate that radiation may induce malignant mesothelioma.

  5. Drugs Approved for Malignant Mesothelioma

    Science.gov (United States)

    ... about Your Treatment Research Drugs Approved for Malignant Mesothelioma This page lists cancer drugs approved by the ... are not listed here. Drugs Approved for Malignant Mesothelioma Alimta (Pemetrexed Disodium) Pemetrexed Disodium Drug Combinations Used ...

  6. Serial Analysis of Gene Expression in Immortalized BEP2D Cells and Malignant Transformed BEP2D Cells Induced by α-particle%SAGE方法分析永生化BEP2D细胞及α粒子诱发恶性转化BEP2D细胞的基因表达

    Institute of Scientific and Technical Information of China (English)

    葛世丽; 李刚; 陈伟; 楼铁柱; 吴德昌

    2001-01-01

    知基因的新功能。%Objective: The authors used the serial analysis of gene expression (SAGE) method to analyze transcripts present in the immortalized BEP2D cells and the malignant transformed BEP2D cells. Methods: As a step toward understanding the complex gene expression differences between the immortalized BEP2D cells and the malignant transformed BEP2D cells induced by α  particle,SAGE method was introduced into this experiment. Technological methods included total RNA extraction, mRNA isolation, full length of dscDNA synthesis, PCR, transformation and sequencing. SAGE SoftWare was used to analyze tag sequences and compare the abundance of tags between two SAGE libraries. Results: Two independent SAGE libraries were constructed from the immortalized BEP2D cells and the malignant transformed BEP2D cells induced by 1.5 Gy α  particles. A total of 2 331 SAGE tags were identified for the sequences, representing 252 unique transcripts. Though up to now the obtained information is limited, comparison of the two SAGE libraries indicated a remarkable similarity in the expression profiles. Of the 252 transcripts detected, 12 transcripts (4.8% ) matched no reliable known genes in UniGene library. Combination of Northern blot hybridization, the expression level of TGF β induced Smad7 gene in the malignant transformed cells was higher than that in the immortalized cells. Conversely, Chemokine receptor CCR11 gene was expressed at lower levels in the malignant transformation cells. Conclusion: (1) Out of results given by SAGE,the tendency of the abundance of gene expression and the gene expression differentiation between two cell lines were described. (2) The expression level of TGF β induced Smad7 gene in the malignant transformed BEP2D cells was higher than that in the immortalized cells and chemokine receptor CCR11 gene was expressed at lower levels in the malignant transformed BEP2D cells. (3)SAGE was a powerful method in a quantitative and simultaneous analysis of a large

  7. Diaphyseal medullary stenosis (sclerosis) with bone malignancy (malignant fibrous histiocytoma): hardcastle syndrome

    International Nuclear Information System (INIS)

    Hardcastle syndrome is a rare, autosomally dominant inherited skeletal dysplasia, characterized by diaphyseal sclerosis, medullary stenosis, pathological fractures, bony infarction, and malignant transformation. A 19-year-old proband is presented and discussed, adding a fourth family to the world literature. Radiographic screening of family members is suggested from puberty onward. Thallium scanning is proposed as a more tumor-sensitive screening agent in affected individuals. (orig.). With 2 figs

  8. Hyaluronan in human malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Sironen, R.K. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Tammi, M.; Tammi, R. [Institute of Biomedicine, Anatomy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Auvinen, P.K. [Department of Oncology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Anttila, M. [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Gynecology and Obstetrics, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland); Kosma, V-M., E-mail: Veli-Matti.Kosma@uef.fi [Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio (Finland); Department of Pathology, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio (Finland)

    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.

  9. Pembrolizumab in Treating Patients With Malignant Mesothelioma

    Science.gov (United States)

    2016-05-10

    Biphasic Mesothelioma; Epithelioid Mesothelioma; Peritoneal Malignant Mesothelioma; Pleural Biphasic Mesothelioma; Pleural Epithelioid Mesothelioma; Pleural Malignant Mesothelioma; Pleural Sarcomatoid Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Sarcomatoid Mesothelioma

  10. Epidemiology of ovarian malignancies

    Directory of Open Access Journals (Sweden)

    Akanksha Sood

    2016-01-01

    Conclusions: The epidemiology and presentation of ovarian tumours has remained unchanged since last 3 decades. Nulliparity is not as significant a factor in the aetiology of ovarian malignancy however contraception leading to anovulatory cycles (OC pills may have a protective role. Infertility can be suggested as a risk factor but the treatment for infertility and its role in oncogenesis remains controversial. [Int J Reprod Contracept Obstet Gynecol 2016; 5(1.000: 186-193

  11. Intravascular malignant lymphomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Duverneuil, N.; Lafitte, F.; Chiras, J. [Service de Neuroradiologie Charcot, Batiment Babinski, Hopital de la Salpetriere, 75013 Paris (France); Mokhtari, K. [Service de Neuropathologie, Hopital de la Salpetriere, 75013 Paris (France); Behin, A.; Hoang-Xuan, K. [Departement de Neurologie, Hopital de la Salpetriere, 75013 Paris (France)

    2002-09-01

    Intravascular malignant lymphomatosis is a rare and probably often overlooked disease characterised by massive intravascular proliferation of lymphoid cells, usually with a poor prognosis. CT and MRI appearances are nonspecific; the most suggestive finding being both asymmetrical, bilateral, contrast enhancing high-signal areas on T2 weighting and infarct-like lesions of the cortex and basal ganglia. We report two patients with previously unreported dural and spinal cord involvement. (orig.)

  12. Malignant Catatonia Mimicking Pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Sophia Wong

    2013-01-01

    Full Text Available Malignant catatonia is an unusual and highly fatal neuropsychiatric condition which can present with clinical and biochemical manifestations similar to those of pheochromocytoma. Differentiating between the two diseases is essential as management options greatly diverge. We describe a case of malignant catatonia in a 20-year-old male who presented with concurrent psychotic symptoms and autonomic instability, with markedly increased 24-hour urinary levels of norepinephrine at 1752 nmol/day (normal, 89–470 nmol/day, epinephrine at 1045 nmol/day (normal, <160 nmol/day, and dopamine at 7.9 μmol/day (normal, 0.4–3.3 μmol/day. The patient was treated with multiple sessions of electroconvulsive therapy, which led to complete clinical resolution. Repeat urine collections within weeks of this presenting event revealed normalization or near normalization of his catecholamine and metanephrine levels. Malignant catatonia should be considered in the differential diagnosis of the hypercatecholamine state, particularly in a patient who also exhibits concurrent catatonic features.

  13. [Malignant biliary obstruction].

    Science.gov (United States)

    Hucl, Tomáš

    2016-01-01

    Pancreatic cancer and cholangiocarcinoma are the most common causes of malignant biliary obstruction. They are diseases of increasing incidence and unfavorable prognosis. Only patients with localized disease indicated for surgery have a chance of long-term survival. These patients represent less than 20 % of all patients, despite the progress in our diagnostic abilities.Locally advanced and metastatic tumors are treated with palliative chemotherapy or chemoradiotherapy; the results of such treatments are unsatisfactory. The average survival of patients with unresectable disease is 6 months and only 5-10 % of patients survive 5 years.Biliary drainage is an integral part of palliative treatment. Endoscopically or percutaneosly placed stents improve quality of life, decrease cholestasis and pruritus, but do not significantly improve survival. Biliary stents get occluded over time, possibly resulting in acute cholangitis and require repeated replacement.Photodynamic therapy and radiofrequency ablation, locally active endoscopic methods, have been increasingly used in recent years in palliative treatment of patients with malignant biliary obstruction. In photodynamic therapy, photosensitizer accumulates in tumor tissue and is activated 48 hours later by light of a specific wave length. Application of low voltage high frequency current during radiofrequency ablation results in tissue destruction by heat. Local ablation techniques can have a significant impact in a large group of patients with malignant biliary obstruction, leading to improved prognosis, quality of life and stent patency. PMID:26898789

  14. Model Transformations? Transformation Models!

    NARCIS (Netherlands)

    Bézivin, J.; Büttner, F.; Gogolla, M.; Jouault, F.; Kurtev, I.; Lindow, A.

    2006-01-01

    Much of the current work on model transformations seems essentially operational and executable in nature. Executable descriptions are necessary from the point of view of implementation. But from a conceptual point of view, transformations can also be viewed as descriptive models by stating only the

  15. Quantitative Immunoexpression of EGFR in Oral Potentially Malignant Disorders: Oral Leukoplakia and Oral Submucous Fibrosis

    OpenAIRE

    Jyothi Meka, Naga; Ugrappa, Sridevi; Velpula, Nagalaxmi; Kumar, Sravan; Naik Maloth, Kotya; Kodangal, Srikanth; Ch, Lalitha; Goyal, Stuti

    2015-01-01

    Background and aims. Many oral squamous cell carcinomas develop from potentially malignant disorders (PMDs)which include a variety of lesions and conditions characterized by an increased risk for malignant transformation. Thisstudy evaluated the quantitative expression of EGFR in normal oral mucosa, oral leukoplakia and oral submucous fibrosis to predict the malignant risk in compliance with the intensity of staining with EGFR. Materials and methods. Thirty subjects were included in the study...

  16. Increased nuclear ?-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia

    OpenAIRE

    Reyes Rojas, Montserrat; Rojas Alcayaga, Gonzalo; Maturana Ramírez, Andrea; Aitken Saavedra, Juan; Rojas, Carolina; Ortega Pinto, Ana Verónica

    2015-01-01

    Background Deregulation of ?-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear ?-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC). Material and Methods Cross sectional study. Immunodetection of ?-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate...

  17. Malignancy within a Tail Gut Cyst: A Case of Retrorectal Carcinoid Tumour

    OpenAIRE

    Abukar, A. A.; B. J. Parcell; Lim, C. B.; P. V. Patil; Ramsanahie, A.; Carey, F.; Steele, R. J. C.; M. A. Thaha

    2014-01-01

    Purpose. Tailgut cysts with malignant transformation are rare entities. We discuss the diagnostic strategy and treatment of a malignancy within a tailgut cyst. Methods. In this study we report on the case of a 61-year-old man with a malignant neuroendocrine tumour arising within a tailgut cyst and an overview of the literature emphasising the histopathological characteristics and differential diagnosis. Results. Our patient presented with lower back pain, rectal pain, and increased urgency...

  18. Correlation between histological grading and ploidy status in potentially malignant disorders of the oral mucosa: A flow cytometric analysis

    Directory of Open Access Journals (Sweden)

    T Vijayavel

    2013-01-01

    Full Text Available Background: Histopathological grading of oral dysplastic lesions is the method of choice for evaluating malignant and potentially malignant disorders. Owing to inter- and intra-observer variability, determination of the DNA ploidy status of lesions may serve as an adjunct in the prediction of malignant transformation. Aim: To correlate histopathological grading and ploidy status in potentially malignant and malignant disorders of the oral mucosa. Settings and Design: A pilot study was done with 30 patients (10 patients with oral potentially malignant disorders predominantly leukoplakia, 10 patients with oral malignant lesions and 10 patients with normal mucosa. Materials and Methods: Incisional biopsy was done after isolating the biopsy site with 1% Toluidine blue staining. Two sections of the tissue were removed and sent for histopathological and Flow-cytometric analysis respectively. Histopathological diagnosis was obtained and compared with Flow-cytometric results which were graded as diploid and aneuploid. Further, the S - phase fraction, DNA index were also calculated to evaluate the severity of malignant transformation or malignancy. Statistical Analysis: The results were analyzed using Pearson Chi-Square Test. Results: There exists a significant correlation between histopathology and ploidy status in both potentially malignant and malignant group. (P = 0.002. Conclusion: The data from this study has shown that DNA Ploidy analysis can be used as a valuable tool in assessing the carcinomatous progression of potentially malignant and malignant lesions.

  19. [EUS results of malignant rectal giant condyloma acuminatum (Buschke-Loewenstein tumor)].

    Science.gov (United States)

    Strock, Paul; Barrioz, Thierry; Lauroy, Johny; Babin, Philippe; Mordi, Abdel; Fort, Eric; Laurin, Christine; Sevestre, Christian; Silvain, Christine

    2004-01-01

    Giant condyloma acuminatum is a large, exophytic, cauliflower-like lesion that usually affects the anogenital region. Localisation in the rectum is uncommon and has a high rate of malignant transformation but does not lead to develop distant metastases. For the time, we report the endosonographic appearance of a malignant intrarectal giant condyloma acuminatum.

  20. Astroglial c-Myc overexpression predisposes mice to primary malignant gliomas

    DEFF Research Database (Denmark)

    Jensen, Niels Aagaard; Pedersen, Karen-Marie; Lihme, Frederikke;

    2003-01-01

    Malignant astrocytomas are common human primary brain tumors that result from neoplastic transformation of astroglia or their progenitors. Here we show that deregulation of the c-Myc pathway in developing astroglia predisposes mice to malignant astrocytomas within 2-3 weeks of age. The geneticall...

  1. Helminths and malignancy

    DEFF Research Database (Denmark)

    Vennervald, Birgitte J; Polman, K.

    2009-01-01

    number of people who are exposed or infected worldwide. Carcinogenesis associated with helminth infections is a complex process, which may involve several different mechanisms, but chronic inflammation is a key feature. Host immune responses and immunopathological processes mediate inflammatory responses......-malignant change has taken place. Three helminth infections have been classified as definitely carcinogenic to humans (group 1 carcinogens), namely Schistosoma haematobium, which is associated with cancer of the urinary bladder and the food-borne liver flukes Clonorchis sinensis and Opisthorchis viverrini...... coupled with health education, especially in relation to food-borne liver fluke infections....

  2. Synchronous colonic malignancy

    Directory of Open Access Journals (Sweden)

    Prasad Dasharath Hake

    2016-09-01

    Full Text Available Synchronous colorectal neoplasias, defined as 2 or more primary tumors identified in the same patient and at the same time, are caused by common genetic and environmental factors. Since intraoperative palpation can miss up to 69% of the SN, currently, synchronous neoplastic lesions are usually diagnosed at a preoperative staging by colonoscopy or virtual colonoscopy; according to data from literature, 3% of the patients with SN are affected by different types of malignant lesions while 33-55% shows villous adenomas. Literature also confirms the presence of primitive synchronous cancers; malignant synchronous lesions are very rare, showing the following incidence: between 0,17% and 0.69% in case of 2-3 synchronous lesions, 0.19% in case of 4-5 synchronous lesions. The most voluminous synchronous cancer is called "first primitive" or "index" cancer. When the index cancer is located in the caecum, the incidence of left colon synchronous cancers is higher than when the index cancer is located in the left colon. Colorectal adenomas standard treatment is usually represented by endoscopic polypectomy; indeed only 5% of synchronous colorectal lesions require a surgical treatment. [Int J Res Med Sci 2016; 4(9.000: 4212-4215

  3. Epigenetics in the hematologic malignancies

    OpenAIRE

    Fong, Chun Yew; Morison, Jessica; Dawson, Mark A.

    2014-01-01

    A wealth of genomic and epigenomic data has identified abnormal regulation of epigenetic processes as a prominent theme in hematologic malignancies. Recurrent somatic alterations in myeloid malignancies of key proteins involved in DNA methylation, post-translational histone modification and chromatin remodeling have highlighted the importance of epigenetic regulation of gene expression in the initiation and maintenance of various malignancies. The rational use of targeted epigenetic therapies...

  4. Ibrutinib for B cell malignancies

    OpenAIRE

    Novero, Aileen; Ravella, Pavan M; Chen, Yamei; Dous, George; Liu, Delong

    2014-01-01

    Research over the role of Bruton’s agammaglobulinemia tyrosine kinase (BTK) in B-lymphocyte development, differentiation, signaling and survival has led to better understanding of the pathogenesis of B-cell malignancies. Down-regulation of BTK activity is an attractive novel strategy for treating patients with B-cell malignancies. Ibrutinib (PCI-32765), a potent inhibitor of BTK induces impressive responses in B-cell malignancies through irreversible bond with cysteine-481 in the active site ...

  5. Temozolomide in malignant glioma

    Directory of Open Access Journals (Sweden)

    Gregor Dresemann

    2010-07-01

    Full Text Available Gregor DresemannCenter for Neurooncology at Aerztehaus Velen, Velen, GermanyAbstract: Glioblastoma multiforme WHO grade IV (GBM is the most aggressive ­malignant glioma and the most frequent primary tumor of the central nervous system. The median ­survival of newly diagnosed GBM patients was between 9 to 12 months prior to treatment with ­temozolomide being introduced. Primary resection that is as complete as possible is recommended for malignant glioma. Conventional fractionated irradiation 55 to 60 gy with concomitant temozolomide followed by standard temozolomide 6 cycles (5/28 (EORTC/NCIC-regime published by R Stupp in 2005 is the standard of care for newly diagnosed GBM after surgery, independent of the methylation status of the MGM-T gene promoter. Age is no ­contraindication for treatment with temozolomide, although comorbidity and performance status have to be ­considered. For temozolomide naive GBM and astrocytoma grade III patients with disease progression, temozolomide is still the treatment of choice outside of clinical studies. A ­general consensus regarding the schedule of choice has not yet been achieved; so far the 5 out of 28 days regimen (5/28 is the standard of care in most countries. Patients with disease progression after standard temozolomide (5/28 are candidates for clinical studies. Outside of clinical ­studies, dose-dense (7/7, prolonged (21/28, or metronomic (28/28 temozolomide, or alternatively a nitrosourea-based regimen can be an option. The excellent toxicity profile of ­temozolomide allows for various combinations with antitumor agents. None of these ­combinations, however, have been demonstrated to be statistically significantly superior compared to temozolomide alone. The role of lower dosed, dose-dense, or continuous regimen with or without drug combination and the role of temozolomide for newly diagnosed astrocytoma grade III and low grade glioma still has to be determined.Keywords: glioblastoma

  6. 单核巨噬细胞在煤焦沥青烟提取物诱导永生化人支气管上皮细胞恶变中的作用%The Effects of monocyte-macrophages on malignant transformation of human bronchial epithelial cells induced by extracts from coal tar pitch

    Institute of Scientific and Technical Information of China (English)

    周凡静; 张少峰; 冯斐斐; 燕贞; 王威; 吴逸明

    2012-01-01

    目的 探讨单核巨噬细胞(THP-1)在煤焦沥青烟提取物(coal tar pitch,CTP)致永生化人支气管上皮细胞(human bronchial epithelial cells,BEAS-2B)恶变过程中的作用及肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α)在该过程中的表达.方法 以THP-1和BEAS-2B为研究对象,设立CTP组、苯并(a)芘[B(a)P]组(阳性对照组)、二甲亚砜对照组(溶剂对照组)、BEAS-2B与THP-1共培养组,建立细胞恶性变模型.应用软琼脂集落形成实验、染色体数目畸变分析、流式细胞仪测定细胞周期中不同培养时期(10、20、30代)细胞的恶变情况,利用ELISA方法测定CTP组及共培养组细胞培养上清中TNF-α的含量.结果 染色体数目异常在实验的早期(10代)已经显现,表现为非整倍体和多倍体比例增加,二倍体数目减少.在第20代:共培养组克隆形成率(17.63‰±0.97‰)明显高于CTP组(13.94‰±0.84‰)和阳性对照组组(12.96‰± 1.62‰),差异有统计学意义(P<0.05);共培养组S期细胞比例(44.49%±0.68%)明显高于CTP组(38.19%±1.26%)和阳性对照组(36.41%±1.19%),差异有统计学意义(P<0.05).共培养组细胞培养上清中TNF-α含量明显高于CTP组,差异有统计学意义(P<0.01).结论 THP-1能够加速CTP诱导的BEAS-2B恶变,增加TNF-α的表达水平.%Objective To study the effects of monocyte-macrophages (THP-1) in malignant transformation of human bronchial epithelial cells (BEAS-2B) cells induced by coal tar pitch (CTP) and the expression of TNF-α in the process of the cell malignant transformation.Methods BEAS-2B cells and THP-1 Cells were divided into four groups:coal tar pitch (CTP) group,benzo(a)pyrene [B(a)P] group,dimethyl sulfoxide (DMSO) group,BEAS-2B and THP-1 co-culture (co-culture group) group.Carcinogenesis model was established.The soft agar colony formation,chromosome aberrations and cell cycle tests were used to detect the cellular malignant transformation.The ELISA

  7. Lung scans and malignancy

    International Nuclear Information System (INIS)

    An experience of pulmonary isotope scanning carried out with mercury 197 labelled mercury chloride and acetate, cobalt 57-labelled bleomycin, and Cu67 and Cu64 labelled copper citrate was presented. The scans were carried out with various isotopes supplied by the French Atomic Energy Authority, and gave comparable results, which may be summarised as follows: increased uptake in more than 90% of cases of carcinoma, absent uptake in all cases of benign tumour, frequent increased uptake in acute or advanced inflammatory lesions, absence of uptake, very commonly, in tuberculoma and chronic lesions with scar formation. Radio-isotope scan using Cu67 labelled copper citrate permitted discrimination of malignant tumours (increased fixation which showed up best at the 24th hour) from inflammatory lesions (increased fixation which was reduced on the 24th hour). The positive or negative character of the fixation in a given lesions remains the same, whatever the isotope used in our experience

  8. Neuroleptic malignant syndrome

    Directory of Open Access Journals (Sweden)

    Mariana Moscovich

    2011-10-01

    Full Text Available Neuroleptic malignant syndrome (NMS is a potentially fatal adverse event associated with the use of antipsychotics (AP. The objective of this study was to investigate the profile of cases of NMS and to compare our findings with those published in similar settings. A series of 18 consecutive patients with an established diagnosis of NMS was analyzed, gathering data on demography, symptoms and signs. Two thirds of all cases involved woman with a past medical history of psychiatric disorder receiving relatively high doses of AP. The signs and symptoms of NMS episodes were similar to those reported in other series and only one case had a fatal outcome, the remaining presenting complete recovery. As expected, more than two thirds of our cases were using classic AP (68%, however the clinical profile of these in comparison with those taking newer agent was similar. Newer AP also carry the potential for NMS.

  9. Oculocutaneous malignancies in xeroderma pigmentosum.

    OpenAIRE

    Varghese R; Raghuveer C

    1997-01-01

    Xeroderma pigmentosum is a rare autosomal recessive genodermatosis characterized by markedly increased sensitivity to sunlight, and the early development of skin tumours. Four cases of XP with malignancy have been described with a brief review of the literature. The cases have been documented with a view to study the evolution of the disease process and the development of malignancy during the follow up period.

  10. Malign katatoni, et neuropsykiatrisk syndrom

    DEFF Research Database (Denmark)

    Moltke, Katinka; Lublin, Henrik

    2010-01-01

    This case report describes a 36-year-old schizophrenic man who developed malignant catatonia during a hospital stay. He was treated with benzodiazepines (BZD) and 26 sessions of electroconvulsive therapy (ECT). After the therapy his condition normalised. Malignant catatonia is a rare condition...

  11. Genetics Home Reference: malignant hyperthermia

    Science.gov (United States)

    ... on PubMed GeneReview: Malignant Hyperthermia Susceptibility Litman RS, Rosenberg H. Malignant hyperthermia: update on susceptibility testing. JAMA. ... 27(10):977-89. Review. Citation on PubMed Rosenberg H, Davis M, James D, Pollock N, Stowell ...

  12. Malignant priapism: a case report.

    LENUS (Irish Health Repository)

    Ellanti, P

    2011-12-01

    Metastatic involvement of the penis is most commonly from a primary malignant genitourinary tumour. It is a rare phenomenon usually reflecting disseminated malignancy associated with a poor prognosis. Metastasis to the penis mimicking priapism is extremely rare, particularly in the absence of disseminated disease.

  13. Arsenic-induced promoter hypomethylation and over-expression of ERCC2 reduces DNA repair capacity in humans by non-disjunction of the ERCC2-Cdk7 complex.

    Science.gov (United States)

    Paul, Somnath; Banerjee, Nilanjana; Chatterjee, Aditi; Sau, Tanmoy J; Das, Jayanta K; Mishra, Prafulla K; Chakrabarti, Partha; Bandyopadhyay, Arun; Giri, Ashok K

    2014-04-01

    Arsenic in drinking water is of critical concern in West Bengal, India, as it results in several physiological symptoms including dermatological lesions and cancers. Impairment of the DNA repair mechanism has been associated with arsenic-induced genetic damage as well as with several cancers. ERCC2 (Excision Repair Cross-Complementing rodent repair, complementation group 2), mediates DNA-repair by interacting with Cdk-activating kinase (CAK) complex, which helps in DNA proof-reading during transcription. Arsenic metabolism alters epigenetic regulation; we tried to elucidate the regulation of ERCC2 in arsenic-exposed humans. Water, urine, nails, hair and blood samples from one hundred and fifty seven exposed and eighty eight unexposed individuals were collected. Dose dependent validation was done in vitro using HepG2 and HEK-293. Arsenic content in the biological samples was higher in the exposed individuals compared with the content in unexposed individuals (p < 0.001). Bisulfite-modified methylation specific PCR showed a significant (p < 0.0001) hypomethylation of the ERCC2 promoter in the arsenic-exposed individuals. Densitometric analysis of immunoblots showed a nearly two-fold increase in expression of ERCC2 in exposed individuals, but there was an enhanced genotoxic insult as measured by micronuclei frequency. Immuno-precipitation and western blotting revealed an increased (p < 0.001) association of Cdk7 with ERCC2 in highly arsenic exposed individuals. The decrease in CAK activity was determined by observing the intensity of Ser(392) phosphorylation in p53, in vitro, which decreased with an increase in arsenic dose. Thus we infer that arsenic biotransformation leads to promoter hypomethylation of ERCC2, which in turn inhibits the normal functioning of the CAK-complex, thus affecting DNA-repair; this effect was highest among the arsenic exposed individuals with dermatological lesions. PMID:24473091

  14. Thermoradiotherapy of malignant tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, Kazuo; Itami, Jun; Arimizu, Noboru (Chiba Univ. (Japan). School of Medicine); Uno, Takashi; Toita, Takafumi; Shiina, Takeki; Mikuriya, Shuuichi; Yamada, Tsunehisa

    1991-06-01

    From October 1986 to June 1989, 79 patients with malignant tumors were treated by radiation therapy combined with hyperthermia at National Medical Center Hospital. Seventy two patients (male: 48, female: 23) were evaluable. Average age was 62.4 years old (ranged 20-81 years old). Irradiation was delivered twice to fifth weekly in tumor doses of 50 to 60 Gy (TDF 82-122). We used 3 types of hyperthermic equipment, Thermotron RF8, BSD 1000 System and Endoradiotherm 100A. Hyperthermia was initiated within 30 minutes following irradiation, most of the patients being treated with adequate equipment, 41-44degC, for 60-70 minutes every 72 hours. Fifteen of 71 patients (20.8%) showed a complete response and 36 patients (50%) showed a partial response, so effective rate was 70.8% of all. In superficial tumors, 4 of 21 patients (21.5%) showed a complete response and 8 of 21 patients showed a partial response, effective rate was 63.2% of all. In deep seated tumor, 10 of 46 patients (21.7%) showed a complete response and 25 of all patients showed a partial response, so effective rate was 76.1% of all. Five patients were heated following only intra-tumor injection of OK-432 and its effective rate was 75%. We think that this modality of therapy will be effective in cases which heating area had been irradiated over tolerable doses. CR rate of superficial tumors according to intra-tumor center temperature tends to higher in the cases of higher tumor temperature. In deep seated tumor, 11 patients (23.9%) had reached over 43degC, 29 patients (63.0%) heated 41-43degC, 6 patients (13.0%) heated under 41degC and CR rate of each group were 36.4%, 17.2%, 16.7%, respectively. We think that thermotherapy with irradiation is an effective therapy in the treatment of malignancies but the improvement of heating equipment will be expected. (author).

  15. Childhood ovarian malignancy.

    Science.gov (United States)

    Mahadik, Kalpana; Ghorpade, Kanchanmala

    2014-04-01

    Objective of this article is to appraise diagnostic aspects and treatment modalities in childhood ovarian tumor in background of available evidence. Literature search on Pubmed revealed various aspects of epidemiology, histopathological diagnosis, and treatment of pediatric ovarian tumor. 85 % of childhood tumors are germ cell tumors. The varied histopathological picture in germ cell tumors poses a diagnostic and therapeutic challenge. Immunohistochemistry and newer genetic markers like SALL4 and karyopherin-2 (KPNA2) have been helpful in differentiating ovarian yolk sac tumor from dysgerminoma, teratomas, and other pictures of hepatoid, endometrioid, clear cell carcinomatous, and adenocarcinomatous tissues with varied malignant potential. Before platinum therapy, these tumors were almost fatal in children. Fertility-conserving surgery with bleomycin, etoposide, and cisplatin has dramatically changed the survival rates in these patients. This modality gives cancer cure with healthy offspring to female patients with childhood ovarian tumor. Evidence also supports this protocol resulting in successful pregnancy rates and safety of cytotoxic drugs in children born to these patients. PMID:24757335

  16. Malignant renal tumors in children

    Directory of Open Access Journals (Sweden)

    Justin Scott Lee

    2015-05-01

    Full Text Available Renal malignancies are common in children. While the majority of malignant renal masses are secondary to Wilms tumor, it can be challenging to distinguish from more aggressive renal masses. For suspicious renal lesions, it is crucial to ensure prompt diagnosis in order to select the appropriate surgical procedure and treatment. This review article will discuss the common differential diagnosis that can be encountered when evaluating a suspicious renal mass in the pediatric population. This includes clear cell sarcoma of the kidney, malignant rhabdoid tumor, renal medullary carcinoma and lymphoma. 

  17. Effects of miR-200 family overexpression on migration of malignantly transformed human bronchial epithelial cells induced by α-particles%过表达miR-200家族对α粒子诱发恶性转化人支气管上皮细胞迁移能力的影响

    Institute of Scientific and Technical Information of China (English)

    高刚; 杨英杰; 刘建香; 田梅; 苏旭

    2013-01-01

    OBJECTIVE: To explore effects of miR-200 family overexpression on migration of malignantly transformed human bronchial epithelial cells (RHT35) induced by α-particles. METHODS:The mRNA and protein levels of ZEB family (ZEB1 and ZEB2) and epithelial-mesenchymal transition marker in RHT35 was measured by Real Time PCR and western blot 72 h after transfection of 100 nmol/L miR-200b mimic, miR-141 mimic or mimic control into RHT35 cells with SiPORT reagent. In vitro wound healing assay was used to investigate whether overexpression of miR- 200b and miR-141 could block migration of malignantly transformed cells induced by α-particles. RESULTS:The protein levels of ZEB1 and ZEB2 in RHT35 cells were upregulated compared with R15H20 and BEP2D cells. Overexpression of miR-200b and miR-141 led to reduced expression of ZEB1 and ZEB2 in RHT35 cells compared with mimic control (P<0.01). Overexpressions of miR-200b and miR-141 upregulated E-cad expression (P<0.05 or P<0.01) and downregulated N-cad expression in RHT35 cells (P<0.01). Overexpressions of miR-200b and miR-141 markedly blocked migration of RHT35 cells compared with mimic control. CONCLUSION:Overexpressions of miR-200b and miR-141 strongly block migration of RHT35 cells.%目的:探讨过表达miR-200家族对α粒子诱发恶性转化人支气管上皮细胞 (RHT35细胞)迁移能力的影响.方法:用SiPORT转染试剂转染100 nmol/L miR-200b mimic和miR-141 mimic或阴性对照 (mimic control)于RHT35细胞中72 h后,分别采用免疫印迹、实时荧光定量PCR技术检测过表达miR-200b和miR-141对 RHT35细胞ZEB家族 (ZEB1和ZEB2)及上皮间质转变相关标志分子表达的影响;并用伤口愈合实验研究过表达miR-200b和miR-141对RHT35细胞迁移能力的影响.结果:ZEB1和ZEB2蛋白在RHT35细胞中高表达.与阴性对照转染组相比,miR-200b mimic和miR-141 mimic转染组中miR-200靶基因ZEB家族表达显著下调(P<0.01);而上皮间质

  18. Treatment Option Overview (Malignant Mesothelioma)

    Science.gov (United States)

    ... chest cavity and covers the lungs ) or the peritoneum (the thin layer of tissue that lines the ... to diagnose malignant mesothelioma in the chest or peritoneum: Physical exam and history : An exam of the ...

  19. Treatment Options for Malignant Mesothelioma

    Science.gov (United States)

    ... chest cavity and covers the lungs ) or the peritoneum (the thin layer of tissue that lines the ... to diagnose malignant mesothelioma in the chest or peritoneum: Physical exam and history : An exam of the ...

  20. General Information about Malignant Mesothelioma

    Science.gov (United States)

    ... chest cavity and covers the lungs ) or the peritoneum (the thin layer of tissue that lines the ... to diagnose malignant mesothelioma in the chest or peritoneum: Physical exam and history : An exam of the ...

  1. AMG 319 Lymphoid Malignancy FIH

    Science.gov (United States)

    2016-01-20

    Cancer; Chronic Lymphocytic Leukemia; Diffuse Large Cell Lymphoma; Hematologic Malignancies; Hematology; Leukemia; Low Grade Lymphoma; Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Oncology; Oncology Patients; T Cell Lymphoma; Tumors

  2. Drugs Approved for Malignant Mesothelioma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  3. Bile duct malignancies.

    Science.gov (United States)

    Tucek, S; Tomasek, J; Halámkova, J; Kiss, I; Andrasina, T; Hemmelová, B; Adámková-Krákorová, D; Vyzula, R

    2010-01-01

    Bile duct malignancies include intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gall bladder carcinoma (GC) and carcinoma of Vater's ampulla (ampulloma). Bile duct neoplasms are rare tumours with overall poor prognosis. The overall incidence affects up to 12.5 per 100,000 persons in the Czech Republic. The mortality rate has risen recently to 9.5 per 100,000 persons. The incidence and mortality have been remarkably stable over the past 3 decades. The survival rate of patients with these tumours is poor, usually not exceeding 12 months. The diagnostic process is complex, uneasy and usually late. Most cases are diagnosed when unresectable, and palliative treatment is the main approach of medical care for these tumours. The treatment remains very challenging. New approaches have not brought much improvement in this field. Standards of palliative care are lacking and quality of life assessments are surprisingly not common. From the scarce data it seems, however, that multimodal individually tailored treatment can prolong patients'survival and improve the health-related quality of life. The care in specialized centres offers methods of surgery, interventional radiology, clinical oncology and high quality supportive care. These methods are discussed in the article in greater detail. Improvements in this field can be sought in new diagnostic methods and new procedures in surgery and interventional radiology. Understanding the tumour biology on the molecular level could shift the strategy to a more successful one, resulting in more cured patients. Further improvements in palliative care can be sought by defining new targets and new drug development. The lack of patients with bile duct neoplasms has been the limiting factor for any improvements. A new design of larger randomized international multicentric clinical trials with prompt data sharing could help to overcome this major problem. Defining standards of palliative care is a necessity

  4. 煤焦沥青烟提取物致BEAS-2B恶性转化细胞中姊妹染色单体分离相关蛋白的改变%Change of structurol maintenance of chromosome(SMC )1, SMC3, separase and securin expression in BEAS-2B malignant transformation cell induced by coal tar pitch smoke extracts

    Institute of Scientific and Technical Information of China (English)

    李智涛; 王威; 赵勇; 王丽霞; 祝寒松; 吴卫东; 吴逸明

    2010-01-01

    目的 通过检测姊妹染色体凝集和分离相关蛋白染色体结构维持蛋白(SMC)1、SMC3、分离酶(Separase)和保全素(Securin)在煤焦沥青致BEAS-2B癌变细胞中的变化,探讨其在煤焦沥青接触者肺癌发生中的作用.方法 用中温煤焦沥青烟提取物作为诱导剂,建立永生化人支气管上皮细胞BEAS-2B的恶性转化模型,用实时定量反转录-聚合酶链反应(RT-PCR)检测相关基因的mRNA表达水平;细胞爬片免疫组化半定量法检测其蛋白表达改变.以二甲亚砜(DMSO)溶剂组和未染毒的正常传代的BEAS-2B细胞为对照组.结果 与正常对照组和DMSO溶剂对照组比较,煤焦沥青烟提取物诱导转化细胞中,SMC1基因和蛋白表达水平的差异无统计学意义(P>0.05);煤焦沥青烟诱导组SMC3和Separase的基因和蛋白表达水平明显升高(基因:SMC3:2.54±0.20、Separase:2.42±0.22,蛋白:SMC3:0.27±0.02、Separase:0.25±0.02),Securin的基因和蛋白表达水平明显降低(基因:0.30±0.04,蛋白:0.17±0.01),与其他两组(DMSO溶剂对照组:基因:SMC3:1.13±0.12、Separase:1.00±0.04、Securin:0.90±0.11,蛋白:SMC3:0.10±0.03、Separase:0.18±0.02、Securin:0.22±0.02;正常对照组:基因:SMC3:1.00±0.11、Separase:1.00±0.08、Securin:1.00±0.11,蛋白:SMC3:0.09±0.01、Separase:0.18±0.01、Securin:0.23±0.02)相比,差异均有统计学意义(P<0.05).结论 在煤焦沥青致支气管上皮细胞恶性转化过程中,姊妹染色单体凝集和分离相关蛋白SMC3和Separase升高,Securin表达水平降低,参与了细胞恶性转化过程.%Objective To study the role of structural maintenance of chromosome (SMC)1, SMC3,Separase and Securin in tumorgenesis that contact with coal tar pitch. Methods The BEAS-2B cells was induced by coal tar pitch smoke extracts to form malignant transformation cell model in vitro. The gene expression levels of mRNA were assessed by real-time quantitative RT-PCR, and the protein expression variation

  5. Liver cell adenoma with malignant transformation: A case report

    OpenAIRE

    Ito, Masahiro; Sasaki, Makoto; Wen, Chun Yang; Nakashima, Masahiro; Ueki, Toshihito; Ishibashi, Hiromi; Yano, Michitami; KAGE, MASAYOSHI; KOJIRO, MASAMICHI

    2003-01-01

    A 57-year-old woman was referred to our hospital because of a liver mass detected by computed tomography. She had taken oral contraceptives for only one month at the age of thirty. Physical examination revealed no abnormalities, and laboratory data, including hepatic function tests, were within the normal range, with the exception of elevated levels of those serum proteins induced by the absence of vitamin K or by raised levels of the antagonist (PIVKA)-II (3502 AU/mL). Abdominal ultrasonogra...

  6. Gastrointestinal neurofibromatosis with malignant transformation: a case report

    Institute of Scientific and Technical Information of China (English)

    Fariba Binesh; Ali Akhavan; Saeed Arefanian; Manuchehr Haidari

    2013-01-01

    Neurofibromatosis type1 (NF1), also known as Von Recklinghausen's disease with approximate occurrence of 1/3000 births, can be considered as a common autosomal dominant condition. Abdominal organs can be involved as neurofibroma and tumor growth in the liver, mesentery, retroperitoneum, stomach and bowel. Association of NF and gastrointestinal peripheral nerve sheath tumor (MPNST), usually arising within a pre-existing plexiform neurofibroma which metastasizes widely heraldinga poor outcome. We report a 55 year old man with gastrointestinal NF which ultimately developed MPNST and deceased.

  7. Malignant transformation of a unicameral bone cyst in a cat.

    Science.gov (United States)

    Berger, Björn; Brühschwein, Andreas; Eddicks, Lina; Meyer-Lindenberg, Andrea

    2016-04-01

    A unicameral bone cyst in the proximal humerus of a 3-year-old Norwegian forest cat was diagnosed by dynamic contrast-enhanced magnetic resonance imaging, surgical exploration, and histopathology. Surgical curettage and incorporation of bone cement led to full recovery. An osteosarcoma developed at the surgical site 17 months later. Thoracic radiographs showed pulmonary lesions consistent with metastasis. PMID:27041754

  8. Genital donovanosis with malignant transformation: An interesting case report

    Directory of Open Access Journals (Sweden)

    K Navya Sri

    2014-01-01

    Full Text Available Donovanosis is a chronic indolent sexually transmitted granulomatous ulceration of genito-inguinal region, caused by Calymmatobacterium granulomatis. It became uncommon due to indiscriminate use of broad spectrum antibiotics. In recent years, much interest is being focused on this condition because genital ulcers facilitate HIV infection. We report an interesting episode of genital donovanosis complicated with squamous cell carcinoma in a middle aged female for its rarity and clinical interest.

  9. Malignant transformation and treatment of cystic mixed germ cell tumor

    Institute of Scientific and Technical Information of China (English)

    Yapeng Zhao; Hongyu Duan; Qinghui Zhang; Bingxin Shi; Hui Liang; Yuqi Zhang

    2016-01-01

    Objective: The authors report an extremely unusual presentation and management of a children pineal mixed germ cell tumor mainly composed of immature teratoma, aiming to summarize main theraptic points by literature review. Methods: A cystic lesion located in the rear of third ventricle in a child was detected 3 years ago with no other therapy performed except for a ventriculo-peritoneal shunt. During the following 3 years, intermitted regular brain MRI demonstrated no evidence of lesion aggrandizement. However from 20 days before admission to our institute the patient began to present acutely with exacerbating clinical symptoms meanwhile brain MRI showed signs of abrupt revulsions of initial lesion without any incentive cause. Neurological examination revealed a significant rising of serum tumor marker level. Then surgical resection was performed immediately after admission which was followed by correlative two-course chemotherapy. Results: Postoperative brain MRI demonstrated totally removing of the lesion in rear of third ventricle. Serum tumor marker level decreased remarkably after surgery and declined to normal level after two-course chemotherapy. No obvious neurological deficit occurred except for short-term memory difficulty which gradually recovered within two weeks. Soon after the second course chemotherapy the patient was currently asymptomatic and returned to school. Conclusions: (1) To ensure definitive diagnosis and proper therapecutic protocols benefit from grasping clinical features of mixed germ cell tumor. (2) Overall preoperative investigation including serum tumor marker level is as critical as neurological imaging examination. (3) Surgical excision is confirmed to be the key modality of treatment. With the regarding of mixed germ cell tumor, never highlight total resection too much. (4) Postoperative adjuvant chemotherapy is recommended as further intensive treatment to improve the prognosis of mix germ cell tumor.

  10. Microwave Ablation of Hepatic Malignancy

    OpenAIRE

    Lubner, Meghan G.; Brace, Christopher L.; Ziemlewicz, Tim J.; Hinshaw, J. Louis; Lee, Fred. T.

    2013-01-01

    Microwave ablation is an extremely promising heat-based thermal ablation modality that has particular applicability in treating hepatic malignancies. Microwaves can generate very high temperatures in very short time periods, potentially leading to improved treatment efficiency and larger ablation zones. As the available technology continues to improve, microwave ablation is emerging as a valuable alternative to radiofrequency ablation in the treatment of hepatic malignancies. This article rev...

  11. Malignant hypertension: a preventable emergency.

    Science.gov (United States)

    van der Merwe, Walter; van der Merwe, Veronica

    2013-08-16

    The Waitemata Hypertension Clinic Database 2009-2012 (Auckland, New Zealand) was searched for patients meeting the definition of Malignant Hypertension. Eighteen of 565 patients met the criteria. All patients had essential hypertension which was either undiagnosed, untreated or undertreated. Most cases responded satisfactorily to standard drug therapy, but a number were left with significant chronic kidney disease. Malignant hypertension is a life-threatening disease which should be entirely preventable with regular blood pressure checks in primary care.

  12. Benign and malignant neurogenic tumors of nerve sheath origin on FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Yun, M. J.; Go, D. H.; Yoo, Y. H.; Shin, K. H.; Lee, J. D [College of Medicine, Yonsei University, Seoul (Korea, Republic of)

    2004-07-01

    The differentiation between benign and malignant nerve sheath tumors is difficult based on conventional radiological imaging. This study was undertaken to investigate the value of FDG PET in distinguishing benign from malignant neurogenic tumors of nerve sheath origin. We performed a retrospective review of the medical record to select patients with nerve sheath tumors who had underdone FDG PET imaging. Fifteen patients (7F: 8M) with benign or malignant nerve sheath tumors were included in this study. Of the 15 patients, 9 were diagnosed with the known neurofibromatosis type I. A total of 19 nerve sheath tumors were included from the 15 patients. All patients had undergone FDG PET to evaluate for malignant potential of the known lesions. Images of FDG PET were semi-quantitatively analyzed and a region of interest (ROI) was placed over the area of the maximum FDG uptake and an average standardized uptake value was taken for final analysis. There were 5 malignant peripheral nerve sheath tumors, 5 schwannomas, and 9 neurofibromas. The mean SUV was 2 (ranged from 1.6 to 3.3) for schwannomas, 1.3 (0.7 to 2.5) for neurofibromas, and 8.4 (4.6 to 12.2) for malignant peripheral nerve sheath tumors. Of 14 benign tumors, all except one schwannoma showed a SUV less than 3. When a cutoff SUV of 4 was used to differentiate the nerve sheath tumors, all tumors were correctly classified as benign or malignant, respectively. Among the 9 patients diagnosed with neurofibromatosis type I. 4 had malignant peripheral nerve sheath tumors and FDG PET accurately detected all the 4 lesions with malignant transformation. According to our results, FDG PET seems to have a great potential for accurately characterizing benign versus malignant nerve sheath tumors. It appears to be extremely useful for patients with neurofibromatosis to localize the lesion with malignant transformation.

  13. Plexiform Neurofibroma of the Wrist: Imaging Features and When to Suspect Malignancy

    Directory of Open Access Journals (Sweden)

    Maria Gosein

    2013-01-01

    Full Text Available Plexiform neurofibromas are essentially pathognomonic for neurofibromatosis type 1 (NF1, occurring when there is diffuse involvement along a nerve segment and its branches. Transformation into a malignant peripheral nerve sheath tumour (MPNST is a major cause of mortality in NF1 patients. These tumours are highly aggressive and particularly difficult to diagnose in NF1 patients due to the clinical overlap between benign and malignant lesions. We present a case of a plexiform neurofibroma and discuss the typical imaging characteristics on ultrasound, CT, and MRI, including the target sign and continuity with the parent nerve. Certain imaging features should raise suspicion for malignancy however, these modalities may not always reliably differentiate between benign and malignant lesions. Recent studies show a very high negative predictive value for FDG-PET making it quite useful in excluding malignancy. In positive scans, PET/CT aids in guiding biopsy to the most metabolically active area of the tumour.

  14. Targeting eradication of malignant cells derived from human bone marrow mesenchymal stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yingbin [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); School of Life Science, Southwest University, Chongqing 400715 (China); Cai, Shaoxi, E-mail: sxcai@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Yang, Li [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); College of Pharmacy, Jinan University, Guangzhou 510632 (China); Yu, Shuhui [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Library of Southwest University, Chongqing 400715 (China); Jiang, Jiahuan; Yan, Xiaoqing [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Zhang, Haoxing [School of Life Science, Southwest University, Chongqing 400715 (China); Liu, Lan [Department of Laboratory of Medicine, Children' s Hospital of Chongqin Medical University, Chongqing 400014 (China); Liu, Qun [College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041 (China); Du, Jun [Center of Microbiology, Biochemistry, and Pharmacology, School of Pharmaceutical Science, Sun Yat-Sen University, Guangzhou 510080 (China); Cai, Shaohui [College of Pharmacy, Jinan University, Guangzhou 510632 (China); Sung, K.L. Paul [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Departments of Orthopaedic Surgery and Bioengineering, University of California, SD 0412 (United States)

    2010-12-10

    Human bone marrow mesenchymal stromal cells (hBMSC) have been shown to participate in malignant transformation. However, hampered by the low frequency of malignant transformation of hBMSC, we do not yet know how to prevent malignant transformation of implanted hBMSC. In this study, in order to establish a model for the eradication of hBMSC-derived malignant cells, a gene fusion consisting of a human telomerase (hTERT) promoter modified with both c-Myc and myeloid zinc finger protein2 (MZF-2) binding elements and followed by the E. coli cytosine deaminase (CD) and luciferase genes was stably transferred into hBMSC via lentiviral transduction; n-phosphonacelyl-L-aspartic acid (PALA) selection was used to generate malignant cell colonies derived from transduced hBMSC after treatment with the carcinogenic reagent BPDE. Cells that were amplified after PALA selection were used for transplantation and 5-FC pro-drug cytotoxicity tests. The results showed that PALA-resistant malignant cells could be generated from hBMSC co-induced with lentiviral transduction and treatment with Benzo(a)pyrene Diol Epoxide (BPDE); the modification of c-Myc and MZF-2 binding elements could remarkably enhance the transcriptional activities of the hTERT promoter in malignant cells, whereas transcriptional activity was depressed in normal hBMSC; malignant cells stably expressing CD under the control of the modified hTERT promoter could be eliminated by 5-FC administration. This study has provided a method for targeted eradication of malignant cells derived from hBMSC.

  15. Targeting eradication of malignant cells derived from human bone marrow mesenchymal stromal cells

    International Nuclear Information System (INIS)

    Human bone marrow mesenchymal stromal cells (hBMSC) have been shown to participate in malignant transformation. However, hampered by the low frequency of malignant transformation of hBMSC, we do not yet know how to prevent malignant transformation of implanted hBMSC. In this study, in order to establish a model for the eradication of hBMSC-derived malignant cells, a gene fusion consisting of a human telomerase (hTERT) promoter modified with both c-Myc and myeloid zinc finger protein2 (MZF-2) binding elements and followed by the E. coli cytosine deaminase (CD) and luciferase genes was stably transferred into hBMSC via lentiviral transduction; n-phosphonacelyl-L-aspartic acid (PALA) selection was used to generate malignant cell colonies derived from transduced hBMSC after treatment with the carcinogenic reagent BPDE. Cells that were amplified after PALA selection were used for transplantation and 5-FC pro-drug cytotoxicity tests. The results showed that PALA-resistant malignant cells could be generated from hBMSC co-induced with lentiviral transduction and treatment with Benzo(a)pyrene Diol Epoxide (BPDE); the modification of c-Myc and MZF-2 binding elements could remarkably enhance the transcriptional activities of the hTERT promoter in malignant cells, whereas transcriptional activity was depressed in normal hBMSC; malignant cells stably expressing CD under the control of the modified hTERT promoter could be eliminated by 5-FC administration. This study has provided a method for targeted eradication of malignant cells derived from hBMSC.

  16. Visualizing Transformation

    DEFF Research Database (Denmark)

    Pedersen, Pia

    2012-01-01

    is not preformed, but formed through the process of transformation; this means that the purpose of transformation is not the styling of charts with pictograms but rather creating a meaningful message. The contribution of this paper is an elaborated understanding of the process of transformation and a demonstration...

  17. Primary Malignant Mixed Germ Cell Tumour with Squamous Cell Carcinoma of the Mandible; A Rare Entity

    OpenAIRE

    Kumar, Saurabh; Paul, Arun; Parmar, Harshad; Chacko, Rabin

    2015-01-01

    Germ cell Tumours (GCT) are neoplasm derived from germ cells. GCT usually occurs inside the gonads. Extragonadal GCT’s are rare. Most common GCT associated with head and neck region are the teratomas. Of the few teratomas found in the head and neck, malignant transformation of a teratomatous element is very uncommon, and primary bone involvement within the head and neck is even rare. We present a case of primary malignant mixed germ cell Tumour involving the mandible, the present case present...

  18. Lenvatinib and Capecitabine in Patients With Advanced Malignancies

    Science.gov (United States)

    2016-09-23

    Advanced Cancer; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

  19. Stenting in Malignant Biliary Obstruction.

    Science.gov (United States)

    Almadi, Majid A; Barkun, Jeffrey S; Barkun, Alan N

    2015-10-01

    Decompression of the biliary system in patients with malignant biliary obstruction has been widely accepted and implemented as part of the care. Despite a wealth of literature, there remains a significant amount of uncertainty as to which approach would be most appropriate in different clinical settings. This review covers stenting of the biliary system in cases of resectable or palliative malignant biliary obstruction, potential candidates for biliary drainage, technical aspects of the procedure, as well as management of biliary stent dysfunction. Furthermore, periprocedural considerations including proper mapping of the location of obstruction and the use of antibiotics are addressed. PMID:26431598

  20. Primary supratentorial intracerebral malignant paraganglioma

    Directory of Open Access Journals (Sweden)

    Ahmed A Al Jishi

    2015-06-01

    Full Text Available Paragangliomas are extra-adrenal neuroendocrine tumors that derive from neural crest. In general, they are benign tumors but few cases had shown a tendency to metastasize. Malignant forms have been reported previously with intracranial metastasis from duodenal origin, but primary intracranial origin represents a rare and unusual location for such tumors. Here, we report a rare case of a 48-year-old lady who presented with symptomatic right-sided insular mass with negative metastatic work up. A complete surgical resection had been done with an unexpected diagnosis of primary gangliocytic paraganglioma with malignant features.

  1. CT triage for lung malignancy

    DEFF Research Database (Denmark)

    Kusk, Martin Weber; Karstoft, Jens; Mussmann, Bo

    2015-01-01

    : To assess detection performance using only coronal multiplanar reformations (MPR) when triaging patients for lung malignancies with CT compared to images in three orthogonal planes, and to evaluate performance comparison of novice and experienced readers. Material and Methods: Retrospective study of 63...... patients with suspicion of lung cancer, scanned on 64-slice multidetector computed tomography (MDCT) with images reconstructed in three planes. Coronal images were presented to four readers, two novice and two experienced. Readers decided whether the patients were suspicious for malignant disease...

  2. Arsenic Induced Decreases in the Vascular Matrix

    OpenAIRE

    Hays, Allison M.; Lantz, R. Clark; Rodgers, Laurel S.; Sollome, James J.; Vaillancourt, Richard R.; Andrew, Angeline S; Hamilton, Joshua W.; Camenisch, Todd D.

    2008-01-01

    Chronic ingestion of arsenic is associated with increased incidence of respiratory and cardiovascular diseases. To investigate the role of arsenic in early events in vascular pathology, C57BL/6 mice ingested drinking water with or without 50 ppb sodium arsenite (AsIII) for four, five or eight weeks. At five and eight weeks, RNA from the lungs of control and AsIII exposed animals was processed for microarray. Sixty-five genes were significantly and differentially expressed. Differential expres...

  3. Malignant neurilemoma with xeroderma pigmentosum

    OpenAIRE

    Wang, Li Na; Ma, Min Jian; Shi, Ji Tong

    2009-01-01

    Xeroderma pigmentosum is a rare autosomal recessive disease characterised by hypersensitivity to sunlight, and is associated with a high incidence of skin cancer. We report a case of xeroderma pigmentosum with malignant neurilemoma in a 46-year-old woman which is unique due to its presentation, which was confirmed histopathologically.

  4. MALIGNANCY IN LARGE COLORECTAL LESIONS

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Oliveira dos SANTOS

    2014-09-01

    Full Text Available Context The size of colorectal lesions, besides a risk factor for malignancy, is a predictor for deeper invasion Objectives To evaluate the malignancy of colorectal lesions ≥20 mm. Methods Between 2007 and 2011, 76 neoplasms ≥20 mm in 70 patients were analyzed Results The mean age of the patients was 67.4 years, and 41 were women. Mean lesion size was 24.7 mm ± 6.2 mm (range: 20 to 50 mm. Half of the neoplasms were polypoid and the other half were non-polypoid. Forty-two (55.3% lesions were located in the left colon, and 34 in the right colon. There was a high prevalence of III L (39.5% and IV (53.9% pit patterns. There were 72 adenomas and 4 adenocarcinomas. Malignancy was observed in 5.3% of the lesions. Thirty-three lesions presented advanced histology (adenomas with high-grade dysplasia or early adenocarcinoma, with no difference in morphology and site. Only one lesion (1.3% invaded the submucosa. Lesions larger than 30 mm had advanced histology (P = 0.001. The primary treatment was endoscopic resection, and invasive carcinoma was referred to surgery. Recurrence rate was 10.6%. Conclusions Large colorectal neoplasms showed a low rate of malignancy. Endoscopic treatment is an effective therapy for these lesions.

  5. Malignant pleural effusions. Bibliographic revision

    International Nuclear Information System (INIS)

    Malignant pleural effusions are a common clinical problem in patients with neoplastic disease. Dyspnea is the most common symptom. The diagnostic is made with X ray and pleural echography. The treatment are thoracentesis, chest tube drainage and pleurodesis. Palliative therapy should be considered, necessitating evaluation of the patient's symptoms, general health and functional status, and expected survival. (The author)

  6. Neuroleptic Malignant Syndrome: A Review

    OpenAIRE

    O'Brien, Richard A.; Young, G. Bryan

    1989-01-01

    There has recently been interest in neuroleptic malignant syndrome (NMS) as the disorder has been better characterized. Nms is still poorly recognized, however, by most physicians. Hyperpyrexia, rigidity, altered consciousness, autonomic instability, and enzymatic evidence of muscle breakdown after drug intake are the cardinal features. The authors of this article review the proposed pathogenesis, complications, and treatment of NMS.

  7. Cutaneous manifestations of internal malignancy

    Directory of Open Access Journals (Sweden)

    A Ayyamperumal

    2012-01-01

    Full Text Available Background: Many malignancies affecting the internal organs display cutaneous manifestations which may be either specific (tumor metastases or nonspecific lesions. Aims: The study is aimed at determining the frequency and significance of cutaneous manifestations among patients with internal malignancy. Materials and Methods: 750 cases of proven internal malignancy, who attended a cancer chemotherapy center in South India, were studied. Specific infiltrates were confirmed by histopathology, fine needle aspiration cytology (FNAC and marker studies. Results: Out of the 750 patients with internal malignancy, skin changes were seen in a total of 52 (6.93% patients. Conclusion: Cutaneous metastases (specific lesions were seen in 20 patients (2.66%: contiguous in 6 (0.8%, and non-contiguous in 14 (1.86%. Nonspecific skin changes were seen in 32 patients (4.26%. None of our patients presented with more than one type of skin lesions. Herpes zoster was the most common nonspecific lesion noticed in our patients, followed by generalized pruritus, multiple eruptive seborrheic keratoses, bullous disorder, erythroderma, flushing, purpura, pyoderma gangrenosum, insect bite allergy and lichenoid dermatitis.

  8. Malignant nodular hidradenoma of scalp

    Directory of Open Access Journals (Sweden)

    Tanmoy Maiti

    2014-01-01

    Full Text Available Malignant nodular hidradenoma (MNH is a rare tumor of sweat gland known by many names in the literature. Scalp is a known and yet uncommon site of occurrence. We describe two patients with scalp MNH with brain parenchymal invasion. Both tumors recurred in spite of total excision and radiotherapy.

  9. Herniation of malignant lung cavity

    Institute of Scientific and Technical Information of China (English)

    Saurabh Kumar Singh; Rakesh Bhargava; Zuber Ahmad; Deepak K.Pandey; Shirin Naaz; Vibhanshu Gupta

    2008-01-01

    @@ Hernia of the lung is defined as a protrusion of lung tissue,covered by parietal and visceral pleurae,through an abnormal opening in the chest wall,diaphragm or mediastinum.1 It is a relatively uncommon condition.We report a case of lung hernia following cavitation in malignant lung mass.

  10. Malignancy and Abnormality Detection of Mammograms using Classifier Ensembling

    Directory of Open Access Journals (Sweden)

    Nawazish Naveed

    2011-07-01

    Full Text Available The breast cancer detection and diagnosis is a critical and complex procedure that demands high degree of accuracy. In computer aided diagnostic systems, the breast cancer detection is a two stage procedure. First, to classify the malignant and benign mammograms, while in second stage, the type of abnormality is detected. In this paper, we have developed a novel architecture to enhance the classification of malignant and benign mammograms using multi-classification of malignant mammograms into six abnormality classes. DWT (Discrete Wavelet Transformation features are extracted from preprocessed images and passed through different classifiers. To improve accuracy, results generated by various classifiers are ensembled. The genetic algorithm is used to find optimal weights rather than assigning weights to the results of classifiers on the basis of heuristics. The mammograms declared as malignant by ensemble classifiers are divided into six classes. The ensemble classifiers are further used for multiclassification using one-against-all technique for classification. The output of all ensemble classifiers is combined by product, median and mean rule. It has been observed that the accuracy of classification of abnormalities is more than 97% in case of mean rule. The Mammographic Image Analysis Society dataset is used for experimentation.

  11. Malignant Proliferating Trichilemmal Tumor in the Right Post Auricular Region

    Institute of Scientific and Technical Information of China (English)

    Lihong Cao; Huifang Zhou; Hua Chen

    2006-01-01

    OBJECTIVE To report a case of a malignant proliferating trichilemmal tumor (PTT) in the right postauricular region, and to describe the clinical and histopathologic findings.METHODS Interventional case report and literature review.RESULTS A 46-year-old woman presented with a 15-year history of a nodule of 30×30×10 mm in diameter in the right postauricular region. It was diagnosed as a sebaceous cyst. A local mass excision was performed. Histopathologic examination revealed proliferation of the outer hair sheath epithelium with multiple central areas of trichilemmal keratinization. The presence of marked cellular atypia and frequent mitoses indicated a malignant transformation. A second operation employing an enlarged excision was conducted followed by a histopathologic examination showing that there was no malignant tumor remaining. Two weeks after the second operation, 50 cGy of regional prophylactic radiotherapy was applied. The patient was well after 26 months of follow-up and neither recurrences nor metastases were observed.CONCLUSION Malignant PTT is a rare skin neoplasm, with its diagnosis depending on a histopathologic examination. An extend excision is the main treatment after diagnosis.

  12. Comparison of the expression of 5 heat shock proteins in benign and malignant salivary gland tumor tissues.

    Science.gov (United States)

    Wang, Guilan; Gu, Xiaolin; Chen, Li; Wang, Yinmei; Cao, Bin; E, Qun

    2013-04-01

    The objective of this study was to analyze the significance and potential value of heat shock proteins (HSPs) in salivary gland tumors. We found that expression of HSP60, HSP70, HSP86 and HSP84 were all upregulated in both salivary gland benign tumors and malignant tumors, and that the expression of HSP70, HSP86 and HSP84 was more greatly overexpressed in the malignant tumors (each Pbenign tumors, with less expression observed in malignant tumors (Pbenign tumors (Pgland tumors. HSP70, HSP86 and HSP84 retained the higher multiplication capability of the malignant tumor cells, however, HSP27 did not. Thus, the upregulation of HSP70, HSP86 and HSP84 and the downregulation of HSP27 may all be used as biomarkers of the occurrence and development of malignant salivary gland tumors. Moreover, the extremely high expression of HSP86 and HSP84 in benign tumors indicates the malignant transformation potential.

  13. Hadamard Transforms

    CERN Document Server

    Agaian, Sos; Egiazarian, Karen; Astola, Jaakko

    2011-01-01

    The Hadamard matrix and Hadamard transform are fundamental problem-solving tools in a wide spectrum of scientific disciplines and technologies, such as communication systems, signal and image processing (signal representation, coding, filtering, recognition, and watermarking), digital logic (Boolean function analysis and synthesis), and fault-tolerant system design. Hadamard Transforms intends to bring together different topics concerning current developments in Hadamard matrices, transforms, and their applications. Each chapter begins with the basics of the theory, progresses to more advanced

  14. An Investigation of the Potential Malignant Characteristics of Endometriosis

    Institute of Scientific and Technical Information of China (English)

    Chengxin Wang; Hongyan Zhou; Xiaonan You; Xiji Shu; Yan Li; Xiaoling Zhao

    2005-01-01

    OBJECTIVE To investigate the potential malignant characteristics and pathogenesis of endometriosis as well as the role of human growth hormone and epidermal growth factor receptor in the pathogenesis of malignant transformation of endometriosis.METHODS The immunohistochemical S-P method was used to examine the expression of human growth hormone and epidermal growth factor receptor in the eutopic and ectopic endometrium of 84 cases of endometriosis.RESULTS The percentage of positive cases of human growth hormone in eutopic and ectopic endometrium was 90.77% (59/65) and 85.71% (72/84) respectively. The percentage of positive cases of epidermal growth factor receptor in eutopic and ectopic endometrium was 81.54% (53/65)and 89.29% (75/84) respectively. The positive rate of epidermal growth factor receptor in ectopic endometrium was higher than that in the eutopic endometrium but without a statistically significant difference (P>0.05).CONCLUSION Endometriosis is caused by multiple factors, which possesses some biologic features of neoplastic tissue such as invasion and metastasis. Both human growth hormone and epidermal growth factor receptor are highly expressed in eutopic and ectopic endometrium, which lead directly or indirectly to the pathogenesis of endometriosis and promote the initiation and malignant transformation of endometriosis.

  15. Do We Know What Causes Malignant Mesothelioma?

    Science.gov (United States)

    ... Next Topic Can malignant mesothelioma be prevented? Do we know what causes malignant mesothelioma? Researchers have found ... genes – the instructions for how our cells function. We usually look like our parents because they are ...

  16. Serum ferritin in liver and bone malignancy

    International Nuclear Information System (INIS)

    Serum ferritin concentration is increased during iron overload, however, during chronic infection and malignant diseases as well. In 383 patients with proven malignancy or suspicion of a malignant disease liver and/or bone scans were performed and serum ferritin was measured in addition. Although there exists a certain linkage between the tumorous disease and serum ferritin level, a definite correlation does not exist. Furthermore serum ferritin is not a measure to differentiate between infectious and malignant diseases. (orig.)

  17. New MRI techniques for staging malignant lymphoma

    NARCIS (Netherlands)

    Kwee, T.C.

    2011-01-01

    Malignant lymphomas are a heterogenous group of malignancies, belonging to the ten most frequent types of cancers worldwide. Once a malignant lymphoma has been diagnosed, it is important to assess disease extent (staging), because this has prognostic and therapeutic implications. Computed tomography

  18. Information transfer by exosomes: A new frontier in hematologic malignancies.

    Science.gov (United States)

    Boyiadzis, Michael; Whiteside, Theresa L

    2015-09-01

    Exosomes are small (30-150 mm) vesicles secreted by all cell types and present in all body fluids. They are emerging as vehicles for delivery of membrane-tethered signaling molecules and membrane enclosed genes to target cells. Exosome-mediated information transfer allows for crosstalk of cells within the hematopoietic system and for interactions between hematopoietic cells and local or distant tissue cells. Exosomes carry physiological signals essential for health and participate in pathological processes, including malignant transformation. In hematologic malignancies, exosomes reprogram the bone marrow microenvironment, creating a niche for abnormal cells and favoring their expansion. The molecular and genetic mechanisms exosomes utilize to shuttle information between cells are currently being examined as are the potential roles exosomes play as biomarkers of disease or future therapeutic targets.

  19. Polycomb group proteins in hematopoietic stem cell aging and malignancies.

    Science.gov (United States)

    Klauke, Karin; de Haan, Gerald

    2011-07-01

    Protection of the transcriptional "stemness" network is important to maintain a healthy hematopoietic stem cells (HSCs) compartment during the lifetime of the organism. Recent evidence shows that fundamental changes in the epigenetic status of HSCs might be one of the driving forces behind many age-related HSC changes and might pave the way for HSC malignant transformation and subsequent leukemia development, the incidence of which increases exponentially with age. Polycomb group (PcG) proteins are key epigenetic regulators of HSC cellular fate decisions and are often found to be misregulated in human hematopoietic malignancies. In this review, we speculate that PcG proteins balance HSC aging against the risk of developing cancer, since a disturbance in PcG genes and proteins affects several important cellular processes such as cell fate decisions, senescence, apoptosis, and DNA damage repair.

  20. Orbital malignant melanoma associated with nevus of Ota.

    Science.gov (United States)

    Radhadevi, Cherungottil V; Charles, Kakkuzhiyil S; Lathika, Vasu K

    2013-06-01

    Nevus of Ota (oculodermal melanosis) is a dermal melanocytic hamartoma with bluish hyperpigmentation along the first and second branches of the trigeminal nerve. Extracutaneous involvement, especially ocular, has been reported. A 45-year-old male presented with malignant melanoma of the left orbit in association with nevus of Ota. Being locally invasive, a modified exenteration with frontal flap repair was done on left eye. Adjuvant chemotherapy was given after wound healing. All pigmented lesions of the eye require close monitoring to help in the early diagnosis. Since malignant transformation has been reported in oculodermal melanosis, close follow-up and patient education will facilitate early diagnosis and prompt management. This case is reported for its rarity and unusual presentation.

  1. Orbital malignant melanoma associated with nevus of Ota

    Directory of Open Access Journals (Sweden)

    Cherungottil V Radhadevi

    2013-01-01

    Full Text Available Nevus of Ota (oculodermal melanosis is a dermal melanocytic hamartoma with bluish hyperpigmentation along the first and second branches of the trigeminal nerve. Extracutaneous involvement, especially ocular, has been reported. A 45-year-old male presented with malignant melanoma of the left orbit in association with nevus of Ota. Being locally invasive, a modified exenteration with frontal flap repair was done on left eye. Adjuvant chemotherapy was given after wound healing. All pigmented lesions of the eye require close monitoring to help in the early diagnosis. Since malignant transformation has been reported in oculodermal melanosis, close follow-up and patient education will facilitate early diagnosis and prompt management. This case is reported for its rarity and unusual presentation.

  2. Recurrence of neuroleptic malignant syndrome.

    Science.gov (United States)

    González-Blanco, Leticia; García-Prada, Hilario; Santamarina, Susana; Jiménez-Treviño, Luis; Bobes, Julio

    2013-01-01

    Neuroleptic malignant syndrome (NMS) is a rare idiosyncratic reaction associated with the use of neuroleptics that has an incidence of 0.02 to 3% among patients taking these drugs. This is a very serious complication with a mortality rate that reaches 10-20%. It is therefore very important to have high clinical suspicion and use appropriate criteria to objectify this clinical picture early, stopping the medication causing the picture and to avoid the subsequent complications as much as possible that would be responsible for both its mortality and sequels. We present that case of an 81-year old woman who was admitted to the Psychiatric Hospitalization Unit (PHU) for a depressive episode with psychotic symptoms who developed a neuroleptic malignant syndrome (NMS) when Haloperidol was introduced. After its suspension and subsequent clinical recovery, antipsychotic treatment with Risperidone was reintroduced and she suffered a recurrence of NMS. Finally, significant improvement was achieved with several sessions of electroshock therapy (EST).

  3. Tumor Metabolism of Malignant Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang, E-mail: deliang.guo@osumc.edu [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center & Arthur G James Cancer Hospital, Columbus, OH 43012 (United States)

    2013-11-08

    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.

  4. Tumor Metabolism of Malignant Gliomas

    Directory of Open Access Journals (Sweden)

    Deliang Guo

    2013-11-01

    Full Text Available 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.

  5. Giant melanoacanthoma mimicking malignant melanoma

    Directory of Open Access Journals (Sweden)

    Vikas Shankar

    2011-01-01

    Full Text Available Melanoacanthoma denotes a rare variant of pigmented seborrheic keratosis. A 65-year-old male farmer had pigmented, verrucous, itchy, highly painful, progressively growing irregularly oval plaque on left side of lower back for the past five years. The indurated lesion, measuring maximum diameter 10 cm Χ 5 cm, had no discharge, bleeding, ulceration, or associated lymphadenopathy. Dermoscopy showed regular pigmentary network and cribiform pattern of ridges without any feature of malignant melanoma. Histopathology showed well-defined islands of basaloid cells interspersed with large and richly dendritic melanocytes. The lesion was totally excised followed by skin grafting. Our patient was unique in its massive size and clinical resemblance with malignant melanoma. The diagnosis was confirmed by dermoscopy and skin biopsy.

  6. Clostridium difficile in haematological malignancy.

    OpenAIRE

    Rampling, A.; Warren, R. E.; Bevan, P C; Hoggarth, C E; Swirsky, D; Hayhoe, F G

    1985-01-01

    Twenty patients with haematological malignancies who developed Clostridium difficile bowel infection or colonisation are described. All isolates of C difficile were toxigenic in vitro and faecal cytotoxin (toxin B) was detected in 20/26 episodes. Ten of 20 episodes with detectable faecal cytotoxin were associated with typical antibiotic associated diarrhoea. In the other 10 episodes (nine patients), there was a severe unusual illness which was associated with detection of C difficile. The unu...

  7. Endobronchial metastases from extrathoracic malignancies.

    Science.gov (United States)

    Akoglu, Sebahat; Uçan, Eyüp S; Celik, Gülperi; Sener, Gülper; Sevinç, Can; Kilinç, Oğuz; Itil, Oya

    2005-01-01

    Endobronchial metastases (EBM) from extrapulmonary malignant tumors are rare. The most common extrathoracic malignancies associated with EBM are breast, renal and colorectal carcinomas. In this study, we aimed to evaluate the clinical, radiographic and bronchoscopic aspects of patients with EBM who were diagnosed between 1992 and 2002. Data about patients' clinical conditions, symptoms, radiographic and endoscopic findings, and histopathological examination results were investigated. EBM was defined as bronchoscopically visible lesions histopathologically identical to the primary tumor in patients with extrapulmonary malignancies. We found 15 cases with EBM. Primary tumors included breast (3), colorectal (3), and renal (2) carcinomas; Malignant Melanoma (2); synovial sarcoma (1), ampulla of Vater adenocarcinoma (1), pheochromocytoma (1), hypernephroma (1), and Hodgkin's Disease (1). The most common symptoms were dyspnea (80%), cough (66.6%) and hemoptysis (33.3%). Multiple (40%) or single (13.3%) pulmonary nodules, mediastinal or hilar lymphadenopathy (40%), and effusion (40%) were the most common radiographic findings. The mean interval from initial diagnosis to diagnosis of EBM was 32.8 months (range, 0-96 months) and median survival time was 18 months (range, 4-84). As a conclusion, various extrapulmonary tumors can metastasize to the bronchus. Symptoms and radiographic findings are similar with those in primary lung cancer. Therefore, EBM should be discriminated from primary lung cancer histopathologically. Although mean survival time is usually short, long-term survivors were reported. Consequently, treatment must be planned according to the histology of the primary tumor, evidence of metastasis to other sites and medical status of the patient. PMID:16475029

  8. Amisulpride and Neuroleptic Malignant Syndrome

    OpenAIRE

    Ming-Che Tu; Cheng-Cheng Hsiao

    2011-01-01

    Neuroleptic malignant syndrome (NMS) is a rare but lethal complication of neuroleptics. Its incidence ranges between 0.02% and 3%. Amisulpride, a second generation neuroleptic, was associated with rhabdomyolysis in one report and NMS in 2 reports. Althoughthe precise pathogenesis is still unclear, dopamine receptor blockade is theorized to play acentral role. Conventional presentations include hyperthermia, muscle rigidity, and elevatedcreatine kinase concentrations. However, similar to other...

  9. Malignant endobronchial lesions of adolescence

    Energy Technology Data Exchange (ETDEWEB)

    Bellah, R.D. (Dept. of Radiology, Children' s Hospital of Philadelphia, PA (United States)); Mahboubi, S. (Dept. of Radiology, Children' s Hospital of Philadelphia, PA (United States)); Berdon, W.E. (Dept. of Radiology, Babies Hospital/Columbia Presbyterian Medical Center, New York, NY (United States))

    1992-12-01

    Rare primary endobronchial malignancies were diagnosed in four adolescents: atypical bronchial carcinoid, mucoepidermoid carcinoma, bronchogenic (squamous cell) carcinoma, and non-Hodgkin's lymphoma. Metastatic disease was evident in each case. Three of the four patients died within one year of diagnosis. This paper describes each of these entities, illustrates their plain film and CT abnormalities (bronchial 'cut-off', hilar mass, local congestive edema, lobar collapse, hyperinflation), and discusses the utility of CT in their diagnosis. (orig.)

  10. Benign chondroblastoma - malignant radiological appearances

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, K.; Treugut, H.; Mueller, G.E.

    1980-04-01

    The very rare benign chondroblastoma occasionally invades soft tissues and may grow beyond the epiphysis into the metaphysis. In the present case such a tumour did not show the typical radiological appearances, but presented malignant features both on plain films and on the angiogram. The importance of biopsy of tumours which cannot be identified with certainty must be stressed before radical surgery is carried out.

  11. Endobronchial metastases from extrathoracic malignancies.

    Science.gov (United States)

    Akoglu, Sebahat; Uçan, Eyüp S; Celik, Gülperi; Sener, Gülper; Sevinç, Can; Kilinç, Oğuz; Itil, Oya

    2005-01-01

    Endobronchial metastases (EBM) from extrapulmonary malignant tumors are rare. The most common extrathoracic malignancies associated with EBM are breast, renal and colorectal carcinomas. In this study, we aimed to evaluate the clinical, radiographic and bronchoscopic aspects of patients with EBM who were diagnosed between 1992 and 2002. Data about patients' clinical conditions, symptoms, radiographic and endoscopic findings, and histopathological examination results were investigated. EBM was defined as bronchoscopically visible lesions histopathologically identical to the primary tumor in patients with extrapulmonary malignancies. We found 15 cases with EBM. Primary tumors included breast (3), colorectal (3), and renal (2) carcinomas; Malignant Melanoma (2); synovial sarcoma (1), ampulla of Vater adenocarcinoma (1), pheochromocytoma (1), hypernephroma (1), and Hodgkin's Disease (1). The most common symptoms were dyspnea (80%), cough (66.6%) and hemoptysis (33.3%). Multiple (40%) or single (13.3%) pulmonary nodules, mediastinal or hilar lymphadenopathy (40%), and effusion (40%) were the most common radiographic findings. The mean interval from initial diagnosis to diagnosis of EBM was 32.8 months (range, 0-96 months) and median survival time was 18 months (range, 4-84). As a conclusion, various extrapulmonary tumors can metastasize to the bronchus. Symptoms and radiographic findings are similar with those in primary lung cancer. Therefore, EBM should be discriminated from primary lung cancer histopathologically. Although mean survival time is usually short, long-term survivors were reported. Consequently, treatment must be planned according to the histology of the primary tumor, evidence of metastasis to other sites and medical status of the patient.

  12. Height at diagnosis of malignancies.

    OpenAIRE

    Pui, C.H.; Dodge, R K; George, S L; Green, A. A.

    1987-01-01

    Studies of the presenting height of children with malignancies have produced conflicting results, from an excess of taller patients to an excess of shorter patients. The problems of measurement bias, inadequate comparison populations, small numbers of patients, subgroup analyses, and overreliance on simple significance tests are all possible reasons for the variation in results. To clarify this issue, we studied heights at diagnosis of 3657 children and adolescents aged under 18 years. Their ...

  13. Malignant tumours of the vulva

    International Nuclear Information System (INIS)

    The thesis analyses 317 patients with vulvar malignancies treated at the University Hospital, Lund, during 1960-1979. The three most common histological types of malignancy have been analysed. The oncological clinic in Lund has since the 1960's used a surgical technique where the primary tumour and the regional lymph nodes are operated on in two separate surgical seances. The vulvectomy is performed with tarm knife technique, and the wound is left open. The 5-year crude survival rate for the entire patient material treated with curative intention was over 60 %, which agrees well with reports from other centres. Our surgical approach using two separate seances has, however, much lower rates of postoperative complications and mortality than the rates in other reports. The overall most important prognostic factors for the patients with invasive vulvar malignancies are the presence of lymphatic metastases at the time of surgery, and the surgical radicality of the primary surgery. The treatment at most stages of tumour development and most histological types should include total vulvectomy preoperative irradiation of the inguinal lymph nodes, and inguinal lymphadenectomy. Only local extirpation and hemivulvectomy are, however, indicated for small microinvasively growing squamous cell carcinoma and basal cell carcinoma. Samll invasive onesided squamous cell carcinoma is best treated with ipsilateral surgery combined with preoperative irradiation of the inguinal lymph nodes. Patients with metastases in the inguinal lymph nodes should receive additional irradiation of the inguinal and pelvic lymph node stations. (Author)

  14. Recurrent malignant carotid body tumor: report of one case and review of the literature

    Institute of Scientific and Technical Information of China (English)

    ZHENG Jia-wei; ZHU Han-guang; YUAN Rong-tao; LI Jiang; WANG Li-zhen; ZHANG Shan-yong; ZHANG Zhi-yuan

    2005-01-01

    @@ Carotid body tumor (CBT) is a rare tumor, which is composed of chromaffin cells, groups of cells associated with the autonomous system, occurring at the carotid bifurcation. This tumor grows slowly, usually with a history of several years and seldom undergoes malignant transformation. The majority of CBT are benign, only few cases of malignant CBTs were reported in the literature.1-3 Over a period of 10 years (1993-2004), 28 patients with CBT were diagnosed and surgically treated in the Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, School of Stomatology, Shanghai Jiaotong University, only one was proven both clinically and histopathologically to be malignant CBT. This paper reports this unusual patient with recurrent malignant carotid body tumor as well as cervical lymph node metastases and reviews the relevant literature.

  15. Cell Fusion in the War on Cancer: A Perspective on the Inception of Malignancy

    Directory of Open Access Journals (Sweden)

    Jeffrey L. Platt

    2016-07-01

    Full Text Available Cell fusion occurs in development and in physiology and rarely in those settings is it associated with malignancy. However, deliberate fusion of cells and possibly untoward fusion of cells not suitably poised can eventuate in aneuploidy, DNA damage and malignant transformation. How often cell fusion may initiate malignancy is unknown. However, cell fusion could explain the high frequency of cancers in tissues with low underlying rates of cell proliferation and mutation. On the other hand, cell fusion might also engage innate and adaptive immune surveillance, thus helping to eliminate or retard malignancies. Here we consider whether and how cell fusion might weigh on the overall burden of cancer in modern societies.

  16. GENE EXPRESSION PROFILING OF GANGLIOGLIOMA MALIGNANT PROGRESSION BY cDNA ARRAY

    Institute of Scientific and Technical Information of China (English)

    ZHANG Quan-bin; HUANG Qiang; DONG Jun; WANG Ai-dong; SUN Ji-yong; LAN Qing; HU Geng-xi

    2005-01-01

    Objective: To establish gene expression profiles associated with malignant progression of ganglioglioma. Methods: The primary and two recurrent glioma specimens were collected intraoperatively from the same patient who experienced tumor transformation into anaplastic astrocytoma and glioblastoma multiform for the first and second recurrence respectively. Gene expression was assayed through cDNA array and bioinformatics analysis. Results: A total of 197 differentially expressed genes with differential ratio value more than 3 compared with normal brain tissue were obtained. Among 109 functionally denned genes, those associated with development ranked the first by frequency, followed by genes associated with metabolism, differentiation, signal transduction and so on. As a result of cluster analysis among 368 genes, eleven genes were up regulated with malignant progression, while six genes were down regulated. Conclusion: Gene expression profiles associated with malignant progression of glioma were successfully established, which provides a powerful tool for research on molecular mechanisms of malignant progression of gliomas.

  17. Nuclear hBD-1 accumulation in malignant salivary gland tumours

    International Nuclear Information System (INIS)

    Whereas the antimicrobial peptides hBD-2 and -3 are related to inflammation, the constitutively expressed hBD-1 might function as 8p tumour suppressor gene and thus play a key role in control of transcription and induction of apoptosis in malignant epithelial tumours. Therefore this study was conducted to characterise proteins involved in cell cycle control and host defence in different benign and malignant salivary gland tumours in comparison with healthy salivary gland tissue. 21 paraffin-embedded tissue samples of benign (n = 7), and malignant (n = 7) salivary gland tumours as well as healthy (n = 7) salivary glands were examined immunohistochemically for the expression of p53, bcl-2, and hBD-1, -2, -3. HBD-1 was distributed in the cytoplasm of healthy salivary glands and benign salivary gland tumours but seems to migrate into the nucleus of malignant salivary gland tumours. Pleomorphic adenomas showed cytoplasmic as well as weak nuclear hBD-1 staining. HBD-1, 2 and 3 are traceable in healthy salivary gland tissue as well as in benign and malignant salivary gland tumours. As hBD-1 is shifted from the cytoplasm to the nucleus in malignant salivary gland tumours, we hypothesize that it might play a role in the oncogenesis of these tumours. In pleomorphic adenomas hBD-1 might be connected to their biologic behaviour of recurrence and malignant transformation

  18. Malignant potential of intrahepatic biliary papillomatosis: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Arkadopoulos Nikolaos

    2006-10-01

    Full Text Available Abstract Background Biliary papillomatosis (BP is a rare disease entity with a strong malignant potential. It is characterized by multiple papillary adenomas involving both the intrahepatic and extrahepatic biliary tree. BP was considered in the past to be a disease with low malignant potential. However, a current review of the English literature revealed a high rate of malignant occurrence of approximately 41% and histological analysis along with the expression pattern of mucin core proteins (MUC and mucin carbohydrate antigens suggests that BP is a borderline or low grade malignant neoplasm with a high malignant potential. Case presentation A 68 year-old male patient was referred to our hospital due to the presence of sudden right upper quadrant abdominal pain, nausea and dark urine. Imaging workup demonstrated dilatation of the left hepatic duct without the presence of a space-occupying lesion. A left hepatectomy and cholecystectomy were carried out and histological analysis revealed a moderately to poorly differentiated carcinoma of the left hepatic duct in the background of biliary papillomatosis. Postoperative course was uneventful. Unfortunately, two years after initial diagnosis the patient rapidly deteriorated and died from multiple pulmonary secondary deposits. Conclusion BP should not be considered to be a benign disease. The clinical behavior, the high recurrence rate and the even higher malignant transformation occurrence, as well as the presence of carcinogenetic indicators (K-ras mutation, overexpression of p53, MUC and Tn antigens strongly support that BP is a low-grade neoplasm with high malignant potential.

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

    Science.gov (United States)

    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

  20. Organelle transformation.

    Science.gov (United States)

    Bhattacharya, Anjanabha; Kumar, Anish; Desai, Nirali; Parikh, Seema

    2012-01-01

    The source of genetic information in a plant cell is contained in nucleus, plastids, and mitochondria. Organelle transformation is getting a lot of attention nowadays because of its superior performance over the conventional and most commonly used nuclear transformation for obtaining transgenic lines. Absence of gene silencing, strong predictable transgene expression, and its application in molecular pharming, both in pharmaceutical and nutraceuticals, are some of many advantages. Other important benefits of utilizing this technology include the absence of transgene flow, as organelles are maternally inherited. This may increase the acceptability of organelle transformation technology in the development of transgenic crops in a wider scale all over the globe. As the need for crop productivity and therapeutic compounds increases, organelle transformation may be able to bridge the gap, thereby having a definite promise for the future. PMID:22610643

  1. Organelle transformation.

    Science.gov (United States)

    Bhattacharya, Anjanabha; Kumar, Anish; Desai, Nirali; Parikh, Seema

    2012-01-01

    The source of genetic information in a plant cell is contained in nucleus, plastids, and mitochondria. Organelle transformation is getting a lot of attention nowadays because of its superior performance over the conventional and most commonly used nuclear transformation for obtaining transgenic lines. Absence of gene silencing, strong predictable transgene expression, and its application in molecular pharming, both in pharmaceutical and nutraceuticals, are some of many advantages. Other important benefits of utilizing this technology include the absence of transgene flow, as organelles are maternally inherited. This may increase the acceptability of organelle transformation technology in the development of transgenic crops in a wider scale all over the globe. As the need for crop productivity and therapeutic compounds increases, organelle transformation may be able to bridge the gap, thereby having a definite promise for the future.

  2. Landskabets transformation

    DEFF Research Database (Denmark)

    Munck Petersen, Rikke

    2005-01-01

    Seminaroplæg fra forskere. Faglige seminarer på KA, forår 2005. Belyser transformation af det danske landskab fysisk som holdningsmæssigt, samt hvordan phd-arbejdets egen proces håndterer den.......Seminaroplæg fra forskere. Faglige seminarer på KA, forår 2005. Belyser transformation af det danske landskab fysisk som holdningsmæssigt, samt hvordan phd-arbejdets egen proces håndterer den....

  3. IR Spectroscopic signs of malignant neoplasms in the thyroid gland

    Science.gov (United States)

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

    2012-03-01

    We use Fourier transform IR spectroscopy to study thyroid tumor tissues which were removed during surgery. The IR spectra of the tissues with pathological foci are compared with data from histologic examination. In the region of N-H, C-H, and C = O stretching vibrations, the IR spectra of the tissues for thyroid cancer are different from the IR spectra of tissues without malignant formations. We identify the spectral signs of thyroid cancer. We show that IR analysis is promising for identification of thyroid pathology at the molecular level.

  4. Sequential transcriptome analysis of human liver cancer indicates late stage acquisition of malignant traits

    DEFF Research Database (Denmark)

    Marquardt, Jens U; Seo, Daekwan; Andersen, Jesper Bøje;

    2014-01-01

    Human hepatocarcinogenesis is as a multi-step process starting from dysplastic lesions to early carcinomas (eHCC) that ultimately progress to HCC (pHCC). However, the sequential molecular alterations driving malignant transformation of the pre-neoplastic lesions are not clearly defined. This lack...

  5. Meningioma after radiotherapy for malignancy.

    Science.gov (United States)

    Morgenstern, Peter F; Shah, Kalee; Dunkel, Ira J; Reiner, Anne S; Khakoo, Yasmin; Rosenblum, Marc K; Gutin, Philip

    2016-08-01

    Complications of radiation exposure have gained importance with increasing cancer survivorship. Secondary malignancies have been associated with cranial radiation exposure. We present our experience with intracranial radiation-induced meningioma (RIM) and discuss the implications of its presentation and natural history for patient management. Patients diagnosed with meningioma who had received radiation therapy between 1960 and 2014 were identified. Records were retrospectively reviewed for details of radiation exposure, previous malignancies, meningioma subtypes, multiplicity and pathologic descriptions, treatment and follow-up. Thirty patients were diagnosed with RIM. Initial malignancies included acute lymphocytic leukemia (33.3%), medulloblastoma (26.7%) and glioma (16.7%) at a mean age of 8.1years (range 0.04-33years). The mean radiation dose was 34Gy (range 16-60Gy) and latency time to meningioma was 26years (range 8-51years). Twenty-one patients (70%) underwent surgery. Of these, 57.1% of tumors were World Health Organization (WHO) grade I while 42.9% were WHO II (atypical). The mean MIB-1 labeling index for patients with WHO I tumors was 5.44%, with 33.3% exhibiting at least 5% staining. Mean follow-up after meningioma diagnosis was 5.8years. Mortality was zero during the follow-up period. Meningioma is an important long-term complication of therapeutic radiation. While more aggressive pathology occurs more frequently in RIM than in sporadic meningioma, it remains unclear whether this translates into an effect on survival. Further study should be aimed at delineating the risks and benefits of routine surveillance for the development of secondary neoplasms after radiation therapy. PMID:27068012

  6. MALIGNANT MYOEPITHELIOMA OF THE BREAST

    Directory of Open Access Journals (Sweden)

    G. Irvanlou F. Mahjoub

    1997-07-01

    Full Text Available A 41 year old woman was referred to our center because of a left breast mass lesion of about two months duration. Routine pathologic examination of the mass revealed a .neoplastic tissue composed of large ovoid cells with clear cytoplasm arranged in broad sheets that were separated by thin bundles of connective tissue. Immunohistochemically tumor cells express smooth muscle actin, cytokeratin, and SI00 protein. Also two axillary lymph nodes were positive for tumor involvement, hence the name malignant myoepithelioma was applied for definition. Because of rarity of this type of tumor and paucity of the reported cases worltlwide, it appears to he an interesting case report.

  7. Life insurance after malignant disease.

    Science.gov (United States)

    Fitzgerald, R H

    1981-11-01

    Forty-five life insurance companies responded to a questionnaire on insurance industry attitudes towards patients with a history of malignancy other than skin carcinoma. Although the criteria for acceptance, provisions of the policy, and philosophy about adjuvant treatment varied, all companies would underwrite such patients provided that at application there was no evidence of persistent or recurrent disease or severe complications of therapy. The concept of excess mortality (observed death rates versus standard expected death rates) is used with other factors in calculating premiums. Legal and ethical responsibilities of physicians associated with insurance applications are briefly discussed.

  8. Rare emerging malignant skin tumours.

    Science.gov (United States)

    Rongioletti, F; Ferreli, C; Pinna, A L; Atzori, L

    2015-08-01

    As clinical skills improve and innovative diagnostic techniques become available in the field of dermatology and dermatopathology, new types or additional variants of malignant skin tumors are described. This article reviews the current nomenclature, clinico-pathological features, differential diagnosis, prognostic and therapeutic implications of some new dermato(patho)logical rare emerging skin tumors, including epithelial tumors (squamous cell carcinoma with mucinous metaplasia), adnexal tumors (endocrine mucin-producing sweat gland carcinoma), soft tissue tumors of vascular differentiation (pseudolymphomatous cutaneous angiosarcoma, pseudomyogenic hemangioendothelioma), hematopoietic tumors (blastic plasmacytoid dendritic cell neoplasm) and mixed epithelial/melanocytic tumor (squamomelanocytic tumor). PMID:26086411

  9. HISTOMORPHOLOGICAL STUDY OF COLORECTAL MALIGNANCIES

    Directory of Open Access Journals (Sweden)

    Sarvesh

    2015-07-01

    Full Text Available BACKGROUND: Colorectal cancer is the most common cancer in men and in women worldwide. Incidence rates of colorectal cancer vary 10 - fold in both sexes worldwide, Within Asia, the incidence rates vary widely and are uniformly low in all south Asian countries and high i n all developed Asian countries. Fortunately, the age adjusted incidence rates of colorectal cancer in all the Indian cancer registries are very close to the lowest rates in the world. The present study is under taken to study the prevalence and types of c olorectal cancer among the patients in the rural population in and around Chidambaram. OBJECTIVES: To study the prevalence of malignant colorectal neoplasms among the speci mens received in the Department of Pathology and the gross and histomorphological pa ttern of the lesions and finally to correlate the findings with clinical data. METHOD: The materials consisted of 68 specimens who were submitted to the Department of Pathology, during the period of Jan 2008 - Dec 2012. Data collected and entered in MS - Excel and were analyzed using SPSS - 16. RESULTS : Out of 8454 colonoscopic specimens, 68(0.8% showed colorectal malignancy. A higher frequency of colorectal was seen in 6 th decade. Out of 68 specimens of malignant neoplasms majority were Carcinoma of the Rectum (79.41% followed in decreasing order of frequency by malignant lesions of descending colon(8.82%, ascending and Sigmoid colon (4.41% each, recto - sigmoid (2.94% and cecum (2.63%, and transverse colon (2.63%. Youngest patient was 19 years old and the o ldest patient was 80 years old with a mean age of 49.5 years and median age of 50 years. CONCLUSION: Colorectal cancer is a common and lethal disease. The adenoma carcinoma. S equence offers a window of opportunity in which the precursor lesion or early car cinoma can be removed endoscopically to prevent systematic disease. The result of a careful and systematic examination of surgical specimens from patients with

  10. Multicentric malignant gastrointestinal stromal tumor

    OpenAIRE

    Shukla Shailaja; Singh Sanjeet; 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 th...

  11. Computed tomography findings of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Computed tomography (CT) findings were assessed in 7 patients with malignant mesothelioma. CT findings were also reviewed in 9 patients with lung cancer and pleuritis carcinomatosa and in 11 patients with tuberculous pleuritis. Five patients with malignant mesothelioma underwent CT scans twice, on admission and from 1 to 7 months after admission. Tuberculous pleuritis could be distinguished from pleuritis carcinomatosa and malignant mesothelioma by the presence or absence of pleural nodularity and chest wall invasion. Although it was difficult to identify specific CT features clearly distinguishing malignant mesothelioma from pleuritis carcinomatosa, characteristic findings of malignant mesothelioma appeared to include the rapid development and progression of pleural rind and a tendency to spread directly into the chest wall. We divided the pleural into the four regions; upper anterior, upper posterior, lower anterior and lower posterior regions. Pleural changes were more frequently seen in the lower pleural regions than in the upper pleural regions in malignant mesothelioma. (author)

  12. Malignant chondroid syringoma of the pinna

    International Nuclear Information System (INIS)

    Chondroid syringoma (CS) represents the cutaneous counterpart of mixed tumor (pleomorphic adenoma) of salivary glands. The malignant counterpart of CS, termed as “malignant CS” is a malignant eccrine neoplasm which lacks distinctive clinical features, often delaying initial diagnosis. Unlike its benign counterpart which often localizes in the head and neck region, malignant CS most often encountered in the trunk and the extremities. We report a rare case of an aggressive malignant CS of the left pinna with cervical lymph node metastasis. Our patient, to the best of our knowledge, possibly is the first case of malignant CS of the pinna and the fourth to arise in the head and neck region. The diagnostic challenges with an added emphasis on the role of positron emission tomography-computed tomography in aiding the management of this rare tumor are discussed

  13. Tissue Microarray Study of Vasculogenic Mimicry in Bi-directional Differentiated Malignant Tumors

    Institute of Scientific and Technical Information of China (English)

    XishanHao; BaocunSun; ShiwuZhang; XiulanZhao

    2004-01-01

    OBJECTIVE To determine if vasculogenic mimicry (VM) exists in bi-directional differentiated malignant tumors. METHODS The blood supply models for bi-directional differentiated tumors were studied with immunohistochemical and PAS double-staining techniques. New sections were made from 158 paraffin-embedded bi-directional malignant-tumor samples, including melanoma (high malignancy n=30, low malignancy n=30); synoviosarcoma(SS) (high malignancy n=26, low malignancy n=13); acinar rhabdomyosarcoma (All) (high malignancy n=16,low malignancy n=13); malignant mesothelioma (MM) (n=26), and epithelioid sarcoma (ES)(n=4). Tissue microarrays were made. The representative points in the paraffin sections were labeled and two tissue microarrays were made, one included 60 cases of melanoma, and the other included the other tumors. Immunohistochemical staining of the platelet-endothelial cell adhesive molecule(CD31 antigen) and periodic acid Schiff(PAS) staining were conducted. The areas were calculated of vessel-like channels consisting of CD31 antigen-positive tumor cells and of PAS positive materials. The VM was studied using the data obtained. RESULTS Some of these bi-directional tumor cells secreted PAS-positive materials and 0D31 positive materials. The walls of the VM consisted of PAS-positive materials lined with CD31 negative tumor cells with red blood cells inside the channel, whereas the walls of the epithelium-dependent vessels were comprised of CD31 positive materials. The positive areas of CD31 were significantly less than that of PAS (P<0.01). The number of cases with VM in highly malignant tumors was greater than that found in the lowly malignant tumors. CONCLUSIONS Bi-directional differentiated malignant tumor cells have the ability to auto-transform and might interact with the extracellular matrix to form a vessel channel system which mimics blood vessels for transporting blood. That process is called VM. Results in this study show that bi

  14. Oncolytic Virotherapy for Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Swarna Bais

    2012-01-01

    Full Text Available Hematological malignancies such as leukemias, lymphomas, multiple myeloma (MM, and the myelodysplastic syndromes (MDSs primarily affect adults and are difficult to treat. For high-risk disease, hematopoietic stem cell transplant (HCT can be used. However, in the setting of autologous HCT, relapse due to contamination of the autograft with cancer cells remains a major challenge. Ex vivo manipulations of the autograft to purge cancer cells using chemotherapies and toxins have been attempted. Because these past strategies lack specificity for malignant cells and often impair the normal hematopoietic stem and progenitor cells, prior efforts to ex vivo purge autografts have resulted in prolonged cytopenias and graft failure. The ideal ex vivo purging agent would selectively target the contaminating cancer cells while spare normal stem and progenitor cells and would be applied quickly without toxicities to the recipient. One agent which meets these criteria is oncolytic viruses. This paper details experimental progress with reovirus, myxoma virus, measles virus, vesicular stomatitis virus, coxsackievirus, and vaccinia virus as well as requirements for translation of these results to the clinic.

  15. Imaging probe for tumor malignancy

    Science.gov (United States)

    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.

  16. [Malignant melanoma coexisting with pregnancy].

    Science.gov (United States)

    Krasomski, G; Broniarczyk, D; Gładysiak, A

    1992-09-01

    An extremely rare case of melanoma amelanoticum coexisting with pregnancy has been discussed. Pregnant A. Ch., age 42, was admitted to the Polish Mother's Health Centre Memorial Hospital on the 22nd of August, 1990 with a diagnosis of the 5th pregnancy, the 2nd delivery, the 30th week of gestation, state after cesarean section. Suspected malignant melanoma. Stomach ulceration. Thrombophlebitis of left lower extremity. General condition--medium hard. For the last three days she did not report fetal movements, fetal heartbeat was not detected either. Us examination confirmed fetal death. On the 24th of August, 1990, spontaneous vaginal delivery terminated the pregnancy, giving a dead, macerated female fetus, body weight of 1500 g. On the 3rd day after delivery the patient died with growing circulation-respiratory insufficiency. Autopsy revealed melanoma malignum amelanoticum disseminatum. Neither an autopsy of the fetus nor histopathological examinations of the secundines were performed for the advanced maceration. The coexistence of pregnancy with malignant melanoma in this case brought a tragic end both for the mother and the fetus. PMID:1305602

  17. Multicentric malignant gastrointestinal stromal tumor

    International Nuclear Information System (INIS)

    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. (author)

  18. Multicentric malignant gastrointestinal stromal tumor.

    Science.gov (United States)

    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

  19. Multicentric malignant gastrointestinal stromal tumor

    Directory of Open Access Journals (Sweden)

    Shukla Shailaja

    2009-01-01

    Full Text Available 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.

  20. ACTUALLY TREATMENT OF THE HEPATIC MALIGNANT TUMORS

    OpenAIRE

    E. Tarcoveanu

    2005-01-01

    The treatment of the hepatic malignant tumors is a challenge for every surgeon. In present days there are a lot of techniques with different indications and results. These methods and their efficacity are presented in some recent papers. Hepatic resection is the gold standard treatment for hepatic malignancies with a decreasing postoperative morbidity and mortality. But only 10 - 20% of the patients with hepatic malignancies are able to be operated. For the other patients the treatment is pal...

  1. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuilt...... theoretical lenses. It is proposed that three parameters concerning the ꞌtransformabilityꞌ of the building can contribute to a more nuanced understanding of sustainable transformation: technical aspects, programmatic requirements and narrative value. It is proposed that the concept of ꞌsustainable...

  2. Mistletoe in the treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Esin Sakallı Çetin

    2014-03-01

    Full Text Available Malignant melanoma is a malignant neoplasia drives from melanocytes. Malignant melanoma, the most causing death, is seen in the third place at skin cancer. Malignant melanoma shows intrinsic resistance to chemotherapeutic agents and variability in the course of the disease which are distinct features separating from other solid tumors. These features prevent the development and standardization of non-surgical treatment models of malignant melanoma. Although there is a large number of chemotherapeutic agents used in the treatment of metastatic malignant melanoma, it hasn’t been demonstrated the survival advantage of adjuvant treatment with chemotherapeutic agents. Because of the different clinical course of malignant melanoma, the disease is thought to be closely associated with immune system. Therefore, immunomodulatory therapy models were developed. Mistletoe stimulates the immune system by increasing the number and activity of dendritic cells, thus it has been shown to effect on tumor growth and metastasis of malignant melanoma patient. Outlined in this review are the recent developments in the understanding the role of mistletoe as a complementary therapy for malignant melanoma. J Clin Exp Invest 2014; 5 (1: 145-152

  3. B-Cell Hematologic Malignancy Vaccination Registry

    Science.gov (United States)

    2015-09-15

    Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

  4. Medicinal therapy of malignant lymphomas; Medikamentoese Therapie maligner Lymphome

    Energy Technology Data Exchange (ETDEWEB)

    Aul, C.; Schroeder, M.; Giagounidis, A. [Medizinische Klinik II, St.-Johannes-Hospital Duisburg (Germany)

    2002-12-01

    Chemotherapy represents the most important therapeutic option in malignant lymphomas. Low to intermediate risk Hodgkin's disease is treated by a combination of chemotherapy and radiation. The new chemotherapy protocol BEACOPP has improved the outcome of advanced stages in comparison with the internationally accepted standard protocol COPP/ABVD. Dependent on the initial staging, cure rates between 50 and 95% can be achieved. Indolent non-Hodgkin's lymphomas usually present in advanced stages of disease. Chemotherapy in these cases has palliative character and aims at improving patients'quality of life and at avoiding complications due to the disease. In aggressive and very aggressive non-Hodgkin's lymphoma chemotherapy is curative and must be initiated immediately irrespective of the staging results. The efficacy of the standard protocol CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone), that was established in the 1970s, has recently been improved by shortening of the therapy interval (CHOP-14 vs.CHOP-21),addition of etoposide (CHOEP) and combination with the monoclonal antibody rituximab (R-CHOP). The value of high dose chemotherapy with stem cell transplantation has been shown unequivocally only for aggressive non-Hodgkin lymphoma and relapsed Hodgkin's disease responsive to chemotherapy. The therapeutic strategy of malignant lymphomas is likely to be improved within the next years due to the introduction of novel cytostatic agents, the broadening application of monoclonal antibodies,upcoming new transplantation procedures and the development of substances with molecular targets.To rapidly increase our current knowledge on the topic it is mandatory to include patients into the large national and international multicenter studies. (orig.) [German] Die Chemotherapie stellt die wichtigste Behandlungsoption maligner Lymphome dar. Bei Hodgkin-Lymphomen niedrigen bzw. intermediaeren Risikoprofils wird eine kombinierte Behandlung

  5. Surgery of malignant pancreatic tumors; Chirurgie maligner Pankreastumoren

    Energy Technology Data Exchange (ETDEWEB)

    Loos, M.; Friess, H.; Kleeff, J. [Klinikum rechts der Isar, Technische Universitaet Muenchen (Germany). Chirurgische Klinik und Poliklinik

    2009-02-15

    Ductal adenocarcinoma is the most common malignant tumor of the pancreas. Despite great efforts in basic and clinical pancreatic cancer research, the prognosis remains poor with an overall 5-year survival rate of less than 5%. Complete surgical resection represents the only curative treatment option and 5-year survival rates of 20-25% can be achieved following curative resection and adjuvant chemotherapy. Although pancreatic surgery is considered one of the most technically demanding and challenging procedures, there has been constant progress in surgical techniques and advances in perioperative care with a modern interdisciplinary approach including anesthesiology, oncology, radiology and nursing. This has reduced morbidity and especially mortality rates in high-volume centers. Among extended resection procedures multivisceral and venous resections are technically feasible and should be considered if a complete tumor resection can be achieved. Multimodal regimens have shown promising results, however, only adjuvant chemotherapy is supported by solid evidence from randomized controlled trials. (orig.) [German] Das duktale Adenokarzinom ist der haeufigste maligne Pankreastumor. Trotz intensiver Anstrengungen auf dem Gebiet der Pankreasforschung konnte die Gesamtprognose in den vergangenen Jahren nicht entscheidend verbessert werden. Die einzige potenziell kurative Therapie ist die chirurgische Resektion. In Kombination mit einer adjuvanten Chemotherapie liegen die 5-Jahres-Ueberlebensraten aktuell bei 20-25%. Dank kontinuierlicher Weiterentwicklung der chirurgischen Operationstechnik und Verbesserungen der perioperativen Versorgung der Patienten mit einer engen interdisziplinaeren Zusammenarbeit (Chirurgie, Anaesthesie, Onkologie, Radiologie und Pflege) konnten die perioperative Morbiditaets- und Mortalitaetsraten in den vergangenen Jahren deutlich gesenkt werden. Unter den erweiterten Resektionsverfahren sind Venen- oder multiviszerale Resektionen technisch sicher

  6. Hereditary multiple exostosis with secondary malignization: case report

    Energy Technology Data Exchange (ETDEWEB)

    Coutinho, A.M.N.; Pitella, F.A.; Coura Filho, G.B.; Costa, P.L.A.; Ono, C.R.; Watanabe, T.; Sapienza, M.T.; Hironaka, F.; Cerri, G.G.; Buchpiguel, C.A. [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Radiologia. Centro de Medicna Nuclear

    2008-07-01

    Full text: Introduction: Hereditary Multiple Exostosis (HME) or multiple osteochondromatosis is a skeletal development anomaly which is characterized by generalized exostoses in the bones, mainly in long bone metaphyses, appearing during childhood and adolescence. The transmission is autosomal dominant, its prevalence varies from 1/50,000 to 9/1,000,000 in Europe, and around 10% of cases show no family history. Case Report: Description of an HME case with two secondary malignization episodes. The data was taken from the patient's chart and from imaging exams from the hospital files. WASB, a 19-year-old male, hospitalized after being pre-diagnosed with HME and complaints of bone-consistent mass in the right gluteal region and a lump in the posterior region of the right leg, associated to multiple bone lumps all over the body. A magnetic resonance imaging (MRI) was performed along with a bone scintillography with {sup 99m}Tc-MDP which showed multiple osteogenic lesions in the thorax, pelvic bones and long bones with periarticular prevalence in the lower limbs. The suspicion of malignancy in the right iliac area was raised due to the MRI result and to the higher intensity captured in the scintillography, confirming chondrosarcoma grade I of malignancy in the biopsy. The patient suffered interileo abdominalis amputation of the right lower limb with good evolution and control scintillography performed after 1 and 1,5 years. In the second controlling procedure, the patient complained about pain in the left knee, and a MRI suggested a new secondary malignization. The hypothesis of a head of left fibula osteochondroma with signs of aggressiveness was confirmed following surgery. Discussion: In HME, the exostoses grow along with the individual, ceasing with the epiphyseal fusion. The growth of these formations after skeletal maturation suggests activity of exostoses and, in most times, it is a sign of malignant transformation, which turns almost every time into

  7. 超声造影及其定量分析对乳腺癌恶性转化过程中血管生成作用的评价%Inspection on angiogenesis in malignant transformation of breast tumor by ultrasound contrast and quantitative analysis

    Institute of Scientific and Technical Information of China (English)

    李颖嘉; 文戈; 杨莉

    2009-01-01

    目的 探讨乳腺癌发生与演进过程中血管生成作用及其变化规律.方法 应用实时超声造影微血管成像(MVI)技术及时间-强度曲线定量分析技术检测30例正常乳腺妇女,30例单纯增生,30例非典型增生(AH),20例导管内原位癌,50例浸润性导管癌患者微血管造影特征,及灌注参数峰值强度(PI)、曲线下面积(AUC)、廓清时间(WOT),免疫组化技术检测微血管密度(MVD)、血管内皮生长因子(VEGF)及受体Flk-1/KDR在各组的表达.结果 随病程演进,MVI显示血管数目增多,结构趋于紊乱,各组灌注参数PI(dB)(分别为38±9,39±13,75±9,75±13,120±11),AUC(dB.s)(分别为363±28,374±78,681±64,697±108,1301±125),WOT(s)(分别为31.4±4.4,32.6±4.1,50.9±2.4,52.9±5.0,74.9±3.2)逐渐延长(均P0.05),VEGF及Flk.1/KDR的表达在AH与原位癌组间差异有统计学意义(均P<0.05).结论 血管生成在乳腺癌发生、发展过程中起着重要作用,异常的血管生成可能是乳腺癌发生过程中的早期事件.超声造影MVI及各主要灌注参数能够一定程度上反映乳腺癌前病变阶段组织血管生成活性的变化规律,是用于高危人群监测随访无创而实用的手段.%Objective To study the effects of angiogenesis on tumorogenesis and the progression of breast carcinoma and precancerous lesion. Methods Real time ultrasound contrast enhanced microvascular imaging(MVI) and time-intensity curve quantitative analysis were conducted on 30 normal controls,30 cases with simple hyperplasia, 30 cases with atypical hyperplasia (AH), 20 cases with intraductal carcinoma in situ, and 50 cases with invasive ductal carcinoma, all female. Specimens of breast tissues were obtained and immunohistochemistry was used to detect the expression of CD34, a marker of vascular endothelial cells, and vascular endothelial growth factoor (VEGF) and its receptor Flk-1/KDR. Results With the progression of malignant transformation of breast tissue, the

  8. ADE Transform

    CERN Document Server

    Donagi, Ron

    2015-01-01

    There is a beautiful correspondence between configurations of lines on a rational surface and tautological bundles over that surface. We extend this correspondence to families, by means of a generalized Fourier-Mukai transform that relates spectral data to bundles over a rational surface fibration.

  9. GASTROINTESTINAL MALIGNANCIES: GETTING A DECADE YOUNGER?

    Directory of Open Access Journals (Sweden)

    Sushmitha

    2014-06-01

    Full Text Available INTRODUCTION: Gastrointestinal malignancies are one of the most common malignancies encountered frequently, with rising incidence in young age due to the changing lifestyle and food habits in India. Oesophagus, stomach and colonic cancers are the commonly affected regions of the GI tract. These malignancies is known to occur in older age of fifth decade onwards. This is a study intended to highlight the rising incidence of such malignancies in the younger age in second to third decade as observed in and around Mangalore. Upper gastrointestinal malignancies are common in oesophagus and stomach, whereas lower gastrointestinal malignancies occur more commonly seen in colon. Colorectal cancer (CRC is one of the most common of all familial malignancies with peak incidence in 60 to 70 years of age, 90% of cases occur in people aged 50 or older.Risk factors include a genetic predisposition, diet and lifestyle changes in the current era. Inheritance plays a role in the pathogenesis of upto a third of CRC cases. AIMS AND OBJECTIVE: To study the prevalence of gastrointestinal malignancies in patients less than fifty years and the association of positive family history and polyps with colorectal carcinomas. MATERIAL AND METHODS: This is a retrospective study of 128 cases of gastrointestinal malignancies from June 2010 to May 2012 received in and around Mangalore. The study includes endoscopic biopsies, colonoscopic biopsies partial and total colectomy specimens with growth seen anywhere from oesophagus to rectum. Representative sections are taken, processed routinely and stained with H & E. The pathological findings are then correlated with clinical data like age and sex distribution, site, family history and presence of other malignancies. RESULTS: In this study gastrointestinal malignancies were studied as upper and lower gastrointestinal lesions. Upper gastrointestinal (GI lesions were those in oesophagus, stomach, and duodenum. A total of 128 cases

  10. Aftercare of malignant thyroid growth

    International Nuclear Information System (INIS)

    The 'standard programme of aftercare for patients with malignant thyroid growths' practised in our department comprises the following measures: - Searching for residual tissues and recurrences in the neck/throat region and for metastases by means of physical examination, scintigraphy, x-ray diagnosis and laboratory tests (including determination of tumour markers); - monitoring and treatment of side effects by thyroidectomy (recurrent paresis, parathyroprival tetany); - prevention, detection and treatment of side effects of high-dosed radio-iodine therapy (on salivary glands and bone marrow) or those of cytostatic treatment (on heart muscle and bone marrow); - monitoring substitutive and suppressive treatment with thyroxines; - psychological guidance and genetic counselling. Corresponding to therapeutic approach, the overall aftercare programme is aimed primarily at papillary and follicular carcinoma and C-cell carcinoma. However, aftercare is hardly effective with anaplastic carcinoma owing to its persistently bad prognosis and its 50% survival time of some three months. (orig./MG)

  11. Malignancies in systemic lupus erythematosus

    Science.gov (United States)

    Kale, Mruganka; Ramsey-Goldman, Rosalind; Gordon, Caroline; Clarke, Ann E; Bernatsky, Sasha

    2013-01-01

    The purpose of this review is to underline important advancements in the understanding of cancer risks in systemic lupus erythematosus (SLE). In SLE, there is an increased risk of specific kinds of malignancy. For example, the risk of non-Hodgkin’s lymphoma is increased several-fold in SLE versus the general population. In addition, heightened risks for lung cancer, thyroid cancer and cervical dysplasia in SLE have been found. Some have postulated that immunosuppressive drugs play a role, as well as other important mediators, such as lupus disease activity itself. One new frontier being explored is the significant finding of a decreased risk of certain nonhematologic cancers (e.g., breast, ovarian, endometrial and prostate) in SLE. The reasons for this are currently under study. PMID:19643208

  12. Malignant cerebral swelling following cranioplasty.

    Science.gov (United States)

    Honeybul, S; Damodaran, O; Lind, C R P; Lee, G

    2016-07-01

    Over the past few years there have been a number of case reports and small cohort studies that have described so called "malignant" cerebral swelling following an uneventful cranioplasty procedure. The pathophysiology remains to be established however it has been suggested that it may be related to a combination of failure of autoregulation and the use of closed vacuum suction drainage. The current study presents three further patients who had had a decompressive hemicraniectomy for ischaemic stroke. If decompressive craniectomy is utilised in the management of neurological emergencies, close attention and wider reporting of this type of complication is required not only to focus attention on possible management strategies, but also to determine which patients are at most risk of this devastating complication. PMID:27189792

  13. Surgery of malignant pancreatic tumors

    International Nuclear Information System (INIS)

    Ductal adenocarcinoma is the most common malignant tumor of the pancreas. Despite great efforts in basic and clinical pancreatic cancer research, the prognosis remains poor with an overall 5-year survival rate of less than 5%. Complete surgical resection represents the only curative treatment option and 5-year survival rates of 20-25% can be achieved following curative resection and adjuvant chemotherapy. Although pancreatic surgery is considered one of the most technically demanding and challenging procedures, there has been constant progress in surgical techniques and advances in perioperative care with a modern interdisciplinary approach including anesthesiology, oncology, radiology and nursing. This has reduced morbidity and especially mortality rates in high-volume centers. Among extended resection procedures multivisceral and venous resections are technically feasible and should be considered if a complete tumor resection can be achieved. Multimodal regimens have shown promising results, however, only adjuvant chemotherapy is supported by solid evidence from randomized controlled trials. (orig.)

  14. Thigmotropism of Malignant Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Pascale Quatresooz

    2012-01-01

    Full Text Available During malignant melanoma (MM progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape. These specifically located paucicellular aggregates of MM cells do not appear to be involved in the tumorigenic growth phase, but rather they participate in the so-called “accretive” growth model. These MM cell collections are often part of the primary neoplasm, but they may, however, correspond to MM micrometastases and predict further local overt metastasis spread.

  15. Thigmotropism of malignant melanoma cells.

    Science.gov (United States)

    Quatresooz, Pascale; Piérard-Franchimont, Claudine; Noël, Fanchon; Piérard, Gérald E

    2012-01-01

    During malignant melanoma (MM) progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape). These specifically located paucicellular aggregates of MM cells do not appear to be involved in the tumorigenic growth phase, but rather they participate in the so-called "accretive" growth model. These MM cell collections are often part of the primary neoplasm, but they may, however, correspond to MM micrometastases and predict further local overt metastasis spread. PMID:22203839

  16. Glucosylceramidases and malignancies in mammals.

    Science.gov (United States)

    Astudillo, Leonardo; Therville, Nicole; Colacios, Céline; Ségui, Bruno; Andrieu-Abadie, Nathalie; Levade, Thierry

    2016-06-01

    Sphingolipids represent a major class of lipids that are essential constituents of eukaryotic cells. They are predominantly located in plasma membrane microdomains, and play an important structural role in regulating membrane fluidity. They are also bioactive effectors involved in diverse key cellular functions such as apoptosis and proliferation. The implication of some sphingolipids in cancer is well established whereas that of some others is still a matter of intense investigation. Glucosylceramide is the backbone of more than 300 structurally different glycosphingolipids including gangliosides and sulfatides, and is essential for mammalian development. Therefore, glucosylceramidases (also named GBA1, GBA2 and GBA3 β-glucosidases), the enzymes that hydrolyse β-glucosylceramide, play important functions. GBA1 is a lysosomal hydrolase whose deficiency causes Gaucher disease, the most prevalent inherited lysosomal storage disorder. GBA2 is a ubiquitous non-lysosomal glucosylceramidase whose mutations have been associated with some forms of hereditary spastic paraplegia. GBA3 is a cytosolic β-glucosidase, mostly present in the kidney, liver, spleen, intestine and lymphocytes of mammals, the function of which is still unclear. Whereas glucosylceramide synthase is implicated in multidrug resistance, the role of glucosylceramide breakdown in cancer is not yet fully appreciated. Defective GBA1 enzyme activity in humans, i.e., Gaucher disease, is associated with an increased risk of multiple myeloma and other malignancies. Putative molecular links between Gaucher disease and cancer, which might implicate the malignant cell and/or its microenvironment, are reviewed. The functions of GBA2 and GBA3 in cancer progression are also discussed.

  17. Native cellular fluorescence characteristics of normal and malignant epithelial cells from human larynx

    Science.gov (United States)

    Parmeswearan, Diagaradjane; Ganesan, Singaravelu; Nalini, R.; Aruna, Prakasa R.; Veeraganesh, V.; Alfano, Robert R.

    1997-08-01

    Many applications of native fluorescence spectroscopy of intrinsic biomolecules such as Try, Tyr, Phe, NADH and FAD are reported on both the characterization and the discrimination of malignant tissues from the normal. In the field of diagnostic oncology, extensive studies have been made to distinguish the normal from malignant condition in breast, cervix, colon and bronchus. From the studies made by Alfano and co-workers, it was found that the emission at 340 and 440 nm under UV excitation have shown statistically significant difference between normal and malignant tissues. As tissues are highly complex in nature, it is worth to known whether the changes arise from cells or from other extracellular tissue components, so as to enable us to have better understanding on the transformation mechanism of normal into malignant and to go for an improved approach in the effective optical diagnosis. In this context, the present study addresses the question of whether there are differences in the native cellular fluorescence characteristics between normal and malignant epithelial cells from human larynx. With this aim, the UV fluorescence emission spectra in the wavelength region of excitation between 270 - 310 nm and the excitation spectra for 340 nm emission were measured and analyzed. In order to quantify the altered fluorescence signal between the normal and malignant cells, different ratio parameters were introduced.

  18. Metastatic malignant struma ovarii with coexistence of Hashimoto’s thyroiditis

    Science.gov (United States)

    Russo, Marco; Marturano, Ilenia; Masucci, Romilda; Caruso, Melania; Fornito, Maria Concetta; Tumino, Dario; Tavarelli, Martina; Squatrito, Sebastiano

    2016-01-01

    Summary Struma ovarii is a rare ovarian teratoma characterized by the presence of thyroid tissue as the major component. Malignant transformation of the thyroidal component (malignant struma ovarii) has been reported in approximately 5% of struma ovarii. The management and follow-up of this unusual disease remain controversial. We report the case of a woman with a history of autoimmune thyroiditis and a previous resection of a benign struma ovarii that underwent hystero-annexiectomy for malignant struma ovarii with multiple papillary thyroid cancer foci and peritoneal involvement. Total thyroidectomy and subsequent radioiodine treatment lead to complete disease remission after 104 months of follow-up. The diagnosis and natural progression of malignant struma ovarii are difficult to discern, and relapses can occur several years after diagnosis. A multidisciplinary approach is mandatory; after surgical excision of malignant struma, thyroidectomy in combination with 131I therapy should be considered after risk stratification in accordance with a standard approach in differentiated thyroid cancer patients. Learning points Malignant struma ovarii is a rare disease; diagnosis is difficult and management is not well defined. Predominant sites of metastasis are adjacent pelvic structures. Thyroidectomy and 131I therapy should be considered after risk stratification in accordance with standard approaches in DTC patients. PMID:27224256

  19. Malignant triton tumor (MTT) of the neck

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  20. Unusual thoracic manifestation of metastatic malignant melanoma

    Directory of Open Access Journals (Sweden)

    Mohan K

    2010-01-01

    Full Text Available Massive pleural effusion due to metastatic malignant melanoma is rare. We report a case of bilateral (massive on left side pleural effusion as a metastatic manifestation of cutaneous malignant melanoma. In our case, successful outcome of pleurodesis with vincristine is significant as this agent is rarely used.

  1. Radiosensitized treatment of malignant brain tumors

    Science.gov (United States)

    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.

  2. FDG-PET imaging in hematological malignancies.

    Science.gov (United States)

    Valls, L; Badve, C; Avril, S; Herrmann, K; Faulhaber, P; O'Donnell, J; Avril, N

    2016-07-01

    The majority of aggressive lymphomas is characterized by an up regulated glycolytic activity, which enables the visualization by F-18 FDG-PET/CT. One-stop hybrid FDG-PET/CT combines the functional and morphologic information, outperforming both, CT and FDG-PET as separate imaging modalities. This has resulted in several recommendations using FDG-PET/CT for staging, restaging, monitoring during therapy, and assessment of treatment response as well as identification of malignant transformation. FDG-PET/CT may obviate the need for a bone marrow biopsy in patients with Hodgkin's lymphoma and diffuse large B cell lymphoma. FDG-PET/CT response assessment is recommended for FDG-avid lymphomas, whereas CT-based response evaluation remains important in lymphomas with low or variable FDG avidity. The treatment induced change in metabolic activity allows for assessment of response after completion of therapy as well as prediction of outcome early during therapy. The five-point scale Deauville Criteria allows the assessment of treatment response based on visual FDG-PET analysis. Although the use of FDG-PET/CT for prediction of therapeutic response is promising it should only be conducted in the context of clinical trials. Surveillance FDG-PET/CT after complete remission is discouraged due to the relative high number of false-positive findings, which in turn may result in further unnecessary investigations. Future directions include the use of new PET tracers such as F-18 fluorothymidine (FLT), a surrogate biomarker of cellular proliferation and Ga-68 CXCR4, a chemokine receptor imaging biomarker as well as innovative digital PET/CT and PET/MRI techniques. PMID:27090170

  3. Discrete transforms

    CERN Document Server

    Firth, Jean M

    1992-01-01

    The analysis of signals and systems using transform methods is a very important aspect of the examination of processes and problems in an increasingly wide range of applications. Whereas the initial impetus in the development of methods appropriate for handling discrete sets of data occurred mainly in an electrical engineering context (for example in the design of digital filters), the same techniques are in use in such disciplines as cardiology, optics, speech analysis and management, as well as in other branches of science and engineering. This text is aimed at a readership whose mathematical background includes some acquaintance with complex numbers, linear differen­ tial equations, matrix algebra, and series. Specifically, a familiarity with Fourier series (in trigonometric and exponential forms) is assumed, and an exposure to the concept of a continuous integral transform is desirable. Such a background can be expected, for example, on completion of the first year of a science or engineering degree cour...

  4. M-CSF TARGETING INTO LCL NUCLEUS BEHAVES AS A MALIGNANCY PROMOTOR

    Institute of Scientific and Technical Information of China (English)

    曹震宇; 吴克复; 宋玉华; 李戈; 林永敏; 饶青; 马小彤

    2003-01-01

    Objective: To investigate the functions of nM-CSF in malignant cells. Methods: recombinant M-CSF was targeted into cell nucleus by employing a eukaryotic expression plasmid vector pCMV/myc/nuc. The constructed plasmid was transfected into cells of EBV transformed lymphoblastoid cell line (LCL). RT-PCR, Western blot and immunofluorescent staining showed that recombinant M-CSF was localized into LCL cell nucleus. The transgenic cells showed elevated proliferation potential, enhanced resistance to apoptosis and increased ability of in vitro migration. Conclusion: Nucleus presenting M-CSF might act as a promoting factor in the processes of cell malignancy.

  5. Gynecologic Malignancies Post-LeFort Colpocleisis

    Directory of Open Access Journals (Sweden)

    Rayan Elkattah

    2014-01-01

    Full Text Available Introduction. LeFort colpocleisis (LFC is a safe and effective obliterative surgical option for older women with advanced pelvic organ prolapse who no longer desire coital activity. A major disadvantage is the limited ability to evaluate for post-LFC gynecologic malignancies. Methods. We present the first case of endometrioid ovarian cancer diagnosed after LFC and review all reported gynecologic malignancies post-LFC in the English medical literature. Results. This is the second reported ovarian cancer post-LFC and the first of the endometrioid subtype. A total of nine other gynecologic malignancies post-LFC have been reported in the English medical literature. Conclusions. Gynecologic malignancies post-LFC are rare. We propose a simple 3-step strategy in evaluating post-LFC malignancies.

  6. Transformative Agency

    DEFF Research Database (Denmark)

    Majgaard, Klaus

    The purpose of this paper is to enhance the conceptual understanding of the mediatory relationship between paradoxes on an organizational and an individual level. It presents a concept of agency that comprises and mediates between a structural and individual pole. The constitution of this agency ...... is achieved through narrative activity that oscillates between the poles and transforms paradoxes through the configuration of plots and metaphors. Empirical cases are introduced in order to illustrate the implications of this understanding....

  7. RF transformer

    Science.gov (United States)

    Smith, James L.; Helenberg, Harold W.; Kilsdonk, Dennis J.

    1979-01-01

    There is provided an improved RF transformer having a single-turn secondary of cylindrical shape and a coiled encapsulated primary contained within the secondary. The coil is tapered so that the narrowest separation between the primary and the secondary is at one end of the coil. The encapsulated primary is removable from the secondary so that a variety of different capacity primaries can be utilized with one secondary.

  8. Identity transformation

    DEFF Research Database (Denmark)

    Neergaard, Helle; Robinson, Sarah; Jones, Sally

    This paper develops the concept of ‘pedagogical nudging’ and examines four interventions in an entrepreneurship classroom and the potential it has for student identity transformation. Pedagogical nudging is positioned as a tool, which in the hands of a reflective, professional, with an understand......This paper develops the concept of ‘pedagogical nudging’ and examines four interventions in an entrepreneurship classroom and the potential it has for student identity transformation. Pedagogical nudging is positioned as a tool, which in the hands of a reflective, professional......, with an understanding and rationale for using it, provides students with the opportunity to explore their own entrepreneurial identity in unforeseen ways. It builds on insights from three different streams of literature: (i) Bordieu’s theory of practice is used to analyze student understandings of themselves and others......) assists students in straddling the divide between identities, the emotions and tensions this elicits, and (iv) transform student understanding. We extend nudging theory into a new territory. Pedagogical nudging techniques may be able to unlock doors and bring our students beyond the unacknowledged...

  9. Subspaces of FMmlet transform

    Institute of Scientific and Technical Information of China (English)

    邹红星; 戴琼海; 赵克; 陈桂明; 李衍达

    2002-01-01

    The subspaces of FMmlet transform are investigated.It is shown that some of the existing transforms like the Fourier transform,short-time Fourier transform,Gabor transform,wavelet transform,chirplet transform,the mean of signal,and the FM-1let transform,and the butterfly subspace are all special cases of FMmlet transform.Therefore the FMmlet transform is more flexible for delineating both the linear and nonlinear time-varying structures of a signal.

  10. Ground water pollution by arsenic and its effects on health. Involvement of metabolic methylation in arsenic-induced genetic damage and tumorigenesis; Muki hiso no mechiru ka taisha to idenshi shogaisei narabini shuyo yuhatsusei

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, K. [Nihon Univ., Tokyo (Japan)] Okada, S. [Shizuoka Prefecture (Japan)

    1997-07-10

    Drinking water contamination has become a worldwide problem. It is pointed out that re-evaluation of genetic damage with carcinogen is considered as an important problem particularly arsenic`s effects on health. To explain the genetic damage development mechanism of arsenic compound, results of the research conducted on the action of arsenic compound which develops during metabolic methylation process and inorganic arsenic are explained in this paper. The results of the study are summarized as follows. Arsenic genetic damage mutation is caused by dimethyl arsenic in main metabolism than inorganic arsenic. Lung DNA damage is induced by the interaction of O2 and arsenic peroxide radical. Dimethyl arsenic shows very important effect on lung cancer formation process which is induced based on 4-nitroquinoline-1-oxide (4NQO). It not only promotes lung cancer but it also plays an important role in malignant tumor`s mutation. 25 refs., 2 figs.

  11. Relations of FMmlet Transform to Some Integral Transforms

    Institute of Scientific and Technical Information of China (English)

    ZOUHongxing; DAIQionghai; WANGDianjun; LIYanda

    2004-01-01

    In this paper, we explore the relationships between FMmlet transform and some of the existing integral transforms, namely, the chirplet transform, dispersion transform, wavelet transform, chirp-Fourier transform, Short-time fourier transform (STFT), Gabor transform, Fourier transform, cosine transform, sine transform,Hartley transform, Laplace transform, z-transform, Mellintransform, Hilbert transform, autocorrelation function,cross-correlation function, energy, and the mean value.It is shown that all of these transforms are subspaces of FMmlet transform with specific parameters.

  12. Pancreatic Lesion: Malignancy or Abscess?

    Science.gov (United States)

    Shulik, Oleg; Cavanagh, Yana; Grossman, Matthew

    2016-01-01

    BACKGROUND Pancreatic abscesses are rare. They may be seen in patients with pancreatic inflammation or pancreatitis. Patients with pancreatic abscesses may have abdominal pain, fever, chills, and nausea/vomiting or an inability to eat. Presentation with alternate symptomatology is extremely unusual. CASE REPORT A 67-year-old Asian male presented with painless, afebrile obstructive jaundice and a CA 19-9 of 1732 IU. He was found to have a 3.1×2.4 cm low-density lesion in the head of the pancreas and the right lobe of the liver, suggesting malignancy. Surgical management was considered, however additional diagnostic workup, including an endoscopic retrograde cholangiopancreatography (ERCP), was performed to complete staging of the presumed mass. A smooth, 3-cm-long, tapering stricture was found it the common bile duct. It was stented from the common hepatic duct to the duodenum. Subsequent endoscopic ultrasound (EUS) evaluation of the pancreatic head lesion revealed a drainable fluid collection that was aspirated and found to contain pyogenic material on pathology. The patient's symptoms resolved, and he was subsequently managed conservatively. A repeat ERCP confirmed complete resolution of the previously visualized cystic lesion. Interestingly, laboratory values showed concomitant normalization of CA 19-9 to 40 IU. CONCLUSIONS EUS-guided biopsy is not widely regarded as a required step before surgery, in the management of patients with pancreatic masses. It is generally reserved for determination of resectability or staging, and only utilized when clinically indicated. However, this practice may be associated with an inherently significant risk of misdiagnosis and subsequent unnecessary surgery, as illustrated by this case. Malignancy was initially suspected in our patient and surgical resection was recommended. Endoscopic measures were only pursued to complete staging. We propose that EUS-guided biopsy may be a crucial diagnostic step in the management algorithm

  13. Hamlet's Transformation.

    Science.gov (United States)

    Usher, P. D.

    1997-12-01

    William Shakespeare's Hamlet has much evidence to suggest that the Bard was aware of the cosmological models of his time, specifically the geocentric bounded Ptolemaic and Tychonic models, and the infinite Diggesian. Moreover, Shakespeare describes how the Ptolemaic model is to be transformed to the Diggesian. Hamlet's "transformation" is the reason that Claudius, who personifies the Ptolemaic model, summons Rosencrantz and Guildenstern, who personify the Tychonic. Pantometria, written by Leonard Digges and his son Thomas in 1571, contains the first technical use of the word "transformation." At age thirty, Thomas Digges went on to propose his Perfit Description, as alluded to in Act Five where Hamlet's age is given as thirty. In Act Five as well, the words "bore" and "arms" refer to Thomas' vocation as muster-master and his scientific interest in ballistics. England's leading astronomer was also the father of the poet whose encomium introduced the First Folio of 1623. His oldest child Dudley became a member of the Virginia Company and facilitated the writing of The Tempest. Taken as a whole, such manifold connections to Thomas Digges support Hotson's contention that Shakespeare knew the Digges family. Rosencrantz and Guildenstern in Hamlet bear Danish names because they personify the Danish model, while the king's name is latinized like that of Claudius Ptolemaeus. The reason Shakespeare anglicized "Amleth" to "Hamlet" was because he saw a parallel between Book Three of Saxo Grammaticus and the eventual triumph of the Diggesian model. But Shakespeare eschewed Book Four, creating this particular ending from an infinity of other possibilities because it "suited his purpose," viz. to celebrate the concept of a boundless universe of stars like the Sun.

  14. Rotary Transformer

    Science.gov (United States)

    McLyman, Colonel Wm. T.

    1996-01-01

    None given. From first Par: Many spacecraft (S/C) and surface rovers require the transfer of signals and power across rotating interfaces. Science instruments, antennas and solar arrays are elements needing rotary power transfer for certain (S/C) configurations. Delivery of signal and power has mainly been done by using the simplest means, the slip ring approach. This approach, although simple, leaves debris generating noise over a period of time...The rotary transformer is a good alternative to slip rings for signal and power transfer.

  15. TRANSFORMER APPARATUS

    Science.gov (United States)

    Wolfgang, F.; Nicol, J.

    1962-11-01

    Transformer apparatus is designed for measuring the amount of a paramagnetic substance dissolved or suspended in a diamagnetic liquid. The apparatus consists of a cluster of tubes, some of which are closed and have sealed within the diamagnetic substance without any of the paramagnetic material. The remaining tubes are open to flow of the mix- ture. Primary and secondary conductors are wrapped around the tubes in such a way as to cancel noise components and also to produce a differential signal on the secondaries based upon variations of the content of the paramagnetic material. (AEC)

  16. Improved radioimmunotherapy of hematologic malignancies

    International Nuclear Information System (INIS)

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides (131Iodine, 111Indium, 90Yttrium, 99mTechnetium, 186Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer

  17. CT of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Malignant pleural mesothelioma is a rare tumor. Although the chest film findings of pleural mesothelioma are well described, there are few descriptions of the findings of computed tomography (CT). This report describes the CT findings in five cases of pleural mesothelioma. In each case the CT showed an extensive, irregular, pleural-based mass surrounding the lung, spreading into the fissures, and extending into the mediastinum. In two cases there was also extension into the contralateral chest, and in one case each there was extension into the abdomen and chest wall. In each case the chest radiographs underestimated the extent of disease, when compared to CT. When an irregular, pleural-based mass involving most of the hemithorax is identified on CT, the diagnosis of mesothelioma can be suggested and at the same time the extent of the tumor may be evaluated. This is important because the diagnosis of mesothelioma is difficult and because treatment and prognosis may depend on the extent of the disease

  18. Treatment of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    In Japan, it is predicted that mesothelioma will rapidly increase in the future. Malignant pleural mesothelioma that accounts for approximately 90% of mesothelioma as a whole has a median survival time of approximately nine months which is considered a poor prognosis. As for the treatment of this disease, extrapleural pneumonectomy or pleurectomy/decortication are available for those patients who can be surgically operated on. However, since a complete cure rate is low when only surgical treatment is performed, generally a multimodality treatment is performed wherein chemotherapy and/or radiotherapy are combined. For chemotherapy, a large-scale randomized phase III study demonstrated that a treatment using two agents: pemetrexed, which is a new multitargeted antifolate, and cisplatin is effective. Pemetrexed will be the drug of first choice for mesothelioma in the future. As other treatment methods, chemohyperthermia, treatments using various kinds of cytokines and angiogenesis inhibitors, genetic treatment and photodynamic therapy have been attempted. The current treatment results for this disease are very poor, and there has been a strong demand for establishing an effective treatment method. (author)

  19. Malignant hyperthermia -a case report

    Directory of Open Access Journals (Sweden)

    Kirti N Saxena

    2007-01-01

    Full Text Available A twenty-eight year old female was scheduled to undergo excisional reconstruction and plating of the mandible following a diagnosis of ameloblastoma on incisional biopsy under local anaesthesia. On preanaesthetic evaluation, there was no significant finding except restricted mouth opening and a swelling over the mandible. On attempting laryngoscopy the patient was found to have masseteric spasm following administration of succinylcholine. After one hour it was noted that the EtCO2 was being maintained at 47 -48 mmHg inspite of slight hyperventilation. Within half an hour EtCO2 rose gradually to 60 mm Hg and then suddenly to 80 mm Hg .The patient′s pulse rate rose gradually to 130 beats per minutes and then suddenly to 160 beats per minutes .At this time the patient was found to have nasopharyngeal temperature of 106.50 F. Aprovisional diagnosis of malignant hyperthermia was made and the patient was treated accordingly. Further the patient was investigated to rule out other conditions and clinch the diagnosis of MH. This is probably the first case report of this disease from India.

  20. Esophageal malignancy: A growing concern

    Institute of Scientific and Technical Information of China (English)

    Jianyuan Chai; M Mazen Jamal

    2012-01-01

    Esophageal cancer is mainly found in Asia and east Africa and is one of the deadliest cancers in the world.However,it has not garnered much attention in the Western world due to its low incidence rate.An increasing amount of data indicate that esophageal cancer,particularly esophageal adenocarcinoma,has been rising by 6-fold annually and is now becoming the fastest growing cancer in the United States.This rise has been associated with the increase of the obese population,as abdominal fat puts extra pressure on the stomach and causes gastroesophageal reflux disease (GERD).Long standing GERD can induce esophagitis and metaplasia and,ultimately,leads to adenocarcinoma.Acid suppression has been the main strategy to treat GERD; however,it has not been proven to control esophageal malignancy effectively.In fact,its side effects have triggered multiple warnings from regulatory agencies.The high mortality and fast growth of esophageal cancer demand more vigorous efforts to look into its deeper mechanisms and come up with better therapeutic options.

  1. Improved radioimmunotherapy of hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  2. Novel immunotherapies in lymphoid malignancies.

    Science.gov (United States)

    Batlevi, Connie Lee; Matsuki, Eri; Brentjens, Renier J; Younes, Anas

    2016-01-01

    The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted 'breakthrough' designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE(®)) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. PMID:26525683

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-15

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

  4. Myb proteins inhibit fibroblast transformation by v-Rel

    Directory of Open Access Journals (Sweden)

    Lipsick Joseph S

    2006-11-01

    Full Text Available Abstract Genes that cause cancer have been divided into two general classes – oncogenes that act in a dominant fashion to transform normal cells into a malignant state, and tumor suppressor genes that act in a dominant fashion to prevent such transformation. In this report, we demonstrate that both the v-myb retroviral oncogene, which causes leukemic transformation of hematopoietic cells, and the c-myb proto-oncogene can also function as inhibitors of fibroblast transformation by the v-rel oncogene. These results imply that the myb genes can function either as oncogenes or as tumor suppressors in different cellular contexts.

  5. A case of intracranial malignant fibrous histiocytoma

    Directory of Open Access Journals (Sweden)

    Amir Hossein Sarrami

    2011-01-01

    Full Text Available We describe a case of intracranial malignant fibrous histiocytoma which had infiltrated pons, cerebellum and basal surface of left temporal lobe without any visible mass. The patient presented with a sudden loss of consciousness and vomiting. Clinical findings, laboratory tests, imaging and examination of the cerebrospinal fluid tended to establish the diagnosis of an infectious condition than a malignancy. Without any response to the antibiotics and with a progressive deterioration of neurologic and mental condition, the patient died after 20 days. In the autopsy, histological and immunohistochemical study of the brain revealed the diagnosis of malignant fibrous histiocytoma (MFH.

  6. Paraneoplastic dermatological manifestation of gastrointestinal malignancies

    Institute of Scientific and Technical Information of China (English)

    Lyubomir A Dourmishev; Peter V Draganov

    2009-01-01

    Numerous dermatological disorders have been associated with underlining malignancies of the gastrointestinal (GI) tract. Such cutaneous manifestations might have an important diagnostic value if they are the sole expressions of otherwise asymptomatic carcinomas. The recognition of some typical paraneoplastic dermatologic disorders can lead to the prompt diagnosis of the underlying malignancy, timely administration of therapy, and ultimately, better prognosis. In this review we discuss the most common paraneoplastic dermatological syndromes from the perspective of the practicing gastroenterologist. We also outline a comprehensive practical approach for the evaluation for occult malignancy in patients presenting with cutaneous findings potentially associated with GI cancers.

  7. Malignant acanthosis nigricans: an early diagnostic clue

    International Nuclear Information System (INIS)

    Acanthosis nigricans (AN) is characterized by velvety, hyper pigmented, verrucosus, symmetric and occasionally pruritic plaques along with papillomatous lesions which have a special predilection for neck, axillae, groin, umbilicu and mucosal regions. Rarely, it presents as a para neoplastic syndrome and prompts a thorough search for an internal malignancy. We present here a case of malignant acanthosis nigricans seen in an elderly patient who was found to have underlying adenocarcinoma of the lower end of esophagus. After diagnosing associated malignancy, he was referred for further evaluation and subsequent surgical resection of tumour. (author)

  8. Molecular genetic study of human malignant gliomas

    International Nuclear Information System (INIS)

    Loss of heterozygosity for loci on chromosome 10 were found in four of 9 (44%) informative cases of malignant gliomas. Deletions on RB1 locus were seen in six of 11 (54%) informative glioblastomas. LOH on chromosome 17p was found in eight of 16 (50%) malignant gliomas, including 2 cases of anaplastic oligodendroglioma. On the basis of the data presented here, it is possible to associate certain molecular abnormalities with malignant gliomas, LOH on chromosome 10, RB1 gene, and 17p. (Author)

  9. Cutaneous malignancies in immunosuppressed organ transplant recipients.

    Science.gov (United States)

    Seda, Ivette M Sosa; Zubair, Adeel; Brewer, Jerry D

    2014-01-01

    During the past century, organ transplantation has delivered the miracle of life to more than 500,000 patients in need. Secondary malignancies have developed as an unforeseen consequence of intense immunosuppressive regimens. Cutaneous malignancies have been recognized as the most frequent cancer that arises post-transplantation. Among organ transplant recipients (OTRs), skin cancer is a substantial cause of morbidity and potential mortality. The authors discuss epidemiology and clinical presentation of cutaneous malignancies; associated risk factors; recommendation for the care of immunosuppressed OTRs, and emerging therapies on the horizon.

  10. Lymphangitis carcinomatosa complicating primary malignant peritoneal mesothelioma.

    OpenAIRE

    Craft, P. S.; Reading, M. S.; Jain, S.; O'Neil, R. A.

    1996-01-01

    A patient with malignant peritoneal mesothelioma and a diffuse pulmonary infiltrate is described. Computed tomographic scanning suggested lymphangitis carcinomatosa. This was confirmed on transbronchial biopsy to be due to metastatic mesothelioma.

  11. ACTINOMYCES NAESLUNDII IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES

    Directory of Open Access Journals (Sweden)

    S. H. Rasa J. V Yusefi

    2006-09-01

    Full Text Available Mycotic infections have been commonly encountered in patients with hematological malignancies. The current study seeks the prevalence of actinomycete infection in patients suffering from blood cells malignancies. A hundred and fifty patients with some kinds of blood cells dyscrasia who underwent the bone marrow aspiration were recruited. In addition to the diagnostic work up, samples were examined for the presence of actinomycete infections. Twenty one samples were positive for actinomycete infections. All of them were infected by Actinomyces naeslundii. All the positive patients were categorized in malignant groups, acute myelocytic leukemia, chronic myelocytic leukemia, and lymphoma and myelodysplastic syndrome. High incidence of actinomycete infections in the present study population was interesting. These results can also be suggestive of a pre-malignancy role for the actinomycosis.

  12. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

    Larsen, Anne K; Krag, Christen; Geertsen, Poul;

    2013-01-01

    SUMMARY: Malignant melanomas rarely develop isolated pancreatic metastases. We describe a unique patient who is still alive 22 years following an isolated pancreatic melanoma metastasis, and we review the sparse literature in the field....

  13. Recent cases of radium-induced malignancy

    International Nuclear Information System (INIS)

    Five cases of malignant disease attributed to radium in patients with measured body burdens have been discovered since 1974, including three bone sarcomas and two mastoid carcinomas. Pertinent findings in these cases are summarized here

  14. Recent cases of radium-induced malignancy

    International Nuclear Information System (INIS)

    Three cases of malignant disease attributed to radium in patients with measured body burdens have been observed since 1978 - one paranasal sinus carcinoma, one mastoid carcinoma, and one fibrosarcoma of bone. These cases are summarized here. 4 references

  15. Adult high-grade malignant gliomas

    Directory of Open Access Journals (Sweden)

    Fable Zustovich

    2011-12-01

    Full Text Available Central nervous system (CNS malignant gliomas are relatively rare diseases. Prognosis is poor but has improved over recent years due to the improvement in the multi-disciplinary treatment: surgery, radiotherapy and chemotherapy...

  16. Current concepts in malignant hyperthermia.

    Science.gov (United States)

    Finsterer, Josef

    2002-12-01

    Malignant hyperthermia (MH) is a rare, potentially lethal, clinically and genetically heterogeneous pharmacogenic myopathy, which during or after general anesthesia manifests as MH crisis (MHC) in genetically predisposed, but otherwise mostly normal, individuals (MH susceptibles) in response to anesthetic-triggering agents. MHC can also occur in patients with central core disease. MCH-like crises have been reported in those with Duchenne/Becker muscular dystrophy, myotonic dystrophy, mitochondriopathy, and various other conditions. MH susceptibility is diagnosed if there is an MHC in the individual or family history or by the in vitro caffeine-halothane contracture test. Although screening for mutations in the ryanodine-receptor-1 gene and the dihydropyridine-receptor gene, respectively, could further substantiate the diagnosis, the caffeine-halothane-contracture test still remains the gold standard for diagnosing MH susceptibility. The most well-known triggers of an MHC are depolarizing muscle relaxants and volatile anesthetics. Therapy of an MHC comprises discontinuation of triggering agents, oxygenation, and correction of the acidosis and electrolyte disturbances, treatment of arrhythmias, cooling, and dantrolene. If MH susceptibility is not known preoperatively and an MHC unexpectedly interrupts anesthesia, consultation by a specialist in MH susceptibility after anesthesia is essential to investigate the patient for MH susceptibility or subclinical myopathy, guide laboratory investigations, manage therapy, and counsel the family on further risk. To further reduce morbidity and mortality of those with MHC, anesthesiologists and neurologists should be well educated and should strengthen their clinical vigilance. Research should be intensified and extended with regard to the development of new in vitro tests to further elucidate the heterogeneous genetic background of MH susceptibility. PMID:19078692

  17. Malignant rectal melanoma. Case report.

    Science.gov (United States)

    Morlino, Andrea; La Torre, Giuseppe; Vitagliano, Giulia; Cammarota, Aldo

    2015-03-26

    Il Melanoma Anorettale è una malattia rara e aggressiva ed è il terzo tipo più comune di melanoma maligno dopo quello della cute e della retina. Il sintomo più comune è il sanguinamento rettale, che è spesso scambiato per sanguinamento associato a emorroidi. La diagnosi è molto difficile, e quella iniziale può essere corretta solo in circa 80% dei casi. Il caso clinico che proponiamo riguarda un uomo di 71 anni giunto alla nostra osservazione per dolore anale, tenesmo rettale, sanguinamento. L’eplorazione rettale ci ha mostrato una neofromazione dolorosa, di colorito brunastro nel canale anale. La colonscopia e la endoscopia hanno evidenziato la presenza di una grande massa stenotica interessante il canale anale ed il retto con un diametro di circa 90 mm. La biopsia è positiva per melanoma a cellule maligne pigmentate. La TAC ha mostrato un ispessimento della parete rettale e linfonodi nel tessuto adiposo, nel distretto otturatore bilaterale e metastasi polmonari bilaterali. Il dato di laboratorio del Ca 19-9 è nei livelli normali. Il paziente è stato sottoposto a resezione addomino-perineale con dissezione linfonodale. Non ci sono studi dimostranti che la resezione radicale del melanoma primario ano-rettale è associata ad un miglioramento del controllo locale e della sopravvivenza. I pazienti con malattia localizzata dovrebbero essere sottoposti a escissione locale ogniqualvolta ciò sia tecnicamente fattibile. Il ruolo predominante del trattamento chemio radioterapico preoperatorio è quello di ridurre le recidive locoregionale e della cavità pelvica, e per ottenere un più alto tasso di conservazione dell’apparato sfinteriale. Inoltre facilita la rimozione delle potenziali micrometastasi e riduce le metastasi a distanza.

  18. Malignant renal tumors in pediatrics

    International Nuclear Information System (INIS)

    Introduction: Professionals who work in pediatric oncology, we see childhood cancer as a common disease, but in fact constitutes about 2% of all cancers diagnosed worldwide. Wilms tumor accounts for 6% of all childhood tumors and presentation bilateral accounts for 4-6% of all Wilms tumors diagnosed. Theoretical Framework: In the period between the year 1994-2003 period were attended in the Pediatric Hematology-Oncology Center, a total of 29 cases of malignant renal tumors, corresponding to 86% (25 cases) to Wilms tumor or nephroblastoma tumor. The Wilms is of embryonic origin, capable of metastatic spread, (85% lungs 15% liver). Very sensitive to chemotherapy and radiotherapy, which confers high cure rates (85%); having a multidisciplinary treatment model, combining surgery, chemotherapy, and radiotherapy. The role of nursing in comprehensive cancer care child is essential in the prevention and early detection of side effects or complications. Case report: S.D. currently 10 years old. In 10/1994, at 8 months of age, was diagnosed with bilateral Wilms tumor. On admission her weight was 8200gr with abdominal circumference 50cm. Conducted pre-operative MDT and 02/1995 nephrectomy of the left kidney and right kidney lumpectomy (tumor nodule 420gr. and a 250gr.). MDT begins in 03/1995 01/1996 ending. 09/2003 with abdominal pain and vomiting, and kidney failure. 10/2003 lumpectomy biopsy (sclerotic nodule associated with maturation nephroblastoma). Currently severe renal insufficiency plan enters dialysis. Nursing process: Objectives: 1) To prepare the child and family to the side effects and possible complications of chemotherapy and / or radiotherapy 2) Prevent and minimize related complications tumor and / or treatment. Care Plan comprises four stages: A) rating and customer income. B) Implement care chemotherapy C) post-operative Care D) Implement radiation care

  19. Arterial Microcalcifications in the Breast Mimicking Malignancy

    Directory of Open Access Journals (Sweden)

    Katrin Janzen

    2012-01-01

    Full Text Available Microcalcifications in the breast are highly suggestive of malignancy; they can occur in many pathological conditions. A 36-years-old nondiabetic woman came to the gynaecologist with a suspect palpable mass in the upper outer quadrant of the right breast. Histopathological examination confirmed a calcification of a small artery (diameter: 0.45 mm. Arterial calcifications can mimic a malignant lesion in the breast.

  20. Arterial Microcalcifications in the Breast Mimicking Malignancy

    OpenAIRE

    Katrin Janzen; Jan Janzen

    2012-01-01

    Microcalcifications in the breast are highly suggestive of malignancy; they can occur in many pathological conditions. A 36-years-old nondiabetic woman came to the gynaecologist with a suspect palpable mass in the upper outer quadrant of the right breast. Histopathological examination confirmed a calcification of a small artery (diameter: 0.45 mm). Arterial calcifications can mimic a malignant lesion in the breast.

  1. Arterial Microcalcifications in the Breast Mimicking Malignancy

    Science.gov (United States)

    Janzen, Katrin; Janzen, Jan

    2012-01-01

    Microcalcifications in the breast are highly suggestive of malignancy; they can occur in many pathological conditions. A 36-years-old nondiabetic woman came to the gynaecologist with a suspect palpable mass in the upper outer quadrant of the right breast. Histopathological examination confirmed a calcification of a small artery (diameter: 0.45 mm). Arterial calcifications can mimic a malignant lesion in the breast. PMID:22606570

  2. Multiple cutaneous malignancies in xeroderma pigmentosum

    Directory of Open Access Journals (Sweden)

    Mohanty Prasenjeet

    2001-01-01

    Full Text Available A case of xeroderma pigmentosum with multiple cutaneous malignancies is being reported. The case presented with freckles, letigens, and keratosis, a non-tender ulcerated nodular lesion on the nose, a nodular ulcerated lesion on the right outer canthus of the conjunctiva, and a nodular growth which developed on the right cheek which on histopathology was found to be squamous cell cercinoma, basal cell carcinoma and malignant melanoma respectively.

  3. Multiple cutaneous malignancies in xeroderma pigmentosum

    OpenAIRE

    Mohanty Prasenjeet; Mohanty L; Devi B

    2001-01-01

    A case of xeroderma pigmentosum with multiple cutaneous malignancies is being reported. The case presented with freckles, letigens, and keratosis, a non-tender ulcerated nodular lesion on the nose, a nodular ulcerated lesion on the right outer canthus of the conjunctiva, and a nodular growth which developed on the right cheek which on histopathology was found to be squamous cell cercinoma, basal cell carcinoma and malignant melanoma respectively.

  4. Malignant catarrhal fever (Coryza gangraenosa bovum)

    OpenAIRE

    Spasojević Filip; Uzelac Đorđe; Milosavljević Zlatko; Vujanac Ivan

    2008-01-01

    Malignant catarrhal fever is a disease of cattle and other ruminants, which most often has a lethal outcome. The disease occurs sporadically and is very difficult to control. At a private mini cattle farm, the occurrence of malignant catarrhal fever was suspected on the grounds of anaemnestic data and results of clinical examinations. The owner said that, in addition to cattle, he also breeds sheep in a separate facility, but said these animals had not been in contact with the diseased cow. I...

  5. Malignant Diseases of the Oral Mucosa

    OpenAIRE

    Burhan Engin; Orkhan Bairamov; Zekayi Kutlubay; Yalçın Tüzün

    2012-01-01

    Oral cancer which is a significant world health problem is a subtype of head and neck cancer. They are the sixth most common malignant tumors worldwide. More than 90% of malignant tumors in the mouth are squamous cell carcinomas. Etiology of the oral squamous cell carcinoma is complex. The most important risk factors, especially in well-developed countries are tobacco smoking and alcohol exposure..

  6. Malignant Diseases of the Oral Mucosa

    Directory of Open Access Journals (Sweden)

    Burhan Engin,

    2012-12-01

    Full Text Available Oral cancer which is a significant world health problem is a subtype of head and neck cancer. They are the sixth most common malignant tumors worldwide. More than 90% of malignant tumors in the mouth are squamous cell carcinomas. Etiology of the oral squamous cell carcinoma is complex. The most important risk factors, especially in well-developed countries are tobacco smoking and alcohol exposure..

  7. Ferritin Assay in Malignant Pleural Effusion

    OpenAIRE

    Chung, Won-Tae; Lee, Jue-Hong; Park, Jang-Geun; Sohn, Gyo-IK; Park, Soon-Kew; Shin, Young-Kee

    1987-01-01

    In order to assess the usefulness of ferritin as a tumor marker, the authors measured and analyzed pleural fluid and serum ferritin concentrations by double antibody radioimmunoassay method in 20 patients with malignant pleural effusion, and in 39 patients with benign pleural effusion. Serum ferritin levels were also measured in a control group of 20 healthy people. The results obtained are summarized as follows: 1) Pleural fluid ferritin levels in the malignant pleural effusion group were si...

  8. ACTINOMYCES NAESLUNDII IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES

    OpenAIRE

    S. H. Rasa J. V Yusefi; F. Agha-Khani; M. Ghazanfari; R. Tohidi; F. A. Nakhjavani; F. Daee-Ghazvini; Mobedi, I

    2006-01-01

    Mycotic infections have been commonly encountered in patients with hematological malignancies. The current study seeks the prevalence of actinomycete infection in patients suffering from blood cells malignancies. A hundred and fifty patients with some kinds of blood cells dyscrasia who underwent the bone marrow aspiration were recruited. In addition to the diagnostic work up, samples were examined for the presence of actinomycete infections. Twenty one samples were positive for actinomycete i...

  9. Particulate Debris Osteolysis Simulating Malignant Tumor

    OpenAIRE

    Brand, Richard A.; Marsh, J. Lawrence

    2004-01-01

    Osteolysis induced by particulate debris from total joint implants is typically confined to bone and benign in radiographic appearance even when extensive. However, they can extend well beyond bone in which case they can simulate malignancies owing either to mass effects and pressure on adjacent tissues or owing to the radiographic appearance. We report two cases which presented as possible malignancy, and review the literature on extensive osteolysis. Recognition of this possibility may aid ...

  10. Primary malignant melanoma of the esophagus

    International Nuclear Information System (INIS)

    Primary malignant melanoma most commonly originates from the skin; other less common extra cutaneous sites include squamous mucous membranes, uvea, retina, leptomeninges, genitourinary tract, digestive tract, biliary tract, and upper respiratory tract. Primary melanoma of the gastrointestinal tract is exceedingly rare. We are reporting a histo-pathologically proven rare case of primary malignant melanoma of the esophagus and its findings on fluorodeoxyglucose positron emission tomography and computed tomography

  11. Malignant peritoneal mesothelioma after radiation therapy

    International Nuclear Information System (INIS)

    A 49-year-old woman developed ascites 31 years after radiation therapy for ovarian cancer and was admitted to hospital 1 year later. Diffuse infiltration of both sheets of the peritoneum was found by CT, which on histological investigation turned out to be an advanced malignant peritoneal carcinoma. When there is a history of radiation exposure, malignant peritoneal mesothelioma should be considered as the cause of ascites. (orig.)

  12. Malignant tumours of childhood in Zaria

    OpenAIRE

    Samaila Modupeola

    2009-01-01

    Background: The increased prevalence of hitherto uncommon tumours in children in our geographic setting formed the basis for this study. This study aimed to determine the current histopathologic distribution pattern of paediatric malignancies in Zaria. Materials and Methods : An eight year (2000-2007) consecutive analysis of malignant tumours in children ages 0 to 15 years in a referral University laboratory. All tissue biopsies were fixed in 10% formalin and processed in wax. Tumour...

  13. Oncogenesis of RON receptor tyrosine kinase: a molecular target for malignant epithelial cancers

    Institute of Scientific and Technical Information of China (English)

    Ming-hai WANG; Hang-ping YAO; Yong-qing ZHOU

    2006-01-01

    Recepteur d'origine nantais (RON) belongs to a subfamily of receptor tyrosine kinases (RTK) with unique expression patterns and biological activities. RON is activated by a serum-derived growth factor macrophage stimulating protein (MSP). The RON gene transcription is essential for embryonic development and critical in regulating certain physiological processes. Recent studies have indicated that altered RON expression contributes significantly to cancer progression and malignancy. In primary tumors, such as colon and breast cancers, overexpression of RON exists in large numbers and is often accompanied by the generation of different splicing variants. These RON variants direct a unique program that controls cell transformation, growth, migration, and invasion, indicating that altered RON expression has the ability to regulate motile/invasive phenotypes. These activities were also seen in transgenic mice, in which targeted expression of RON in lung epithelial cells resulted in numerous tumors with pathological features of human bronchioloalveolar carcinoma. Thus, abnormal RON activation is a pathogenic factor that transduces oncogenic signals leading to uncontrolled cell growth and subsequent malignant transformation. Considering these facts, RON and its variants can be considered as potential targets for therapeutic intervention. Experiments using small interfering RNA and neutralizing monoclonal antibodies demonstrated that suppressing RON expression and activation decreases cancer cell proliferation, increases apoptotic death, prevents tumor formation in nude mice, and reduces malignant phenotypes. Thus, blocking RON expression and activation has clinical significance in reversing malignant phenotypes and controlling tumor growth.

  14. Endoscopic treatment of malignant biliary strictures.

    Science.gov (United States)

    Rustagi, Tarun; Jamidar, Priya A

    2015-01-01

    Endoscopic stenting is a widely accepted strategy for providing effective drainage in both extrahepatic and intrahepatic malignant strictures. In patients with extrahepatic malignancies, uncovered self-expanding metal stents (SEMS) provide excellent palliation. Hilar malignancies are probably best palliated by placement of uncovered SEMS although some disagreement exists among experts regarding the type and number of stents for optimal palliation. Preoperative biliary drainage (PBD) is commonly performed although a higher risk of complications and the lack of clear benefit raise questions about this practice. Certain groups of patients such as those with markedly elevated bilirubin levels, and in those in whom neoadjuvant therapy is planned, are good candidates for PBD. Considerable controversy exists regarding the optimal method as well as type of stent for PBD in patients with hilar malignancies. Novel endoscopic therapies, including photodynamic therapy and radiofrequency ablation, have emerged as potential adjuvant therapies in the management of malignant bile duct strictures but need further long-term evaluation to establish survival benefit. This review focuses on the current status of endoscopic therapies for malignant biliary obstructions.

  15. Incidence and overall survival of malignant ameloblastoma.

    Directory of Open Access Journals (Sweden)

    Alexandra Rizzitelli

    Full Text Available Malignant ameloblastoma, comprising metastasizing ameloblastoma and ameloblastic carcinoma, represents 1.6-2.2% of all odontogenic tumors. Due to its rare nature, malignant ameloblastoma has only been reported in the literature in small case series or case reports. Using the Surveillance, Epidemiology and End-Results (SEER database, we have performed a population-based study to determine the incidence rate and the absolute survival of malignant ameloblastoma.Using the International Classification of Diseases for Oncology (ICD-O codes 9310/3 and 9270/3, data from the SEER database were used to calculate the incidence rate and absolute survival rate of population with malignant ameloblastoma.The overall incidence rate of malignant ameloblastoma was 1.79 per 10 million person/year. The incidence rate was higher in males than females and also higher in black versus white population. The median overall survival was 17.6 years from the time of diagnosis and increasing age was associated with a statistically significant poorer survival.To our best knowledge, we report the largest population-based series of malignant ameloblastoma. The incidence rate was 1.79 per 10 million person/year and the overall survival was 17.6 years.

  16. Expression of protein kinase A regulatory subunits in benign and malignant human thyroid tissues: A systematic review.

    Science.gov (United States)

    Del Gobbo, Alessandro; Peverelli, Erika; Treppiedi, Donatella; Lania, Andrea; Mantovani, Giovanna; Ferrero, Stefano

    2016-08-01

    In this review, we discuss the molecular mechanisms and prognostic implications of the protein kinase A (PKA) signaling pathway in human tumors, with special emphasis on the malignant thyroid. The PKA signaling pathway is differentially activated by the expression of regulatory subunits 1 (R1) and 2 (R2), whose levels change during development, differentiation, and neoplastic transformation. Following the identification of gene mutations within the PKA regulatory subunit R1A (PRKAR1A) that cause Carney complex-associated neoplasms, several investigators have studied PRKAR1A expression in sporadic thyroid tumors. The PKA regulatory subunit R2B (PRKAR2B) is highly expressed in benign, as well as in malignant differentiated and undifferentiated lesions. PRKAR1A is highly expressed in follicular adenomas and malignant lesions with a statistically significant gradient between benign and malignant tumors; however, it is not expressed in hyperplastic nodules. Although the importance of PKA in human malignancy outcomes is not completely understood, PRKAR1A expression correlates with tumor dimension in malignant lesions. Additional studies are needed to determine whether a relationship exists between PKA subunit expression and clinical outcomes, particularly in undifferentiated tumors. In conclusion, the R1A subunit might be a good molecular candidate for the targeted treatment of malignant thyroid tumors. PMID:27321957

  17. Extension of a malignant tailgut cyst to a subcutaneous space in the buttock.

    Science.gov (United States)

    Fujisawa, Yasuhiro; Yanagisawa, Kazuhiko; Nakamura, Yasuhiro; Kawachi, Yasuhiro; Otsuka, Fujio

    2010-01-01

    Tailgut cysts are rare benign cystic lesions of the retrorectal space. The recommended treatment is complete resection because these cysts have occasionally shown malignant transformation. However, a high index of clinical suspicion is required to reach a diagnosis. We report a 68-year-old man complaining of a subcutaneous mass in his right buttock. Magnetic resonance imaging (MRI) showed a large cystic mass extending 25.7 cm from the pelvis to the buttock. Radiological features indicated a benign cystic tumor, but the level of serum carcinoembryonic antigen (CEA) (87.5 ng/mL) was increased. An incisional biopsy did not define the true histological nature of the lesion and was not useful for surgical planning. Although MRI could not detect malignant changes, the elevated serum CEA indicated malignant degeneration. The patient required a Miles operation for complete resection. Surgical pathology revealed focal areas of high-grade adenomatous and adenocarcinomatous changes in the cyst wall. After surgery, the serum CEA level decreased to below the normal range. The case presented here shows that early malignant degeneration of TGC is difficult to detect by MRI. Thus, a tailgut cyst should be completely removed, even if radiological examination cannot detect malignant features. Measurement of serum CEA may be helpful when the tumor expresses this antigen. PMID:20956108

  18. Molecular and therapeutic advances in the diagnosis and management of malignant pheochromocytomas and paragangliomas.

    LENUS (Irish Health Repository)

    Lowery, Aoife J

    2013-01-01

    Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors derived from chromaffin cells originating in the neural crest. These tumors represent a significant diagnostic and therapeutic challenge because the diagnosis of malignancy is frequently made in retrospect by the development of metastatic or recurrent disease. Complete surgical resection offers the only potential for cure; however, recurrence can occur even after apparently successful resection of the primary tumor. The prognosis for malignant disease is poor because traditional treatment modalities have been limited. The last decade has witnessed exciting discoveries in the study of PCCs and PGLs; advances in molecular genetics have uncovered hereditary and germline mutations of at least 10 genes that contribute to the development of these tumors, and increasing knowledge of genotype-phenotype interactions has facilitated more accurate determination of malignant potential. Elucidating the molecular mechanisms responsible for malignant transformation in these tumors has opened avenues of investigation into targeted therapeutics that show promising results. There have also been significant advances in functional and radiological imaging and in the surgical approach to adrenalectomy, which remains the mainstay of treatment for PCC. In this review, we discuss the currently available diagnostic and therapeutic options for patients with malignant PCCs and PGLs and detail the molecular rationale and clinical evidence for novel and emerging diagnostic and therapeutic strategies.

  19. Metastatic malignant struma ovarii with coexistence of Hashimoto’s thyroiditis

    Directory of Open Access Journals (Sweden)

    Marco Russo

    2016-05-01

    Full Text Available Struma ovarii is a rare ovarian teratoma characterized by the presence of thyroid tissue as the major component. Malignant transformation of the thyroidal component (malignant struma ovarii has been reported in approximately 5% of struma ovarii. The management and follow-up of this unusual disease remain controversial. We report the case of a woman with a history of autoimmune thyroiditis and a previous resection of a benign struma ovarii that underwent hystero-annexiectomy for malignant struma ovarii with multiple papillary thyroid cancer foci and peritoneal involvement. Total thyroidectomy and subsequent radioiodine treatment lead to complete disease remission after 104 months of follow-up. The diagnosis and natural progression of malignant struma ovarii are difficult to discern, and relapses can occur several years after diagnosis. A multidisciplinary approach is mandatory; after surgical excision of malignant struma, thyroidectomy in combination with 131I therapy should be considered after risk stratification in accordance with a standard approach in differentiated thyroid cancer patients.

  20. [Malignant lymphoma in the central nervous system: overview].

    Science.gov (United States)

    Namekawa, Michito

    2014-08-01

    Malignant lymphoma can affect the central nervous system (CNS) in three different ways: as a consequence (relapse or invasion) of systemic lymphoma, as a primary CNS lymphoma (PCNSL) without systemic involvement, and through intravascular lymphomatosis (IVL). It is essential to distinguish PCNSL from the others, since the therapeutic strategy for treating this disease differs. FDG-PET/CT fusion imagery is a powerful tool for detecting systemic lesions. If a marked elevation of lactate dehydrogenase and the soluble IL-2 receptor suggests IVL, a random skin biopsy can permit a differential diagnosis. It is not certain why PCNSL occurs solely in the CNS, where there is no lymphatic system. The special environment, so-called "sanctuary site", where is free from attack of the immune system and penetration of chemotherapeutic agents by blood-brain barrier is deeply related to malignant transformation. The prognoses for patients with CNS invasion of systemic lymphoma and those with PCNSL remain bleak in the post-rituximab era. Over half of the patients who received high-dose methotrexate will subsequently relapse. Therefore, novel therapeutic strategies are earnestly sought. PMID:25082313

  1. Natural killer cells in non-hematopoietic malignancies.

    Science.gov (United States)

    Desbois, Mélanie; Rusakiewicz, Sylvie; Locher, Clara; Zitvogel, Laurence; Chaput, Nathalie

    2012-01-01

    Natural killer (NK) cells belong to the innate immune system and were initially described functionallywise by their spontaneous cytotoxic potential against transformed or virus-infected cells. A delicate balance between activating and inhibiting receptors regulates NK cell tolerance. A better understanding of tissue resident NK cells, of NK cell maturation stages and migration patterns has evolved allowing a thoughtful evaluation of their modus operandi. While evidence has been brought up for their relevance as gate keepers in some hematopoietic malignancies, the role of NK cells against progression and dissemination of solid tumors remains questionable. Hence, many studies pointed out the functional defects of the rare NK cell infiltrates found in tumor beds and the lack of efficacy of adoptively transferred NK cells in patients. However, several preclinical evidences suggest their anti-metastatic role in a variety of mouse tumor models. In the present review, we discuss NK cell functions according to their maturation stage and environmental milieu, the receptor/ligand interactions dictating tumor cell recognition and recapitulate translational studies aimed at deciphering their prognostic or predictive role against human solid malignancies. PMID:23269924

  2. Nevus of the Eyelid Margin Mimicking a Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    A. Echchaoui

    2016-06-01

    Full Text Available Nevi are a benign skin lesions commonly found on the eyelid margin, these tumors are usually pigmented and have thickness. Nevi are not typically visible at birth; they appear during childhood and often exhibit a more rapid increase in pigmentation about the time of puberty. Most eyelid nevi can be diagnosed by clinical examination; suspicious lesions should be biopsied when rapid growth, loss of eyelashes or discoloration of the nevus is noted. Eyelid nevi require treatment if malignant transformation and/or cosmetically bothersome to the patient. We report a case of a 37-year-old female patient exhibited a single cutaneous tumor at the free margin of the lower left eyelid, she noticed a dark spot on their eyelid since childhood. It was a brown, fleshy, thickened, and nodular well-circumscribed exophytic mass, measuring 6 mm in diameter; its clinical appearance argued for a possible nodular melanoma. Excisional-biopsy was performed using a full-thickness pentagonal wedge excision technique. Histopathology showed that the lesion was a benign melanocytic nevocellular nevus. The post-operative courses were uneventful with excellent cosmetic and functional result. Preventive measures (cap, sunglasses... and regular monitoring of the lesion by assessing ABCDE criteria (asymmetry, irregular borders, multiple colors, diameter ≥ 6 mm, and enlargement remain necessary to detect and rule out a possible risk of malignant melanoma.

  3. Histochemical identification of malignant and premalignant lesions

    Science.gov (United States)

    Liebow, Charles; Maloney, M. J.

    1991-06-01

    Malignant and transforming cells can be identified by biochemical parameters which can be used to localize lesions in situ for laser surgery. These cells express unique proteins, proteins in unusual quantities, or other biochemical alterations which can be utilized to image lesions of such cells. Several methods have been identified, both in vitro and in vivo, to identify such lesions. Several antibodies were examined for their properties of tissue identification, including CEA, F36/22, and AE1/AE3. F36/22, an antibody developed by M. T. Chu against human breast cancer cells, associated with two lines of oral cancer (KB and HCPC), and against two naturally occurring human oral squamous cell cancers. CEA, an antibody developed against human colon cancer, also reacted against both cell lines and both pathological samples. AE1/AE3, developed against normal fibrous components, also reacted against the samples, but in a much less regular manner. F36/22 associated with the histologically identifiably most dedifferentiated cells at the leading edge of the invading cancer. CEA, on the other hand, associated with more quiescent, older, established cancer cells. This demonstrates that antibodies developed against cancers of different organs can be used to identify a wide variety of cancers, and may have prognostic value. F36/22 coupled to fluorescein was used to identify oral cancer cells. Other properties of cancers and developing cancers can also be exploited to identify cancers, including their over-expression of tyrosine kinase and tyrosine kinase stimulating hormones such as Epidermal Growth Factor (EGF). A model of premalignant lesion produced in the hamster buccal cheek pouch with 6 week application of DMBA over-expresses constitutive tyrosine kinase which can be demonstrated biochemically. This initiated lesion can be promoted to frank cancer by growth factors released in response to laser surgery. Preliminary results suggest that these lesions can be identified by

  4. Immunohistological Expression of p16INK4a is Commonly Present Both in Benign and Malignant Sweat Gland Neoplasias.

    Science.gov (United States)

    Tsujita, Jun; Kaku, Yumiko; Ichiki, Toshio; Eto, Ayaka; Maemura, Hiromi; Otsuka, Akiko; Nakaie, Risa; Kitagawa, Noriko; Morioka, Yuka; Matsuda, Tomoyo; Yoshida, Maiko; Furue, Masutaka

    2015-12-01

    The expression of p16INK4a has been reported to be a significant marker for malignant transformation of epidermal tumors. However, little is known about sweat gland tumors. We examined the immunohistological expression of p16INK4a in benign and malignant sweat gland tumors. The ductal and acrosyringial portion of normal eccrine glands were positively stained with p16INK4a while it was negative in the normal epidermis. Moderate to strong expression of p16INK4a was found in 16 of 17 eccrine poromas, 4 of 5 hidradenomas, 3 of 3 syringocystadenoma papilliferums, 2 of 2 mixed tumors, and 3 of 3 syringomas. The p16INK4a expression was observed focally or diffusely in 4 of 4 porocarcinomas, 4 of 4 apocrine carcinomas and 12 of 17 extramammary Paget's diseases. We conclude that the p16INK4a expression is not a good marker for dictating malignant transformation of sweat gland tumors.

  5. Helicobacter pylori and Gastrointestinal Malignancies.

    Science.gov (United States)

    Venerito, Marino; Vasapolli, Riccardo; Rokkas, Theodoros; Malfertheiner, Peter

    2015-09-01

    Helicobacter pylori infection is the principal trigger of gastric carcinogenesis and gastric cancer (GC) and remains the third leading cause of cancer-related death in both sexes worldwide. In a big Japanese study, the risk of developing GC in patients with peptic ulcer disease who received H. pylori eradication therapy and annual endoscopic surveillance for a mean of 9.9 years was significantly lower after successful eradication therapy compared to the group with persistent infection (0.21%/year and 0.45%/year, respectively, p = .049). According to a recent meta-analysis, H. pylori eradication is insufficient in GC risk reduction in subjects with advanced precancerous conditions (i.e., intestinal metaplasia and dysplasia). A microsimulation model suggested screening smokers over the age of 50 in the U.S. for serum pepsinogens. This would allow to detect advanced gastric atrophy with endoscopic follow-up of subjects testing positive as a cost-effective strategy to reduce GC mortality. In a Taiwanese study, the anti-H. pylori IgG-based test-and-treat program had lower incremental cost-effectiveness ratios than that with (13)C-urea breath test in both sexes to prevent GC whereas expected years of life lost for GC were higher and the incremental cost-effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 years old) than in elders (>70 years old). With respect to gastrointestinal malignancies other than GC, a meta-analysis confirmed the inverse association between H. pylori infection and esophageal adenocarcinoma. In a Finnish study, H. pylori seropositivity was associated with an increased risk of biliary tract cancers (multivariate adjusted OR 2.63; 95% CI: 1.08-6.37), another meta-analysis showed a slightly increased rate of pancreatic cancer in patients with CagA-negative strains (OR: 1.30; 95% CI: 1.02-1.65), whereas current data suggest that the association between H. pylori and colorectal neoplasms may be population

  6. Serum fucosyl transferase activity and serum fucose levels as diagnostic tools in malignancy.

    OpenAIRE

    Sen,Umi; Guha,Subhas; Chowdhury, J Roy

    1983-01-01

    Glycoproteins play a significant role in neoplastic transformations. Both the levels of fucose and the activity of fucosyl transferase, which mediates the assembly of the oligosaccharide moieties of the glycoprotein chains, have been found to be elevated in neoplastic conditions. Since these elevations are common features of a variety of neoplastic cells, these two have been designated as non-specific markers of malignancy. In the present study, the fucose level and fucosyl transferase activi...

  7. Malignant Struma Ovarii in a Postmenopausal Asymptomatic Woman: A Case Report

    OpenAIRE

    Behiye Pınar Çilesiz Göksedef; Hüsnü Görgen; Şafak Yılmaz Baran

    2011-01-01

    Introduction: Struma ovarii is an ovarian tumor that consists predominantly thyroid tissue and accounts for only 2% of all mature teratomas. It is usually a benign condition - malignant transformation has been reported to occur in about 5% of all struma ovarii cases. Case: A 58-year-old postmenopausal woman attended our outpatient clinic for her annual gynecologic exam, on which a palpable ovary was incidentally found. Ultrasound and magnetic resonance imaging work-up ...

  8. The Prediction of Malignant Course in Cerebral Infarction by Electroencephalography

    Directory of Open Access Journals (Sweden)

    Mohammadali Shafa

    2014-12-01

    Full Text Available Background: Prediction of the malignant course is important in patients with stroke in order to begin interventional treatment strategies. In this study, predictive value of electroencephalography was evaluated in detection of malignant cases. Materials and Methods: In this cross-section study electroencephalography findings were evaluate in 36 patients suffering stroke. Data were analyzed with Fishers exact test. Results: Fourteen patients had malignant and 22 patients had a non-malignant course. Six patients in malignant course group and 1 patient in non-malignant course group had focal delta activity (p=0.008. Conclusion: Electroencephalography findings had predictive value in malignant course in stroke patients.

  9. Endoscopic laser treatment in pre-malignant and malignant vocal fold epithelial lesions.

    NARCIS (Netherlands)

    Remijn, E.E.; Marres, H.A.M.; Hoogen, F.J.A. van den

    2002-01-01

    Endoscopic laser treatment was performed in 43 patients with pre-malignant or malignant vocal fold epithelial lesions, 10 were treated with endoscopic laser surgery for dysplasia, 12 for carcinoma in situ (CIS), five for verrucous carcinoma and 16 patients for squamous cell carcinoma (SCC). Thirty-t

  10. Epstein–Barr virus growth-transformed cells are converted to malignancy following transfection of a 1.3-kb CATR1 antisense construct independent of a change in the level of c-myc expression followed by a 8;14 chromosomal translocation

    OpenAIRE

    Li, Dawei; Sun, Xiao Li; Casto, Bruce; Fang, Jin; Theil, Karl; Glaser, Ronald; Milo, George

    1998-01-01

    The AGLCL Epstein–Barr virus (EBV) growth-transformed cell line is incapable of inducing tumors in nude mice. When the cells were transfected with a 1.3-kb CATR1 antisense cDNA construct, progressively growing lymphomas could be induced in nude mice. Chromosome analysis of the parental, transfected, and tumor cells revealed that a chromosomal translocation t(8;14)(q24.1;q32) had occurred in the transfected cells and was retained in cells derived from tumors. Moreover, enhanced c-myc expressio...

  11. Malignant phyllode tumor metastatic to the duodenum

    Institute of Scientific and Technical Information of China (English)

    Oktar Asoglu; Hasan Karanlik; Umut Barbaros; Hakan Yanar; Yersu Kapran; Mustafa Kecer; Mesut Parlak

    2006-01-01

    Phyllode tumor (PT) is extremely rare tumor of the breast. Distant metastasis occurs in 10-20% of patients with malignant phyllode tumor. The most common sites of metastases are the lungs and bones. Although theoretically any organ may have metastasis, an isolated duodenum metastasis has not been documented as yet in the English-language literature. We report herein a case with a isolated duodenal metastasis from PT of breast in a 31 year-old-woman who underwent right mastectomy 4 years before because of the recurrent malignant PT. She presented to our hospital with massive upper gastrointestinal bleeding. Clinical evaluation revealed a huge mass originated from duodenum. Urgent laparotomy and pancreaticoduodenectomy were carried out in order to remove the bleeding duodenal mass.The pathologic examination of the resected specimen showed a malignant spindle cell tumor consistent with metastatic malignant PT. Our case of gastrointestinal bleeding due to an isolated duodenal metastasis as a result of hematogenous spread from malignant phyllode tumor of breast is unique in the English literature and pancreaticoduodenectomy is a curative treatment for patients with isolated duodenal involvement.

  12. Advances in diffuse malignant peritoneal mesothelioma

    Directory of Open Access Journals (Sweden)

    Tristan D. Yan

    2011-12-01

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

  13. Skeletal scintigraphy in benign and malignant disease

    International Nuclear Information System (INIS)

    This paper begins with a discussion of the technical factors in skeletal scintigraphy, including collimation, the use of three-phase bone scan, and single-photon emission computed tomography. Skeletal scintigraphy for benign conditions is commonly indicated for the patient presenting with pain (trauma, sports-related injury, posttraumatic pain syndrome, painful orthopedic prosthesis) and for the patient with abnormal laboratory test results (metabolic bone disease, Paget disease). For malignant conditions, the bone scan is useful in the evaluation of metastases in patients with extraosseous malignancies and primary bone tumors. The discussion addresses the various scan patterns seen in the more common tumors, such as prostate carcinoma, breast carcinoma, and lung carcinoma. Bone scintigraphy is an exquisitely sensitive modality. With some understanding of the techniques necessary for obtaining the optimal bone scan, and of the patterns that can be seen in various clinical conditions, the radiologist will find the bone scan a very specific tool for evaluating both benign and malignant diseases

  14. Malignant fibrous histiocytoma with skeletal involvement

    Directory of Open Access Journals (Sweden)

    Takechi,Hideo

    1978-10-01

    Full Text Available Malignant fibrous histiocytoma of soft part is rather common but malignant fibrous histiocytoma of the bone is rarely encountered clinically. Authors present five cases of malignant fibrous histiocytoma with skeletal involvement and discuss their clinical course, x-ray findings and histological features. This tumor has marked tendency for local recurrence and metastasis. Other bone tumors such as giant cell tumor, aneurysmal bone cyst, non ossifying fibroma, osteosarcoma, fibrosarcoma of bone and metastatic cancer can be excluded by several characteristic findings observed in x-rays as well as histopathological features. All information on the patient should be carefully analysed, because it is difficult to decide whether bone involvement is primary or secondary. Four out of five cases definitely originated within the bone.

  15. The case of malignancy mimicking legionella pneumonia

    Directory of Open Access Journals (Sweden)

    Ali Karakuş

    2013-09-01

    Full Text Available Legionella pneumophila is a bacterium, which can grow inwater pipe networks and climate systems. Contaminationoccurs by aspiration of infected water or aerosol inhalation.It is usually presented with fever, bradycardia, andchange in mental status, hyponatremia, elevation of liverenzymes and deterioration of renal function. The definitediagnosis is established by detection of the antigens andcultivating in the culture medium. Also, malign lung tumorscan encounter with the same clinical findings, so lungcancer should be remembered in differential diagnosis.The patient hospitalized for the Legionella pneumophiladue to the physical examination and laboratory findingsduring the first evaluation in the emergency department.However, further examinations pointed to the cancer. Weaimed to emphasize the probability of malignant tumorsin terms of hyponatremia, increase in the liver enzymes,and failure in the renal functions, which were usually experiencedin emergency unit. J Clin Exp Invest 2013; 4(3: 390-392Key words: Legionella pneumophila, pneumonia, lung malignancy

  16. Molecular probes for malignant melanoma imaging.

    Science.gov (United States)

    Ren, Gang; Pan, Ying; Cheng, Zhen

    2010-09-01

    Malignant melanoma represents a serious public health problem and is a deadly disease when it is diagnosed at late stage. Though (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has been widely used clinically for melanoma imaging, other approaches to specifically identify, characterize, monitor and guide therapeutics for malignant melanoma are still needed. Consequently, many probes targeting general molecular events including metabolism, angiogenesis, hypoxia and apoptosis in melanoma have been successfully developed. Furthermore, probes targeting melanoma associated targets such as melanocortin receptor 1 (MC1R), melanin, etc. have undergone active investigation and have demonstrated high melanoma specificity. In this review, these molecular probes targeting diverse melanoma biomarkers have been summarized. Some of them may eventually contribute to the improvement of personalized management of malignant melanoma. PMID:20497118

  17. Malignant melanoma of the oral cavity

    Directory of Open Access Journals (Sweden)

    Ebenezer Jagadish

    2006-01-01

    Full Text Available Oral malignant melanoma is a rare disease. The common sites of its occurrence are the palate and gingiva with the maxillary arch being affected 80% of the time. Because of their presence at relatively obscure areas in the oral cavity, most of the malignant melanomas of the oral cavity are diagnosed at a late stage. These lesions are associated with poor prognosis. The dental clinician must therefore carefully examine the head, neck, and oral cavity, and any pigmented lesion that may exhibit growth potential must be biopsied. This article describes a case of malignant melanoma that was present in the oral cavity and briefly reviews the relevant literature that explains the nature of this lesion.

  18. Synchronous dual malignancy: Successfully treated cases

    Directory of Open Access Journals (Sweden)

    Agrawal Rashi

    2007-01-01

    Full Text Available The occurrence of a second malignancy in a patient with a known malignant tumour is not uncommon. Synchronous primary malignancies are still unusual We are presenting two cases treated successfully at our centre. Case report 1-A 70 year old female presented to us with lump in right breast for two years and bleeding per vaginum for two years.Histopathology of cervix showed squamous cell carcinoma (large cell non keratinizing and clinical stage was IIIB. HPE mastectomy specimen showed infiltrating duct carcinoma and stage II. Patient was treated with external beam radiotherapy for carcinoma cervix and breast simultaneously and chemotherapy as required. Patient is on regular follow up and clinically no evidence of disease. Case Report 2 -A 40 year old female presented with mild headache off and on for one year, projectile vomiting for three months and right side facial swelling for three months. HPE brain tissue showed astrocytoma grade II and HPE parotid tumour showed low grade muco-epidermoid carcinoma. Patient was treated with surgery first then radiotherapy. Patient is in regular follow up,having no complain,clinically no neurological dysfunction and no evidence of disease at right parotid and neck region. Thus it was concluded that patients responded well to treatment. Treatment strategies in case of synchronous double malignancy depend on treating the malignancy that is more advanced first or sometimes both could be treated simultaneously. In our case we concluded that synchronous double malignancy may be treated successfully. Both sites should be treated fully as if they were occurring separately considering toxicities.

  19. Malignant Mesothelioma after Household Exposure to Asbestos

    Directory of Open Access Journals (Sweden)

    Raya Saba

    2013-01-01

    Full Text Available Malignant mesothelioma (MM is an aggressive cancer that has been closely linked to asbestos exposure. Initially recognized as an occupational cancer in male workers, MM was later found to occur in their family members as well. We report the case of an 89-year-old female who presented with abdominal distention, pain, and findings consistent with malignant ascites. Family history was significant for fatal mesothelioma in her husband of 40 years, who was a worker at a tile factory. The diagnosis of MM was confirmed on pathologic examination of the omental core biopsy.

  20. Malignant peritoneal mesothelioma following asbestos exposure.

    Science.gov (United States)

    Manavoğlu, O; Orhan, B; Evrensel, T; Ozçelik, T; Yolcu, I; Kunt, E

    1996-01-01

    Clinical, epidemiological, and pathological studies have demonstrated that asbestosis plays a major role in the etiology of mesothelioma. The direct exposure of workers in industrialized countries to asbestos fibers and nonoccupational household contact elevate the risk of malignant mesothelioma. An increased risk has been found in certain geographic areas of Turkey due to the presence of asbestos deposits and the use of the material known as "white soil" as an insulation. We present a malignant mesothelioma case from rural eastern Turkey with a history of asbestos exposure from using "white soil". We review the epidemiological aspects of asbestos as they relate to mesothelioma. PMID:9216805

  1. Giant metastasizing malignant hidradenoma in a child

    Directory of Open Access Journals (Sweden)

    Sunil K Bajaj

    2016-01-01

    Full Text Available An 8-year-old girl presented with a scalp swelling. The swelling was recurrent, reappearing everytime after local excision. She underwent surgery and the histopathologic diagnosis was malignant hidradenoma. This very rare and aggressive tumor is known to occur in elderly population and is histopathologically distinct from its commonly occuring benign counterpart. Malignant hidradenoma is resistant to chemotherapy and radiotherapy. We empahsize that being cognizant of the possibility of this rare tumor would assist in timely action in the form of wide resection, with possible reduction in morbidity and mortality.

  2. MALIGNANT MELANOMA OF THE ORAL CAVITY

    Directory of Open Access Journals (Sweden)

    Vishnu Prasad

    2016-02-01

    Full Text Available Oral malignant melanoma is a rare aggressive neoplasm commonly affects males and is more frequently seen at the level of the hard palate and gingiva. In many cases, melanoma has evolved from the pre-existing pigmented lesions. These neoplasms are biologically aggressive, but they often go unnoticed since they usually present merely as a hyperpigmented patch on the gingival surface. Performing biopsies of doubtful pigmented lesions helps in early treatment and better prognosis. The surgical excision combined with the chemotherapy is the treatment of choice. Here, we report a rare case of an elderly male patient with oral malignant melanoma with metastasis to vertebral column.

  3. MALIGNANT MELANOMA OF THE HEAD SKIN

    OpenAIRE

    Camelia Tamas; Doinita Radulescu; Lucian Popa; C. Tarasi; Cristina Stanescu; R. Nita

    2006-01-01

    Malignant melanoma (MM) is known as a tumor with high malignancy. The development of a melanoma on the head skin is even more severe, as prognosis, because of the limitted possibilities for large excision and high potential of diffusion in the wide vascular network. We treated 11 cases with MM head localisation in a period of 10 years. The rate of survival is very poor (6 months – 4 years after surgery). We used skin graft or fasciocutaneous flap for the regional reconstruction after exc...

  4. Transformer Protection Using the Wavelet Transform

    OpenAIRE

    ÖZGÖNENEL, Okan; ÖNBİLGİN, Güven; KOCAMAN, Çağrı

    2005-01-01

    This paper introduces a novel approach for power transformer protection algorithm. Power system signals such as current and voltage have traditionally been analysed by the Fast Fourier Transform. This paper aims to prove that the Wavelet Transform is a reliable and computationally efficient tool for distinguishing between the inrush currents and fault currents. The simulated results presented clearly show that the proposed technique for power transformer protection facilitates the a...

  5. 樱桃汁和草莓汁激活Nrf2信号通路对砷诱导的人支气管上皮细胞损伤的保护作用%Juices of cherry and strawberry confer protection of human bronchial epithelial cells against arsenic-induced toxicity via activation of Nrf2 signaling pathway

    Institute of Scientific and Technical Information of China (English)

    孔得刚; 王莉莉; 周洪雷; 任冬梅; 娄红祥; 沈涛

    2014-01-01

    目的:研究草莓汁和樱桃汁对NF-E2相关因子2(Nrf2)信号通路的影响,以及两种果汁对砷诱导的人支气管上皮(HBE)细胞损伤的保护作用。方法选择人乳腺癌MDA-MB-231细胞系,分为空白对照组、萝卜硫素组,以及樱桃(草莓)汁1∶10、1∶20、1∶40和1∶80组(果汁稀释比例分别为1∶10、1∶20、1∶40和1∶80),采用抗氧化反应原件(ARE)荧光素酶报告基因和Westerm blotting筛选并确证两种果汁对Nrf2信号通路的影响;选择HBE细胞,分为空白对照组、萝卜硫素组,以及樱桃(草莓)汁1∶10、1∶20、1∶40组(果汁稀释比例分别为1∶10、1∶20和1∶40),采用QuantiChrom谷胱甘肽(GSH)试剂盒测定两种果汁对内源性抗氧化剂GSH水平的影响;采用MTT法和细胞转染技术评价两种果汁对砷诱导的HB E细胞的保护作用。结果草莓汁和樱桃汁能够剂量依赖地增强ARE荧光强度,上调MDA-MB-231细胞中Nrf2及其下游基因NADPH苯醌氧化还原醇(NQO1)和γ-谷氨酰半胱氨酸合成酶(γGCS)蛋白的表达;两种果汁能够提高HBE细胞内源性抗氧化剂GSH水平;两种果汁和砷处理HBE细胞后,果汁预处理的细胞生存率高于砷单独处理的细胞生存率,两种果汁表现出对砷诱导细胞毒性的保护作用,而这种保护作用在转染Nrf2-siRNA后消失。结论草莓汁和樱桃汁通过激活Nrf2信号通路抑制砷诱导的细胞毒性,对HBE细胞具有保护作用。%Objective To investigate the effects of cherry and strawberry juices on NF-E2-related factor 2(Nrf2)signa-ling pathway,and to evaluate their protection effects on arsenic-induced toxicity in human bronchial epithelial (HBE) cells.Methods Human breast cancer 23 1 cells were randomly divided into the control group,sulforaphen treated group,and juice treated groups (juice dilution ratios were 1∶10,1∶20,1∶40 and 1∶80,respectively

  6. European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility

    DEFF Research Database (Denmark)

    Hopkins, P M; Rüffert, H; Snoeck, M M;

    2015-01-01

    of anaesthetic drugs in these patients with increased risk of developing malignant hyperthermia during general anaesthesia, representing an early and successful example of stratified medicine. In 2001, our group also published a guideline for the use of DNA-based screening of malignant hyperthermia...... susceptibility. We now present an updated and complete guideline for the diagnostic pathway for patients potentially at increased risk of developing malignant hyperthermia. We introduce the new guideline with a narrative commentary that describes its development, the changes to previously published protocols and...

  7. Generalized Fourier transforms classes

    DEFF Research Database (Denmark)

    Berntsen, Svend; Møller, Steen

    2002-01-01

    The Fourier class of integral transforms with kernels $B(\\omega r)$ has by definition inverse transforms with kernel $B(-\\omega r)$. The space of such transforms is explicitly constructed. A slightly more general class of generalized Fourier transforms are introduced. From the general theory foll...... follows that integral transform with kernels which are products of a Bessel and a Hankel function or which is of a certain general hypergeometric type have inverse transforms of the same structure....

  8. Malignant Fibrous Histiocytoma in the Infratemporal Fossa

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Hee; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [Dept. of Oral and Maxillofacial Radiology and Dental Research Institute, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1999-08-15

    Malignant fibrous histiocytoma is one of the most common soft tissue sarcomas in late adult life, but its incidence in oral and maxillofacial region is extremely rare. We report a case of malignant fibrous histiocytoma which occurred in the infratemporal fossa. Conventional radiograph of this case showed an ill-defined radiolucent lesion in the alveolar bone of the right maxillary first molar area, the lateral wall of the maxillary sinus, and the ascending ramus of mandible. MRI demonstrated well defined mass of intermediate signal intensity in T1 weighted images but T2 weighted images showed two distinctive regions of different characteristics. Infratemporal portion of the lesion was of hyperintense signal but under that region, the signal intensity decreased clearly, which might mean this case composed of two different subtypes, though it couldn't be confirmed by histopathological examination. Biopsy was taken in the only soft tissue of the maxillary posterior alveolar region and confirmed the lesion as the storiform-pleomorphic type of malignant fibrous histiocytoma. Histopathological subtype was well consistent with the relatively aggressive imaging findings of that region. We expect more detailed analysis of the nature of malignant fibrous histiocytoma with improvement of the imaging modality and the identification of the relationship between diagnostic imaging and histopathologic findings.

  9. Malignant osteopetrosis: hypercalcaemia after bone marrow transplantation.

    OpenAIRE

    Rawlinson, P S; Green, R H; Coggins, A M; Boyle, I T; Gibson, B.E.

    1991-01-01

    A 3 year old girl presented with malignant osteopetrosis, which was treated by allogeneic bone marrow transplantation. Successful engraftment was complicated by prolonged hypercalcaemia, which was controlled by a combination of a bisphosphonate, phosphate infusions, vigorous resalination, and salmon calcitonin. She was alive and well 16 months after the transplant.

  10. Malignant Fibrous Histiocytoma in the Infratemporal Fossa

    International Nuclear Information System (INIS)

    Malignant fibrous histiocytoma is one of the most common soft tissue sarcomas in late adult life, but its incidence in oral and maxillofacial region is extremely rare. We report a case of malignant fibrous histiocytoma which occurred in the infratemporal fossa. Conventional radiograph of this case showed an ill-defined radiolucent lesion in the alveolar bone of the right maxillary first molar area, the lateral wall of the maxillary sinus, and the ascending ramus of mandible. MRI demonstrated well defined mass of intermediate signal intensity in T1 weighted images but T2 weighted images showed two distinctive regions of different characteristics. Infratemporal portion of the lesion was of hyperintense signal but under that region, the signal intensity decreased clearly, which might mean this case composed of two different subtypes, though it couldn't be confirmed by histopathological examination. Biopsy was taken in the only soft tissue of the maxillary posterior alveolar region and confirmed the lesion as the storiform-pleomorphic type of malignant fibrous histiocytoma. Histopathological subtype was well consistent with the relatively aggressive imaging findings of that region. We expect more detailed analysis of the nature of malignant fibrous histiocytoma with improvement of the imaging modality and the identification of the relationship between diagnostic imaging and histopathologic findings.

  11. Oesphageal Stenting for palliation of malignant mesothelioma

    Directory of Open Access Journals (Sweden)

    Rahamim Joseph

    2008-01-01

    Full Text Available Abstract Dyspahgia in patients with malignant mesothelioma is usually due to direct infiltration of the eosophagus by the tumour. It can be distressing for the patient and challenging for the physician to treat. We describe three cases in which this condition has been successfully palliated with self expanding esophageal stents.

  12. Clinical diagnosis of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    We evaluated clinical and thoracoscopic findings of cases that underwent thoracoscopic biopsy for the diagnosis of malignant pleural mesothelioma. We reviewed 32 cases suspected of having malignant pleural mesothelioma from 2003 to 2006. We made a diagnosis of malignant pleural mesothelioma via thoracoscopic biopsy (19 cases). The cut-off level of hyaluronic acid in malignant effusions, selected on the basis of the best diagnostic efficacy, was 100 μg/ml. We can decrease the incidence of false negative cases by the combination of CT findings and the presence of hyaluronic acid in pleural effusion. In the pleural thickening type of thoracoscopic appearance, the parietal pleurae were thickened, and small nodules were rare. As for this type, tumor cells were histologically absent or confined to the submesothelial tissue. We considered that determinations of specific sites were difficult. Adequate tissue samples obtained via video-assisted thoracoscopy were necessary for diagnosis. We can decrease the incidence of false negative cases by the combination of the presence of hyaluronic acid in pleural effusion and thoracoscopic biopsy. (author)

  13. Acute cardiac failure in neuroleptic malignant syndrome.

    LENUS (Irish Health Repository)

    Sparrow, Patrick

    2012-02-03

    We present a case of rapid onset acute cardiac failure developing as part of neuroleptic malignant syndrome in a 35-year-old woman following treatment with thioridazine and lithium. Post mortem histology of cardiac and skeletal muscle showed similar changes of focal cellular necrosis and vacuolation suggesting a common disease process.

  14. Ocular malignant lymphoma. A clinical pathological study

    Directory of Open Access Journals (Sweden)

    Panda A

    1987-01-01

    Full Text Available Eleven histologically proved cases of ocular malignant lymphoma diagnosed and managed during the year 1974-81 are reported. The follow-up period ranges from 2-7 years. The difficulties in diagnosis, treatment and prognosis are discussed.

  15. Second malignancies in children: the usual suspects?

    Energy Technology Data Exchange (ETDEWEB)

    Moppett, John; Oakhill, Anthony E-mail: anthony.oakhill@nildram.co.uk; Duncan, Andrew W

    2001-06-01

    The aim of this article is to provide an up to date review of second malignant neoplasms (SMN's) following treatment for childhood cancer, referring to their incidence, the role of genetic factors, and how the primary malignancy and treatment received influence the type, site and prognosis of SMN's. The role of genetic factors will be discussed as far as they impact upon a predisposition to later development of SMN's. The primary malignancies that have important associations with SMN's will then be discussed, in particular Hodgkin's disease, retinoblastoma and acute lymphoblastic leukaemia. The important second malignancies will be highlighted, including tumours of the CNS and thyroid, osteosarcoma, secondary acute myeloid leukaemia and melanoma. Emphasis will be put upon identifying which patients are most likely to suffer from these tumours. An important part of the article are case histories. These are provided in combination with illustrations as a useful adjunct to the text, with a particular emphasis on radiological features, diagnosis and screening. Finally, the important but different roles of causal agents, in particular chemotherapy and radiotherapy are highlighted.

  16. Update in systemic therapy of urologic malignancies.

    Science.gov (United States)

    Mooney, David; Paluri, Ravikumar; Mehta, Amitkumar; Goyal, Jatinder; Sonpavde, Guru

    2014-01-01

    Systemic therapy of advanced prostate and renal cancers has gained several recent additions to the therapeutic armamentarium. Treatment of patients with castration-resistant prostate cancer now includes additional immunotherapy (sipuleucel-T), chemotherapy (cabazitaxel), androgen-signaling inhibitors (abiraterone acetate, enzalutamide), and a radiopharmaceutical (alpharadin), based on extension of patient survival. Similarly, therapy for patients with renal cell carcinoma, a chemoresistant malignancy, has undergone dramatic changes based on an understanding of the role of angiogenesis. Multiple vascular endothelial growth factor inhibitors (sorafenib, sunitinib, pazopanib, axitinib, bevacizumab) and mammalian target of rapamycin inhibitors (temsirolimus, everolimus) have been added to the therapeutic arsenal. Additionally, immunotherapy retains an important treatment role, with a continuing application of high-dose interleukin-2 in select patients and the emergence of novel immunotherapeutic agents that may have significant benefit. Other major urologic malignancies, including urothelial, testicular, and penile cancers, have witnessed relatively few or no recent advances in therapy, although testicular germ cell tumors are one of the most curable malignancies. An agent for treatment of advanced urothelial cancer now has commercial approval, the chemotherapeutic agent, vinflunine, as second-line therapy in multiple countries-but not in the United States. Our review summarizes and updates the field of systemic therapy for advanced urologic malignancies, with a focus on castration-resistant prostate cancer and renal cell carcinoma. PMID:24393751

  17. Mixed malignant germ cell tumor of ovary

    Directory of Open Access Journals (Sweden)

    Sviračević Branko

    2011-01-01

    Full Text Available Introduction. Malignant tumours of ovary germ epithelium are very rare and account for about 2-5% of all ovarian tumours of germ origin. In adolescent patients under 20 years of age diagnosed to have ovarian tumour, these tumours originate from germ cells in about 70% of cases. Depending on the stage of the disease, medical treatment and age, the death rate ranges from 25% to 84%. A special group of germ tumours are mixed germ cells tumours built of two or more different types of germ tumours. Case report. This paper gives a diagnostic-therapeutic procedure and the clinical picture with the course and outcome of the decease in a nineteen-year old patient with a mixed malignant germ tumour (dysgerminoma, choriocarcinoma, immature teratoma found in one of the ovaries. It also deals with the appearance and development, some characteristics and histological build of the tumours diagnosed in this case. Conclusion. Malignant tumours of ovary germ epithelium are very rare and develop in female population under 30 years of age. They are characterized by a high degree of malignity. They are resistant to cytostatic treatment, they spread very quickly with the lethal outcome. The course of the disease is not characteristic and is usually masked under some other acute gynaecological disease. The definitive diagnosis is made after laparotomy and pathohistological analysis of the tumour tissue.

  18. Malignancy markers in the cerebrospinal fluid.

    Science.gov (United States)

    Koskiniemi, M

    1988-10-01

    The specificity and sensitivity of malignancy marker determinations in cerebrospinal fluid (CSF) are often insufficient. Even at the subclinical stage of the disease the marker should be present. The effect of therapy should be monitored and relapses noted. Thus high standards of methodology are required. There are many substances that may indicate a malignant process in the central nervous system. However, there are many pitfalls in their determination. Malignant cells may occur in CSF via processes involving leptomeningeal structures such as metastases and leukaemia, but primary brain tumours seldom show cells in CSF. Human chorionic gonadotrophin and alpha-fetoprotein determinations assist in the early detection of cerebral germ cell tumours and of relapses, even in the subclinical stage. Desmosterol may aid in the diagnosis of medulloblastomas and malignant gliomas and in monitoring therapy. Putrescine levels are elevated in CSF of patients with medulloblastoma and correlate with the clinical state, and serial analyses may reveal relapses. Fibronectin, when determined in CSF at the time of diagnosis, appears to be of great significance for the prognosis of acute lymphoblastic leukaemia. Ferritin and beta-2-microglobulin may help in some well-defined conditions. Brain-specific proteins and antibodies to them are non-specific markers whereas tumour-specific antigens and growth factors may be more significant. PMID:3058481

  19. Malignant biliary obstruction: From palliation to treatment

    Science.gov (United States)

    Boulay, Brian R; Birg, Aleksandr

    2016-01-01

    Malignant obstruction of the bile duct from cholangiocarcinoma, pancreatic adenocarcinoma, or other tumors is a common problem which may cause debilitating symptoms and increase the risk of subsequent surgery. The optimal treatment - including the decision whether to treat prior to resection - depends on the type of malignancy, as well as the stage of disease. Preoperative biliary drainage is generally discouraged due to the risk of infectious complications, though some situations may benefit. Patients who require neoadjuvant therapy will require decompression for the prolonged period until attempted surgical cure. For pancreatic cancer patients, self-expanding metallic stents are superior to plastic stents for achieving lasting decompression without stent occlusion. For cholangiocarcinoma patients, treatment with percutaneous methods or nasobiliary drainage may be superior to endoscopic stent placement, with less risk of infectious complications or failure. For patients of either malignancy who have advanced disease with palliative goals only, the choice of stent for endoscopic decompression depends on estimated survival, with plastic stents favored for survival of stent patency and patient survival for these patients by achieving local control of the obstructing tumor. Both photodynamic therapy and radiofrequency ablation may play a role in extending survival of patients with malignant biliary obstruction. PMID:27326319

  20. Treatment of malignant epulis in the dog

    Energy Technology Data Exchange (ETDEWEB)

    Odendaal, J.S.J.; Cronje, J.D.E. (National Hospital, Bloemfontein (South Africa). Dept. of Oncotherapy)

    1984-12-01

    The successful radiotherapy of malignant epulis in a 12 year-old Dachshund is discussed. Regrowth of the tumour, which was first removed by surgery, was treated with radiotherapy over a period of 36 days in 3 fractions. The total dose was 1800 rads. The lesion healed unevetfully. After 600 days, there was still no new growth but only scar tissue to be seen.

  1. Bacteremia and candidemia in hematological malignancies

    DEFF Research Database (Denmark)

    Bruun, B; Bangsborg, Jette Marie; Hovgaard, D;

    1988-01-01

    The microorganisms isolated in 1981-1985 from 171 cases of septicemia in patients with hematological malignancies were on the whole the same as those found in 1970-1972. The distribution between species was also quite similar for the two periods except within staphylococci, where the isolation ra...

  2. Bacteremia and candidemia in hematological malignancies

    DEFF Research Database (Denmark)

    Hovgaard, D; Skinhøj, P; Bangsborg, Jette Marie;

    1988-01-01

    171 episodes of bacteremia and candidemia in 142 patients were recorded during the period 1981-1985 in patients with hematological malignancies. Overall mortality, within 1 week of onset of bacteremia, was 20%. Increased mortality was found in patients with poor disease-prognosis (39%), with gran...

  3. Neuroleptic malignant syndrome : Successful treatment with bromocriptine

    NARCIS (Netherlands)

    Verhoeven, W.M.A.; Elderson, Arthur; Westenberg, H.G.M.

    1985-01-01

    The neuroleptic malignant syndrome (NMS) is a potentially fatal complication of antipsychotic drugs and is characterized by severe muscle rigidity, hyperpyrexia, and autonomic dysfunctions. The pathogenesis of NMS is considered to be related to dopamine-receptor blockade in the basal ganglia and hyp

  4. [Malignant Lymphoma of the Brain, and Dementia].

    Science.gov (United States)

    Mizutani, Saneyuki; Mizutani, Tomohiko

    2016-04-01

    A differential diagnosis of acute and subacute progressive dementias includes malignant lymphoma of the brain. We reviewed primary central nervous system lymphoma (PCNSL), intravascular lymphomatosis (IVL), lymphomatosis cerebri, and the relapse and invasion of systemic lymphomas. PCNSL is confined to the central nervous system; the infiltration and compression by the lymphoma result in adverse neurological symptoms. IVL is a rare form of malignant lymphoma that is characterized by the proliferation of primarily B-cell type lymphoma cells within the blood vessels of various organs. This causes ischemia and results in the associated neurological symptoms. Medical history and neuroimaging studies provide crucial informations to distinguish the lymphomas from other diseases that cause dementia, such an Alzheimer's disease. MRI imaging of the brain using contrast agent, and the biopsy of diseased tissues are essential for the diagnosis of the lymphomas. A histopathological examination is the most effective way to diagnose malignant lymphomas of the brain. Presently, the treatment of choice for PCNSL is the intravenous administration of high dose methotrexate with and without radiation therapy. Futhermore, Rituximab-containing chemotherapy has proved to greatly improve the prognosis of IVL. A better outcome can be achieved with the earlier diagnosis and treatment of the malignant lymphoma of the brain.

  5. Malignant phyllodes tumor of the left atrium.

    Science.gov (United States)

    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

  6. Malignant brain tumor treatments and hyperbaric oxygenation

    Energy Technology Data Exchange (ETDEWEB)

    Kohshi, Kiyotaka [Univ. of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan)

    2000-09-01

    Malignant brain tumor treatment and hyperbaric oxygenation: Combined hyperbaric oxygenation (HBO) therapy and radiation therapy of malignant gliomas is reviewed. Malignant glioma tissue is hypoxic, and the efficacy of radiation therapy is increased by raising the oxygen density in glioma tissue. Residual tumor was reduced by a radiation dose of approximately 40 Gy in many cases when radiation therapy was begun within 15 minutes after HBO. In the experiment in animal models with different hypoxic fractions (HFs) of cells (SCCVII and 9L gliosarcoma), the tumor reduction effect was more significant in the SCCVII model, which has a higher HF. When the SCCVII model was irradiated within 30 minutes after HBO, the improvement effect was more significant (1.60-1.78 times) than by irradiation alone. HBO was effective in the treatment of radionecrosis of the brain. However, there were some cases in which radionecrosis progressed when the HBO treatments were discontinued, and the optimal duration of HBO treatment should be determined. It is difficult to differentiate between radionecrosis and tumor recurrence after radiosurgery of a malignant intracranial tumor. When no lesion reduction is observed in response to HBO treatment and steroid administration for about one month, the lesion is concluded to be a recurrence of the tumor, and additional irradiation should be performed. HBO treatment in combination with chemotherapy is also discussed. (K.H.)

  7. Malignant Hyperthermia Association of the United States

    Science.gov (United States)

    ... Videos Blog Get Involved Shop Ask a question right here... MHAUS On Facebook Now view more On Twitter Now view more Tweets by @ ... Malignant Hyperthermia Association of the United States. All rights reserved. ... advertiser and not necessarily the views or opinions of MHAUS, its staff or its ...

  8. Angiogenic and Metastatic Determinants of Malignant Melanoma

    NARCIS (Netherlands)

    A. Mooppilmadham Das (Asha)

    2015-01-01

    markdownabstractCutaneous melanoma or malignant melanoma of the skin is a highly metastatic disease, with an increasing rate of incidence, poor prognosis and high resistance to therapeutic intervention. Although early diagnosis and surgical resection of the primary lesion could significantly improve

  9. Somatostatin receptor scintigraphy in malignant lymphoma

    NARCIS (Netherlands)

    P.J. Lugtenburg (Pieternella)

    2001-01-01

    textabstractThe prognosis of patients with malignant lymphomas has improved over the last 30 years. Besides from improvements in therapy the better outcome of these patients has resulted also from the introduction of better diagnostic techniques detecting involved sites. Diagnostic radiology plays a

  10. Malignant fibrous histiocytoma mimicking pulmonary embolism.

    OpenAIRE

    Sleyster, T J; Heystraten, F M

    1988-01-01

    A rare case of malignant fibrous histiocytoma occurring in the pulmonary artery is reported. Such primary pulmonary artery sarcomas may have the diagnosis suggested by angiography or echocardiography; radiographically and in perfusion-ventilation scanning their usual unilateral origin (with later spread) and the persistence of the perfusion defect are among the features normally distinguishing them from thromboembolism.

  11. Enumeration of the Simian Virus 40 Early Region Elements Necessary for Human Cell Transformation

    OpenAIRE

    Hahn, William C.; Scott K Dessain; Brooks, Mary W.; King, Jessie E.; Elenbaas, Brian; Sabatini, David M.; DeCaprio, James A.; Weinberg, Robert A.

    2002-01-01

    While it is clear that cancer arises from the accumulation of genetic mutations that endow the malignant cell with the properties of uncontrolled growth and proliferation, the precise combinations of mutations that program human tumor cell growth remain unknown. The study of the transforming proteins derived from DNA tumor viruses in experimental models of transformation has provided fundamental insights into the process of cell transformation. We recently reported that coexpression of the si...

  12. Heterospecific transformation among cyanobacteria.

    OpenAIRE

    Stevens, S E; Porter, R D

    1986-01-01

    Heterospecific transformation occurred between cyanobacteria currently classified in either the genus Synechococcus or Synechocystis. Cyanobacterial strains 73109 and 6906 were capable of physiological transformation.

  13. Huge pelvi-abdominal malignant inflammatory myofibroblastic tumor with rapid recurrence in a 14-year-old boy

    Institute of Scientific and Technical Information of China (English)

    Chia-Hsun; Lu; Hsuan-Ying; Huang; Han-Koo; Chen; Jiin-Haur; Chuang; Shu-Hang; Ng; Sheung-Fat; Ko

    2010-01-01

    Inflammatory myofibroblastic tumor(IMT) is an uncommon benign neoplasm with locally aggressive behavior but malignant change is rare.We report an unusual case of pelvic-abdominal inflammatory myofibroblastic tumor with malignant transformation in a 14-year-old boy presenting with abdominal pain and 9 kg body weight loss in one month.Computed tomography revealed a huge pelvi-abdominal mass(30 cm),possibly originating from the pelvic extraperitoneal space,protruding into the abdomen leading to upward displace...

  14. Anogenital malignancies and premalignancies: facts and controversies.

    Science.gov (United States)

    Kutlubay, Zekayi; Engin, Burhan; Zara, Tuba; Tüzün, Yalçın

    2013-01-01

    Anogenital malignancies and premalignancies are an important personal/public health problem due to their effects on individuals' physical, mental, and sexual health. Also, due to their etiological association with human papillomavirus (HPV) infection, anogenital malignancies and premalignancies constitute an immense public health burden. In addition to HPV infection, immunosuppression, HIV infection, chronic dermatoses, such as lichen sclerosis, previous radiotherapy and chemotherapy treatments, and smoking, are the other important etiopathologic factors in the development of anogenital malignancies and premalignancies. The incidence of anal squamous cell carcinoma (SCC) has increased considerably in the past decade, mainly due to the growing number of cases in high-risk groups, such as men who have sex with men, immunosuppressed individuals, and patients with HIV infection. Also, an increase in vulvar intraepithelial neoplasia (VIN) and VIN-related invasive vulvar cancer has been noted in women younger than age 50 years due to its association with HPV infections over the past decade. SCC of the scrotum seems to be the first cancer linked to occupational exposure. Bowen's disease, Bowenoid papulosis, and erythroplasia of Queyrat are the most widely seen premalignancies of anogenital region and are all forms of squamous intraepithelial neoplasia. Histopathologically, these conditions share identical histologic features of SCC in situ, but their clinical features differ. Early diagnosis is vital to improve prognosis, especially in anogenital malignancies. Also, if a delay occurs in diagnosis, treatment options used will be associated with significant negative effects on the patient's psychological well-being and quality of life; hence, management of anogenital malignancies and premalignancies should be organized in a multidisciplinary fashion. PMID:23806153

  15. Malignancy within a Tail Gut Cyst: A Case of Retrorectal Carcinoid Tumour.

    Science.gov (United States)

    Abukar, A A; Parcell, B J; Lim, C B; Patil, P V; Ramsanahie, A; Carey, F; Steele, R J C; Thaha, M A

    2014-01-01

    Purpose. Tailgut cysts with malignant transformation are rare entities. We discuss the diagnostic strategy and treatment of a malignancy within a tailgut cyst. Methods. In this study we report on the case of a 61-year-old man with a malignant neuroendocrine tumour arising within a tailgut cyst and an overview of the literature emphasising the histopathological characteristics and differential diagnosis. Results. Our patient presented with lower back pain, rectal pain, and increased urgency of defecation. MRI scan and CT-guided biopsy on histological analysis revealed a diagnosis of carcinoid tumour of the presacral space. The patient subsequently underwent an abdominoperineal excision of the rectum. Conclusions. This case highlights the importance of tailgut cysts as a differential diagnosis of presacral masses. It is a rare congenital lesion developing from remnants of the embryonic postanal gut and is predominantly benign in nature. Approximately half of cases remain asymptomatic; therefore, diagnosis is often delayed. Magnetic resonance imaging is the investigation of choice and an awareness of the possibility of malignant potential is critical to avoiding missed diagnosis and subsequent morbidity. Complete surgical excision allows accurate diagnosis, confirmation of oncological clearance, and prevention of mortality. PMID:25478281

  16. Malignancy within a Tail Gut Cyst: A Case of Retrorectal Carcinoid Tumour

    Directory of Open Access Journals (Sweden)

    A. A. Abukar

    2014-01-01

    Full Text Available Purpose. Tailgut cysts with malignant transformation are rare entities. We discuss the diagnostic strategy and treatment of a malignancy within a tailgut cyst. Methods. In this study we report on the case of a 61-year-old man with a malignant neuroendocrine tumour arising within a tailgut cyst and an overview of the literature emphasising the histopathological characteristics and differential diagnosis. Results. Our patient presented with lower back pain, rectal pain, and increased urgency of defecation. MRI scan and CT-guided biopsy on histological analysis revealed a diagnosis of carcinoid tumour of the presacral space. The patient subsequently underwent an abdominoperineal excision of the rectum. Conclusions. This case highlights the importance of tailgut cysts as a differential diagnosis of presacral masses. It is a rare congenital lesion developing from remnants of the embryonic postanal gut and is predominantly benign in nature. Approximately half of cases remain asymptomatic; therefore, diagnosis is often delayed. Magnetic resonance imaging is the investigation of choice and an awareness of the possibility of malignant potential is critical to avoiding missed diagnosis and subsequent morbidity. Complete surgical excision allows accurate diagnosis, confirmation of oncological clearance, and prevention of mortality.

  17. Computerized lung cancer malignancy level analysis using 3D texture features

    Science.gov (United States)

    Sun, Wenqing; Huang, Xia; Tseng, Tzu-Liang; Zhang, Jianying; Qian, Wei

    2016-03-01

    Based on the likelihood of malignancy, the nodules are classified into five different levels in Lung Image Database Consortium (LIDC) database. In this study, we tested the possibility of using threedimensional (3D) texture features to identify the malignancy level of each nodule. Five groups of features were implemented and tested on 172 nodules with confident malignancy levels from four radiologists. These five feature groups are: grey level co-occurrence matrix (GLCM) features, local binary pattern (LBP) features, scale-invariant feature transform (SIFT) features, steerable features, and wavelet features. Because of the high dimensionality of our proposed features, multidimensional scaling (MDS) was used for dimension reduction. RUSBoost was applied for our extracted features for classification, due to its advantages in handling imbalanced dataset. Each group of features and the final combined features were used to classify nodules highly suspicious for cancer (level 5) and moderately suspicious (level 4). The results showed that the area under the curve (AUC) and accuracy are 0.7659 and 0.8365 when using the finalized features. These features were also tested on differentiating benign and malignant cases, and the reported AUC and accuracy were 0.8901 and 0.9353.

  18. Cancer and malignant resistance of cells as phenomena of adaptation to damaging factors.

    Science.gov (United States)

    Monceviciute-Eringiene, E

    1996-05-01

    I propose the hypothesis that mechanisms of general biological persistent resistance to damaging factors are closely related to the development of tumour cells. This phenomenon is characteristic of bacterial variants whose resistance to antibiotics and other chemotherapeutic drugs appears through L-transformation. As somatic cells are exposed to carcinogens and develop into tumour cells, they also acquire resistance to the toxic effects of carcinogens through multistage malignant transformation. Many cancerous cells, which have acquired persistent resistance to chemotherapy drugs or irradiation, often reappear locally or in metastases after courses of treatment. Thus, these cells undergo a kind of repeated development of malignancy. After a certain remission period, they begin to multiply more intensively locally, and are more likely to spread by metastasis. All resistant cells have the following characteristics: simplified metabolism, genetic, biochemical and morphological properties; lower requirements from their nutrient medium; rapid growth; parasitic qualities; invasiveness. It is as if they regress into a more primitive mode of existence (atavism) to survive under unfavourable circumstances. Somatic cells, resistant to carcinogens and the cells which undergo progression to more malignant types under the influence of drugs become similar to unicellular organisms or to forms of the latter which are resistant to damaging factors. The more primitive the cells become, the better they survive. Thus, cancer is a special case of the general resistance of cells to damaging factors. PMID:8735884

  19. Mitochondria Biogenesis and Bioenergetics Gene Profiles in Isogenic Prostate Cells with Different Malignant Phenotypes

    Directory of Open Access Journals (Sweden)

    Tanya C. Burch

    2016-01-01

    Full Text Available Background. The most significant hallmarks of cancer are directly or indirectly linked to deregulated mitochondria. In this study, we sought to profile mitochondria associated genes in isogenic prostate cell lines with different tumorigenic phenotypes from the same patient. Results. Two isogenic human prostate cell lines RC77N/E (nonmalignant cells and RC77T/E (malignant cells were profiled for expression of mitochondrial biogenesis and energy metabolism genes by qRT-PCR using the Human Mitochondria and the Mitochondrial Energy Metabolism RT2 PCR arrays. Forty-seven genes were differentially regulated between the two cell lines. The interaction and regulatory networks of these genes were generated by Ingenuity Pathway Analysis. UCP2 was the most significantly upregulated gene in primary adenocarcinoma cells in the current study. The overexpression of UCP2 upon malignant transformation was further validated using human prostatectomy clinical specimens. Conclusions. This study demonstrates the overexpression of multiple genes that are involved in mitochondria biogenesis, bioenergetics, and modulation of apoptosis. These genes may play a role in malignant transformation and disease progression. The upregulation of some of these genes in clinical samples indicates that some of the differentially transcribed genes could be the potential targets for therapeutic interventions.

  20. Mitochondria Biogenesis and Bioenergetics Gene Profiles in Isogenic Prostate Cells with Different Malignant Phenotypes.

    Science.gov (United States)

    Burch, Tanya C; Rhim, Johng S; Nyalwidhe, Julius O

    2016-01-01

    Background. The most significant hallmarks of cancer are directly or indirectly linked to deregulated mitochondria. In this study, we sought to profile mitochondria associated genes in isogenic prostate cell lines with different tumorigenic phenotypes from the same patient. Results. Two isogenic human prostate cell lines RC77N/E (nonmalignant cells) and RC77T/E (malignant cells) were profiled for expression of mitochondrial biogenesis and energy metabolism genes by qRT-PCR using the Human Mitochondria and the Mitochondrial Energy Metabolism RT(2) PCR arrays. Forty-seven genes were differentially regulated between the two cell lines. The interaction and regulatory networks of these genes were generated by Ingenuity Pathway Analysis. UCP2 was the most significantly upregulated gene in primary adenocarcinoma cells in the current study. The overexpression of UCP2 upon malignant transformation was further validated using human prostatectomy clinical specimens. Conclusions. This study demonstrates the overexpression of multiple genes that are involved in mitochondria biogenesis, bioenergetics, and modulation of apoptosis. These genes may play a role in malignant transformation and disease progression. The upregulation of some of these genes in clinical samples indicates that some of the differentially transcribed genes could be the potential targets for therapeutic interventions. PMID:27478826