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Sample records for sarcoma kaposi

  1. Epidemic Kaposi Sarcoma

    Science.gov (United States)

    ... and its treatment, see the AIDSinfo website . Nonepidemic Gay-related Kaposi Sarcoma There is a type of ... trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website. ...

  2. Classic Kaposi Sarcoma

    Science.gov (United States)

    ... and its treatment, see the AIDSinfo website . Nonepidemic Gay-related Kaposi Sarcoma There is a type of ... trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website. ...

  3. Treatment Options for Kaposi Sarcoma

    Science.gov (United States)

    ... Treatment Childhood Vascular Tumors Treatment Research Kaposi Sarcoma Treatment (PDQ®)–Patient Version General Information About Kaposi Sarcoma ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  4. General Information about Kaposi Sarcoma

    Science.gov (United States)

    ... and its treatment, see the AIDSinfo website . Nonepidemic Gay-related Kaposi Sarcoma There is a type of ... trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website. ...

  5. Treatment Option Overview (Kaposi Sarcoma)

    Science.gov (United States)

    ... and its treatment, see the AIDSinfo website . Nonepidemic Gay-related Kaposi Sarcoma There is a type of ... trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website. ...

  6. Drugs Approved for Kaposi Sarcoma

    Science.gov (United States)

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

  7. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ...

    African Journals Online (AJOL)

    Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of ...

  8. Immunosuppressive Therapy-Related Kaposi Sarcoma

    Science.gov (United States)

    ... and its treatment, see the AIDSinfo website . Nonepidemic Gay-related Kaposi Sarcoma There is a type of ... trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website. ...

  9. Kaposi sarcoma - lesion on the foot (image)

    Science.gov (United States)

    Kaposi sarcoma lesion on the foot. This once-rare malignancy of the blood vessels is now associated with AIDS. It is ... users. The malignancy results in purplish grape-like lesions in the skin, gastrointestinal tract and other organs.

  10. Acroangiodermatitis (Pseudo-Kaposi sarcoma

    Directory of Open Access Journals (Sweden)

    Satyendra Kumar Singh

    2014-01-01

    Full Text Available Acroangiodermatitis or Pseudo-Kaposi sarcoma is a rare angioproliferative entity, related to chronic venous insufficiency or certain other vascular anomalies. It is often associated with chronic venous insufficiency, arteriovenous malformation of the legs, chronic renal failure treated with dialysis, paralyzed legs and amputation stumps. We hereby describe a case of 45 year old female presenting with pitting pedal edema, multiple ulcers over bilateral lower limbs with irregular margins with erythema and hyperpigmentation of the surrounding skin. Color Doppler study of bilateral lower limbs was normal. Histopathological examination from one of the lesions showed hyperplastic epidermis, proliferation of capillaries in dermis, hemosiderin deposits and lymphocytic infiltrate. These features thus confirmed the diagnosis of Acroangiodermatitis.

  11. Histopathology of Kaposi\\'s sarcoma in Jos: A 16-year review ...

    African Journals Online (AJOL)

    Background/objective: To study the pathology of Kaposi\\'s sarcoma and review relevant literature on this condition. Method: A retrospective analysis of histologically confirmed cases of Kaposi\\'s sarcoma over a period of 16 years was undertaken. Fresh sections of slides were reviewed independently by two pathologists.

  12. Molecular piracy of Kaposi's sarcoma associated herpesvirus.

    Science.gov (United States)

    Choi, J; Means, R E; Damania, B; Jung, J U

    2001-01-01

    Kaposi's Sarcoma associated Herpesvirus (KSHV) is the most recently discovered human tumor virus and is associated with the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma, and Multicentric Casttleman's disease. KSHV contains numerous open reading frames with striking homology to cellular genes. These viral gene products play a variety of roles in KSHV-associated pathogenesis by disrupting cellular signal transduction pathways, which include interferon-mediated anti-viral responses, cytokine-regulated cell growth, apoptosis, and cell cycle control. In this review, we will attempt to cover our understanding of how viral proteins deregulate cellular signaling pathways, which ultimately contribute to the conversion of normal cells to cancerous cells.

  13. Treatment of classical Kaposi's sarcoma with gemcitabine

    NARCIS (Netherlands)

    Brambilla, L; Labianca, R; Ferrucci, SM; Taglioni, M; Boneschi, [No Value

    2001-01-01

    Background: Several drugs are active in aggressive classical Kaposi's sarcoma (CKS); chemotherapeutic agents with fewer side-effects, more rapid response and able to overcome resistance to previous treatment are advisable when treating patients in a second line. Gemcitabine, an analogue of

  14. Lymphangiectatic Kaposi's sarcoma in a patient with AIDS Sarcoma de Kaposi linfangiectásico em paciente com Aids

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    Mônica Santos

    2013-04-01

    Full Text Available Kaposi's sarcoma is a malignant disease that originates in the lymphatic endothelium. It has a broad spectrum of clinical manifestations. Its four distinct clinical forms are: classic, endemic, iatrogenic and epidemic Kaposi's sarcoma. In non-HIV-associated Kaposi's sarcoma, the disease is typically limited to the lower extremities, but in immunodeficient patients, it is a multifocal systemic disease. The clinical course of the disease differs among patients, ranging from a single or a few indolent lesions to an aggressive diffuse disease. Advanced Kaposi's sarcoma lesions, typically those on the lower extremities, are often associated with lymphedema. In this paper, we report a case of a patient with a rare form of AIDS-associated Kaposi sarcoma called lymphangiectatic Kaposis's sarcoma.O sarcoma de Kaposi é uma neoplasia originária do endotélio linfatico, que apresenta um amplo espectro de manifestações, com quatro formas clínicas: sarcoma de Kaposi clássico, endêmico, iatrogêncio e epidêmico ou associado ao HIV. Em pacientes imunocompetentes, a doença é tipicamente limitada às extremidades. Porém em pacientes imunideprimidos, o sarcoma de Kaposi é uma doença sistêmica multifocal. Apresenta cursos clínicos diferentes, desde simples lesões cutâneas isoladas até lesões agressivas e difusas, com ou sem envolvimento sistêmico. Lesões avançadas de sarcoma de Kaposi, principalmente as localizadas nas extremidades, podem apresentar linfedema. Neste trabalho, reportamos caso de paciente com forma rara de Sarcoma de Kaposi associado a Aids, chamada de sarcoma de Kaposi linfangiectásico.

  15. Acroangiodermatite (pseudo-sarcoma de Kaposi

    Directory of Open Access Journals (Sweden)

    Azulay Rubem David

    2004-01-01

    Full Text Available Acroangiodermatite é enfermidade rara, caracterizada por lesões eritêmato-violáceas bem delimitadas que acometem pernas e pés com aspecto semelhante ao do sarcoma de Kaposi. É relatado o caso de paciente do sexo feminino, de 57 anos, com início súbito de lesões eritêmato-violáceas nas pernas sem outras alterações. O caso acrescenta aprendizado por sua dificuldade diagnóstica e reafirma a importância da imuno-histoquímica. Trata-se da publicação do primeiro caso brasileiro.

  16. Advanced oral HIV-associated Kaposi sarcoma with facial ...

    African Journals Online (AJOL)

    associated Kaposi sarcoma with HAART during the early maculopapular stage of ... then systemic chemotherapy should be added promptly, in order to prevent or delay the development of extensive exophytic oral lesions with facial lymphoedoema.

  17. Kaposi sarcoma appearing 20 year post renal transplant | Yassir ...

    African Journals Online (AJOL)

    A kidney- transplanted Saudi patient presented with a skin rash for which he was treated as fungal infection .The patient developed these lesions 20 years after transplantation. The clinical picture was that of Kaposi\\'s sarcoma which was confirmed by histopathology .The patient developed these lesions after he was shifted ...

  18. [Association of Kaposi sarcoma--multiple myeloma. A new case].

    Science.gov (United States)

    Cohen, J D; Thomas, E; Garnier, N; Hellier, I; Durand, L; Guilhou, J J; Baldet, P; Blotman, F

    2000-11-01

    Kaposi's disease is an angiogenic multifocal cancer process that has several forms, namely Mediterranean, African, HIV-associated, and secondary to a preexisting immunodepressive state (hematological disorder, corticosteroid therapy, immunodepressive treatment). Whatever its form, Kaposi's sarcoma is probably associated with a chronic viral human herpes type 8 infection (HHV8). This virus has been implicated in the pathogenesis of multiple myeloma (17 cases recorded to date). In the present study, a further case of Kaposi's sarcoma associated with multiple myeloma has been reported. However, Epstein-Barr virus, cytomegalovirus, hepatitis B and C, HIV and HHV8 serologies were negative. Radiotherapy on the lower limbs was initiated. It is concluded that HHV8 does not appear to play a pathogenic role in cases of multiple myeloma, given the rarity of the association between Kaposi's sarcoma/multiple myeloma/HHV8.

  19. Sarcoma de Kaposi en paciente con SIDA

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    Jesús Ramón León Polanco

    2015-01-01

    Full Text Available Se presenta el caso de un paciente masculino de 33 años de edad, con antecedentes de VIH-SIDA desde hace 10 años, que se mantiene en tratamiento con antirretrovirales. Durante todo este tiempo ha presentado varios episodios de infecciones respiratorias, incluyendo tuberculosis pulmonar 5 años atrás. Acude a consulta refiriendo edemas en miembros inferiores acompañado de lesiones en piel de color violáceo de un año de evolución, previamente interpretado como linfangitis rebelde al tratamiento y que se extendió a la cara interna de los muslos y a los miembros inferiores. Con pérdida de peso, no prurito en las lesiones, fiebre, lesiones en la mucosa oral. Se determinó hemoglobina 89 g/L, leucocitos 4,5 x 109 /L, se estudiaron las funciones hepática y renales resultando normales. Radiografías de tórax y ultrasonido abdominal normales. Se realizó estudio anatomopatológico de piel que informó Sarcoma de Kaposi. Se impuso tratamiento con quimioterapia

  20. [Oral lesions in Kaposi sarcoma: clinical and radiotherapeutic considerations].

    Science.gov (United States)

    Barberis, M; Brenna Betti, N; Lauritano, D; Sangiani, L; Spadari, F; Villa, S

    1996-01-01

    The epidemic form of Kaposi's sarcoma is the most frequent tumor in sieropositive patients. Every part of the body including oral cavity is affected by these lesions. According to modern acknowledgement in treating oropharynge carcinoma, radiotherapy is used for management of oral Kaposi's sarcoma. This paper reports a study of 10 patients suffering from Kaposi's sarcoma correlated to AIDS (EKS) treated with radiotherapy and chemiotherapy, achieving good results, at the Istituto Nazionale per lo Studio e la Cura dei Tumori of Milan (Divisone di Radioterapia C) from 1988 to 1992. Treatment has been performed using linear accelerator (6 Mev) or Co 60 unity in order to reach the deepest layer of mucosa lesions. Radiotherapy schedule consisted of 150-200 cGy daily fractions given 5 times/week (w) for 4-5 w in split-course.

  1. Hepatic Kaposi sarcoma. Sonographic and computed tomographic aspects

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    Defalque, D.; Menu, Y.; Nahum, H.; Matheron, S.; Girard, P.M.

    1988-10-01

    AIDS-related Kaposi sarcoma is most often multicentric and extensive. Hepatic involvement is unusual and asymptomatic. An anicteric cholestasis may exist. Ultrasonography shows a pedicular echogenic infiltration and a heterogeneous parenchyma with small hyperechoic nodules. On CT, these hypodense lesions are related to the involvement of the hepatic pedicle. This is linked to angiosarcomatous tumorous tissue infiltration of the liver evolving along portal branches. In a patient suffering from cutaneous or digestive Kaposi sarcoma lesions, these radiological aspects are suggestive of hepatic involvement.

  2. Kaposi's sarcoma-associated herpesvirus infection and Kaposi's sarcoma in Brazil

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    S. Ramos-da-Silva

    2006-05-01

    Full Text Available Kaposi's sarcoma (KS became a critical health issue with the emergence of acquired immunodeficiency syndrome (AIDS in the 1980s. Four clinical-epidemiological forms of KS have been described: classical KS, endemic KS, iatrogenic KS, and AIDS-associated KS. In 1994, Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus type 8 was identified by Chang and colleagues, and has been detected worldwide at frequencies ranging from 80 to 100%. The aim of the present study was to evaluate the frequency of KSHV infection in KS lesions from HIV-positive and HIV-negative patients in Brazil, as well as to review the current knowledge about KS transmission and detection. For these purposes, DNA from 51 cases of KS was assessed by PCR: 20 (39.2% cases of classical KS, 29 (56.9% of AIDS-associated KS and 2 (3.9% of iatrogenic KS. Most patients were males (7.5:1, M/F, and mean age was 47.9 years (SD = ± 18.7 years. As expected, HIV-positive KS patients were younger than patients with classical KS. On the other hand, patients with AIDS-associated KS have early lesions (patch and plaque compared to classical KS patients (predominantly nodular lesions. This is assumed to be the result of the early diagnose of KS in the HIV-positive setting. KSHV infection was detected by PCR in almost all cases (48/51; 94.1%, irrespectively of the clinical-epidemiological form of KS. These results show that KSHV is associated with all forms of KS in Brazilian patients, a fact that supports the role of this virus in KS pathogenesis.

  3. Advanced oral HIV-associated Kaposi sarcoma with facial ...

    African Journals Online (AJOL)

    2012-02-14

    Feb 14, 2012 ... S Afr Fam Pract 2012;54(6):545-547. Advanced oral HIV-associated Kaposi sarcoma with facial lymphoedoema as an indicator of poor prognosis. Feller L, DMD, MDent, Head of Department; Essop R, BCom, BChD, Part-Time Lecturer. Department of Periodontology and Oral Medicine, School of Oral Health ...

  4. Kaposi's Sarcoma Of The Lung: A Case Report.

    African Journals Online (AJOL)

    user

    2004-12-02

    Dec 2, 2004 ... Daunorubicin and Doxorubicin and Paclitaxel. (Taxol)14,15,16,17. Combination chemotherapy has been found to have a dramatic clinical and functional improvement than a single agent. It has been found that patients with AIDS- associated pulmonary Kaposi's sarcoma on chemotherapy and Highly Active ...

  5. Kaposi's sarcoma in renal transplant recipients: Experience at ...

    African Journals Online (AJOL)

    Between August 1966 and December 1989, 989 renal transplant recipients were followed up at the Renal Transplant Unit of Johannesburg Hospital. Seventy-five (7%) patients developed a total of 95 malignancies of which 5 (6%) were Kaposi's sarcoma. All patients received immunosuppressive agents; steroids, ...

  6. Case Presentation: Regression of Kaposi's Sarcoma in a Sudanese ...

    African Journals Online (AJOL)

    Introduction: Post-transplant malignancy is an increasing problem among patients receiving solid organ transplant worldwide. It has been related to recipient morbidity and mortality. Kaposi's sarcoma (KS) is a relatively common malignancy after kidney and solid organ transplantation, accounting for the majority of ...

  7. Kaposi's sarcoma of the lung: A case report | Ussiri | East and ...

    African Journals Online (AJOL)

    Pulmonary Kaposi's sarcoma is a rare condition. Its diagnosis may be tricky due to its similarities in clinical and radiological features with pulmonary opportunistic infections as well as other lung lesions. Treatment for Kaposi's sarcoma include radiotherapy, chemotherapy and/or immunotherapy whereby lung Kaposi's ...

  8. Detection Of Human Herpes Virus Type-8 Dna In Kaposi\\'s Sarcoma ...

    African Journals Online (AJOL)

    Background: Since the discovery of Human Herpes viru-8 [HHV-8], many workers try to search its presence in skin lesions of different diseases, and in the peripheral blood of healthy and diseased individuals. Objective: of this work is to study the role of HHV-8 in inducing Kaposi's sarcoma “KS”, in HIV sero-negative patients ...

  9. Isolated Kaposi Sarcoma of the Tonsil: A Case Report and Review of the Scientific Literature

    Science.gov (United States)

    Pittore, Barbara; Pelagatti, Carlo Loris; Deiana, Francesco; Ortu, Francesco; Maricosu, Elena; Cossu, Sergio; Sotgiu, Giovanni

    2015-01-01

    Kaposi sarcoma is a tumour caused by human herpes virus 8, also known as Kaposi sarcoma-associated herpes virus. It usually affects the skin and oral mucosa; however, it can also sometimes affect the lungs, the liver, the stomach, the bowel, and lymph nodes. Several body sites may be affected simultaneously. The involvement of the tonsils is rare. We described an isolated localization of Kaposi's sarcoma of the right tonsil in a HIV-positive patient. PMID:25755902

  10. Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus Latency and Reactivation

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    Fengchun Ye

    2011-01-01

    Full Text Available The life cycle of Kaposi's sarcoma-associated herpesvirus (KSHV consists of latent and lytic replication phases. During latent infection, only a limited number of KSHV genes are expressed. However, this phase of replication is essential for persistent infection, evasion of host immune response, and induction of KSHV-related malignancies. KSHV reactivation from latency produces a wide range of viral products and infectious virions. The resulting de novo infection and viral lytic products modulate diverse cellular pathways and stromal microenvironment, which promote the development of Kaposi's sarcoma (KS. The mechanisms controlling KSHV latency and reactivation are complex, involving both viral and host factors, and are modulated by diverse environmental factors. Here, we review the cellular and molecular basis of KSHV latency and reactivation with a focus on the most recent advancements in the field.

  11. Acroangiodermatitis mimicking Kaposi's sarcoma in an HIV-positive man.

    Science.gov (United States)

    Goorney, B P; Newsham, J; Fitzgerald, D; Motta, L

    2018-01-01

    Kaposi's sarcoma (KS) is the commonest human immunodeficiency virus (HIV)-related malignancy with its characteristic cutaneous morphological appearance and histopathological features. However, it can be simulated by other co-morbid opportunistic infections and unrelated dermatological conditions. We describe such a case of acroangiodermatitis in an HIV co-infected man, based on exclusion of KS histologically and the absence of human herpesvirus 8, the causative agent of KS.

  12. Structural Analysis of Thymidylate Synthase from Kaposi?s Sarcoma-Associated Herpesvirus with the Anticancer Drug Raltitrexed

    OpenAIRE

    Choi, Yong Mi; Yeo, Hyun Ku; Park, Young Woo; Lee, Jae Young

    2016-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a highly infectious human herpesvirus that causes Kaposi's sarcoma. KSHV encodes functional thymidylate synthase, which is a target for anticancer drugs such as raltitrexed or 5-fluorouracil. Thymidylate synthase catalyzes the conversion of 2'-deoxyuridine-5'-monophosphate (dUMP) to thymidine-5'-monophosphate (dTMP) using 5,10-methylenetetrahydrofolate (mTHF) as a co-substrate. The crystal structures of thymidylate synthase from KSHV (apo), co...

  13. Detection of Human Herpes Virus 8 in Kaposi's sarcoma tissues at ...

    African Journals Online (AJOL)

    Introduction: Human herpes virus-8, a γ2-herpes virus, is the aetiological agent of Kaposi sarcoma. Recently, Kaposi's sarcoma cases have increased in Zambia. However, the diagnosis of this disease is based on morphological appearance of affected tissues using histological techniques, and the association with its ...

  14. Imaging of Kaposi sarcoma in a transplanted liver: A rare case report

    Directory of Open Access Journals (Sweden)

    Saumya Gupta

    2015-06-01

    Full Text Available In post-transplant patients, de novo malignancies such as post-transplant lymphoproliferative disease (PTLD, lung carcinoma, renal cell carcinoma, cutaneous malignancies, and Kaposi sarcoma are now seen. The immunotherapy used to prevent graft failure indirectly increases their risk. We present a rare case of visceral Kaposi sarcoma in a patient with orthotopic liver transplant.

  15. Hepatic Kaposi's sarcoma in a patient affected by AIDS

    Directory of Open Access Journals (Sweden)

    Zhibin Lv

    2016-12-01

    Full Text Available Kaposi's sarcoma is a rare malignant tumor characterized by spindle cells and angiomatoid structures. Hepatic KS is rarely reported in living patients, while autopsies show liver involvement in 35% of patients with KS. The characteristic findings on imaging are: 1 multiple nodules located mainly along the periportal area, intrahepatic bile ducts and peripheral branches of the portal vein; 2 delayed contrast enhancement, or sometimes enhanced in the type of hepatic hemangioma; 3 dilated intrahepatic bile ducts; 4 enlarged lymph nodes in the retroperitoneal region; 5 multifocal lesions in various organs. Those findings are considered indicative of hepatic KS.

  16. Isolated Kaposi Sarcoma of the Tonsil: A Case Report and Review of the Scientific Literature

    Directory of Open Access Journals (Sweden)

    Barbara Pittore

    2015-01-01

    Full Text Available Kaposi sarcoma is a tumour caused by human herpes virus 8, also known as Kaposi sarcoma-associated herpes virus. It usually affects the skin and oral mucosa; however, it can also sometimes affect the lungs, the liver, the stomach, the bowel, and lymph nodes. Several body sites may be affected simultaneously. The involvement of the tonsils is rare. We described an isolated localization of Kaposi’s sarcoma of the right tonsil in a HIV-positive patient.

  17. Cutaneous Horn-Related Kaposi's Sarcoma: A Case Report

    Science.gov (United States)

    Onak Kandemir, Nilufer; Gun, Banu Dogan; Barut, Figen; Solak Tekin, Nilgun; Ozdamar, Sukru Oguz

    2010-01-01

    Cutaneous horn is characterized by the accumulation of abnormal keratinized material and may occur in association with a variety of benign, premalignant, and malignant cutaneous lesions. Cutaneous horn occurs very rarely in association with soft-tissue neoplasias. A cutaneous horn located on the toe was completely removed by excision in a 78-year-old male patient. Macroscopic examination revealed a hemorrhagic nodular lesion, 0.5 cm in diameter, located on the dermis underlying the cutaneous horn with a height of 1 cm. Histopathological examination revealed a neoplastic lesion consisting of fusiform cells and extravasated erythrocytes underlying the compact keratin mass. The immunohistochemical analysis showed immunoexpression of endothelial markers and HHV8 in fusiform cells. The case was evaluated as “cutaneous horn developed in a nodular stage Kaposi's sarcoma.” Our case is the second case of cutaneous horn related to Kaposi's sarcoma reported in the English literature and is presented in this case report with its clinical and histopathological features. PMID:20862349

  18. Cutaneous Horn-Related Kaposi's Sarcoma: A Case Report

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    Nilufer Onak Kandemir

    2010-01-01

    Full Text Available Cutaneous horn is characterized by the accumulation of abnormal keratinized material and may occur in association with a variety of benign, premalignant, and malignant cutaneous lesions. Cutaneous horn occurs very rarely in association with soft-tissue neoplasias. A cutaneous horn located on the toe was completely removed by excision in a 78-year-old male patient. Macroscopic examination revealed a hemorrhagic nodular lesion, 0.5 cm in diameter, located on the dermis underlying the cutaneous horn with a height of 1 cm. Histopathological examination revealed a neoplastic lesion consisting of fusiform cells and extravasated erythrocytes underlying the compact keratin mass. The immunohistochemical analysis showed immunoexpression of endothelial markers and HHV8 in fusiform cells. The case was evaluated as “cutaneous horn developed in a nodular stage Kaposi's sarcoma.” Our case is the second case of cutaneous horn related to Kaposi's sarcoma reported in the English literature and is presented in this case report with its clinical and histopathological features.

  19. Morphologic and immunophenotypic evidence of in-situ Kaposi's sarcoma

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    Pantanowitz Liron

    2006-10-01

    Full Text Available Abstract Background The spectrum of Kaposi's sarcoma (KS has been expanded to include pre-KS lesions. Case Presentation We report, for the first time, a case providing direct histological evidence of the development of early (in-situ KS from mediastinal lymphatic vessels in the setting of chronic lymphedema in an HIV-positive patient. Spindle-shaped and endothelial cells in these early KS-appearing lesions were immunoreactive for HHV8, D2-40 and CD34. Conclusion Our findings suggest that HHV8-infected spindle-shaped cells associated with lymphangiogenesis that evolve into KS lesions, acquire from the outset an aberrant mixed vascular and lymphatic endothelial cell phenotype.

  20. Risk of Kaposi's sarcoma-associated herpes virus transmission from donor allografts among Italian posttransplant Kaposi's sarcoma patients.

    Science.gov (United States)

    Parravicini, C; Olsen, S J; Capra, M; Poli, F; Sirchia, G; Gao, S J; Berti, E; Nocera, A; Rossi, E; Bestetti, G; Pizzuto, M; Galli, M; Moroni, M; Moore, P S; Corbellino, M

    1997-10-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a newly discovered herpes virus found in all forms of Kaposi's sarcoma (KS) including KS among immunosuppressed transplant patients. It is unknown whether this virus is transmitted by organ transplantation or is reactivated during immunosuppression among those patients infected before transplantation. To investigate the risk of KSHV transmission during organ transplantation, we conducted a case-control study of transplant recipients with and without KS matched to their respective donors. Sera were collected at time of transplantation and tested in a randomized and blinded fashion using four KSHV serologic assays testing for antibodies to both latent and lytic phase antigens. Ten (91%) of 11 organ recipients who developed KS were seropositive prior to transplantation by one or more of the assays compared with two (12%) of 17 control organ recipients (OR = 75, 95% CI = 4.7, 3500). KS cases were more likely to have been born in southern Italy where KS is endemic than the recipient controls or either donor group. Only four (36%) of 11 donors to case patients and three (18%) of 17 donors to control patients were seropositive (P = .38, two-tailed Fisher's exact test). KSHV transmission could not be ruled out for the single KS patient seronegative at transplantation and clear evidence for organ-related transmission was found for another KS patient outside of the case-control study. Antibodies to KSHV are detectable in the sera from most transplant recipients before initiation of immunosuppressive treatment suggesting that KS among immunosuppressed transplant patients is primarily due to virus reactivation. KSHV transmission, however, from an infected allograft can occur, and our study reports the first documented case of person-to-person transmission of KSHV.

  1. Sarcoma de Kaposi primário do pênis Primary Kaposi's sarcoma of the penis

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    Maira Mitsue Mukai

    2009-10-01

    Full Text Available Sarcoma de Kaposi é um tumor vascular que afeta a parede dos vasos linfáticos. Possui quatro formas: clássica, endêmica, iatrogênica e associada ao HIV. É uma doença sistêmica, maligna, multifatorial e de curso variável. A apresentação inicial no pênis é rara, e mais observada em pacientes HIV positivos. Em pacientes HIV negativos, os casos que ocorrem nesta região, apresentam-se com pápulas, nódulos, placas e lesões verruciformes, assintomáticas. Para o tratamento da forma clássica, dispõem-se de excisão cirúrgica, crioterapia, eletrocirurgia, laser e radioterapia. Neste trabalho, é relatado um caso raro de um paciente com a forma clássica, em região peniana tratado com sucesso com radioterapia.Kaposi's sarcoma is a vascular tumor involving the wall of lymphatic vessels. There are four types: classic, endemic, iatrogenic and HIV-associated. It is a systemic, malignant and multifactorial disease and has a variable course. The primary presentation on the penis is uncommon and is mainly observed in HIV-positive patients. In HIV-negative individuals, asymptomatic papules, nodules, plaques and verrucous lesions are found. The treatment for the classic form involves surgery, cryotherapy, electrosurgery, laser and radiation therapy. The authors present a rare case of a patient with the classic form on the penis, who was successfully treated by radiation therapy.

  2. Molecularly targeted therapy for Kaposi's sarcoma in a kidney transplant patient: case report, "what worked and what did not"

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    Correa-Rotter Ricardo

    2007-03-01

    Full Text Available Abstract Background Imatinib is a tyrosine-kinase inhibitor; for which there is limited information regarding its effects on AIDS Kaposi's sarcoma and none in patients with transplant-associated Kaposi's sarcoma. Sirolimus, an immunosuppressive drug used for kidney transplant, exhibits antiangiogenic activity related to impaired production of VEGF (vascular endothelial growth factor, clinical benefit has been reported in Kaposi's sarcoma associated with renal graft. Case Presentation Here we report a case of an 80 year old male, who developed Kaposi's Sarcoma nine months after receiving a living non-related donor kidney transplant at age 74. Three years after treatment with different chemotherapeutic agents for progressive cutaneous Kaposi's Sarcoma with no visceral involvement, he was prescribed Imatinib (200 mg/day for two weeks followed by 400 mg/day after four weeks of treatment he developed anasarca, further progression of KS and agranulocytosis. Imatinib was discontinued and there was significant clinical recovery. One year later his immunosuppressive therapy was changed to Sirolimus and regression of the Kaposi's sarcoma occurred. Conclusion The lack of benefit and severe toxicity associated with the use of Imatinib in this patient should alert clinicians of potentially adverse consequence of its use in patients with transplant associated Kaposi's sarcoma. On the other hand the positive response seen in this patient to Sirolimus even after a long evolution of Kaposi's sarcoma, multiple chemotherapy regimens and extensive cutaneous disease further suggest it therapeutical utility for transplant associated Kaposi's sarcoma.

  3. Sarcoma de kaposi endemico en un paciente VIH negativo

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    José Revilla-López

    Full Text Available El sarcoma de Kaposi (SK es un cáncer angioproliferativo inflamatorio multifocal asociado a herpes virus 8 (VHH-8. Se han descrito cuatro variantes clínico-epidemiológicas: clásico, endémico, iatrogénico y epidémico o asociado a VIH. Clínicamente puede ser indolente o agresivo, afecta principalmente áreas mucocutáneas con eventual compromiso visceral y de ganglios linfáticos. Se presenta frecuentemente y de forma más agresiva en la población VIH positiva. Presentamos un caso de un paciente varón de 27 años VIH negativo con lesión tumoral sangrante en el anillo de Waldeyer, múltiples adenopatías y lesiones exofíticas en pie que remiten con quimioterapia de emergencia basada en antraciclinas. El SK VIH negativo es una condición poco frecuente. Es importante tener en cuenta al Perú como región endémica para el VHH-8. La afectación oral del SK es una manifestación rara y de mal pronóstico, sin embargo, el factor VIH negativo podría conferirle un buen pronóstico

  4. Interleukin-6 concentrations in the serum of patients with AIDS-associated Kaposi's sarcoma during treatment with interferon-alpha

    NARCIS (Netherlands)

    de Wit, R.; Raasveld, M. H.; ten Berge, R. J.; van der Wouw, P. A.; Bakker, P. J.; Veenhof, C. H.

    1991-01-01

    Interleukin-6 (IL-6) levels were determined in the serum of 14 HIV-1-infected patients with Kaposi's sarcoma, 10 HIV-1-infected patients without symptoms, and 10 healthy male subjects. IL-6 levels were also determined in the serum of the 14 patients with Kaposi's sarcoma during treatment with

  5. Beral et al's 1990 paper on Kaposi's sarcoma among persons with AIDS: demonstrating the power of descriptive epidemiology.

    Science.gov (United States)

    Newton, Robert; Whitby, Denise

    2016-10-01

    Here we discuss the impact of Beral et al's 1990 paper "Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection?" Not only did this paper galvanise research into the underlying infectious cause of Kaposi's sarcoma, it also demonstrated the power of observational epidemiology in pointing the way towards major discoveries. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Complete histological regression of Kaposi's sarcoma following treatment with protease inhibitors despite persistence of HHV-8 in lesions

    DEFF Research Database (Denmark)

    Benfield, T L; Kirk, O; Elbrønd, B

    1998-01-01

    There is no current curative treatment for HIV-related Kaposi's sarcoma. The identification of human herpesvirus-8 as a possible aetiological agent suggests potential efficacy of anti-viral agents. We report here on the complete histological remission of Kaposi's sarcoma following treatment...... with protease inhibitors, even in patients with limited virological response and persistence of HHV-8....

  7. The prevalence of human herpesvirus 8 genotypes in Kaposi\\\\\\'s sarcoma in Iran by using molecular technique

    Directory of Open Access Journals (Sweden)

    Reza Shah Siah

    2013-10-01

    Full Text Available Background: In the Mediterranean region , Kaposi's sarcoma (KS has a high prevalence especially in patients with AIDS. Iran is located close to the Mediterranean region and the HIV prevalence is increasing in our country . In some stages, Kaposi's sarcoma is morphologically similar to other vascular tumors. Owing to the presence of human herpesvirus 8 (HHV-8 in all cases of Kaposi's sarcoma , detection of virus DNA by PCR method can help in the identification of non-diagnostic cases. Moreover, the prevalence of HHV-8 genotypes is different in various regions of the world and in different races. There are limited studies performed on the HHV-8 genotypes in Iranian population. Methods: Patients with Kaposi's sarcoma from 2001 to 2011 who refer to Tehran Razi Hospital were enrolled in this study. HHV-8 DNA was extracted from paraffin blocks and amplification of the virus genome was performed by PCR method . Finally, the target DNA fragment was used for sequencing and genotype determination. Results: PCR was performed on 53 cases. In 8 cases with suspicious morphology, PCR was negative and they were excluded from study. Of remaining 45 cases, 35 had positive PCR results, 7 had negative results and 3 had low PCR product. Samples from 28 cases that had positive PCR results, which were acceptable for genotyping, were chosen for sequencing. Twenty cases had genotype C, 7 cases had genotype A and one case was negative. The results are consistent with other studies in our geographical area. No correlation was found between the different microscopic stages and HHV-8 Genotypes. Conclusion: Since the HHV-8 is obtained in almost 100% of KS lesions and PCR s ensitivity in detection of the virus is close to 100 %, KS diagnosis can be confirmed in suspicious cases by detection of HHV-8 DNA on paraffin blocks. Moreover the prevalence of HHV-8 genotype was determined in Iran.

  8. Kaposi Sarcoma of the Adrenal Gland Resembling Epithelioid Angiosarcoma: A Case Report

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    Hassan Huwait

    2011-01-01

    Full Text Available Patients with human immunodeficiency virus infection are known to have increased risk of various neoplasms, including Kaposi sarcoma, which classically involves the skin and mucosal locations. The anaplastic variant of Kaposi sarcoma is rare and poorly documented in the literature. It is characterised clinically by a more aggressive behaviour and increased metastatic potential, and histologically by increased cellularity, mitotic rate, and rarely by epithelioid angiosarcoma-like morphology. We report herein a 64-year-old man with a long-standing history of human immunodeficiency virus infection who developed a right adrenal tumor with a high-grade anaplastic angiosarcoma-like morphology. Immunohistochemistry for human herpes virus-8 was strongly positive in the tumor cells. To the best of our knowledge, this is the first report of an anaplastic Kaposi sarcoma in the adrenal gland.

  9. The T-Cell Immune Response against Kaposi's Sarcoma-Associated Herpesvirus.

    Science.gov (United States)

    Robey, Rebecca C; Mletzko, Salvinia; Gotch, Frances M

    2010-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the aetiological agent of Kaposi's sarcoma (KS), the most frequently arising malignancy in individuals with untreated HIV/AIDS. There are several lines of evidence to indicate that Kaposi's sarcoma oncogenesis is associated with loss of T-cell-mediated control of KSHV-infected cells. KSHV can establish life-long asymptomatic infection in immune-competent individuals. However, when T-cell immune control declines, for example, through AIDS or treatment with immunosuppressive drugs, both the prevalence of KSHV infection and the incidence of KS in KSHV carriers dramatically increase. Moreover, a dramatic and spontaneous improvement in KS is frequently seen when immunity is restored, for example, through antiretroviral therapy or the cessation of iatrogenic drugs. In this paper we describe the current state of knowledge on the T-cell immune responses against KSHV.

  10. The T-Cell Immune Response against Kaposi's Sarcoma-Associated Herpesvirus

    Directory of Open Access Journals (Sweden)

    Rebecca C. Robey

    2010-01-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is the aetiological agent of Kaposi's sarcoma (KS, the most frequently arising malignancy in individuals with untreated HIV/AIDS. There are several lines of evidence to indicate that Kaposi's sarcoma oncogenesis is associated with loss of T-cell-mediated control of KSHV-infected cells. KSHV can establish life-long asymptomatic infection in immune-competent individuals. However, when T-cell immune control declines, for example, through AIDS or treatment with immunosuppressive drugs, both the prevalence of KSHV infection and the incidence of KS in KSHV carriers dramatically increase. Moreover, a dramatic and spontaneous improvement in KS is frequently seen when immunity is restored, for example, through antiretroviral therapy or the cessation of iatrogenic drugs. In this paper we describe the current state of knowledge on the T-cell immune responses against KSHV.

  11. Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis.

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    Sonja Koopal

    2007-09-01

    Full Text Available Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus (KSHV-infected tumor cells that express endothelial cell (EC markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs. We show that v-cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in ECs, which leads to senescence and activation of the DNA damage response. We find that antiproliferative checkpoints are activated upon KSHV infection of ECs, and in early-stage but not late-stage lesions of clinical Kaposi sarcoma specimens. These are some of the first results suggesting that DNA damage checkpoint response also functions as an anticancer barrier in virally induced cancers.

  12. De novo anaplastic Kaposi sarcoma in a HIV-negative man: A case report and review of the literature

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    Slim Charfi

    2017-07-01

    Full Text Available Anaplastic Kaposi sarcoma is a rare variant of Kaposi’s and is typically associated with an agressive clinical course. We report a case of a 67-year-old HIV negative man, presented with multiple, pink nodules on the left ankle and a keratotic lesion of the right heel. Initial histopathological exam concluded to an undifferentiated sarcoma. A second biopsy was performed and concluded to an anaplastic Kaposi sarcoma. Immunohistochemical study was positive for HHV8. Treatment consisted on a tumor excision of all lesions. Our case and the review of the literature highlight the benefit of the non conservative surgical treatment for this aggressive form of Kaposi sarcoma.

  13. Latent BK virus infection and Kaposi's sarcoma pathogenesis.

    Science.gov (United States)

    Monini, P; Rotola, A; de Lellis, L; Corallini, A; Secchiero, P; Albini, A; Benelli, R; Parravicini, C; Barbanti-Brodano, G; Cassai, E

    1996-06-11

    We have analyzed by PCR skin lesions from classic, endemic and AIDS-related Kaposi's sarcoma (KS), as well as from KS-derived cell lines, the presence of ubiquitous transforming viruses. BK virus (BKV), a transforming human papovavirus which has been associated with human tumors, was detected in 100% of KS skin lesions and 75% of KS cell lines. KS specimens contained a full-length, intact BKV early region, but minor rearrangements were observed in some tumors. BKV was also detected with a high prevalence (57-67%) in genital tissues and sperm, thus fulfilling the role of a sexually transmitted agent in KS. The closely related JC virus (JCV), which has never been associated with human malignancies, was present in 11-20% of KS specimens and was detected with a low prevalence (0-21%) in genital tissues and sperm. Simian virus 40 (SV40) was not detected in any KS lesions. Herpes simplex virus (HSV) DNA sequences were detected in 20-25% of KS lesions. Malignant human papillomavirus (HPV) types 16 and 18 and benign HPV types 6 and 11 were detected in KS specimens with a similar prevalence of 11-83%, suggesting that the presence of HPV-transforming sequences is not a specific trait of HPV interaction with KS tissue. Furthermore, JCV, SV40, HSV and HPV DNA sequences were not detected in KS cell lines, suggesting that these viruses are not associated to KS neoplastic cells in KS tissue. KS cell lines were also negative for DNA sequences of KS-HV, the novel herpesvirus detected in primary KS lesions. The constant association of BKV DNA with KS lesions and KS cell lines suggests that BKV-transforming functions may participate in the development of KS.

  14. Fatal Disseminated Kaposi's Sarcoma due to Immune Reconstitution Inflammatory Syndrome following HAART Initiation

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    Fatuma Catherine Atieno Odongo

    2013-01-01

    Full Text Available This is a case report of disseminated Kaposi's sarcoma in the context of immune reconstitution inflammatory syndrome in an HIV-infected patient on HAART regimen for 2 months. The patient rapidly progressed to death in 5 days after worsening pulmonary infiltrates and multiple organ failure.

  15. A patient with classical Kaposi's sarcoma and angiosarcoma: bad luck or a common aetiology?

    Science.gov (United States)

    Steiner, M C; Smith, M E; Spittle, M F

    1997-01-01

    Classical Kaposi's sarcoma and angiosarcoma are rare malignant tumours arising from vascular tissue. However, they have distinct histological features and appear also to differ in their epidemiology and pathogenesis. We present the case history of a patient in whom both these tumours occurred simultaneously. The relationship between these events is discussed in the light of the new virus, human herpes virus 8.

  16. Gene expression profile of AIDS-related Kaposi's sarcoma

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    van Noesel Carel JM

    2003-03-01

    Full Text Available Abstract Background Kaposi's Sarcoma (KS is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV. Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome. Methods In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE. Semi-quantitative RT-PCR was then used to validate the results. Results The expression profile of AIDS-related KS (AIDS-KS reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages. Conclusion The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169. Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages.

  17. Clinical and laboratory characteristics, staging, and outcomes of individuals with AIDS-associated Kaposi's sarcoma at an university hospital

    OpenAIRE

    de Lima, Catarina Ten?rio; de Ara?jo, Paulo S?rgio Ramos; TEIXEIRA,Heberton Medeiros; dos Santos, Josemir Belo; da Silveira, Vera Magalh?es

    2017-01-01

    Abstract: Background: Kaposi's sarcoma continues to be the most common human immunodeficiency virus - associated neoplasm with considerable morbidity and mortality. Objective: To describe the clinical and laboratory characteristics, initial staging, and outcomes of aids patients with Kaposi's sarcoma at an university hospital of Recife, Pernambuco. Methods: This is a descriptive study with analytic character, retrospective, of a case series between 2004 and 2014. Results: Of the 22 patien...

  18. Adult soft tissue sarcoma

    Science.gov (United States)

    STS; Leiomyosarcoma; Hemangiosarcoma; Kaposi's sarcoma; Lymphangiosarcoma; Synovial sarcoma; Neurofibrosarcoma; Liposarcoma; Fibrosarcoma; Malignant fibrous histiocytoma; Dermatofibrosarcoma; Angiosarcoma

  19. Pre-micro RNA signatures delineate stages of endothelial cell transformation in Kaposi sarcoma.

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    Andrea J O'Hara

    2009-04-01

    Full Text Available MicroRNAs (miRNA have emerged as key regulators of cell lineage differentiation and cancer. We used precursor miRNA profiling by a novel real-time QPCR method (i to define progressive stages of endothelial cell transformation cumulating in Kaposi sarcoma (KS and (ii to identify specific miRNAs that serve as biomarkers for tumor progression. We were able to compare primary patient biopsies to well-established culture and mouse tumor models. Loss of mir-221 and gain of mir-15 expression demarked the transition from merely immortalized to fully tumorigenic endothelial cells. Mir-140 and Kaposi sarcoma-associated herpesvirus viral miRNAs increased linearly with the degree of transformation. Mir-24 emerged as a biomarker specific for KS.

  20. Kaposi's Sarcoma-Associated Herpesvirus-Related Solid Lymphoma Involving the Heart and Brain

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    Jason R. Andrews

    2011-01-01

    Full Text Available Since its discovery in 1994, Kaposi's sarcoma-associated herpesvirus (KSHV has been associated with lymphoproliferative disorders, particularly in patients infected with human immunodeficiency virus (HIV. The disorders most strongly linked to KSHV are multicentric Castleman's Disease (MCD, primary effusion lymphoma, and diffuse large B-cell lymphomas. We report an unusual case of KSHV-associated lymphoma in an HIV-infected patient manifesting with myocardial and central nervous system involvement. We discuss this case in the context of increasing array of KSHV-associated lymphomas. In the HIV-infected patient with a mass lesion, a history of cutaneous Kaposi's sarcoma and prolonged immunosuppression should alert clinicians as to the possibility of KSHV-associated lymphoproliferative disorders, in order to establish a timely diagnosis.

  1. Children with Kaposi Sarcoma in Two Southern African Hospitals: Clinical Presentation, Management, and Outcome

    OpenAIRE

    de Bruin, G.P.; Stefan, D. C.

    2013-01-01

    Introduction. In 2010 more than 3 million children with human immunodeficiency virus (HIV) were living in Sub-Saharan Africa. The AIDS epidemic has contributed to an abrupt increase of the frequency of Kaposi sarcoma (KS), especially in Southern Africa. There is a need to describe the clinical features of this disease, its management, and its outcome in HIV positive children in Southern Africa. The aim of the study is to describe two different populations with HIV and KS from two African hosp...

  2. Photodynamic therapy for treatment of AIDS-related mucocutaneous Kaposi's sarcoma (Invited Paper)

    Science.gov (United States)

    Schweitzer, Vanessa G.

    1992-06-01

    Since 1975, Phase I/II studies have demonstrated the successfulness of hematoporphyrin derivative photodynamic therapy (PDT) in the treatment of various malignancies of the skin, eye, bladder, lung, and head and neck. Moreover, in 1981 two cases of traditional Western cutaneous Kaposi's sarcoma (TKS) have been treated with photodynamic therapy with both early and late complete response. To date, attempts to cure and palliation of the more aggressive AIDS-related oral Kaposi's sarcoma with conventional radiation, chemotherapy or immunotherapy, or surgical excision have been limited and often associated with debilitating mucositis and further immunosuppression. Certain aspects of photodynamic therapy may be efficacious for treatment of mucocutaneous Kaposi's sarcoma: (1) the selective retention of hematoporphyrin derivative by neoplastic lesions (endothelial cell tumors); (2) a tumor- specific cytotoxic agent (i.e., free oxygen radical); (3) absence of systemic toxicity from immunosuppression; (4) the potential for retreatment without increasing side effects; and (5) porphyrin-mediated photoinactivation of enveloped viruses. Herein presented are seven cases of AIDS-related KS (EKS) with diffuse, superficial, and nodular mucocutaneous lesions treated with dihematoporphyrin derivative and photodynamic therapy with subsequent dramatic early partial and complete responses.

  3. Detection of Human Herpes Virus 8 in Kaposi's sarcoma tissues at the University Teaching Hospital, Lusaka, Zambia.

    Science.gov (United States)

    Tembo, Rabecca; Kaile, Trevor; Kafita, Doris; Chisanga, Chrispin; Kalonda, Annie; Zulu, Ephraim; Samutela, Mulemba; Polepole, Pascal; Kwenda, Geoffrey

    2017-01-01

    Human herpes virus-8, a γ2-herpes virus, is the aetiological agent of Kaposi sarcoma. Recently, Kaposi's sarcoma cases have increased in Zambia. However, the diagnosis of this disease is based on morphological appearance of affected tissues using histological techniques, and the association with its causative agent, Human Herpes virus 8 is not sought. This means poor prognosis for affected patients since the causative agent is not targeted during diagnosis and KS lesions may be mistaken for other reactive and neoplastic vascular proliferations when only histological techniques are used. Therefore, this study was aimed at providing evidence of Human Herpes virus 8 infection in Kaposi's sarcoma tissues at the University Teaching Hospital in Lusaka, Zambia. One hundred and twenty suspected Kaposi's sarcoma archival formalin-fixed paraffin-wax embedded tissues stored from January 2013 to December 2014 in the Histopathology Laboratory at the University Teaching Hospital, Lusaka, Zambia were analysed using histology and Polymerase Chain Reaction targeting the ORF26 gene of Human Herpes virus 8. The predominant histological type of Kaposi's sarcoma detected was the Nodular type (60.7%) followed by the plaque type (22.6%) and patch type (16.7%). The nodular lesion was identified mostly in males (40.5%, 34/84) than females (20.2%, 17/84) (p=0.041). Human Herpes virus 8 DNA was detected in 53.6% (45/84) and mostly in the nodular KS lesions (60%, 27/84) (p=0.035). The findings in this study show that the Human Herpes virus-8 is detectable in Kaposi's sarcoma tissues, and, as previously reported in other settings, is closely associated with Kaposi's sarcoma. The study has provided important baseline data for use in the diagnosis of this disease and the identification of the virus in the tissues will aid in targeted therapy.

  4. Clinical Features, Presence of Human Herpesvirus-8 and Treatment Results in Classic Kaposi Sarcoma

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    Özlem Su

    2008-12-01

    Full Text Available Background and Design: Classic Kaposi sarcoma (KS occurs predominantly among the elderly, with Jews, Italians and Greeks. Classic KS has been seen relatively frequently in Turkey. Our aim was to evaluate the demographic, clinical features of Kaposi sarcoma and etiopathological role of human herpesvirus-8 (HHV-8. Treatment results of 18 classic Kaposi’s sarcoma were also concluded.Material and Method: Eighteen cases of classic Kaposi sarcoma diagnosed as clinically and histopathologically between January 2001 and August 2008 in our dermatology department were taken to this study. Demographic, clinical features and treatment results were reviewed retrospectively in all patients. HHV-8 was investigated in the lesional skin of 7 patients.Results: A male/female ratio of 2/1 was found. Mean age at diagnosis was 67.2 (37-94 years. Bilaterally lower extremities were involved in 15 patients (83.3%, the trunk was involved in 3 patients (16.6%. Plaques and nodules were the common type of lesions (66.6% and 55.5%. Nine patients had no symptoms (50%. Edema was the most common symptom (38.8%. A second primary malignancy was found in 2 patients (11.1%. HHV-8 was detected in 6 of the 7 patients(85.7%. Majority of the patients were treated with interferon alfa (subcutaneously and cryotherapy as a monotherapy or a combination therapy. Imiquimod was the second agent in combined treatment (27.7%. Conclusion: We suggest that interferon alfa and imiquimod can be used as first line therapy agents with their antiviral and immunmodulatuar features in the treatment of KKS. (Turkderm 2008; 42: 122-6

  5. PAN's Labyrinth: Molecular biology of Kaposi's sarcoma-associated herpesvirus (KSHV) PAN RNA, a multifunctional long noncoding RNA.

    Science.gov (United States)

    Rossetto, Cyprian C; Pari, Gregory S

    2014-11-04

    Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesivrus, the causative agent of Kaposi's sarcoma and body cavity lymphomas. During infection KSHV produces a highly abundant long non-coding polyadenylated RNA that is retained in the nucleus known as PAN RNA. Long noncoding RNAs (lncRNA) are key regulators of gene expression and are known to interact with specific chromatin modification complexes, working in cis and trans to regulate gene expression. Data strongly supports a model where PAN RNA is a multifunctional regulatory transcript that controls KSHV gene expression by mediating the modification of chromatin by targeting the KSHV repressed genome.

  6. Kaposi'S sarcoma of the stomach and duodenum in human immunodeficiency virus infection.

    Science.gov (United States)

    Kibria, Rizwan; Siraj, Urmee; Barde, Christopher

    2010-07-01

    Kaposi's sarcoma (KS) of the upper gastrointestinal tract without extensive cutaneous disease is uncommon and usually asymptomatic. Herein, the case of a 37-year-old man who presented with iron deficiency anemia is reported. A colonoscopy was unremarkable and upper endoscopy revealed multiple raised, hemorrhagic, plaque-like lesions throughout the stomach and the small intestine. Histopathology confirmed KS; further testing revealed the patient to be HIV-positive and a diagnosis of AIDS-related KS was made. Although a rare entity, physicians should be aware of this condition in order to facilitate a prompt diagnosis and necessary intervention.

  7. The assembly domain of the small capsid protein of Kaposi's sarcoma-associated herpesvirus.

    Science.gov (United States)

    Kreitler, Dale; Capuano, Christopher M; Henson, Brandon W; Pryce, Erin N; Anacker, Daniel; McCaffery, J Michael; Desai, Prashant J

    2012-11-01

    Self-assembly of Kaposi's sarcoma-associated herpesvirus capsids occurs when six proteins are coexpressed in insect cells using recombinant baculoviruses; however, if the small capsid protein (SCP) is omitted from the coinfection, assembly does not occur. Herein we delineate and identify precisely the assembly domain and the residues of SCP required for assembly. Hence, six residues, R14, D18, V25, R46, G66, and R70 in the assembly domain, when changed to alanine, completely abolish or reduce capsid assembly.

  8. Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma

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    Érico Arruda

    Full Text Available Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50% in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

  9. Kaposi's sarcoma associated herpesvirus (KSHV entry into target cells

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    Sayan eChakraborty

    2012-01-01

    Full Text Available Herpesvirus infection of target cells is a complex process involving multiple host cell surface molecules (receptors and multiple viral envelope glycoproteins. Kaposi’s sarcoma associated herpesvirus (KSHV or HHV-8 infects a variety of in vivo target cells such as endothelial cells, B cells, monocytes, epithelial cells, and keratinocytes. KSHV also infects a diversity of in vitro target cells and establishes in vitro latency in many of these cell types. KSHV interactions with the host cell surface molecules and its mode of entry in the various target cells are critical for the understanding of KSHV pathogenesis. KSHV is the first herpesvirus shown to interact with adherent target cell integrins and this interaction initiates the host cell pre-existing signal pathways that are utilized for successful infection. This chapter discusses the various aspects of the early stage of KSHV infection of target cells, receptors used and issues that need to be clarified and future directions. The various signaling events triggered by KSHV infection and the potential role of signaling events in the different stages of infection are summarized providing the framework and starting point for further detailed studies essential to fully comprehend the pathogenesis of KSHV.

  10. Structural Analysis of Thymidylate Synthase from Kaposi's Sarcoma-Associated Herpesvirus with the Anticancer Drug Raltitrexed.

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    Yong Mi Choi

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is a highly infectious human herpesvirus that causes Kaposi's sarcoma. KSHV encodes functional thymidylate synthase, which is a target for anticancer drugs such as raltitrexed or 5-fluorouracil. Thymidylate synthase catalyzes the conversion of 2'-deoxyuridine-5'-monophosphate (dUMP to thymidine-5'-monophosphate (dTMP using 5,10-methylenetetrahydrofolate (mTHF as a co-substrate. The crystal structures of thymidylate synthase from KSHV (apo, complexes with dUMP (binary, and complexes with both dUMP and raltitrexed (ternary were determined at 1.7 Å, 2.0 Å, and 2.4 Å, respectively. While the ternary complex structures of human thymidylate synthase and E. coli thymidylate synthase had a closed conformation, the ternary complex structure of KSHV thymidylate synthase was observed in an open conformation, similar to that of rat thymidylate synthase. The complex structures of KSHV thymidylate synthase did not have a covalent bond between the sulfhydryl group of Cys219 and C6 atom of dUMP, unlike the human thymidylate synthase. The catalytic Cys residue demonstrated a dual conformation in the apo structure, and its sulfhydryl group was oriented toward the C6 atom of dUMP with no covalent bond upon ligand binding in the complex structures. These structural data provide the potential use of antifolates such as raltitrexed as a viral induced anticancer drug and structural basis to design drugs for targeting the thymidylate synthase of KSHV.

  11. Structural Analysis of Thymidylate Synthase from Kaposi's Sarcoma-Associated Herpesvirus with the Anticancer Drug Raltitrexed.

    Science.gov (United States)

    Choi, Yong Mi; Yeo, Hyun Ku; Park, Young Woo; Lee, Jae Young

    2016-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a highly infectious human herpesvirus that causes Kaposi's sarcoma. KSHV encodes functional thymidylate synthase, which is a target for anticancer drugs such as raltitrexed or 5-fluorouracil. Thymidylate synthase catalyzes the conversion of 2'-deoxyuridine-5'-monophosphate (dUMP) to thymidine-5'-monophosphate (dTMP) using 5,10-methylenetetrahydrofolate (mTHF) as a co-substrate. The crystal structures of thymidylate synthase from KSHV (apo), complexes with dUMP (binary), and complexes with both dUMP and raltitrexed (ternary) were determined at 1.7 Å, 2.0 Å, and 2.4 Å, respectively. While the ternary complex structures of human thymidylate synthase and E. coli thymidylate synthase had a closed conformation, the ternary complex structure of KSHV thymidylate synthase was observed in an open conformation, similar to that of rat thymidylate synthase. The complex structures of KSHV thymidylate synthase did not have a covalent bond between the sulfhydryl group of Cys219 and C6 atom of dUMP, unlike the human thymidylate synthase. The catalytic Cys residue demonstrated a dual conformation in the apo structure, and its sulfhydryl group was oriented toward the C6 atom of dUMP with no covalent bond upon ligand binding in the complex structures. These structural data provide the potential use of antifolates such as raltitrexed as a viral induced anticancer drug and structural basis to design drugs for targeting the thymidylate synthase of KSHV.

  12. Detection of Kaposi's sarcoma associated herpesvirus nucleic acids using a smartphone accessory.

    Science.gov (United States)

    Mancuso, Matthew; Cesarman, Ethel; Erickson, David

    2014-10-07

    Kaposi's sarcoma (KS) is an infectious cancer occurring in immune-compromised patients, caused by Kaposi's sarcoma associated herpesvirus (KSHV). Our vision is to simplify the process of KS diagnosis through the creation of a smartphone based point-of-care system capable of yielding an actionable diagnostic readout starting from a raw biopsy sample. In this work we develop the sensing mechanism for the overall system, a smartphone accessory capable of detecting KSHV nucleic acids. The accessory reads out microfluidic chips filled with a colorimetric nanoparticle assay targeted at KSHV. We calculate that our final device can read out gold nanoparticle solutions with an accuracy of 0.05 OD, and we demonstrate that it can detect DNA sequences from KSHV down to 1 nM. We believe that through integration with our previously developed components, a smartphone based system like the one studied here can provide accurate detection information, as well as a simple platform for field based clinical diagnosis and research.

  13. Kaposi's sarcoma-associated herpesvirus ORF6 gene is essential in viral lytic replication.

    Directory of Open Access Journals (Sweden)

    Can Peng

    Full Text Available Kaposi's sarcoma associated herpesvirus (KSHV is associated with Kaposis's sarcoma (KS, primary effusion lymphoma and multicentric Castleman's disease. KSHV encodes at least 8 open reading frames (ORFs that play important roles in its lytic DNA replication. Among which, ORF6 of KSHV encodes an ssDNA binding protein that has been proved to participate in origin-dependent DNA replication in transient assays. To define further the function of ORF6 in the virus life cycle, we constructed a recombinant virus genome with a large deletion within the ORF6 locus by using a bacterial artificial chromosome (BAC system. Stable 293T cells carrying the BAC36 (wild type and BACΔ6 genomes were generated. When monolayers of 293T-BAC36 and 293T-BACΔ6 cells were induced with 12-O-tetradecanoylphorbol-13-acetate (TPA and sodium butyrate, infectious virus was detected from the 293T-BAC36 cell supernatants only and not from the 293T- BACΔ6 cell supernatants. DNA synthesis was defective in 293T-BACΔ6 cells. Expression of ORF6 in trans in BACΔ6-containing cells was able to rescue both defects. Our results provide genetic evidence that ORF6 is essential for KSHV lytic replication. The stable 293T cells carrying the BAC36 and BACΔ6 genomes could be used as tools to investigate the detailed functions of ORF6 in the lytic replication of KSHV.

  14. Seroprevalence of Kaposi's sarcoma-associated herpesvirus infection among blood donors from Texas.

    Science.gov (United States)

    Baillargeon, J; Deng, J H; Hettler, E; Harrison, C; Grady, J J; Korte, L G; Alexander, J; Montalvo, E; Jenson, H B; Gao, S J

    2001-10-01

    Kaposi's sarcoma-associated herpesvirus (KSHV), a gammaherpesvirus recently discovered among AIDS patients with Kaposi's sarcoma, is a potential candidate for screening in blood and plasma donors. While a number of studies have assessed KSHV infection among U.S. blood donors, larger-scale population-based studies would be necessary to develop more refined estimates of the magnitude and variation of KSHV infection across different geographic regions of the U.S. blood supply. The goal of the present study, therefore, was to determine the seroprevalence of KSHV infection and to assess demographic correlates of KSHV infection among south Texas blood donors. KSHV infection was determined using specific serologic assays that measure antibodies to KSHV latent and lytic antigens. The overall seroprevalence of KSHV in Texas blood donors (15.0%) is substantially higher than previously reported among blood donor and general population samples in the United States. This high rate of KSHV infection persisted across most of the sociodemographic subgroups under study but was particularly elevated among participants with less than a high school education. The infection rate also increased linearly with age. The elevated infection rate reported in the present study suggests that screening methods to detect KSHV infection in blood donors should be considered. In view of the etiologic role of KSHV for several malignancies, it would be important for future studies to directly assess the risk of KSHV transmission via blood transfusion.

  15. KSHV/HHV-8 and HIV infection in Kaposi's sarcoma development

    Directory of Open Access Journals (Sweden)

    Kaaya Ephata

    2007-02-01

    Full Text Available Abstract Kaposi's sarcoma (KS is a highly and abnormally vascularized tumor-like lesion affecting the skin, lymphnodes and viscera, which develops from early inflammatory stages of patch/plaque to late, nodular tumors composed predominant of spindle cells (SC. These SC are infected with the Kaposi's sarcoma-associated herpesvirus or human herpesvirus-8 (KSHV/HHV-8. KS is promoted during HIV infection by various angiogenic and pro-inflammatory factors including HIV-Tat. The latency associated nuclear antigen type 1 (LANA-1 protein is well expressed in SC, highly immunogenic and considered important in the generation and maintenance of HHV-8 associated malignancies. Various studies favour an endothelial origin of the KS SC, expressing "mixed" lymphatic and vascular endothelial cell markers, possibly representing hybrid phenotypes of endothelial cells (EC. A significant number of SC during KS development are apparently not HHV8 infected, which heterogeneity in viral permissiveness may indicate that non-infected SC may continuously be recruited in to the lesion from progenitor cells and locally triggered to develop permissiveness to HHV8 infection. In the present study various aspects of KS pathogenesis are discussed, focusing on the histopathological as well as cytogenetic and molecular genetic changes in KS.

  16. Viral Interleukin-6: Role in Kaposi's Sarcoma-Associated Herpesvirus–Associated Malignancies

    Science.gov (United States)

    Sakakibara, Shuhei

    2011-01-01

    Viral interleukin-6 (vIL-6) is a product of Kaposi's sarcoma-associated herpesvirus (KSHV) expressed in latently infected cells and to a higher degree during viral replication. A distinctive feature of vIL-6 is the ability to directly bind and activate gp130 signaling in the absence of other receptor subunits. Secretion of vIL-6 is generally poor, but vIL-6 can activate gp130 from inside the cell. Due to the wide cell distribution of gp130, vIL-6 has the potential to induce a wide range of biological effects. Expression of vIL-6 is variable in KSHV-associated Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD), and in a newly described MCD-like systemic inflammatory syndrome observed in human immunodeficiency virus-positive patients. PEL effusions usually contain vIL-6 at high concentrations; since vIL-6 induces vascular endothelial growth factor, vIL-6 likely contributes to vascular permeability and formation of PEL effusions. Lymph nodes affected with MCD contain vIL-6-positive cells, and vIL-6 levels rise in conjunction with flares of the disease and likely contribute to symptoms of inflammation. The development of vIL-6 inhibitors is a potentially important advance in the treatment of KSHV-associated malignancies where vIL-6 is expressed. PMID:21767154

  17. Non-human primate model of Kaposi's sarcoma-associated herpesvirus infection.

    Directory of Open Access Journals (Sweden)

    Heesoon Chang

    2009-10-01

    Full Text Available Since Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus 8 was first identified in Kaposi's sarcoma (KS lesions of HIV-infected individuals with AIDS, the basic biological understanding of KSHV has progressed remarkably. However, the absence of a proper animal model for KSHV continues to impede direct in vivo studies of viral replication, persistence, and pathogenesis. In response to this need for an animal model of KSHV infection, we have explored whether common marmosets can be experimentally infected with human KSHV. Here, we report the successful zoonotic transmission of KSHV into common marmosets (Callithrix jacchus, Cj, a New World primate. Marmosets infected with recombinant KSHV rapidly seroconverted and maintained a vigorous anti-KSHV antibody response. KSHV DNA and latent nuclear antigen (LANA were readily detected in the peripheral blood mononuclear cells (PBMCs and various tissues of infected marmosets. Remarkably, one orally infected marmoset developed a KS-like skin lesion with the characteristic infiltration of leukocytes by spindle cells positive for KSHV DNA and proteins. These results demonstrate that human KSHV infects common marmosets, establishes an efficient persistent infection, and occasionally leads to a KS-like skin lesion. This is the first animal model to significantly elaborate the important aspects of KSHV infection in humans and will aid in the future design of vaccines against KSHV and anti-viral therapies targeting KSHV coinfected tumor cells.

  18. The HIV protease inhibitor nelfinavir inhibits Kaposi's sarcoma-associated herpesvirus replication in vitro.

    Science.gov (United States)

    Gantt, Soren; Carlsson, Jacquelyn; Ikoma, Minako; Gachelet, Eliora; Gray, Matthew; Geballe, Adam P; Corey, Lawrence; Casper, Corey; Lagunoff, Michael; Vieira, Jeffrey

    2011-06-01

    Kaposi's sarcoma (KS) is the most common HIV-associated cancer worldwide and is associated with high levels of morbidity and mortality in some regions. Antiretroviral (ARV) combination regimens have had mixed results for KS progression and resolution. Anecdotal case reports suggest that protease inhibitors (PIs) may have effects against KS that are independent of their effect on HIV infection. As such, we evaluated whether PIs or other ARVs directly inhibit replication of Kaposi's sarcoma-associated herpesvirus (KSHV), the gammaherpesvirus that causes KS. Among a broad panel of ARVs tested, only the PI nelfinavir consistently displayed potent inhibitory activity against KSHV in vitro as demonstrated by an efficient quantitative assay for infectious KSHV using a recombinant virus, rKSHV.294, which expresses the secreted alkaline phosphatase. This inhibitory activity of nelfinavir against KSHV replication was confirmed using virus derived from a second primary effusion lymphoma cell line. Nelfinavir was similarly found to inhibit in vitro replication of an alphaherpesvirus (herpes simplex virus) and a betaherpesvirus (human cytomegalovirus). No activity was observed with nelfinavir against vaccinia virus or adenovirus. Nelfinavir may provide unique benefits for the prevention or treatment of HIV-associated KS and potentially other human herpesviruses by direct inhibition of replication.

  19. Association between malaria exposure and Kaposi's sarcoma-associated herpes virus seropositivity in Uganda.

    Science.gov (United States)

    Nalwoga, Angela; Cose, Stephen; Wakeham, Katie; Miley, Wendell; Ndibazza, Juliet; Drakeley, Christopher; Elliott, Alison; Whitby, Denise; Newton, Robert

    2015-05-01

    Unlike other herpes viruses, Kaposi's sarcoma-associated herpes virus (KSHV) is not ubiquitous worldwide and is most prevalent in sub-Saharan Africa. The reasons for this are unclear. As part of a wider investigation of factors that facilitate transmission in Uganda, a high prevalence country, we examined the association between antimalaria antibodies and seropositivity against KSHV. Antibodies against P. falciparum merozoite surface protein (PfMSP)-1, P. falciparum apical membrane antigen (PfAMA)-1 and KSHV antigens (ORF73 and K8.1) were measured in samples from 1164 mothers and 1227 children. Kaposi's sarcoma-associated herpes virus seroprevalence was 69% among mothers and 15% children. Among mothers, KSHV seroprevalence increased with malaria antibody titres: from 60% to 82% and from 54% to 77%, comparing those with the lowest and highest titres for PfMSP-1 and PfAMA-1, respectively (P < 0.0001). Among children, only antibodies to PfAMA-1 were significantly associated with KSHV seropositivity, (P < 0.0001). In both mothers and children, anti-ORF73 antibodies were more strongly associated with malaria antibodies than anti-K8.1 antibodies. The association between malaria exposure and KSHV seropositivity suggests that malaria is a cofactor for KSHV infection or reactivation. © 2015 The Authors. Tropical Medicine & International Health published by John Wiley & Sons Ltd.

  20. Risk of classic Kaposi sarcoma with residential exposure to volcanic and related soils in Sicily.

    Science.gov (United States)

    Pelser, Colleen; Dazzi, Carmelo; Graubard, Barry I; Lauria, Carmela; Vitale, Francesco; Goedert, James J

    2009-08-01

    Before AIDS, endemic (African) Kaposi sarcoma (KS) was noted to occur in volcanic areas and was postulated to result from dirt chronically embedded in the skin of the lower extremities. The primary cause of all KS types is KS-associated herpesvirus (KSHV) infection, but cofactors contribute to the neoplasia. We investigated whether residential exposure to volcanic or related soils was associated with the risk of classic Kaposi sarcoma (cKS) in Sicily. Risk of incident cKS (N=141) compared with population-based KSHV seropositive controls (N=123) was estimated for residential exposure to four types of soil, categorized with maps from the European Soil Database and direct surveying. Questionnaire data provided covariates. Residents in communities high in luvisols were approximately 2.7 times more likely to have cKS than those in communities with no luvisols. Risk was not specific for cKS on the limbs, but it was elevated approximately four- to five-fold with frequent bathing or tap water drinking in communities with high luvisols. Risk was unrelated to communities high in andosols, tephra, or clay soils. Iron and alumino-silicate clay, major components of luvisols, may increase cKS risk, but formal investigation and consideration of other soil types and exposures are needed.

  1. Mucosal Kaposi sarcoma, a Rare Cancer Network study

    Directory of Open Access Journals (Sweden)

    Robert C. Miller

    2012-10-01

    Full Text Available Kaposi’s sarcoma (KS most often affect the skin but occasionally affect the mucosa of different anatomic sites. The management of mucosal KS is seldom described in the literature. Data from 15 eligible patients with mucosal KS treated between 1994 and 2008 in five institutions within three countries of the Rare Cancer Network group were collected. The inclusion criteria were as follows: age >16 years, confirmed pathological diagnosis, mucosal stages I and II, and a minimum of 6 months’ follow-up after treatment. Head and neck sites were the most common (66%. Eleven cases were HIV-positive. CD4 counts correlated with disease stage. Twelve patients had biopsy only while three patients underwent local resection. Radiotherapy (RT was delivered whatever their CD4 status was. Median total radiation dose was 16.2 Gy (0-45 delivered in median 17 days (0-40 with four patients receiving no RT. Six patients underwent chemotherapy and received from 1 to 11 cycles of various regimens namely vinblastin, caelyx, bleomycine, or interferon, whatever their CD4 counts was. Five-year disease free survival were 81.6% and 75.0% in patients undergoing RT or not, respectively. Median survival was 66.9 months. Radiation-induced toxicity was at worse grade 1-2 and was manageable whatever patients’ HIV status. This small series of mucosal KSs revealed that relatively low-dose RT is overall safe and efficient in HIV-positive and negative patients. Since there are distant relapses either in multicentric cutaneous or visceral forms in head and neck cases, the role of systemic treatments may be worth investigations in addition to RT of localized disease. Surgery may be used for symptomatic lesions, with caution given the risk of bleeding.

  2. Immune reconstitution and risk of Kaposi sarcoma and non-Hodgkin lymphoma in HIV-infected adults

    NARCIS (Netherlands)

    Jaffe, Harold W.; de Stavola, Bianca L.; Carpenter, Lucy M.; Porter, Kholoud; Cox, David R.; del Amo, Julia; Meyer, Laurence; Bucher, Heiner C.; Chêne, Geneviève; Hamouda, Osamah; Pillay, Deenan; Prins, Maria; Rosinska, Magda; Sabin, Caroline; Touloumi, Giota; Lodi, Sara; Coughlin, Kate; Walker, Sarah; Babiker, Abdel; de Luca, Andrea; Fisher, Martin; Muga, Roberto; Zangerle, Robert; Kelleher, A. D.; Cooper, D. A.; Grey, Pat; Finlayson, Robert; Bloch, Mark; Kelleher, Tony; Ramacciotti, Tim; Gelgor, Linda; Cooper, David; Gill, John; Jørgensen, Louise B.; Tartu, U.; Lutsar, Irja; Dabis, Francois; Thiebaut, Rodolphe; Masquelier, Bernard; Costagliola, Dominique; Guiguet, Marguerite; Vanhems, Philippe; Chaix, Marie-Laure; Ghosn, Jade; Boufassa, Faroudy; Kücherer, Claudia; Bartmeyer, Barbara; Pantazis, Nikos; Katsarou, Olga; Rezza, Giovanni; Dorrucci, Maria; D'Arminio Monforte, Antonella; Geskus, Ronald; van der Helm, Jannie; Schuitemaker, Hanneke; Sannes, Mette; Brubakk, Oddbjorn; Kran, Anne-Marte Bakken; Rosinska, Magdalena; Tor, Jordi; Garcia de Olalla, Patricia; Cayla, Joan; Moreno, Santiago; Monge, Susana; Pérez-Hoyos, Santiago; Rickenbach, Martin; Francioli, Patrick; Malyuta, Ruslan; Brettle, Ray; Johnson, Anne; Phillips, Andrew; Delpech, Valerie; Morrison, Charles; Salata, Robert; Mugerwa, Roy; Chipato, Tsungai; Amornkul, Pauli

    2011-01-01

    Given the well documented occurrence of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients who recently started combination antiretroviral therapy (cART), we examined whether cART initiation increased the risk of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) using data from

  3. Radiation therapy for Kaposi's sarcoma associated with acquired immunodeficiency syndrome. Tokyo Metropolitan Komagome Hospital experience

    Energy Technology Data Exchange (ETDEWEB)

    Ebara, Takeshi [Municipal Kanbara General Hospital, Fujikawa, Shizuoka (Japan); Karasawa, Katsuyuki; Maebayashi, Katsuya; Kurosaki, Hiromasa; Ishikawa, Hitoshi; Kaizu, Toshihide; Tanaka, Yoshiaki; Akagi, Kumiko; Masuda, Gota

    2000-12-01

    Kaposi's sarcoma is frequently found in association with acquired immunodeficiency syndrome (AIDS). We report on radiotherapy for patients with AIDS-related Kaposi's sarcoma at Tokyo Metropolitan Komagome Hospital. Between April 1991 and May 1997, radiotherapy was given to 11 lesions in eight men with AIDS-related Kaposi's sarcoma to relieve their symptoms. The lesions involved the head and neck region, the legs, and the gastrointestinal tract. Radiotherapy was carried out with 4-MV photon through parallel opposed field or high energy electrons. Total doses ranged from 20 to 38 Gy, with a median of 30 Gy, delivered in 2- to 3-Gy fractions. Four patients were given other treatments prior to the radiotherapy. Acute reaction was evaluated according to the modified acute radiation morbidity scoring criteria of the Radiation Therapy Oncology Group (RTOG). Radiotherapy had relieved the symptoms in all patients at completion of this therapy. Lesions that involved the hard palate and vocal cords had completely disappeared. The lesions that received radiotherapy were controlled without symptoms until the patients died. Patients who had the head and neck region treated exhibited severe acute mucosal reaction (at a dose of 30 Gy, there was grade 2 morbidity by modified RTOG criteria, in two patients, and grade 3 in three patients) although the radiation therapy was completed for these patients. Radiotherapy promises a favorable outcome for symptom relief in AIDS-related Kaposi's sarcoma. (author)

  4. Human herpes virus-8 DNA in bronchoalveolar lavage samples from patients with AIDS-associated pulmonary Kaposi's sarcoma

    DEFF Research Database (Denmark)

    Benfield, T L; Dodt, K K; Lundgren, Jens Dilling

    1997-01-01

    Kaposi's sarcoma (KS) is the most frequent AIDS-associated neoplasm, and often disseminates to visceral organs, including the lungs. An ante-mortem diagnosis of pulmonary KS is difficult. Recently, DNA sequences resembling a new human herpes virus (HHV-8), have been identified in various forms...

  5. Human herpesvirus 8 (HHV-8 and the etiopathogenesis of Kaposi's sarcoma Herpesvírus humano tipo 8 (HHV-8 e a etiopatogênese do sarcoma de Kaposi

    Directory of Open Access Journals (Sweden)

    Jair Carneiro Leão

    2002-08-01

    Full Text Available OBJECTIVE: To review the current literature on human herpesvirus 8 with particular attention to the aspects related to the etiopathogenesis of Kaposi's sarcoma. MATERIALS AND METHODS: The authors searched original research and review articles on specific aspects of human herpesvirus 8 infection, including virology, epidemiology, transmission, diagnosis, natural history, therapy, and Kaposi's sarcoma etiopathogenesis. The relevant material was evaluated and reviewed. RESULTS: Human herpesvirus 8 is a recently discovered DNA virus that is present throughout the world but with major geographic variation. In the Western world, the virus, transmitted mainly by means of sexual contact, is strongly associated with Kaposi's sarcoma and body cavity-based lymphoma and more controversially with multiple myeloma and other non-proliferative disorders. There is no specific effective treatment, but HIV protease inhibitors may play an indirect role in the clearance of human herpesvirus 8 DNA from peripheral blood mononuclear cells of HIV-infected patients. Human herpesvirus 8 DNA is present in saliva, but there are as yet no documented cases of nosocomial transmission to health care workers. The prevalence of human herpesvirus 8 among health care workers is probably similar to that in the general population. CONCLUSION: Human herpesvirus 8 appears to be, at least in Western Europe and United States, restricted to a population at risk of developing Kaposi's sarcoma. Human herpesvirus 8 certainly has the means to overcome cellular control and immune responses and thus predispose carriers to malignancy, particularly Kaposi's sarcoma. The wide diffusion of Human herpesvirus 8 in classic Kaposi's sarcoma areas appears to represent an important factor in the high incidence of the disease. However, additional co-factors are likely to play a role in the development of Kaposi's sarcoma.OBJETIVO: O objetivo do presente artigo foi revisar a literatura recente em rela

  6. Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma

    Directory of Open Access Journals (Sweden)

    Érico Arruda

    2014-05-01

    There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

  7. Coexistent lymphoma with tuberculosis and Kaposi's sarcoma with tuberculosis occurring in lymph node in patients with AIDS: a report of two cases.

    Science.gov (United States)

    Lanjewar, D N; Lanjewar, Sonali D; Chavan, Gajanan

    2010-01-01

    Although there have been a few reports of simultaneous infections and neoplasm in patients with acquired immune deficiency syndrome, no reports of coexistent lymphoma with tuberculosis and Kaposi's sarcoma with tuberculosis occurring in the same lymph node have been described. In this article, we describe coexistent lymphoma with tuberculosis in one case and Kaposi's sarcoma with tuberculosis in another case of human immune deficiency virus-infected individuals.

  8. Kaposi sarcoma and lymphadenopathy syndrome: limitations of abdominal CT in acquired immunodeficiency syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Moon, K.L. Jr.; Federle, M.P.; Abrams, D.I.; Volberding, P.; Lewis, B.J.

    1984-02-01

    Abdominal computed tomography (CT) was performed in 31 patients with Kaposi sarcoma (KS) related to acquired immunodeficiency syndrome (AIDS), three patients with classic KS, and 12 patients with the newly described lymphadenopathy syndrome (LNS). The frequency, distribution, and appearance of lymphadenopathy and splenomegaly were similar in the AIDS-related KS and LNS groups. Rectal and perirectal disease was identified in 86% of homosexual men studied; rectal KS could not be distinguished from proctitis on CT criteria alone. No CT abnormalities were seen in patients with classic KS. The CT demonstration of retroperitoneal, mesenteric, or pelvic adenopathy or of rectal or perirectal disease in patients with AIDS-related KS is not necessarily indicative of widespread involvement with the disease.

  9. Disseminated kaposi's sarcoma in an HIV-positive patient: A rare entity in an Indian patient

    Directory of Open Access Journals (Sweden)

    Biswanath Behera

    2016-01-01

    Full Text Available AIDS-associated disseminated Kaposi sarcoma (KS is a rare entity, especially in India due to the low prevalence of human herpes virus-8 infections in Indian population. Due to its rapid and progressive nature, early diagnosis and institution of highly active antiretroviral therapy is crucial in AIDS-associated KS, with a view to achieving favorable prognosis. We report a case of disseminated KS in an HIV-1 positive patient, who presented with two months history of multiple violaceous patches and plaques over the trunk, bilateral upper limbs, lower limbs, and hard palate. The patient died of recurrent massive pleural effusion before starting antiretroviral therapy. This case is being reported due to the paucity of KS in the Indian literature, especially the disseminated type and to highlight its rapidly progressive course which can be fatal.

  10. Relationship between oral Kaposi 's sarcoma and HAART: contribution of two case reports.

    Science.gov (United States)

    Campo-Trapero, Julián; Del Romero-Guerrero, Jorge; Cano-Sánchez, Jorge; Rodríguez-Martín, Carmen; Martínez-González, José Ma; Bascones-Martínez, Antonio

    2008-11-01

    Two HIV infected patients not receiving Highly Active Antiretroviral Treatment (HAART) presented with epidemic Kaposi's sarcoma of the oral cavity. One patient initially refused HAART, but when the lesion became large enough to be noticeable he agreed to HAART associated with excision of the intraoral lesion by CO2 laser. The other patient developed KS and progressed to AIDS at two years after ceasing HAART due to adverse effects; he was referred to hospital for renewed administration of HAART. In both cases, the lesions observed in the oral cavity were the first clinical manifestation of AIDS. These reports underline the close relationship between the use of HAART and the control of KS lesions, highlighting the important role of the dentist in the identification and early diagnosis of these oral lesions.

  11. The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes.

    Directory of Open Access Journals (Sweden)

    Thomas Günther

    Full Text Available Herpesvirus latency is generally thought to be governed by epigenetic modifications, but the dynamics of viral chromatin at early timepoints of latent infection are poorly understood. Here, we report a comprehensive spatial and temporal analysis of DNA methylation and histone modifications during latent infection with Kaposi Sarcoma-associated herpesvirus (KSHV, the etiologic agent of Kaposi Sarcoma and primary effusion lymphoma (PEL. By use of high resolution tiling microarrays in conjunction with immunoprecipitation of methylated DNA (MeDIP or modified histones (chromatin IP, ChIP, our study revealed highly distinct landscapes of epigenetic modifications associated with latent KSHV infection in several tumor-derived cell lines as well as de novo infected endothelial cells. We find that KSHV genomes are subject to profound methylation at CpG dinucleotides, leading to the establishment of characteristic global DNA methylation patterns. However, such patterns evolve slowly and thus are unlikely to control early latency. In contrast, we observed that latency-specific histone modification patterns were rapidly established upon a de novo infection. Our analysis furthermore demonstrates that such patterns are not characterized by the absence of activating histone modifications, as H3K9/K14-ac and H3K4-me3 marks were prominently detected at several loci, including the promoter of the lytic cycle transactivator Rta. While these regions were furthermore largely devoid of the constitutive heterochromatin marker H3K9-me3, we observed rapid and widespread deposition of H3K27-me3 across latent KSHV genomes, a bivalent modification which is able to repress transcription in spite of the simultaneous presence of activating marks. Our findings suggest that the modification patterns identified here induce a poised state of repression during viral latency, which can be rapidly reversed once the lytic cycle is induced.

  12. Regulation of viral and cellular gene expression by Kaposi's sarcoma-associated herpesvirus polyadenylated nuclear RNA.

    Science.gov (United States)

    Rossetto, Cyprian C; Tarrant-Elorza, Margaret; Verma, Subhash; Purushothaman, Pravinkumar; Pari, Gregory S

    2013-05-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of Kaposi's sarcoma and body cavity lymphoma. In cell culture, KSHV results in a latent infection, and lytic reactivation is usually induced with the expression of K-Rta or by treatment with phorbol 12-myristate 13-acetate (TPA) and/or n-butyrate. Lytic infection is marked by the activation of the entire viral genomic transcription cascade and the production of infectious virus. KSHV-infected cells express a highly abundant, long, noncoding transcript referred to as polyadenylated nuclear RNA (PAN RNA). PAN RNA interacts with specific demethylases and physically binds to the KSHV genome to mediate activation of viral gene expression. A recombinant BACmid lacking the PAN RNA locus fails to express K-Rta and does not produce virus. We now show that the lack of PAN RNA expression results in the failure of the initiation of the entire KSHV transcription program. In addition to previous findings of an interaction with demethylases, we show that PAN RNA binds to protein components of Polycomb repression complex 2 (PRC2). RNA-Seq analysis using cell lines that express PAN RNA shows that transcription involving the expression of proteins involved in cell cycle, immune response, and inflammation is dysregulated. Expression of PAN RNA in various cell types results in an enhanced growth phenotype, higher cell densities, and increased survival compared to control cells. Also, PAN RNA expression mediates a decrease in the production of inflammatory cytokines. These data support a role for PAN RNA as a major global regulator of viral and cellular gene expression.

  13. Kaposi's Sarcoma

    Science.gov (United States)

    ... system. It generally occurs in children of tropical Africa under the age of 10 years. It has an aggressive nature and its victims usually die within 2 years. AIDS-Associated Epidemic KS - In those with advanced HIV disease this can develop as red to purple ...

  14. Kaposi Sarcoma

    Science.gov (United States)

    ... in People with weak immune systems, due to HIV/AIDS, drugs taken after an organ transplant, or another disease Older men of Jewish or Mediterranean descent Young men in Africa The skin lesions may not cause symptoms. But ...

  15. Kaposi sarcoma

    Science.gov (United States)

    ... Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Updated Edition . 8th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap 143. Lambert PF, Sugden B. Viruses and human cancer. In: ...

  16. Absolute dose measurement Gafchromic R EBT2 movies. Case Study of Kaposis sarcoma; Medida de dosis absoluta con peliculas Gafchromic EBT2. Caso practico de un sarcoma de Kaposi

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, L.; Moral, F. del; Meilan, E.; Azevedo Gomes, J. C. de; Tejeiro Garcia, A. G.; Andrade Alvarez, B.; Vazquez, J.; Nieto, I.; Medal, D.; Lopez Medina, A.; Francisco, S.; Salgado, M.; Munoz, V.

    2011-07-01

    Because of its high spatial resolution, low energy dependence and good response over a wide energy range, EBT2 Gafchromic films are widely used in many applications in radiotherapy for measuring relative dose. Despite being the most common use can be used to measure absolute dose. This text is an example of using films as EBT2 for in vivo absolute dose in a Kaposis sarcoma.

  17. Human immunodeficiency virus-associated giant conjunctival Kaposi's sarcoma: complete remission with antiretroviral therapy and systemic chemotherapy.

    Science.gov (United States)

    Eduardo-Sánchez, Y W; Fernández-Agrafojo, D

    2017-09-05

    A 35-year-old male patient with a large unilateral haemorrhagic conjunctival tumour lesion and another contralateral haemorrhagic conjunctival flat lesion associated with violaceous cutaneous macules on the extremities and angiomatous lesions in the upper gastrointestinal tract as initial clinical manifestation of HIV-related immunodeficiency. Cutaneous, gastric mucosal and conjunctival biopsy was consistent with Kaposi's sarcoma with complete remission after highly active antiretroviral therapy and systemic chemotherapy. HIV-related conjunctival Kaposi's sarcoma, even a large one, can have a good response to antiretroviral therapy and systemic chemotherapy without any additional topical eye treatment. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa.

    Science.gov (United States)

    Chu, Kathryn M; Mahlangeni, Gcina; Swannet, Sarah; Ford, Nathan P; Boulle, Andrew; Van Cutsem, Gilles

    2010-07-08

    AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-to-follow-up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease

  19. Palatal Actinomycosis and Kaposi Sarcoma in an HIV-Infected Subject with Disseminated Mycobacterium avium-intracellulare Infection

    Directory of Open Access Journals (Sweden)

    Yuria Ablanedo-Terrazas

    2012-01-01

    Full Text Available Actinomyces and Mycobacterium avium-intracellulare are facultative intracellular organisms, members of the bacterial order actinomycetales. Although Actinomyces can behave as copathogen when anatomic barriers are compromised, its coinfection with Mycobacterium avium-intracellulare has not previously been reported. We present the first reported case of palatal actinomycosis co-infection with disseminated MAC, in an HIV-infected subject with Kaposi sarcoma and diabetes. We discuss the pathogenesis of the complex condition of this subject.

  20. Kaposi's Sarcoma-Associated Herpesvirus ORF18 and ORF30 Are Essential for Late Gene Expression during Lytic Replication

    OpenAIRE

    Gong, Danyang; Wu, Nicholas C.; Xie, Yafang; Feng, Jun; Tong, Leming; Brulois, Kevin F.; Luan, Harding; Du, Yushen; Jung, Jae U.; Wang, Cun-Yu; Kang, Mo Kwan; Park, No-Hee; Sun, Ren; Wu, Ting-Ting

    2014-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with several human malignances. As saliva is likely the major vehicle for KSHV transmission, we studied in vitro KSHV infection of oral epithelial cells. Through infection of two types of oral epithelial cells, normal human oral keratinocytes (NHOKs) and papilloma-immortalized human oral keratinocyte (HOK16B) cells, we found that KSHV can undergo robust lytic replication in oral epithelial cells. By employing de novo lytic infection...

  1. Kaposi's Sarcoma-Associated Herpesvirus Hijacks RNA Polymerase II To Create a Viral Transcriptional Factory

    Science.gov (United States)

    Chen, Christopher Phillip; Lyu, Yuanzhi; Chuang, Frank; Nakano, Kazushi; Izumiya, Chie; Jin, Di; Campbell, Mel

    2017-01-01

    ABSTRACT Locally concentrated nuclear factors ensure efficient binding to DNA templates, facilitating RNA polymerase II recruitment and frequent reutilization of stable preinitiation complexes. We have uncovered a mechanism for effective viral transcription by focal assembly of RNA polymerase II around Kaposi's sarcoma-associated herpesvirus (KSHV) genomes in the host cell nucleus. Using immunofluorescence labeling of latent nuclear antigen (LANA) protein, together with fluorescence in situ RNA hybridization (RNA-FISH) of the intron region of immediate early transcripts, we visualized active transcription of viral genomes in naturally infected cells. At the single-cell level, we found that not all episomes were uniformly transcribed following reactivation stimuli. However, those episomes that were being transcribed would spontaneously aggregate to form transcriptional “factories,” which recruited a significant fraction of cellular RNA polymerase II. Focal assembly of “viral transcriptional factories” decreased the pool of cellular RNA polymerase II available for cellular gene transcription, which consequently impaired cellular gene expression globally, with the exception of selected ones. The viral transcriptional factories localized with replicating viral genomic DNAs. The observed colocalization of viral transcriptional factories with replicating viral genomic DNA suggests that KSHV assembles an “all-in-one” factory for both gene transcription and DNA replication. We propose that the assembly of RNA polymerase II around viral episomes in the nucleus may be a previously unexplored aspect of KSHV gene regulation by confiscation of a limited supply of RNA polymerase II in infected cells. IMPORTANCE B cells infected with Kaposi's sarcoma-associated herpesvirus (KSHV) harbor multiple copies of the KSHV genome in the form of episomes. Three-dimensional imaging of viral gene expression in the nucleus allows us to study interactions and changes in the

  2. Gastrointestinal Bleeding and Diffuse Skin Thickening as Kaposi Sarcoma Clinical Presentation

    Directory of Open Access Journals (Sweden)

    Sara Querido

    2015-01-01

    Full Text Available A 56-year-old African patient received a kidney from a deceased donor with 4 HLA mismatches in April 2013. He received immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil, and prednisone. Immediate diuresis and a good allograft function were soon observed. Six months later, the serum creatinine level increased to 2.6 mg/dL. A renal allograft biopsy revealed interstitial fibrosis and tubular atrophy grade II. Toxicity of calcineurin inhibitor was assumed and, after a switch for everolimus, renal function improved. However, since March 2014, renal function progressively deteriorated. A second allograft biopsy showed no new lesions. Two months later, the patient was admitted due to anuria, haematochezia with anaemia, requiring 5 units of packed red blood cells, and diffuse skin thickening. Colonoscopy showed haemorrhagic patches in the colon and the rectum; histology diagnosis was Kaposi sarcoma (KS. A skin biopsy revealed cutaneous involvement of KS. Rapid clinical deterioration culminated in death in June 2014. This case is unusual as less than 20 cases of KS with gross gastrointestinal bleeding have been reported and only 6 cases had the referred bleeding originating in the lower gastrointestinal tract. So, KS should be considered in differential diagnosis of gastrointestinal bleeding in some kidney transplant patients.

  3. Control of Kaposi's sarcoma-associated herpesvirus reactivation induced by multiple signals.

    Directory of Open Access Journals (Sweden)

    Fuqu Yu

    Full Text Available The ability to control cellular functions can bring about many developments in basic biological research and its applications. The presence of multiple signals, internal as well as externally imposed, introduces several challenges for controlling cellular functions. Additionally the lack of clear understanding of the cellular signaling network limits our ability to infer the responses to a number of signals. This work investigates the control of Kaposi's sarcoma-associated herpesvirus reactivation upon treatment with a combination of multiple signals. We utilize mathematical model-based as well as experiment-based approaches to achieve the desired goals of maximizing virus reactivation. The results show that appropriately selected control signals can induce virus lytic gene expression about ten folds higher than a single drug; these results were validated by comparing the results of the two approaches, and experimentally using multiple assays. Additionally, we have quantitatively analyzed potential interactions between the used combinations of drugs. Some of these interactions were consistent with existing literature, and new interactions emerged and warrant further studies. The work presents a general method that can be used to quantitatively and systematically study multi-signal induced responses. It enables optimization of combinations to achieve desired responses. It also allows identifying critical nodes mediating the multi-signal induced responses. The concept and the approach used in this work will be directly applicable to other diseases such as AIDS and cancer.

  4. Epidemiology of Kaposi's sarcoma-associated herpesvirus in Asia: Challenges and opportunities.

    Science.gov (United States)

    Zhang, Tiejun; Wang, Linding

    2017-04-01

    Kaposi's sarcoma-associated herpes virus (KSHV) also referred to as human herpesvirus-8 (HHV-8), is a gamma herpes virus and recently discovered human virus. Since its discovery, a myriad of studies has been conducted to explore its pathogenesis mechanisms. However, despite our consistently increasing understanding of KSHV biology and its clinical manifestations, only little progress has been made in understanding of its epidemiology characteristics which in turn hampered the management of KSHV-associated diseases and public health. Asia, the largest continent with a diversity of populations, has been thought to be with relative lower KSHV prevalence and diseases burden. The epidemiology of KSHV in this area is obscure either. The present review summarizes the current knowledge pertaining to the epidemiology of KSHV across Asian countries. Studies available in the literature have shown a substantial variation in this region indicating the virus is not ubiquitous in Asia countries as is the case with other human herpes viruses. Also, the MSM has been reconfirmed to be at the highest risk of KSHV infection in Asia highlighting the need for an increased focus on this previously marginalized population. Because of the paucity of data available, the epidemiologic characteristics of KSHV are difficult to determine in Asian countries. Future systematic collection of data to inform KSHV prevention strategies in Asia is urgently needed. J. Med. Virol. 89:563-570, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Kaposi's sarcoma with HHV8 infection and ANCA-associated vasculitis in a hemodialysis patient.

    Science.gov (United States)

    Fatma, Lilia Ben; Rais, Lamia; Mebazza, Amel; Azzouz, Haifa; Beji, Somaya; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Zouaghi, Karim; Zitouna, Moncef; Osmane, Amel Ben; Moussa, Fatma Ben

    2013-11-01

    The association between Kaposi's sarcoma (KS) and human herpes virus eight (HHV-8) infection is rarely reported in hemodialysis (HD) patients. We report here the rare association of KS, HHV-8 and hepatitis C virus (HCV) infection as well as syphilis in a HD patient. We report the case of a 72-year-old woman who presented with microscopic polyangiitis with alveolar hemorrhage and pauci-immune necrosing and crescentic glomerulonephritis as well as renal failure requiring HD. Biological tests showed positive HCV and syphilis tests. The patient was treated by HD and intravenous pulse, followed by oral corticosteroids and six cyclophosphamide monthly pulses with remission of the alveolar hemorrhage, but without renal functional recovery as the patient remained HD dependent. Five months after the first treatment administration, she developed extensive purpuric lesions on her lower limbs, abdomen face and neck. A skin biopsy showed KS. The HHV-8 test was positive, with positive polymerase chain reaction-HHV8 in the serum and skin. After immunosuppression withdrawal, the KS skin lesions regressed rapidly without relapse after 12 months of follow-up, but alveolar hemorrhage relapsed after 16 months of follow-up. Our case showed that the immunosuppressed state related to multiple factors such as aging, vasculitis, HHV-8, HCV, syphilis, immunosuppressive therapy and HD may all have contributed to the development of KS in our patient.

  6. Oral manifestations in HIV infection: fungal and bacterial infections, Kaposi's sarcoma.

    Science.gov (United States)

    Reichart, Peter A

    2003-08-01

    Oral candidiasis (OC) is a frequent oral manifestation of HIV infection, is a marker disease and occurs as a pseudomembranous, erythematous or rarely hyperplastic variant; angular cheilitis is also seen. Candida albicans is frequently isolated but other species such as C. krusei and C. dublienensis are emerging. Resistance against fluconazole is common. Bacterial oral infections are comparatively rare and are predominantly localized to the gingiva and periodontium. Linear gingival erythema, necrotizing ulcerative gingivitis and necrotizing ulcerative periodontitis have been described in HIV-infected patients. Initially, these diseases were considered specific for HIV infection. In recent years, however, it has become apparent that gingivitis and periodontitis in HIV-infected patients do not differ from those in immunocompetent individuals. AIDS-associated Kaposi's sarcoma (KS) predominantly occurs at the palate, the gingiva and the dorsum of the tongue. Histopathologically, oral KS is identical to classical KS. Oral KS has been treated surgically, using laser, radiotherapy and intralesional injections with chemo- and immunotherapy. After introduction of highly active antiretroviral therapy (HAART) oral manifestations, such as OC, gingivo-periodontitis and KS are rarely seen.

  7. Changing Incidence and Risk Factors for Kaposi Sarcoma by Time Since Starting Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Wyss, Natascha; Zwahlen, Marcel; Bohlius, Julia

    2016-01-01

    BACKGROUND:  Kaposi sarcoma (KS) remains a frequent cancer in human immunodeficiency virus (HIV)-positive patients starting combination antiretroviral therapy (cART). We examined incidence rates and risk factors for developing KS in different periods after starting cART in patients from European...... observational HIV cohorts. METHODS:  We included HIV-positive adults starting cART after 1 January 1996. We analyzed incidence rates and risk factors for developing KS up to 90 and 180 days and 1, 2, 5, and 8 years after cART start and fitted univariable and multivariable Cox regression models. RESULTS:  We...... included 109 461 patients from 21 prospective clinical cohorts in Europe with 916 incident KS cases. The incidence rate per 100 000 person-years was highest 6 months after starting cART, at 953 (95% confidence interval, 866-1048), declining to 82 (68-100) after 5-8 years. In multivariable analyses adjusted...

  8. Aqueous immersion technique for the irradiation with photons Kaposi's sarcoma multiple foot and ankle; Tecnica de inmersion acuosa para la irradiacion con fotones del sarcoma de Kaposi multiple en pies y tobillos

    Energy Technology Data Exchange (ETDEWEB)

    Velazquez Miranda, S.; Munoz Carmona, D. M.; Ortyiz Seidel, M.; Gomez-Millan Barrachina, J.; Delgado Gil, M. M.; Ortega Rodriguez, M. J.; Dominguez Rodriguez, M.; Marquez Garcia Salazar, M.; Bayo Lozano, E.

    2011-07-01

    Classic Kaposi sarcoma presents as asymptomatic red-violaceus plaques, usually on the legs below the knees, ankles and soles preferentially. When the disease is spread on the skin preferential treatment is radiation therapy at low doses. Homogeneous irradiation of the various lesions could be very complex due to the irregular geometry of the feet, interdigital lesions on different planes. To overcome this problem, and in the case of disseminated disease and low doses, we propose the technique of dipping the tip in Cuba expanded polystyrene filled with saline with a methacrylate plate 2 cm in depth and irradiation with parallel opposed fields.

  9. Efficient infection by a recombinant Kaposi's sarcoma-associated herpesvirus cloned in a bacterial artificial chromosome: application for genetic analysis.

    Science.gov (United States)

    Zhou, Fu-Chun; Zhang, Yan-Jin; Deng, Jian-Hong; Wang, Xin-Ping; Pan, Hong-Yi; Hettler, Evelyn; Gao, Shou-Jiang

    2002-06-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically associated with Kaposi's sarcoma and several other malignancies. The lack of an efficient infection system has impeded the understanding of KSHV-related pathogenesis. A genetic approach was used to isolate infectious KSHV. Recombinant bacteria artificial chromosome (BAC) KSHV containing hygromycin resistance and green fluorescent protein (GFP) markers was generated by homologous recombination in KSHV-infected BCBL-1 cells. Recombinant KSHV genomes from cell clones that were resistant to hygromycin, expressed GFP, and produced infectious virions after induction with tetradecanoyl phorbol acetate (TPA) were rescued in Escherichia coli and reconstituted in 293 cells. Several 293 cell lines resulting from infection with recombinant virions induced from a full-length recombinant KSHV genome, named BAC36, were obtained. BAC36 virions established stable latent infection in 293 cells, harboring 1 to 2 copies of viral genome per cell and expressing viral latent proteins, with approximately 0.5% of cells undergoing spontaneous lytic replication, which is reminiscent of KSHV infection in Kaposi's sarcoma tumors. TPA treatment induced BAC36-infected 293 cell lines into productive lytic replication, expressing lytic proteins and producing virions that efficiently infected normal 293 cells with a approximately 50% primary infection rate. BAC36 virions were also infectious to HeLa and E6E7-immortalized human endothelial cells. Since BAC36 can be efficiently shuttled between bacteria and mammalian cells, it is useful for KSHV genetic analysis. The feasibility of the system was illustrated through the generation of a KSHV mutant with the vIRF gene deleted. This cellular model is useful for the investigation of KSHV infection and pathogenesis.

  10. Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells

    OpenAIRE

    Cai, Xuezhong; Lu, Shihua; Zhang, Zhihong; Gonzalez, Carlos M.; Damania, Blossom; Cullen, Bryan R.

    2005-01-01

    MicroRNAs (miRNAs) are an endogenously encoded class of small RNAs that have been proposed to function as key posttranscriptional regulators of gene expression in a range of eukaryotic species, including humans. The small size of miRNA precursors makes them potentially ideal for use by viruses as inhibitors of host cell defense pathways. Here, we demonstrate that the pathogenic human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) encodes an array of 11 distinct miRNAs, all of whic...

  11. Propranolol Decreases Proliferation of Endothelial Cells Transformed by Kaposi's Sarcoma-Associated Herpesvirus and Induces Lytic Viral Gene Expression

    Science.gov (United States)

    Hanson, Ryan S.; Manion, Rory D.

    2015-01-01

    Kaposi's sarcoma (KS) is common in Africa, but economic constraints hinder successful treatment in most patients. Propranolol, a generic β-adrenergic antagonist, decreased proliferation of KS-associated herpesvirus (KSHV)-infected cells. Downregulation of cyclin A2 and cyclin-dependent kinase 1 (CDK1) recapitulated this phenotype. Additionally, propranolol induced lytic gene expression in association with downregulation of CDK6. Thus, propranolol has diverse effects on KSHV-infected cells, and this generic drug has potential as a therapeutic agent for KS. PMID:26269192

  12. Sarcoma de Kaposi clássico, a propósito de um caso clínico

    OpenAIRE

    Patrocínio, J; Espírito Santo, AR; Patrocínio, J; Pereira, R; Gomes, F; Louro, F

    2016-01-01

    O Sarcoma de Kaposi (SK) é um distúrbio angioproliferativo descrito como doença benigna de pessoas idosas. Divide- se em 4 tipos: O Clássico, epidémico, endêmico e iatrogénico. Os autores descrevem o caso de um homem caucasiano de 50 anos, português, que iniciou a sintomatologia 6 anos antes do internamento com lesões urticariformes na perna direita e perda ponderal de 10 kg em 6 meses. Por agravamento das lesões e aparecimento de púrpura nos membros inferiores recorreu ao hosp...

  13. Nationwide registry-based analysis of cancer clustering detects strong familial occurrence of Kaposi sarcoma.

    Directory of Open Access Journals (Sweden)

    Eevi Kaasinen

    Full Text Available Many cancer predisposition syndromes are rare or have incomplete penetrance, and traditional epidemiological tools are not well suited for their detection. Here we have used an approach that employs the entire population based data in the Finnish Cancer Registry (FCR for analyzing familial aggregation of all types of cancer, in order to find evidence for previously unrecognized cancer susceptibility conditions. We performed a systematic clustering of 878,593 patients in FCR based on family name at birth, municipality of birth, and tumor type, diagnosed between years 1952 and 2011. We also estimated the familial occurrence of the tumor types using cluster score that reflects the proportion of patients belonging to the most significant clusters compared to all patients in Finland. The clustering effort identified 25,910 birth name-municipality based clusters representing 183 different tumor types characterized by topography and morphology. We produced information about familial occurrence of hundreds of tumor types, and many of the tumor types with high cluster score represented known cancer syndromes. Unexpectedly, Kaposi sarcoma (KS also produced a very high score (cluster score 1.91, p-value <0.0001. We verified from population records that many of the KS patients forming the clusters were indeed close relatives, and identified one family with five affected individuals in two generations and several families with two first degree relatives. Our approach is unique in enabling systematic examination of a national epidemiological database to derive evidence of aberrant familial aggregation of all tumor types, both common and rare. It allowed effortless identification of families displaying features of both known as well as potentially novel cancer predisposition conditions, including striking familial aggregation of KS. Further work with high-throughput methods should elucidate the molecular basis of the potentially novel predisposition conditions

  14. Antagonism of host antiviral responses by Kaposi's sarcoma-associated herpesvirus tegument protein ORF45.

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    Fan Xiu Zhu

    2010-05-01

    Full Text Available Virus infection of a cell generally evokes an immune response by the host to defeat the intruder in its effort. Many viruses have developed an array of strategies to evade or antagonize host antiviral responses. Kaposi's sarcoma-associated herpesvirus (KSHV is demonstrated in this report to be able to prevent activation of host antiviral defense mechanisms upon infection. Cells infected with wild-type KSHV were permissive for superinfection with vesicular stomatitis virus (VSV, suggesting that KSHV virions fail to induce host antiviral responses. We previously showed that ORF45, a KSHV immediate-early protein as well as a tegument protein of virions, interacts with IRF-7 and inhibits virus-mediated type I interferon induction by blocking IRF-7 phosphorylation and nuclear translocation (Zhu et al., Proc. Natl. Acad. Sci. USA. 99:5573-5578, 2002. Here, using an ORF45-null recombinant virus, we demonstrate a profound role of ORF45 in inhibiting host antiviral responses. Infection of cells with an ORF45-null mutant recombinant KSHV (BAC-stop45 triggered an immune response that resisted VSV super-infection, concomitantly associated with appreciable increases in transcription of type I IFN and downstream anti-viral effector genes. Gain-of-function analysis showed that ectopic expression of ORF45 in human fibroblast cells by a lentivirus vector decreased the antiviral responses of the cells. shRNA-mediated silencing of IRF-7, that predominantly regulates both the early and late phase induction of type I IFNs, clearly indicated its critical contribution to the innate antiviral responses generated against incoming KSHV particles. Thus ORF45 through its targeting of the crucial IRF-7 regulated type I IFN antiviral responses significantly contributes to the KSHV survival immediately following a primary infection allowing for progression onto subsequent stages in its life-cycle.

  15. A novel mechanism inducing genome instability in Kaposi's sarcoma-associated herpesvirus infected cells.

    Directory of Open Access Journals (Sweden)

    Brian R Jackson

    2014-05-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is an oncogenic herpesvirus associated with multiple AIDS-related malignancies. Like other herpesviruses, KSHV has a biphasic life cycle and both the lytic and latent phases are required for tumorigenesis. Evidence suggests that KSHV lytic replication can cause genome instability in KSHV-infected cells, although no mechanism has thus far been described. A surprising link has recently been suggested between mRNA export, genome instability and cancer development. Notably, aberrations in the cellular transcription and export complex (hTREX proteins have been identified in high-grade tumours and these defects contribute to genome instability. We have previously shown that the lytically expressed KSHV ORF57 protein interacts with the complete hTREX complex; therefore, we investigated the possible intriguing link between ORF57, hTREX and KSHV-induced genome instability. Herein, we show that lytically active KSHV infected cells induce a DNA damage response and, importantly, we demonstrate directly that this is due to DNA strand breaks. Furthermore, we show that sequestration of the hTREX complex by the KSHV ORF57 protein leads to this double strand break response and significant DNA damage. Moreover, we describe a novel mechanism showing that the genetic instability observed is a consequence of R-loop formation. Importantly, the link between hTREX sequestration and DNA damage may be a common feature in herpesvirus infection, as a similar phenotype was observed with the herpes simplex virus 1 (HSV-1 ICP27 protein. Our data provide a model of R-loop induced DNA damage in KSHV infected cells and describes a novel system for studying genome instability caused by aberrant hTREX.

  16. Kaposi's Sarcoma Associated-Herpes Virus (KSHV Seroprevalence in Pregnant Women in South Africa

    Directory of Open Access Journals (Sweden)

    Malope-Kgokong Babatyi I

    2010-08-01

    Full Text Available Abstract Background Factors previously associated with Kaposi's sarcoma-associated herpesvirus (KSHV transmission in Africa include sexual, familial, and proximity to river water. We measured the seroprevalence of KSHV in relation to HIV, syphilis, and demographic factors among pregnant women attending public antenatal clinics in the Gauteng province of South Africa. Methods We tested for antibodies to KSHV lytic K8.1 and latent Orf73 antigens in 1740 pregnant women attending antenatal clinics who contributed blood to the "National HIV and Syphilis Sero-Prevalence Survey - South Africa, 2001". Information on HIV and syphilis serology, age, education, residential area, gravidity, and parity was anonymously linked to evaluate risk factors for KSHV seropositivity. Clinics were grouped by municipality regions and their proximity to the two main river catchments defined. Results KSHV seropositivity (reactive to either lytic K8.1 and latent Orf73 was nearly twice that of HIV (44.6% vs. 23.1%. HIV and syphilis seropositivity was 12.7% and 14.9% in women without KSHV, and 36.1% and 19.9% respectively in those with KSHV. Women who are KSHV seropositive were 4 times more likely to be HIV positive than those who were KSHV seronegative (AOR 4.1 95%CI: 3.4 - 5.7. Although, women with HIV infection were more likely to be syphilis seropositive (AOR 1.8 95%CI: 1.3 - 2.4, no association between KSHV and syphilis seropositivity was observed. Those with higher levels of education had lower levels of KSHV seropositivity compared to those with lower education levels. KSHV seropositivity showed a heterogeneous pattern of prevalence in some localities. Conclusions The association between KSHV and HIV seropositivity and a lack of common association with syphilis, suggests that KSHV transmission may involve geographical and cultural factors other than sexual transmission.

  17. Clinical presentation and outcome of epidemic Kaposi sarcoma in Ugandan children.

    Science.gov (United States)

    Gantt, Soren; Kakuru, Abel; Wald, Anna; Walusansa, Victoria; Corey, Lawrence; Casper, Corey; Orem, Jackson

    2010-05-01

    Kaposi sarcoma (KS) is one of the most common pediatric cancers in sub-Saharan Africa. Few data are available about the clinical presentation or response to treatment of children with epidemic (HIV-associated) KS. Medical records of all children with KS and HIV infection referred to the Uganda Cancer Institute in Kampala, Uganda from October 2004 to June 2007 were reviewed. Charts were abstracted for age, sex, location of KS lesions at presentation, biopsy results, CD4 T-cell count and percentage, and KS treatment and outcome. Seventy-three children with epidemic KS were identified, 37 males and 36 females. The median age was 10.1 years (range 2-18). KS presented with lymph node (LN) involvement in 60% of cases. The median absolute and percentage CD4 T-cells at presentation were 210 cells/microl and 7.4%, respectively. Those children with lymphadenopathic KS were younger (mean difference 3.7 years; P = 0.01) and had higher CD4 T-cell counts (mean difference 242 cells/microl; P = 0.03) than those without LN involvement. Of 32 patients for whom outcome data were available, a complete response to chemotherapy and/or antiretroviral therapy was documented in 20 (62.5%) patients. In comparison to cutaneous involvement, LN involvement of epidemic KS occurs at younger ages and at higher CD4 levels. This clinical presentation may reflect recent infection with human herpesvirus 8 followed by a rapid progression to malignancy. Favorable response to treatment was observed in the majority of cases, but prospective studies are needed to determine optimal management.

  18. Case Report: Pulmonary Kaposi Sarcoma in a non-HIV patient [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Arber Kodra

    2015-10-01

    Full Text Available Kaposi Sarcoma (KS is an angioproliferative tumor associated with human herpes virus 8 (HHV-8.  Often known as one of the acquired immunodeficiency syndrome (AIDS-defining skin diseases, pulmonary involvement in KS has only been discussed in a handful of case reports, rarely in a non-HIV patient. Herein we report the case of a 77 year-old- male who presented with a 6-week history of progressive dyspnea on exertion accompanied by productive cough of yellow sputum and intermittent hemoptysis. His past medical history was significant for Non-Hodgkin’s Follicular B-Cell Lymphoma (NHL. Patient also had biopsy-confirmed cutaneous KS. His physical exam was notable for a 2cm firm, non-tender, mobile right submandibular lymph node.  Lungs were clear to auscultation. He had multiple violet non-tender skin lesions localized to the lower extremities. CT scan of the chest showed numerous nodular opacities and small pleural effusions in both lungs. A thoracenthesis was performed, showing sero-sanguineous exudative effusions. Histopathology failed to demonstrate malignant cells or lymphoma. A subsequent bronchoscopy revealed diffusely hyperemic, swollen mucosa of the lower airways with mucopurulent secretions. Bronchoalveolar lavage PCR for HHV-8 showed 5800 DNA copies/mL.  It was believed that his pulmonary symptoms were likely due to disseminated KS.  This case illustrates the potential for significant lung injury from KS. It also demonstrates the use of PCR for HHV-8 to diagnose KS in a bronchoalveolar lavage sample in a case when bronchoscopic biopsy was not safe. Furthermore, this case is unique in that the patient did not match the typical KS subgroups as HIV infection and other immune disorders were ruled out. Recognition of this syndrome is critical to the institution of appropriate therapy. As such, this case should be of interest to a broad readership across internal medicine including the specialties of Pulmonology and Critical Care.

  19. HHV-8 infection in patients with AIDS-related Kaposi's sarcoma in Brazil

    Directory of Open Access Journals (Sweden)

    Keller R.

    2001-01-01

    Full Text Available The aims of the present study were to determine the prevalence of human herpesvirus type 8 (HHV-8 in HIV-positive Brazilian patients with (HIV+/KS+ and without Kaposi's sarcoma (HIV+/KS- using PCR and immunofluorescence assays, to assess its association with KS disease, to evaluate the performance of these tests in detecting HHV-8 infection, and to investigate the association between anti-HHV-8 antibody titers, CD4 counts and staging of KS disease. Blood samples from 66 patients, 39 HIV+/KS+ and 27 HIV+/KS-, were analyzed for HHV-8 viremia in peripheral blood mononuclear cells by PCR and HHV-8 antigenemia for latent and lytic infection by immunofluorescence assay. Positive samples for latent nuclear HHV-8 antigen (LNA antibodies were titrated out from 1/100 to 1/409,600 dilution. Clinical information was collected from medical records and risk behavior was assessed through an interview. HHV-8 DNA sequences were detected by PCR in 74.3% of KS+ patients and in 3.7% of KS- patients. Serological assays were similar in detecting anti-LNA antibodies and anti-lytic antigens in sera from KS+ patients (79.5% and KS- patients (18.5%. HHV-8 was associated with KS whatever the method used, i.e., PCR (odds ratio (OR = 7.4, 95% confidence interval (CI = 2.16-25.61 or anti-LNA and anti-lytic antibodies (OR = 17.0, 95%CI = 4.91-59.14. Among KS+ patients, HHV-8 titration levels correlated positively with CD4 counts (rho 0.48, P = 0.02, but not with KS staging. HHV-8 is involved in the development of KS in different geographic areas worldwide, as it is in Brazil, where HHV-8 is more frequent among HIV+ patients. KS severity was associated with immunodeficiency, but no correlation was found between HHV-8 antibody titers and KS staging.

  20. Prognosis and delay of diagnosis among Kaposi's sarcoma patients in Uganda: a cross-sectional study.

    Science.gov (United States)

    De Boer, Christopher; Niyonzima, Nixon; Orem, Jackson; Bartlett, John; Zafar, S Yousuf

    2014-01-01

    In low- and middle-income countries, the association between delay to treatment and prognosis for Kaposi's sarcoma (KS) patients is yet to be studied. This is a prospective study of HIV-infected adults with histologically-confirmed KS treated at the Uganda Cancer Institute (UCI). Standardized interviews were conducted in English or Luganda. Medical records were abstracted for KS stage at admission to UCI. Multivariable logistic regression assessed relationships between diagnostic delay and stage at diagnosis. Of 161 patients (90% response rate), 69% were men, and the mean age was 34.0 years (SD 7.7). 26% had been seen in an HIV clinic within 3 months, 72% were on antiretroviral therapy, and 26% had visited a traditional healer prior to diagnosis. 45% delayed seeking care at UCI for ≥3 months from symptom onset. Among those who delayed, 36% waited 6 months, and 25% waited 12 months. Common reasons for delay were lack of pain (48%), no money (32%), and distance to UCI (8%). In adjusted analysis patients who experienced diagnostic delay were more likely than those who did not delay to have poor-risk KS stage (OR 3.41, p = 0.002, 95% CI: 1.46-7.45). In adjusted analyses visiting a traditional healer was the only variable associated with greater likelihood of delay (OR 2.69, p = 0.020, 95% CI: 1.17-6.17). Diagnostic delay was associated with poor-risk stage at diagnosis, and visiting a traditional healer was associated with higher odds of delay. The relationship between traditional and Western medicine presents a critical intervention point to improve KS-related outcomes in Uganda.

  1. Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities

    Energy Technology Data Exchange (ETDEWEB)

    Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta; Ikeda, Osamu; Okabe, Kanako; Kitai, Yuichi; Kon, Shigeyuki [Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812 (Japan); Oritani, Kenji [Department of Hematology and Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Matsuda, Tadashi, E-mail: tmatsuda@pharm.hokudai.ac.jp [Department of Immunology, Graduate School of Pharmaceutical Sciences Hokkaido University, Sapporo 060-0812 (Japan)

    2015-07-31

    Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activated GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR.

  2. Mesenchymal-to-endothelial transition in Kaposi sarcoma: a histogenetic hypothesis based on a case series and literature review.

    Directory of Open Access Journals (Sweden)

    Simona Gurzu

    Full Text Available OBJECTIVES: Although several studies have been conducted regarding Kaposi sarcoma (KS, its histogenesis still remains to be elucidated. The aim of our study was to analyze the immunophenotype of Kaposi sarcoma and to present a hypothesis about the histogenesis of this tumor, based on a case series and a review of relevant literature. METHODS: In 15 cases of KSs diagnosed during 2000-2011, the clinicopathological features were correlated with the immunoexpression of c-Kit, SMA, CD34, CD31, vascular endothelial growth factor (VEGF, COX-2, c-KIT, smooth muscle antigen (SMA, and stem cell surface marker CD105. RESULTS: Both CD105 and c-KIT rate of the spindle-shaped tumor cell positivity increased in parallel to the pathological stage. All cases displayed CD105 and weak c-KIT positivity in the endothelial cells. SMA, VEGF, and COX-2 were focally expressed in all cases. CD34 marked both endothelium and spindle-shaped tumor cells. No c-KIT expression was noticed in KS of the internal organs. CONCLUSIONS: KS seems to be a variant of myofibroblastic tumors that originates from the viral modified pluripotent mesenchymal cells of the connective tissue transformed in spindle-shaped KS cells, followed by a mesenchymal-endothelial transition and a myofibroblastic-like differentiation. This paper mailnly showed that KS cannot be considered a pure vascular tumor.

  3. Kaposi's sarcoma of the hand mimicking squamous cell carcinoma in a woman with no evidence of HIV infection: a case report

    Directory of Open Access Journals (Sweden)

    Kosmidis Christophoros

    2008-06-01

    Full Text Available Abstract Introduction Kaposi's sarcoma is a vascular neoplasm mainly affecting the skin of the lower extremities. Although it is the most common neoplasm affecting patients with AIDS, sporadic cases in HIV-negative people have been reported. It is a lesion mainly affecting men and its clinical presentation presents a challenge, as it can resemble other benign or malignant skin lesions. Case presentation We report a rare case of Kaposi's sarcoma presenting in a 68-year-old Mediterranean woman with no evidence of HIV infection. The patient had a 6-month history of a slowly progressing pigmented lesion on the dorsum of her left hand. The lesion clinically resembled a squamous cell carcinoma. The patient was treated with a wide excision of the lesion and primary reconstruction with a full thickness skin graft. Histopathological and immunohistochemical analysis of the excised lesion revealed the presence of Kaposi's sarcoma. Serologic investigation for HIV was negative but polymerase chain reaction for human herpes virus type 8 infection was positive. Thorough clinical and imaging investigation of the abdomen and chest were both negative for loci of disease. Conclusion Kaposi's sarcoma, although rare in its sporadic form, should be considered in the differential diagnosis of indeterminate skin lesions, especially those affecting the extremities.

  4. Changing patterns of Kaposi's sarcoma in Danish acquired immunodeficiency syndrome patients with complete follow-up. The Danish Study Group for HIV Infection (DASHI)

    DEFF Research Database (Denmark)

    Lundgren, Jens Dilling; Melbye, M; Pedersen, C

    1995-01-01

    clinically and with consecutive CD4 cell count measurement from time of AIDS-defining illness to date of death or censoring date, whichever came first. The proportion of homo-/bisexual men (n = 520) with Kaposi's sarcoma (n = 100) at AIDS diagnosis declined from 31% before 1985 to 13% in 1990, whereas...

  5. Primary effect of chemotherapy on the transcription profile of AIDS-related Kaposi's sarcoma

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    van Noesel Carel JM

    2002-09-01

    Full Text Available Abstract Background Drugs & used in anticancer chemotherapy have severe effects upon the cellular transcription and replication machinery. From in vitro studies it has become clear that these drugs can affect specific genes, as well as have an effect upon the total transcriptome. Methods Total mRNA from two skin lesions from a single AIDS-KS patient was analyzed with the SAGE (Serial Analysis of Gene Expression technique to assess changes in the transcriptome induced by chemotherapy. SAGE libraries were constructed from material obtained 24 (KS-24 and 48 (KS-48 hrs after combination therapy with bleomycin, doxorubicin and vincristine. KS-24 and KS-48 were compared to SAGE libraries of untreated AIDS-KS, and to libraries generated from normal skin and from isolated CD4+ T-cells, using the programs USAGE and HTM. SAGE libraries were also compared with the SAGEmap database. Results In order to assess the primary response of AIDS-related Kaposi's sarcoma (AIDS-KS to chemotherapy in vivo, we analyzed the transcriptome of AIDS-KS skin lesions from a HIV-1 seropositive patient at two time points after therapy. The mRNA profile was found to have changed dramatically within 24 hours after drug treatment. There was an almost complete absence of transcripts highly expressed in AIDS-KS, probably due to a transcription block. Analysis of KS-24 suggested that mRNA pool used in its construction originated from poly(A binding protein (PABP mRNP complexes, which are probably located in nuclear structures known as interchromatin granule clusters (IGCs. IGCs are known to fuse after transcription inhibition, probably affecting poly(A+RNA distribution. Forty-eight hours after chemotherapy, mRNA isolated from the lesion was largely derived from infiltrating lymphocytes, confirming the transcriptional block in the AIDS-KS tissue. Conclusions These in vivo findings indicate that the effect of anti-cancer drugs is likely to be more global than up- or downregulation of

  6. Predictive clinical factors in the diagnosis of gastrointestinal Kaposi's sarcoma and its endoscopic severity.

    Directory of Open Access Journals (Sweden)

    Naoyoshi Nagata

    Full Text Available BACKGROUND: The diagnosis of gastrointestinal (GI involvement in Kaposi's sarcoma (KS is important to make because the need for treatment depends on the extent of the disease. Moreover, severe GI lesions can cause serious complications. Endoscopy with biopsy is an extremely useful method to diagnose GI-KS. However, determining the indications for endoscopy is difficult because KS can occur without GI symptoms or cutaneous KS. This study sought to clarify predictive clinical factors for GI-KS and its severity on endoscopy. METHODOLOGY/PRINCIPAL FINDINGS: A total of 1,027 HIV-infected patients who underwent endoscopy were analyzed. Sexual behavior, CD4 count, HIV RNA, history of highly active antiretroviral therapy (HAART, GI symptoms, and cutaneous KS were assessed. Endoscopic severity including bulky tumor, ulceration, and number of lesions were evaluated. Thirty-three patients had GI-KS and 46 patients cutaneous KS. Among the GI-KS patients, 78.8% (26/33 had no GI symptoms and 24.2% (8/33 had no cutaneous KS. Univariate analysis identified men who have sex with men (MSM, CD4 <100 cells/µL, HIV RNA ≥10,000 copies/mL, no history of HAART, and cutaneous KS were significantly associated with GI-KS. Among these factors, cutaneous KS was closely related to GI-KS on multivariable analysis. Among patients without cutaneous KS, MSM and CD4 count <100 cells/µL were the only independent clinical factors related to GI-KS. Bulky tumor was significantly associated with CD4 <100 cells/µL and large number of lesions was significantly associated with HIV-RNA ≥10,000 copies/mL. CONCLUSIONS: To diagnose GI-KS, clinical factors need to be considered before endoscopy. The presence of GI symptoms is not useful in predicting GI-KS. MSM and CD4 count <100 cells/µL are predictive factors among patients without cutaneous KS. Caution should be exercised especially in patients with low CD4 counts or high HIV viral loads as they are more likely to develop severe GI

  7. Glycolysis, Glutaminolysis, and Fatty Acid Synthesis Are Required for Distinct Stages of Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication.

    Science.gov (United States)

    Sanchez, Erica L; Pulliam, Thomas H; Dimaio, Terri A; Thalhofer, Angel B; Delgado, Tracie; Lagunoff, Michael

    2017-05-15

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). KSHV infection induces and requires multiple metabolic pathways, including the glycolysis, glutaminolysis, and fatty acid synthesis (FAS) pathways, for the survival of latently infected endothelial cells. To determine the metabolic requirements for productive KSHV infection, we induced lytic replication in the presence of inhibitors of different metabolic pathways. We found that glycolysis, glutaminolysis, and FAS are all required for maximal KSHV virus production and that these pathways appear to participate in virus production at different stages of the viral life cycle. Glycolysis and glutaminolysis, but not FAS, inhibit viral genome replication and, interestingly, are required for different early steps of lytic gene expression. Glycolysis is necessary for early gene transcription, while glutaminolysis is necessary for early gene translation but not transcription. Inhibition of FAS resulted in decreased production of extracellular virions but did not reduce intracellular genome levels or block intracellular virion production. However, in the presence of FAS inhibitors, the intracellular virions are noninfectious, indicating that FAS is required for virion assembly or maturation. KS tumors support both latent and lytic KSHV replication. Previous work has shown that multiple cellular metabolic pathways are required for latency, and we now show that these metabolic pathways are required for efficient lytic replication, providing novel therapeutic avenues for KS tumors. IMPORTANCE KSHV is the etiologic agent of Kaposi's sarcoma, the most common tumor of AIDS patients. KS spindle cells, the main tumor cells, all contain KSHV, mostly in the latent state, during which there is limited viral gene expression. However, a percentage of spindle cells support lytic replication and production of virus and these cells are thought to contribute to overall tumor formation. Our

  8. Kaposis sarkom tolket som haematom

    DEFF Research Database (Denmark)

    Balle, Jesper R; Hasselager, Thomas

    2010-01-01

    Kaposi's sarcoma is a frequent skin cancer in HIV-positive patients, but is relatively uncommon in HIV-negative and non-immune compromised patients. We present a case of Kaposi's sarcoma of the face and scalp in a HIV-negative male with previous facial basal cell carcinoma.......Kaposi's sarcoma is a frequent skin cancer in HIV-positive patients, but is relatively uncommon in HIV-negative and non-immune compromised patients. We present a case of Kaposi's sarcoma of the face and scalp in a HIV-negative male with previous facial basal cell carcinoma....

  9. A negative element involved in Kaposi's sarcoma-associated herpesvirus-encoded ORF11 gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lei [Los Alamos National Laboratory

    2009-01-01

    The ORF11 of the Kaposi's sarcoma-associated herpesvirus (KSHV) is a lytic viral gene with delayed-early expression kinetics. How the ORF11 gene expression is regulated in the KSHV lytic cascade is largely unknown. Here we report that the deletion of the KSHV viral IL-6 gene from the viral genome leads to deregulated ORF11 gene expression. The KSHV-encoded viral IL-6 protein was found not to be essentially involved in the regulation of ORF11, suggesting a potential transcriptional cis-regulation. A negative element was identified downstream of the ORF11 gene, which suppresses the ORF11 basal promoter activity in a position-independent manner.

  10. Steroid-exacerbated HIV-associated cutaneous Kaposi's sarcoma immune reconstitution inflammatory syndrome: 'Where a good intention turns bad'.

    Science.gov (United States)

    Chabria, Shiven; Barakat, Lydia; Ogbuagu, Onyema

    2016-10-01

    A 51-year-old man with head and neck skin lesions was diagnosed with Kaposi's sarcoma (KS) as his initial presentation of acquired immunodeficiency syndrome. Following initiation of antiretroviral therapy and subsequent full virologic suppression, his facial lesions worsened, consistent with immune reconstitution inflammatory syndrome (IRIS). He was started on glucocorticoids in an attempt to ameliorate the KS-IRIS but experienced paradoxical worsening of the KS lesions. Steroids were subsequently discontinued and he required chemotherapy for severe and cosmetically disfiguring skin lesions. This article describes the potential for worsening of KS lesions in individuals started on glucocorticoids for KS-IRIS as this has been reported rarely in published literature. The mechanisms underlying this phenomenon remain poorly understood but potential explanations are offered in the case discussion. This article aims to raise clinician awareness on the harms of steroid use in patients with KS-IRIS. © The Author(s) 2016.

  11. Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV-8)-infected B cells in HIV+ multicentric Castleman disease (MCD).

    Science.gov (United States)

    Chadburn, A; Hyjek, E M; Tam, W; Liu, Y; Rengifo, T; Cesarman, E; Knowles, D M

    2008-11-01

    Kaposi sarcoma herpesvirus (KSHV) is aetiologically related to Kaposi sarcoma, classical and extracavitary primary effusion lymphoma (PEL; EC-PEL) and multicentric Castleman disease (MCD), entities preferentially occurring in HIV-infected individuals. Characterization of HIV-associated PELs/EC-PELs suggests that the KSHV-infected malignant cells originate from a pre-terminal stage of B-cell differentiation. However, only limited phenotypic studies have been performed on HIV+ MCD, including for PR domain containing 1 with zinc finger domain/B lymphocyte-induced maturation protein 1 (PRDM1/BLIMP1), a key regulator of terminal B-cell differentiation. The aim was to characterize KSHV-infected cells in 17 cases of HIV+ MCD. Double immunohistochemistry and immunohistochemistry-in situ hybridization were used to characterize the KSHV-infected cells in MCD; the results were compared with the phenotypic profiles of 39 PELs/EC-PELs and seven PEL cell lines. Whereas the immunophenotype of KSHV-infected cells in MCD and malignant KSHV+ PEL cells was similar (PAX5, Bcl-6-; PRDM1/BLIMP1, IRF4/MUM1+; Ki67+), the MCD KSHV-infected cells differed, as they expressed OCT2, cytoplasmic lambda immunoglobulin; variably expressed CD27; lacked CD138; and were Epstein-Barr virus negative. Although both PEL and MCD originate from KSHV-infected pre-terminally differentiated B cells, these findings, with previously reported genetic studies, indicate HIV+ MCD may arise from extrafollicular B cells, whereas PELs may originate from cells that have traversed the germinal centre.

  12. The Crystal Structure of PF-8, the DNA Polymerase Accessory Subunit from Kaposi's Sarcoma-Associated Herpesvirus

    Energy Technology Data Exchange (ETDEWEB)

    Baltz, Jennifer L.; Filman, David J.; Ciustea, Mihai; Silverman, Janice Elaine Y.; Lautenschlager, Catherine L.; Coen, Donald M.; Ricciardi, Robert P.; Hogle, James M.; (UPENN)

    2009-12-01

    Kaposi's sarcoma-associated herpesvirus is an emerging pathogen whose mechanism of replication is poorly understood. PF-8, the presumed processivity factor of Kaposi's sarcoma-associated herpesvirus DNA polymerase, acts in combination with the catalytic subunit, Pol-8, to synthesize viral DNA. We have solved the crystal structure of residues 1 to 304 of PF-8 at a resolution of 2.8 {angstrom}. This structure reveals that each monomer of PF-8 shares a fold common to processivity factors. Like human cytomegalovirus UL44, PF-8 forms a head-to-head dimer in the form of a C clamp, with its concave face containing a number of basic residues that are predicted to be important for DNA binding. However, there are several differences with related proteins, especially in loops that extend from each monomer into the center of the C clamp and in the loops that connect the two subdomains of each protein, which may be important for determining PF-8's mode of binding to DNA and to Pol-8. Using the crystal structures of PF-8, the herpes simplex virus catalytic subunit, and RB69 bacteriophage DNA polymerase in complex with DNA and initial experiments testing the effects of inhibition of PF-8-stimulated DNA synthesis by peptides derived from Pol-8, we suggest a model for how PF-8 might form a ternary complex with Pol-8 and DNA. The structure and the model suggest interesting similarities and differences in how PF-8 functions relative to structurally similar proteins.

  13. The Crystal Structure of PF-8, the DNA Polymerase Accessory Subunit from Kaposi's Sarcoma-Associated Herpesvirus▿

    Science.gov (United States)

    Baltz, Jennifer L.; Filman, David J.; Ciustea, Mihai; Silverman, Janice Elaine Y.; Lautenschlager, Catherine L.; Coen, Donald M.; Ricciardi, Robert P.; Hogle, James M.

    2009-01-01

    Kaposi's sarcoma-associated herpesvirus is an emerging pathogen whose mechanism of replication is poorly understood. PF-8, the presumed processivity factor of Kaposi's sarcoma-associated herpesvirus DNA polymerase, acts in combination with the catalytic subunit, Pol-8, to synthesize viral DNA. We have solved the crystal structure of residues 1 to 304 of PF-8 at a resolution of 2.8 Å. This structure reveals that each monomer of PF-8 shares a fold common to processivity factors. Like human cytomegalovirus UL44, PF-8 forms a head-to-head dimer in the form of a C clamp, with its concave face containing a number of basic residues that are predicted to be important for DNA binding. However, there are several differences with related proteins, especially in loops that extend from each monomer into the center of the C clamp and in the loops that connect the two subdomains of each protein, which may be important for determining PF-8's mode of binding to DNA and to Pol-8. Using the crystal structures of PF-8, the herpes simplex virus catalytic subunit, and RB69 bacteriophage DNA polymerase in complex with DNA and initial experiments testing the effects of inhibition of PF-8-stimulated DNA synthesis by peptides derived from Pol-8, we suggest a model for how PF-8 might form a ternary complex with Pol-8 and DNA. The structure and the model suggest interesting similarities and differences in how PF-8 functions relative to structurally similar proteins. PMID:19759157

  14. Exploitation of the complement system by oncogenic Kaposi's sarcoma-associated herpesvirus for cell survival and persistent infection.

    Directory of Open Access Journals (Sweden)

    Myung-Shin Lee

    2014-09-01

    Full Text Available During evolution, herpesviruses have developed numerous, and often very ingenious, strategies to counteract efficient host immunity. Specifically, Kaposi's sarcoma-associated herpesvirus (KSHV eludes host immunity by undergoing a dormant stage, called latency wherein it expresses a minimal number of viral proteins to evade host immune activation. Here, we show that during latency, KSHV hijacks the complement pathway to promote cell survival. We detected strong deposition of complement membrane attack complex C5b-9 and the complement component C3 activated product C3b on Kaposi's sarcoma spindle tumor cells, and on human endothelial cells latently infected by KSHV, TIME-KSHV and TIVE-LTC, but not on their respective uninfected control cells, TIME and TIVE. We further showed that complement activation in latently KSHV-infected cells was mediated by the alternative complement pathway through down-regulation of cell surface complement regulatory proteins CD55 and CD59. Interestingly, complement activation caused minimal cell death but promoted the survival of latently KSHV-infected cells grown in medium depleted of growth factors. We found that complement activation increased STAT3 tyrosine phosphorylation (Y705 of KSHV-infected cells, which was required for the enhanced cell survival. Furthermore, overexpression of either CD55 or CD59 in latently KSHV-infected cells was sufficient to inhibit complement activation, prevent STAT3 Y705 phosphorylation and abolish the enhanced survival of cells cultured in growth factor-depleted condition. Together, these results demonstrate a novel mechanism by which an oncogenic virus subverts and exploits the host innate immune system to promote viral persistent infection.

  15. Kaposi's Sarcoma-Associated Herpesvirus Utilizes and Manipulates RNA N6-Adenosine Methylation To Promote Lytic Replication

    Science.gov (United States)

    Chen, E. Ricky; Nilsen, Timothy W.

    2017-01-01

    ABSTRACT N6-adenosine methylation (m6A) is the most common posttranscriptional RNA modification in mammalian cells. We found that most transcripts encoded by the Kaposi's sarcoma-associated herpesvirus (KSHV) genome undergo m6A modification. The levels of m6A-modified mRNAs increased substantially upon stimulation for lytic replication. The blockage of m6A inhibited splicing of the pre-mRNA encoding the replication transcription activator (RTA), a key KSHV lytic switch protein, and halted viral lytic replication. We identified several m6A sites in RTA pre-mRNA crucial for splicing through interactions with YTH domain containing 1 (YTHDC1), an m6A nuclear reader protein, in conjunction with serine/arginine-rich splicing factor 3 (SRSF3) and SRSF10. Interestingly, RTA induced m6A and enhanced its own pre-mRNA splicing. Our results not only demonstrate an essential role of m6A in regulating RTA pre-mRNA splicing but also suggest that KSHV has evolved a mechanism to manipulate the host m6A machinery to its advantage in promoting lytic replication. IMPORTANCE KSHV productive lytic replication plays a pivotal role in the initiation and progression of Kaposi's sarcoma tumors. Previous studies suggested that the KSHV switch from latency to lytic replication is primarily controlled at the chromatin level through histone and DNA modifications. The present work reports for the first time that KSHV genome-encoded mRNAs undergo m6A modification, which represents a new mechanism at the posttranscriptional level in the control of viral replication. PMID:28592530

  16. Effect of electrochemotherapy on human herpesvirus 8 kinetics in classic Kaposi sarcoma.

    Science.gov (United States)

    Starita, Noemy; Di Monta, Gianluca; Cerasuolo, Andrea; Marone, Ugo; Anniciello, Anna Maria; Botti, Gerardo; Buonaguro, Luigi; Buonaguro, Franco M; Tornesello, Maria Lina

    2017-01-01

    Electrochemotherapy (ECT) has shown to be an effective treatment for cutaneous and subcutaneous Kaposi sarcoma (KS) lesions. However, no study has investigated the impact of ECT treatment on the kinetics of human herpesvirus type 8 (HHV8), which is considered the necessary causal agent of KS. We aimed to evaluate HHV8 viral load and expression levels in patients affected by classic KS who received one or more ECT treatments and have been followed semi annually for up to four years. A total of 27 classic KS patients were enrolled in this study. Tumour biopsies and blood samples were obtained before ECT treatment. Additional blood samples were collected at six month intervals for 12-48 months. HHV8 viral load and expression profiles of latent (ORF72 and ORF73) and lytic (K2, K8, K8.1, K10/K10.1, K10.5/K10.6 and ORF16) genes were assessed in all samples by real-time PCR. HHV8 ORF26 and K1 regions were amplified and subjected to direct nucleotide sequencing followed by phylogenetic analysis for variant identification. All KS biopsies and 46.4% of peripheral blood mononuclear cells (PBMCs) collected before ECT treatment were positive for HHV8 DNA. Viral load ranged from 0.02 to 2.3 copies per cell in KS lesions and 3.0 × 10-7 to 6.9 × 10-4 copies per cell in PBMCs. Overall, latent ORF72 and ORF73 as well as lytic K2, K8 and K10/K10.1 were expressed in all KS biopsies. ORF16 mRNA was detected in 71.4% and both K8.1 and K10.5/K10.6 mRNAs in 57.1% of KS samples. The ORF72, ORF73 and K2 transcripts were amplified in 37.5%, 25% and 25% of PBMCs collected before ECT, respectively. After the first ECT session, complete response was achieved in 20 out of 27 (74.1%) patients and HHV8 DNA was detected in four out of 27 (14.8%) PBMC samples at six month follow up. Phylogenetic analysis of ORF26 amplimers showed that most viral variants belonged to A/C (82.3%), and few to C2 (5.9%) or C3 (11.8%) subtype. The K1/VR1 variants fell into A (33.3%) and C (66.7%) HHV8 clade. No

  17. Asynchronous Progression through the Lytic Cascade and Variations in Intracellular Viral Loads Revealed by High-Throughput Single-Cell Analysis of Kaposi's Sarcoma-Associated Herpesvirus Infection

    OpenAIRE

    Adang, Laura A.; Parsons, Christopher H.; Kedes, Dean H.

    2006-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus-8) is frequently tumorigenic in immunocompromised patients. The average intracellular viral copy number within infected cells, however, varies markedly by tumor type. Since the KSHV-encoded latency-associated nuclear antigen (LANA) tethers viral episomes to host heterochromatin and displays a punctate pattern by fluorescence microscopy, we investigated whether accurate quantification of individual LANA dots is predictive of in...

  18. Complete response of endemic Kaposi sarcoma lesions with high-dose-rate brachytherapy: treatment method, results, and toxicity using skin surface applicators.

    Science.gov (United States)

    Kasper, Michael E; Richter, Sam; Warren, Nicholas; Benda, Rashmi; Shang, Charles; Ouhib, Zoubir

    2013-01-01

    To analyze the clinical outcome of Kaposi sarcoma skin lesions treated with high-dose-rate (HDR) brachytherapy in patients with a minimum of 2 years of followup. Between February 2006 and July 2008, all patients with Kaposi sarcoma who received (192)Ir HDR brachytherapy using a skin surface applicator were evaluated for clinical response. Responses to treatment and toxicity were scored using standard criteria. Sixteen cases were collected. Treatment was delivered in four to six fractions, over a period of approximately 12 days. The specified dose ranged from 24 to 35Gy. Median followup the lesion was 41.4 months. No lesion was greater than 2cm. All patients had a complete response to treatment, with no evidence of local recurrence or tumor progression. Thirteen lesions developed Grade 1 and two lesions had Grade 2 acute skin reactions. One patient developed late skin changes with telangiectasias and hypopigmentation. HDR brachytherapy treatment seems to be an effective noninvasive option for patients with small cutaneous Kaposi sarcoma lesions, delivering excellent cosmesis and local control in our small series. Fewer fractions over a shorter period used in our group offer patients more convenience compared with other common regimens. Although HDR is being used more frequently for many surface applications, additional clinical studies with larger numbers of patients and longer followup are needed to confirm the general impression that it is an excellent option for many patients. Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  19. Kaposis sarkom tolket som haematom

    DEFF Research Database (Denmark)

    Balle, Jesper R; Hasselager, Thomas

    2010-01-01

    Kaposi's sarcoma is a frequent skin cancer in HIV-positive patients, but is relatively uncommon in HIV-negative and non-immune compromised patients. We present a case of Kaposi's sarcoma of the face and scalp in a HIV-negative male with previous facial basal cell carcinoma....

  20. Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence.

    Science.gov (United States)

    Sun, Qiming; Tsurimoto, Toshiki; Juillard, Franceline; Li, Lin; Li, Shijun; De León Vázquez, Erika; Chen, She; Kaye, Kenneth

    2014-08-12

    Kaposi's sarcoma-associated herpesvirus (KSHV) latently infects tumor cells and persists as a multiple-copy, extrachromosomal, circular episome. To persist, the viral genome must replicate with each cell cycle. The KSHV latency-associated nuclear antigen (LANA) mediates viral DNA replication and persistence, but little is known regarding the underlying mechanisms. We find that LANA recruits replication factor C (RFC), the DNA polymerase clamp [proliferating cell nuclear antigen (PCNA)] loader, to drive DNA replication efficiently. Mutated LANA lacking RFC interaction was deficient for LANA-mediated DNA replication and episome persistence. RFC depletion had a negative impact on LANA's ability to replicate and maintain viral DNA in cells containing artificial KSHV episomes or in infected cells, leading to loss of virus. LANA substantially increased PCNA loading onto DNA in vitro and recruited RFC and PCNA to KSHV DNA in cells. These findings suggest that PCNA loading is a rate-limiting step in DNA replication that is incompatible with viral survival. LANA enhancement of PCNA loading permits efficient virus replication and persistence, revealing a previously unidentified mechanism for KSHV latency.

  1. New insights into the expression and functions of the Kaposi's sarcoma-associated herpesvirus long noncoding PAN RNA.

    Science.gov (United States)

    Conrad, Nicholas K

    2016-01-02

    The Kaposi's sarcoma-associated herpesvirus (KSHV) is a clinically relevant pathogen associated with several human diseases that primarily affect immunocompromised individuals. KSHV encodes a noncoding polyadenylated nuclear (PAN) RNA that is essential for viral propagation and viral gene expression. PAN RNA is the most abundant viral transcript produced during lytic replication. The accumulation of PAN RNA depends on high levels of transcription driven by the Rta protein, a KSHV transcription factor necessary and sufficient for latent-to-lytic phase transition. In addition, KSHV uses several posttranscriptional mechanisms to stabilize PAN RNA. A cis-acting element, called the ENE, prevents PAN RNA decay by forming a triple helix with its poly(A) tail. The viral ORF57 and the cellular PABPC1 proteins further contribute to PAN RNA stability during lytic phase. PAN RNA functions are only beginning to be uncovered, but PAN RNA has been proposed to control gene expression by several different mechanisms. PAN RNA associates with the KSHV genome and may regulate gene expression by recruiting chromatin-modifying factors. Moreover, PAN RNA binds the viral latency-associated nuclear antigen (LANA) protein and decreases its repressive activity by sequestering it from the viral genome. Surprisingly, PAN RNA was found to associate with translating ribosomes, so this noncoding RNA may be additionally used to produce viral peptides. In this review, I highlight the mechanisms of PAN RNA accumulation and describe recent insights into potential functions of PAN RNA. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. The Cancer-Associated Virus Landscape in HIV Patients with Oral Hairy Leukoplakia, Kaposi's Sarcoma, and Non-Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Peter D. Burbelo

    2012-01-01

    Full Text Available Although HIV-positive patients are at higher risk for developing a variety of infection-related cancers, the prevalence of infections with the seven known cancer-associated viruses has not been studied. Luciferase immunoprecipitation systems were used to evaluate antiviral antibodies in four 23-person groups: healthy blood donors and HIV-infected patients with oral hairy leukoplakia (OLP, Kaposi's sarcoma (KS, or non-Hodgkin lymphoma (NHL. Antibody profiling revealed that all HIV-positive individuals were strongly seropositive for anti-gp41 and antireverse transcriptase antibodies. However, anti-p24 HIV antibody levels were highly variable and some OLP and KS patients demonstrated weak or negative responses. Profiling two EBV antigens revealed no statistical difference in antibody levels among the three HIV-infected groups. A high frequency of KSHV infection was detected in HIV patients including 100% of KS, 78% of OLP, and 57% of NHL patients. Most HIV-infected subjects (84% showed anti-HBV core antibodies, but only a few showed antibodies against HCV. MCV seropositivity was also common (94% in the HIV-infected individuals and KS patients showed statistically higher antibody levels compared to the OLP and NHL patients. Overall, 68% of the HIV-infected patients showed seropositivity with at least four cancer-associated viruses. Antibody profiles against these and other infectious agents could be useful for enhancing the clinical management of HIV patients.

  3. Effective inhibition of Rta expression and lytic replication of Kaposi's sarcoma-associated herpesvirus by human RNase P.

    Science.gov (United States)

    Zhu, Jiaming; Trang, Phong; Kim, Kihoon; Zhou, Tianhong; Deng, Hongyu; Liu, Fenyong

    2004-06-15

    Ribonuclease P (RNase P) complexed with external guide sequence (EGS) represents a nucleic acid-based gene interference approach to knock-down gene expression. Unlike other strategies, such as antisense oligonucleotides, ribozymes, and RNA interference, the RNase P-based technology is unique because a custom-designed EGS molecule can bind to any complementary mRNA sequence and recruit intracellular RNase P for specific degradation of the target mRNA. In this study, we demonstrate that the RNase P-based strategy is effective in blocking gene expression and growth of Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), the causative agent of the leading AIDS-associated neoplasms, such as KS and primary-effusion lymphoma. We constructed 2'-O-methyl-modified EGS molecules that target the mRNA encoding KSHV immediate-early transcription activator Rta, and we administered them directly to human primary-effusion lymphoma cells infected with KSHV. A reduction of 90% in Rta expression and a reduction of approximately 150-fold in viral growth were observed in cells treated with a functional EGS. In contrast, a reduction of EGSs are highly effective in inhibiting KSHV gene expression and growth. Exogenous administration of chemically modified EGSs in inducing RNase P-mediated cleavage represents an approach for inhibiting specific gene expression and for treating human diseases, including KSHV-associated tumors.

  4. Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells

    Science.gov (United States)

    Cai, Xuezhong; Lu, Shihua; Zhang, Zhihong; Gonzalez, Carlos M.; Damania, Blossom; Cullen, Bryan R.

    2005-01-01

    MicroRNAs (miRNAs) are an endogenously encoded class of small RNAs that have been proposed to function as key posttranscriptional regulators of gene expression in a range of eukaryotic species, including humans. The small size of miRNA precursors makes them potentially ideal for use by viruses as inhibitors of host cell defense pathways. Here, we demonstrate that the pathogenic human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) encodes an array of 11 distinct miRNAs, all of which are expressed at readily detectable levels in latently KSHV infected cells. Individual KSHV miRNAs were expressed at up to 2,200 copies per cell. The KSHV miRNAs are expressed from what appears to be a single genetic locus that largely coincides with an ≈4-kb noncoding sequence located between the KSHV v-cyclin and K12/Kaposin genes, both of which are also expressed in latently infected cells. Computer analysis of potential mRNA targets for these viral miRNAs identified a number of interesting candidate genes, including several mRNAs previously shown to be down-regulated in KSHV-infected cells. We hypothesize that these viral miRNAs play a critical role in the establishment and/or maintenance of KSHV latent infection in vivo and, hence, in KSHV-induced oncogenesis. PMID:15800047

  5. Kaposi's sarcoma: a population-based cancer registry descriptive study of 57 consecutive cases diagnosed between 1977 and 2009.

    Science.gov (United States)

    Laresche, Claire; Fournier, Evelyne; Dupond, Anne Sophie; Woronoff, Anne Sophie; Drobacheff-Thiebaut, Christine; Humbert, Philippe; Aubin, Francois

    2014-12-01

    There are few epidemiological data available on rare skin cancer, including Kaposi's sarcoma (KS), which is a multifocal illness affecting the skin, mucosa, and viscera. Four different types of KS have been described: classic, AIDS-associated, iatrogenic, and African. The purpose of this study was to describe the epidemiology and evolution of the different types of KS in the Doubs region of France. A retrospective population-based study was conducted, including 57 patients with KS from the Doubs region between 1977 and 2009. These patients were identified by the tumor registry of the Doubs region. A larger proportion of AIDS-associated KS (61%) was observed compared to classic KS (30%) and iatrogenic KS (9%). No cases of African KS were observed. Most new cases were observed between 1987 and 1996 due to the AIDS explosion. The patients were predominantly male, with a male/female ratio at 10 : 4 (34 for AIDS-associated KS). The mean age of patients was 50.2 (higher in classic and iatrogenic KS and lower in AIDS-associated KS). Mucosal and visceral forms were more common in AIDS-associated KS, explaining the higher rate of mortality due to KS (21%). KS, which used to be a rare illness, as it existed only in the classic form, has become more common since the appearance of HIV and, to a lesser extent, of immunosuppressive treatment. © 2014 The International Society of Dermatology.

  6. Identification and characterization of Kaposi's sarcoma-associated herpesvirus open reading frame 11 promotor activation

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    Chen, Lei [Los Alamos National Laboratory

    2008-01-01

    Open reading frame 11 (ORF11) of Kaposi's sarcoma-associated herpesvirus belongs to a herpesviral homologous protein family shared by some members of the gamma- herpesvirus subfamily. Little is known about this ORF11 homologous protein family. We have characterized an unknown open reading frame, ORF11, located adjacent and in the opposite orientation to a well-characterized viral IL-6 gene. Northern blot analysis reveals that ORF11 is expressed during the KSHV lytic cycle with delayed-early transcription kinetics. We have determined the 5{prime} and 3{prime} untranslated region of the unspliced ORF11 transcript and identified both the transcription start site and the transcription termination site. Core promoter region, representing ORF11 promoter activity, was mapped to a 159nt fragment 5{prime} most proximal to the transcription start site. A functional TATA box was identified in the core promoter region. Interestingly, we found that ORF11 transcriptional activation is not responsive to Rta, the KSHV lytic switch protein. We also discovered that part of the ORF11 promoter region, the 209nt fragment upstream of the transcription start site, was repressed by phorbol esters. Our data help to understand transcription regulation of ORF11 and to elucidate roles of ORF11 in KSHV pathogenesis and life cycle.

  7. Immunological changes in psoriasis patients under long-term treatment with fumaric acid esters: risk of Kaposi sarcoma occurrence?

    Science.gov (United States)

    Philipp, Sandra; Kokolakis, Georgios; Hund, Martina; Witte, Ellen; Witte, Katrin; Kunz, Stefanie; Roewert, Hans Joachim; Sterry, Wolfram; Sabat, Robert

    2013-01-01

    Psoriasis is a chronic skin disorder. The most frequently used systemic anti-psoriatic therapy in Germany is fumaric acid esters (FAE). We aimed to characterize immunological changes in psoriasis patients under FAE treatment. Over 200 flow-cytometry analyses of blood from 27 psoriasis patients and histological, molecular, and serological analyses of samples from a patient who developed Kaposi sarcoma (KS) during FAE therapy were performed. The patients receiving FAE showed decreased CD8+ T cell counts, in particular during the first six months. The CD4+ T cell decline was less pronounced and delayed in time. In a patient with KS, we found a profound CD4 and CD8 lymphocytopenia, as well as a NK cell number reduction, although leukocyte and lymphocyte counts were within the recommended limits. The patient was HIV negative, but positive for HHV8. After cessation of FAE therapy, KS regressed. HHV8 infection and iatrogenic T cell reduction, prominently of CD8+ T cells, could have contributed to KS development in this patient. Therefore, we suggest a control of CD4+ and CD8+ T cell counts in addition to the commonly-used differential blood counts in patients with a higher HHV8 prevalence or at high risk of other latent viral infections.

  8. Radiation therapy of epidemic kaposi sarcoma: the Henri-Mondor hospital experience (643 patients); Radiotherapie du sarcome de kaposi epidemique: l`experience de l`hopital Henri-Mondor (643 patients)

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    Belembaogo, E.; Kirova, Y.; Frikha, H.; Yu, S.; Piedbois, P.; Le Bourgeois, J.P. [Hopital Henri-Mondor, 94 - Creteil (France). Dept. de cancerologie

    1998-01-01

    From June 1986 to December 1996, 643 patients presenting with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi`s sarcoma were treated with irradiation at the Oncology Department of Henri Mondor University Hospital. Three-hundred eighty-seven patients (60 %) had previously received a treatment with interferon (259 patients, 40.2 %), vinblastine (225 patients, 34.5 %), doxorubicin (22 patients, 3.4 %), bleomycin (19 patients, 2.9 %), and/or antiviral treatment (216, 33.5 %). The radiotherapy was delivered by 4 MeV OR 8 MeV electron beam for extended cutaneous fields and 45-100 kV x-ray for localized fields. The delivered dose was 20 Gy in 2 weeks (2.5 Gy/fraction, 4 fractions/week) followed by 2 weeks rest and second series of 10 Gy in 1 week. For oral cavity lesions, we used a series of 15.2 Gy was delivered (1.9 Gy/fraction, 4 fractions/week), followed for three patients by a 3 week rest and by a similar second series of 15.2 Gy.Six-hundred and twenty-one patients were evaluable and the objective response rate was 92 %, with e complete regression of clinical and functional symptoms for all patients. The skin tolerance was good, with 7.3 % grade I reactions, 69.3 % of grade II reactions, and 23.4 % grade III reactions. There was a correlation between recurrence rate and the occurrence of opportunistic infections. This analysis shows the efficacy of dose radiotherapy for treatment of epidemic Kaposi sarcoma. (author)

  9. Pegylated liposomal doxorubicin: a review of its use in metastatic breast cancer, ovarian cancer, multiple myeloma and AIDS-related Kaposi's sarcoma.

    Science.gov (United States)

    Duggan, Sean T; Keating, Gillian M

    2011-12-24

    Pegylated liposomal doxorubicin (Caelyx™, Doxil®) represents an improved formulation of conventional doxorubicin, with reduced cardiotoxicity and an improved pharmacokinetic profile. This article reviews the efficacy and tolerability of pegylated liposomal doxorubicin in metastatic breast cancer, progressive ovarian cancer, relapsed or refractory multiple myeloma and AIDS-related Kaposi's sarcoma, as well as summarizing its pharmacological properties. In three randomized, open-label, multicentre trials, monotherapy with pegylated liposomal doxorubicin was as effective as doxorubicin or capecitabine in the first-line treatment of metastatic breast cancer, and as effective as vinorelbine or combination mitomycin plus vinblastine in taxane-refractory metastatic breast cancer. Pegylated liposomal doxorubicin alone was as effective as topotecan or gemcitabine alone in patients with progressive ovarian cancer resistant or refractory to platinum- or paclitaxel-based therapy, according to the results of three randomized multicentre trials. In addition, in patients with progressive ovarian cancer who had received prior platinum-based therapy, progression-free survival was significantly longer with pegylated liposomal doxorubicin plus carboplatin than with paclitaxel plus carboplatin, according to the results of a randomized, open-label multicentre trial. Combination therapy with pegylated liposomal doxorubicin plus bortezomib was more effective than bortezomib alone in patients with relapsed or refractory multiple myeloma, according to the results of a randomized, open-label, multinational trial. Randomized multinational trials also demonstrated the efficacy of pegylated liposomal doxorubicin in patients with advanced AIDS-related Kaposi's sarcoma. Pegylated liposomal doxorubicin exhibited a relatively favourable safety profile compared with conventional doxorubicin and other available chemotherapy agents. The most common treatment-related adverse events included

  10. Was Kaposi's sarcoma-associated herpesvirus introduced into China via the ancient Silk Road? An evolutionary perspective.

    Science.gov (United States)

    Liu, Zhenqiu; Fang, Qiwen; Zuo, Jialu; Minhas, Veenu; Wood, Charles; He, Na; Zhang, Tiejun

    2017-07-07

    Kaposi's sarcoma-associated herpesvirus (KSHV) has become widely dispersed worldwide since it was first reported in 1994, but the seroprevalence of KSHV varies geographically. KSHV is relatively ubiquitous in Mediterranean areas and the Xinjiang Uygur Autonomous Region, China. The origin of KSHV has long been puzzling. In the present study, we collected and analysed 154 KSHV ORF-K1 sequences obtained from samples originating from Xinjiang, Italy, Greece, Iran and southern Siberia using Bayesian evolutionary analysis in BEAST to test the hypothesis that KSHV was introduced into Xinjiang via the ancient Silk Road. According to the phylogenetic analysis, 72 sequences were subtype A and 82 subtype C, with C2 (n = 56) being the predominant subtype. The times to the most recent common ancestors (tMRCAs) of KSHV were 29,872 years (95% highest probability density [HPD], 26,851-32,760 years) for all analysed sequences and 2037 years (95% HPD, 1843-2229 years) for Xinjiang sequences in particular. The tMRCA of Xinjiang KSHV was exactly matched with the time period of the ancient Silk Road approximately two thousand years ago. This route began in Chang'an, the capital of the Han dynasty of China, and crossed Central Asia, ending in the Roman Empire. The evolution rate of KSHV was slow, with 3.44 × 10-6 substitutions per site per year (95% HPD, 2.26 × 10-6 to 4.71 × 10-6), although 11 codons were discovered to be under positive selection pressure. The geographic distances from Italy to Iran and Xinjiang are more than 4000 and 7000 kilometres, respectively, but no explicit relationship between genetic distance and geographic distance was detected.

  11. Regulation of the Abundance of Kaposi's Sarcoma-Associated Herpesvirus ORF50 Protein by Oncoprotein MDM2.

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    Tzu-Hsuan Chang

    2016-10-01

    Full Text Available The switch between latency and the lytic cycle of Kaposi's sarcoma-associated herpesvirus (KSHV is controlled by the expression of virally encoded ORF50 protein. Thus far, the regulatory mechanism underlying the protein stability of ORF50 is unknown. Our earlier studies have demonstrated that a protein abundance regulatory signal (PARS at the ORF50 C-terminal region modulates its protein abundance. The PARS region consists of PARS-I (aa 490-535 and PARS-II (aa 590-650, and mutations in either component result in abundant expression of ORF50. Here, we show that ORF50 protein is polyubiquitinated and its abundance is controlled through the proteasomal degradation pathway. The PARS-I motif mainly functions as a nuclear localization signal in the control of ORF50 abundance, whereas the PARS-II motif is required for the binding of ubiquitin enzymes in the nucleus. We find that human oncoprotein MDM2, an ubiquitin E3 ligase, is capable of interacting with ORF50 and promoting ORF50 degradation in cells. The interaction domains between both proteins are mapped to the PARS region of ORF50 and the N-terminal 220-aa region of MDM2. Additionally, we identify lysine residues at positions 152 and 154 in the N-terminal domain of ORF50 critically involved in MDM2-mediated downregulation of ORF50 levels. Within KSHV-infected cells, the levels of MDM2 were greatly reduced during viral lytic cycle and genetic knockdown of MDM2 in these cells favored the enhancement of ORF50 expression, supporting that MDM2 is a negative regulator of ORF50 expression. Collectively, the study elucidates the regulatory mechanism of ORF50 stability and implicates that MDM2 may have a significant role in the maintenance of viral latency by lowering basal level of ORF50.

  12. Hsp70 Isoforms Are Essential for the Formation of Kaposi's Sarcoma-Associated Herpesvirus Replication and Transcription Compartments.

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    Belinda Baquero-Pérez

    2015-11-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is an oncogenic herpesvirus associated with various AIDS-related malignancies. Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, viral DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication and transcription compartments (RTCs. Here we utilised a novel methodology, combining subcellular fractionation and quantitative proteomics, to identify cellular proteins which are recruited to KSHV-induced RTCs and thus play a key role in KSHV lytic replication. We show that several isoforms of the HSP70 chaperone family, Hsc70 and iHsp70, are redistributed from the cytoplasm into the nucleus coinciding with the initial formation of KSHV-induced RTCs. We demonstrate that nuclear chaperone foci are dynamic, initially forming adjacent to newly formed KSHV RTCs, however during later time points the chaperones move within KSHV RTCs and completely co-localise with actively replicating viral DNA. The functional significance of Hsp70 isoforms recruitment into KSHV RTCs was also examined using the specific Hsp70 isoform small molecule inhibitor, VER-155008. Intriguingly, results highlight an essential role of Hsp70 isoforms in the KSHV replication cycle independent of protein stability and maturation. Notably, inhibition of Hsp70 isoforms precluded KSHV RTC formation and RNA polymerase II (RNAPII relocalisation to the viral genome leading to the abolishment of global KSHV transcription and subsequent viral protein synthesis and DNA replication. These new findings have revealed novel mechanisms that regulate KSHV lytic replication and highlight the potential of HSP70 inhibitors as novel antiviral agents.

  13. Human Herpesvirus 8 (HHV8 sequentially shapes the NK cell repertoire during the course of asymptomatic infection and Kaposi sarcoma.

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    Stéphanie Dupuy

    2012-01-01

    Full Text Available The contribution of innate immunity to immunosurveillance of the oncogenic Human Herpes Virus 8 (HHV8 has not been studied in depth. We investigated NK cell phenotype and function in 70 HHV8-infected subjects, either asymptomatic carriers or having developed Kaposi's sarcoma (KS. Our results revealed substantial alterations of the NK cell receptor repertoire in healthy HHV8 carriers, with reduced expression of NKp30, NKp46 and CD161 receptors. In addition, down-modulation of the activating NKG2D receptor, associated with impaired NK-cell lytic capacity, was observed in patients with active KS. Resolution of KS after treatment was accompanied with restoration of NKG2D levels and NK cell activity. HHV8-latently infected endothelial cells overexpressed ligands of several NK cell receptors, including NKG2D ligands. The strong expression of NKG2D ligands by tumor cells was confirmed in situ by immunohistochemical staining of KS biopsies. However, no tumor-infiltrating NK cells were detected, suggesting a defect in NK cell homing or survival in the KS microenvironment. Among the known KS-derived immunoregulatory factors, we identified prostaglandin E2 (PGE2 as a critical element responsible for the down-modulation of NKG2D expression on resting NK cells. Moreover, PGE2 prevented up-regulation of the NKG2D and NKp30 receptors on IL-15-activated NK cells, and inhibited the IL-15-induced proliferation and survival of NK cells. Altogether, our observations are consistent with distinct immunoevasion mechanisms that allow HHV8 to escape NK cell responses stepwise, first at early stages of infection to facilitate the maintenance of viral latency, and later to promote tumor cell growth through suppression of NKG2D-mediated functions. Importantly, our results provide additional support to the use of PGE2 inhibitors as an attractive approach to treat aggressive KS, as they could restore activation and survival of tumoricidal NK cells.

  14. Prevalence of Kaposi's sarcoma-associated herpesvirus infection in sex workers and women from the general population in Spain.

    Science.gov (United States)

    de Sanjosé, Sílvia; Marshall, Vickie; Solà, Judit; Palacio, Virgilio; Almirall, Rosa; Goedert, James J; Bosch, F Xavier; Whitby, Denise

    2002-03-01

    Transmission routes of Kaposi's sarcoma-associated herpesvirus (KSHV) in the general population are poorly understood. Whereas sexual transmission appears to be common in homosexual men, the evidence for heterosexual transmission is less convincing. In our study, prevalence of KSHV infection was examined among women in the Spanish general population and among sex workers. Subjects consisted of 100 prostitutes and 100 women randomly sampled from the general population and age-matched to the prostitutes. Women had a personal interview and gynecologic examinations in which a blood sample, cervical cells and oral cells were obtained. Peripheral blood mononuclear cells (PBMC), oral and cervical samples were tested for KSHV DNA by quantitative real-time PCR. Sera were tested for antibodies against human immunodeficiency virus (HIV) by ELISA and against KSHV by latent IFA and K8.1 ELISA. Women who were positive in either serologic assay or PCR were considered infected by KSHV. Human papillomavirus (HPV) DNA in cervical scrapes were evaluated using the Hybrid Capture System. The study population had an average age of 30 years and were HIV-negative. Women from the general population were largely of Spanish nationality, and 61% reported lifetime monogamy. The majority of the prostitutes (76%) were immigrants, primarily from South America. Sex workers were twice as likely to be infected with KSHV than women in the general population (16% vs. 8%, prevalence odds ratio [OR] = 2.2). KSHV was more prevalent among HPV DNA-positive women (OR = 2.5) and among women with an early age at first sexual intercourse (OR = 2.7, p women in the general population. All PBMC samples were negative. These results suggest that in low-risk countries for KSHV, oral shedding and heterosexual contacts are potential pathways for KSHV transmission. Copyright 2001 Wiley-Liss, Inc.

  15. Kaposi's sarcoma-associated herpesvirus ORF57 protein binds and protects a nuclear noncoding RNA from cellular RNA decay pathways.

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    Brooke B Sahin

    2010-03-01

    Full Text Available The control of RNA stability is a key determinant in cellular gene expression. The stability of any transcript is modulated through the activity of cis- or trans-acting regulatory factors as well as cellular quality control systems that ensure the integrity of a transcript. As a result, invading viral pathogens must be able to subvert cellular RNA decay pathways capable of destroying viral transcripts. Here we report that the Kaposi's sarcoma-associated herpesvirus (KSHV ORF57 protein binds to a unique KSHV polyadenylated nuclear RNA, called PAN RNA, and protects it from degradation by cellular factors. ORF57 increases PAN RNA levels and its effects are greatest on unstable alleles of PAN RNA. Kinetic analysis of transcription pulse assays shows that ORF57 protects PAN RNA from a rapid cellular RNA decay process, but ORF57 has little effect on transcription or PAN RNA localization based on chromatin immunoprecipitation and in situ hybridization experiments, respectively. Using a UV cross-linking technique, we further demonstrate that ORF57 binds PAN RNA directly in living cells and we show that binding correlates with function. In addition, we define an ORF57-responsive element (ORE that is necessary for ORF57 binding to PAN RNA and sufficient to confer ORF57-response to a heterologous intronless beta-globin mRNA, but not its spliced counterparts. We conclude that ORF57 binds to viral transcripts in the nucleus and protects them from a cellular RNA decay pathway. We propose that KSHV ORF57 protein functions to enhance the nuclear stability of intronless viral transcripts by protecting them from a cellular RNA quality control pathway.

  16. Epstein-Barr virus (EBV Rta-mediated EBV and Kaposi's sarcoma-associated herpesvirus lytic reactivations in 293 cells.

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    Yen-Ju Chen

    Full Text Available Epstein-Barr virus (EBV Rta belongs to a lytic switch gene family that is evolutionarily conserved in all gamma-herpesviruses. Emerging evidence indicates that cell cycle arrest is a common means by which herpesviral immediate-early protein hijacks the host cell to advance the virus's lytic cycle progression. To examine the role of Rta in cell cycle regulation, we recently established a doxycycline (Dox-inducible Rta system in 293 cells. In this cell background, inducible Rta modulated the levels of signature G1 arrest proteins, followed by induction of the cellular senescence marker, SA-β-Gal. To delineate the relationship between Rta-induced cell growth arrest and EBV reactivation, recombinant viral genomes were transferred into Rta-inducible 293 cells. Somewhat unexpectedly, we found that Dox-inducible Rta reactivated both EBV and Kaposi's sarcoma-associated herpesvirus (KSHV, to similar efficacy. As a consequence, the Rta-mediated EBV and KSHV lytic replication systems, designated as EREV8 and ERKV, respectively, were homogenous, robust, and concurrent with cell death likely due to permissive lytic replication. In addition, the expression kinetics of EBV lytic genes in Dox-treated EREV8 cells was similar to that of their KSHV counterparts in Dox-induced ERKV cells, suggesting that a common pathway is used to disrupt viral latency in both cell systems. When the time course was compared, cell cycle arrest was achieved between 6 and 48 h, EBV or KSHV reactivation was initiated abruptly at 48 h, and the cellular senescence marker was not detected until 120 h after Dox treatment. These results lead us to hypothesize that in 293 cells, Rta-induced G1 cell cycle arrest could provide (1 an ideal environment for virus reactivation if EBV or KSHV coexists and (2 a preparatory milieu for cell senescence if no viral genome is available. The latter is hypothetical in a transient-lytic situation.

  17. A hydrophobic domain within the small capsid protein of Kaposi's sarcoma-associated herpesvirus is required for assembly.

    Science.gov (United States)

    Capuano, Christopher M; Grzesik, Peter; Kreitler, Dale; Pryce, Erin N; Desai, Keshal V; Coombs, Gavin; McCaffery, J Michael; Desai, Prashant J

    2014-08-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) capsids can be produced in insect cells using recombinant baculoviruses for protein expression. All six capsid proteins are required for this process to occur and, unlike for alphaherpesviruses, the small capsid protein (SCP) ORF65 is essential for this process. This protein decorates the capsid shell by virtue of its interaction with the capsomeres. In this study, we have explored the SCP interaction with the major capsid protein (MCP) using GFP fusions. The assembly site within the nucleus of infected cells was visualized by light microscopy using fluorescence produced by the SCP-GFP polypeptide, and the relocalization of the SCP to these sites was evident only when the MCP and the scaffold protein were also present - indicative of an interaction between these proteins that ensures delivery of the SCP to assembly sites. Biochemical assays demonstrated a physical interaction between the SCP and MCP, and also between this complex and the scaffold protein. Self-assembly of capsids with the SCP-GFP polypeptide was evident. Potentially, this result can be used to engineer fluorescent KSHV particles. A similar SCP-His6 polypeptide was used to purify capsids from infected cell lysates using immobilized affinity chromatography and to directly label this protein in capsids using chemically derivatized gold particles. Additional studies with SCP-GFP polypeptide truncation mutants identified a domain residing between aa 50 and 60 of ORF65 that was required for the relocalization of SCP-GFP to nuclear assembly sites. Substitution of residues in this region and specifically at residue 54 with a polar amino acid (lysine) disrupted or abolished this localization as well as capsid assembly, whereas substitution with non-polar residues did not affect the interaction. Thus, this study identified a small conserved hydrophobic domain that is important for the SCP-MCP interaction. © 2014 The Authors.

  18. Simultaneous Hodgkin′s disease and kaposi sarcoma in a renal transplant recipient

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    Yaich S

    2010-01-01

    Full Text Available A 38-year-old women underwent first cadaver kidney transplantation. Her panel re-active antibody was 0%, and she had never previously been transfused nor pregnant. She received induction therapy with antithymoglobulin (ATG as standard protocol and maintained on immuno-suppressive treatment of cyclosporine A, mycophenolate mofetil (MMF, and prednisone. Nine months after transplantation, she presented with anorexia, asthenia and weight loss. Cutaneous Ka-posi′s sarcoma and a Hodgkin disease were diagnosed. MMF was discontinued and cyclosporin A was switched to sirolimus. She also received a poly-chemotherapy associated with 4 courses of rituximab. Twelve months later, the patient had normal graft function and both malignancies were in complete remission.

  19. NEDDylation is essential for Kaposi's sarcoma-associated herpesvirus latency and lytic reactivation and represents a novel anti-KSHV target.

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    David J Hughes

    2015-03-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is the causative agent of Kaposi's sarcoma (KS and primary effusion lymphoma (PEL, which are aggressive malignancies associated with immunocompromised patients. For many non-viral malignancies, therapeutically targeting the ubiquitin proteasome system (UPS has been successful. Likewise, laboratory studies have demonstrated that inhibition of the UPS might provide a promising avenue for the treatment of KSHV-associated diseases. The largest class of E3 ubiquitin ligases are the cullin-RING ligases (CRLs that are activated by an additional ubiquitin-like protein, NEDD8. We show that pharmacological inhibition of NEDDylation (using the small molecule inhibitor MLN4924 is cytotoxic to PEL cells by inhibiting NF-κB. We also show that CRL4B is a novel regulator of latency as its inhibition reactivated lytic gene expression. Furthermore, we uncovered a requirement for NEDDylation during the reactivation of the KSHV lytic cycle. Intriguingly, inhibition prevented viral DNA replication but not lytic cycle-associated gene expression, highlighting a novel mechanism that uncouples these two features of KSHV biology. Mechanistically, we show that MLN4924 treatment precluded the recruitment of the viral pre-replication complex to the origin of lytic DNA replication (OriLyt. These new findings have revealed novel mechanisms that regulate KSHV latency and reactivation. Moreover, they demonstrate that inhibition of NEDDylation represents a novel approach for the treatment of KSHV-associated malignancies.

  20. Kaposin-B enhances the PROX1 mRNA stability during lymphatic reprogramming of vascular endothelial cells by Kaposi's sarcoma herpes virus.

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    Jaehyuk Yoo

    2010-08-01

    Full Text Available Kaposi's sarcoma (KS is the most common cancer among HIV-positive patients. Histogenetic origin of KS has long been elusive due to a mixed expression of both blood and lymphatic endothelial markers in KS tumor cells. However, we and others discovered that Kaposi's sarcoma herpes virus (KSHV induces lymphatic reprogramming of blood vascular endothelial cells by upregulating PROX1, which functions as the master regulator for lymphatic endothelial differentiation. Here, we demonstrate that the KSHV latent gene kaposin-B enhances the PROX1 mRNA stability and plays an important role in KSHV-mediated PROX1 upregulation. We found that PROX1 mRNA contains a canonical AU-rich element (ARE in its 3'-untranslated region that promotes PROX1 mRNA turnover and that kaposin-B stimulates cytoplasmic accumulation of the ARE-binding protein HuR through activation of the p38/MK2 pathway. Moreover, HuR binds to and stabilizes PROX1 mRNA through its ARE and is necessary for KSHV-mediated PROX1 mRNA stabilization. Together, our study demonstrates that kaposin-B plays a key role in PROX1 upregulation during lymphatic reprogramming of blood vascular endothelial cells by KSHV.

  1. Seroprevalence and risk factors of Kaposi's sarcoma-associated herpesvirus infection among the general Uygur population from south and north region of Xinjiang, China

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    Wang Hui

    2011-12-01

    Full Text Available Abstract Background Kaposi sarcoma (KS is a complex multifocal neoplasm and is the major cause of death for about 50% of acquired immunodeficiency syndrome (AIDS patients. Kaposi's sarcoma-associated herpesvirus (KSHV is an oncogenic virus with a causal role in the development of all types of KS. KS is prevalent among the Uygur people in Xinjiang, especially in south area. Here we carried out a cross-sectional study among 1534 general Uygur individuals from south and north region of Xinjiang to assess the seroprevalence of KSHV and to identify the potential correlation between KSHV seroprevalence and KS incidence. Results Seroprevalence of KSHV in South and North Xinjiang was 23.1% and 25.9%, respectively. Older age was independently associated with higher KSHV seroprevalence. In subjects from South Xinjiang, lower educational level and reported drinking were each independently associated with higher KSHV seroprevalence. Furthermore, the antibody titer was significantly lower in both south and north KSHV seropositive individuals compared with KS patients, as analyzed by gradient dilution (P Conclusion KSHV is highly prevalent in the general Uygur population in both South and North Xinjiang. Interestingly, the infection rate of KSHV in these two geographical areas did not correlate well with KS incidence. Perhaps unknown factors exist that promote the progression of KSHV infection to KS development in the local minority groups.

  2. Generation of high-titre virus stocks using BrK.219, a B-cell line infected stably with recombinant Kaposi's sarcoma-associated herpesvirus.

    Science.gov (United States)

    Kati, Semra; Hage, Elias; Mynarek, Martin; Ganzenmueller, Tina; Indenbirken, Daniela; Grundhoff, Adam; Schulz, Thomas F

    2015-06-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is a gamma-2-lymphotropic human oncogenic herpesvirus associated with Kaposi's sarcoma (KS) and two B-cell lymphoproliferative diseases, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). KSHV establishes latency soon after infection in vivo and in vitro. Consequently, it is technically difficult to generate high-titre virus stocks required for infection experiments in tissue culture. Currently used methods of KSHV stock production involve induction of the lytic/productive cycle in PEL cell lines or in adherent cell lines harbouring recombinant KSHV genomes. In this study, the BJAB-derived B-cell line BrK.219, which is infected latently with a recombinant KSHV (rKSHV.219), is used to produce high-titre virus stocks. BrK.219 cells enter the lytic KSHV replication cycle upon cross-linking of B-cell receptors (BCRs) with anti-IgM antibodies without the need for additional, potentially toxic chemical inducers. High cell concentrations can be cultured and induced easily in spinner flasks, saving time and resources. The established protocol allows the generation of KSHV virus stocks with titres of up to 10(6) IU/ml in unconcentrated culture supernatants, representing a 10(3)-10(4)-fold improvement compared to conventional methods. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Herpes simplex virus type 2 triggers reactivation of Kaposi's sarcoma-associated herpesvirus from latency and collaborates with HIV-1 Tat.

    Science.gov (United States)

    Tang, Qiao; Qin, Di; Lv, Zhigang; Zhu, Xiaolei; Ma, Xinting; Yan, Qin; Zeng, Yi; Guo, Yuanyuan; Feng, Ninghan; Lu, Chun

    2012-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) infection was necessary but not sufficient for Kaposi's sarcoma (KS) development without other cofactors. Previously, we identified that both human immunodeficiency type 1 (HIV-1) Tat and herpes simplex virus 1 (HSV-1) were important cofactors reactivating KSHV from latency. Here, we further investigated the potential of herpes simplex virus 2 (HSV-2) to influence KSHV replication and examined the role of Tat in this procedure. We demonstrated that HSV-2 was a potentially important factor in the pathogenesis of KS, as determined by production of lytic phase mRNA transcripts, viral proteins and infectious viral particles in BCBL-1 cells. These results were further confirmed by an RNA interference experiment using small interfering RNA targeting KSHV Rta and a luciferase reporter assay testing Rta promoter-driven luciferase activity. Mechanistic studies showed that HSV-2 infection activated nuclear factor-kappa B (NF-κB) signaling pathway. Inhibition of NF-κB pathway enhanced HSV-2-mediated KSHV activation, whereas activation of NF-κB pathway suppressed KSHV replication in HSV-2-infected BCBL-1 cells. Additionally, ectopic expression of Tat enhanced HSV-2-induced KSHV replication. These novel findings suggest a role of HSV-2 in the pathogenesis of KS and provide the first laboratory evidence that Tat may participate HSV-2-mediated KSHV activation, implying the complicated pathogenesis of acquired immunodeficiency syndrome (AIDS)-related KS (AIDS-KS) patients.

  4. Herpes simplex virus type 2 triggers reactivation of Kaposi's sarcoma-associated herpesvirus from latency and collaborates with HIV-1 Tat.

    Directory of Open Access Journals (Sweden)

    Qiao Tang

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV infection was necessary but not sufficient for Kaposi's sarcoma (KS development without other cofactors. Previously, we identified that both human immunodeficiency type 1 (HIV-1 Tat and herpes simplex virus 1 (HSV-1 were important cofactors reactivating KSHV from latency. Here, we further investigated the potential of herpes simplex virus 2 (HSV-2 to influence KSHV replication and examined the role of Tat in this procedure. We demonstrated that HSV-2 was a potentially important factor in the pathogenesis of KS, as determined by production of lytic phase mRNA transcripts, viral proteins and infectious viral particles in BCBL-1 cells. These results were further confirmed by an RNA interference experiment using small interfering RNA targeting KSHV Rta and a luciferase reporter assay testing Rta promoter-driven luciferase activity. Mechanistic studies showed that HSV-2 infection activated nuclear factor-kappa B (NF-κB signaling pathway. Inhibition of NF-κB pathway enhanced HSV-2-mediated KSHV activation, whereas activation of NF-κB pathway suppressed KSHV replication in HSV-2-infected BCBL-1 cells. Additionally, ectopic expression of Tat enhanced HSV-2-induced KSHV replication. These novel findings suggest a role of HSV-2 in the pathogenesis of KS and provide the first laboratory evidence that Tat may participate HSV-2-mediated KSHV activation, implying the complicated pathogenesis of acquired immunodeficiency syndrome (AIDS-related KS (AIDS-KS patients.

  5. Kaposi sarcoma-associated herpes virus targets the lymphotactin receptor with both a broad spectrum antagonist vCCL2 and a highly selective and potent agonist vCCL3

    DEFF Research Database (Denmark)

    Lüttichau, Hans R; Johnsen, Anders H; Jurlander, Jesper

    2007-01-01

    Large DNA viruses such as herpesvirus and poxvirus encode proteins that target and exploit the chemokine system of their host. These proteins have the potential to block or change the orchestrated recruitment of leukocytes to sites of viral infection. The genome of Kaposi sarcoma-associated herpes...

  6. Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV-MCD) and the KSHV Inflammatory Cytokine Syndrome.

    Science.gov (United States)

    Polizzotto, Mark N; Uldrick, Thomas S; Hu, Duosha; Yarchoan, Robert

    2012-01-01

    Soon after the discovery of Kaposi sarcoma (KS)-associated herpesvirus (KSHV), it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD) arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV-MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV-MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV-MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6). Patients with KSHV-MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h) IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV-MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS) has been described. Its clinical manifestations resemble those of KSHV-MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV-MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV-MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some patients with

  7. Clinical Manifestations of Kaposi Sarcoma Herpesvirus Lytic Activation: Multicentric Castleman Disease (KSHV–MCD) and the KSHV Inflammatory Cytokine Syndrome

    Science.gov (United States)

    Polizzotto, Mark N.; Uldrick, Thomas S.; Hu, Duosha; Yarchoan, Robert

    2012-01-01

    Soon after the discovery of Kaposi sarcoma (KS)-associated herpesvirus (KSHV), it was appreciated that this virus was associated with most cases of multicentric Castleman disease (MCD) arising in patients infected with human immunodeficiency virus. It has subsequently been recognized that KSHV–MCD is a distinct entity from other forms of MCD. Like MCD that is unrelated to KSHV, the clinical presentation of KSHV–MCD is dominated by systemic inflammatory symptoms including fevers, cachexia, and laboratory abnormalities including cytopenias, hypoalbuminemia, hyponatremia, and elevated C-reactive protein. Pathologically KSHV–MCD is characterized by polyclonal, IgM-lambda restricted plasmacytoid cells in the intrafollicular areas of affected lymph nodes. A portion of these cells are infected with KSHV and a sizable subset of these cells express KSHV lytic genes including a viral homolog of interleukin-6 (vIL-6). Patients with KSHV–MCD generally have elevated KSHV viral loads in their peripheral blood. Production of vIL-6 and induction of human (h) IL-6 both contribute to symptoms, perhaps in combination with overproduction of IL-10 and other cytokines. Until recently, the prognosis of patients with KSHV–MCD was poor. Recent therapeutic advances targeting KSHV-infected B cells with the anti-CD20 monoclonal antibody rituximab and utilizing KSHV enzymes to target KSHV-infected cells have substantially improved patient outcomes. Recently another KSHV-associated condition, the KSHV inflammatory cytokine syndrome (KICS) has been described. Its clinical manifestations resemble those of KSHV–MCD but lymphadenopathy is not prominent and the pathologic nodal changes of KSHV–MCD are absent. Patients with KICS exhibit elevated KSHV viral loads and elevation of vIL-6, homolog of human interleukin-6 and IL-10 comparable to those seen in KSHV–MCD; the cellular origin of these is a matter of investigation. KICS may contribute to the inflammatory symptoms seen in some

  8. Kaposi's sarcoma-associated herpesvirus ORF18 and ORF30 are essential for late gene expression during lytic replication.

    Science.gov (United States)

    Gong, Danyang; Wu, Nicholas C; Xie, Yafang; Feng, Jun; Tong, Leming; Brulois, Kevin F; Luan, Harding; Du, Yushen; Jung, Jae U; Wang, Cun-yu; Kang, Mo Kwan; Park, No-Hee; Sun, Ren; Wu, Ting-Ting

    2014-10-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with several human malignances. As saliva is likely the major vehicle for KSHV transmission, we studied in vitro KSHV infection of oral epithelial cells. Through infection of two types of oral epithelial cells, normal human oral keratinocytes (NHOKs) and papilloma-immortalized human oral keratinocyte (HOK16B) cells, we found that KSHV can undergo robust lytic replication in oral epithelial cells. By employing de novo lytic infection of HOK16B cells, we studied the functions of two previously uncharacterized genes, ORF18 and ORF30, during the KSHV lytic cycle. For this purpose, an ORF18-deficient virus and an ORF30-deficient virus were generated using a mutagenesis strategy based on bacterial artificial chromosome (BAC) technology. We found that neither ORF18 nor ORF30 is required for immediately early or early gene expression or viral DNA replication, but each is essential for late gene expression during both de novo lytic replication and reactivation. This critical role of ORF18 and ORF30 in late gene expression was also observed during KSHV reactivation. In addition, global analysis of viral transcripts by RNA sequencing indicated that ORF18 and ORF30 control the same set of viral genes. Therefore, we suggest that these two viral ORFs are involved in the same mechanism or pathway that coregulates the viral late genes as a group. While KSHV can infect multiple cell types in vitro, only a few can support a full lytic replication cycle with progeny virions produced. Consequently, KSHV lytic replication is mostly studied through reactivation, which requires chemicals to induce the lytic cycle or overexpression of the viral transcriptional activator, RTA. In this study, we present a robust de novo lytic infection system based on oral epithelial cells. Using this system, we demonstrate the role of two viral ORFs, ORF18 and ORF30, in regulating viral gene expression during KSHV lytic replication. As the major

  9. COX-2/PGE2: molecular ambassadors of Kaposi's sarcoma-associated herpes virus oncoprotein-v-FLIP

    Science.gov (United States)

    Sharma-Walia, N; Patel, K; Chandran, K; Marginean, A; Bottero, V; Kerur, N; Paul, A G

    2012-01-01

    Kaposi's sarcoma herpesvirus (KSHV) latent oncoprotein viral FLICE (FADD-like interferon converting enzyme)-like inhibitory protein (v-FLIP) or K13, a potent activator of NF-κB, has well-established roles in KSHV latency and oncogenesis. KSHV-induced COX-2 represents a novel strategy employed by KSHV to promote latency and inflammation/angiogenesis/invasion. Here, we demonstrate that v-FLIP/K13 promotes tumorigenic effects via the induction of host protein COX-2 and its inflammatory metabolite PGE2 in an NF-κB-dependent manner. In addition to our previous studies demonstrating COX-2/PGE2's role in transcriptional regulation of KSHV latency promoter and latent gene expression, the current study adds to the complexity that though LANA-1 (latency associated nuclear antigen) is utilizing COX-2/PGE2 as critical factors for its transcriptional regulation, it is the v-FLIP/K13 gene in the KSHV latency cluster that maintains continuous COX-2/PGE2 levels in the infected cells. We demonstrate that COX-2 inhibition, via its chemical inhibitors (NS-398 or celecoxib), reduced v-FLIP/K13-mediated NF-κB induction, and extracellular matrix (ECM) interaction-mediated signaling, mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) levels, and subsequently downregulated detachment-induced apoptosis (anoikis) resistance. vFLIP expression mediated the secretion of cytokines, and spindle cell differentiation activated the phosphorylation of p38, RSK, FAK, Src, Akt and Rac1-GTPase. The COX-2 inhibition in v-FLIP/K13-HMVECs reduced inflammation and invasion/metastasis-related genes, along with reduced anchorage-independent colony formation via modulating ‘extrinsic' as well as ‘intrinsic' cell death pathways. COX-2 blockade in v-FLIP/K13-HMVEC cells drastically augmented cell death induced by removal of essential growth/survival factors secreted in the microenvironment. Transformed cells obtained from anchorage-independent colonies of COX-2 inhibitor-treated v

  10. Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion lymphomas.

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    Irina Haecker

    Full Text Available KSHV is the etiological agent of Kaposi's sarcoma (KS, primary effusion lymphoma (PEL, and a subset of multicentricCastleman's disease (MCD. The fact that KSHV-encoded miRNAs are readily detectable in all KSHV-associated tumors suggests a potential role in viral pathogenesis and tumorigenesis. MiRNA-mediated regulation of gene expression is a complex network with each miRNA having many potential targets, and to date only few KSHV miRNA targets have been experimentally determined. A detailed understanding of KSHV miRNA functions requires high-through putribonomics to globally analyze putative miRNA targets in a cell type-specific manner. We performed Ago HITS-CLIP to identify viral and cellular miRNAs and their cognate targets in two latently KSHV-infected PEL cell lines. Ago HITS-CLIP recovered 1170 and 950 cellular KSHV miRNA targets from BCBL-1 and BC-3, respectively. Importantly, enriched clusters contained KSHV miRNA seed matches in the 3'UTRs of numerous well characterized targets, among them THBS1, BACH1, and C/EBPβ. KSHV miRNA targets were strongly enriched for genes involved in multiple pathways central for KSHV biology, such as apoptosis, cell cycle regulation, lymphocyte proliferation, and immune evasion, thus further supporting a role in KSHV pathogenesis and potentially tumorigenesis. A limited number of viral transcripts were also enriched by HITS-CLIP including vIL-6 expressed only in a subset of PEL cells during latency. Interestingly, Ago HITS-CLIP revealed extremely high levels of Ago-associated KSHV miRNAs especially in BC-3 cells where more than 70% of all miRNAs are of viral origin. This suggests that in addition to seed match-specific targeting of cellular genes, KSHV miRNAs may also function by hijacking RISCs, thereby contributing to a global de-repression of cellular gene expression due to the loss of regulation by human miRNAs. In summary, we provide an extensive list of cellular and viral miRNA targets representing an

  11. Treatment Response and Mortality among Patients Starting Antiretroviral Therapy with and without Kaposi Sarcoma: A Cohort Study

    Science.gov (United States)

    Maskew, Mhairi; Fox, Matthew P.; van Cutsem, Gilles; Chu, Kathryn; MacPhail, Patrick; Boulle, Andrew; Egger, Matthias; Africa, for IeDEA Southern

    2013-01-01

    Background Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART. Methods We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment. Results Between January 2001–January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2%) were similar to those without KS (n = 13600,98%) with respect to age (35 vs. 35yrs), presenting CD4 count (74 vs. 85cells/mm3) and proportion on TB treatment (37% vs. 30%). In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71–4.84) than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95–5.55) and attenuated thereafter (HR: 2.30; 95% CI: 1.08–4.89). Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7–52cells/mm3) and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99–2.06) within the first 6-months of treatment. Conclusions HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS

  12. A microRNA encoded by Kaposi sarcoma-associated herpesvirus promotes B-cell expansion in vivo.

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    Christine Dahlke

    Full Text Available The human gammaherpesvirus Kaposi sarcoma-associated herpesvirus is strongly linked to neoplasms of endothelial and B-cell origin. The majority of tumor cells in these malignancies are latently infected, and latency genes are consequently thought to play a critical role in virus-induced tumorigenesis. One such factor is kshv-miR-K12-11, a viral microRNA that is constitutively expressed in cell lines derived from KSHV-associated tumors, and that shares perfect homology of its seed sequence with the cellular miR-155. Since miR-155 is overexpressed in a number of human tumors, it is conceivable that mimicry of miR-155 by miR-K12-11 may contribute to cellular transformation in KSHV-associated disease. Here, we have performed a side-by-side study of phenotypic alterations associated with constitutive expression of either human miR-155 or viral miR-K12-11 in bone marrow-derived hematopoietic stem cells. We demonstrate that retroviral-mediated gene transfer and hematopoietic progenitor cell transplantation into C57BL/6 mice leads to increased B-cell fractions in lymphoid organs, as well as to enhanced germinal center formation in both microRNA-expressing mouse cohorts. We furthermore identify Jarid2, a component of Polycomb repressive complex 2, as a novel validated target of miR-K12-11, and confirm its downregulation in miR-K12-11 as well as miR-155 expressing bone marrow cells. Our findings confirm and extend previous observations made in other mouse models, and underscore the notion that miR-K12-11 may have arisen to mimic miR-155 functions in KSHV-infected B-cells. The expression of miR-K12-11 may represent one mechanism by which KSHV presumably aims to reprogram naïve B-cells towards supporting long-term latency, which at the same time is likely to pre-dispose infected lymphocytes to malignant transformation.

  13. ESCRT-0 Component Hrs Promotes Macropinocytosis of Kaposi's Sarcoma-Associated Herpesvirus in Human Dermal Microvascular Endothelial Cells.

    Science.gov (United States)

    Veettil, Mohanan Valiya; Kumar, Binod; Ansari, Mairaj Ahmed; Dutta, Dipanjan; Iqbal, Jawed; Gjyshi, Olsi; Bottero, Virginie; Chandran, Bala

    2016-04-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) enters human dermal microvascular endothelial cells (HMVEC-d), its naturalin vivotarget cells, by lipid raft-dependent macropinocytosis. The internalized viral envelope fuses with the macropinocytic membrane, and released capsid is transported to the nuclear vicinity, resulting in the nuclear entry of viral DNA. The endosomal sorting complexes required for transport (ESCRT) proteins, which include ESCRT-0, -I, -II, and -III, play a central role in endosomal trafficking and sorting of internalized and ubiquitinated receptors. Here, we examined the role of ESCRT-0 component Hrs (hepatocyte growth factor-regulated tyrosine kinase substrate) in KSHV entry into HMVEC-d by macropinocytosis. Knockdown of Hrs by short hairpin RNA (shRNA) transduction resulted in significant decreases in KSHV entry and viral gene expression. Immunofluorescence analysis (IFA) and plasma membrane isolation and proximity ligation assay (PLA) demonstrated the translocation of Hrs from the cytosol to the plasma membrane of infected cells and association with α-actinin-4. In addition, infection induced the plasma membrane translocation and activation of the serine/threonine kinase ROCK1, a downstream target of the RhoA GTPase. Hrs knockdown reduced these associations, suggesting that the recruitment of ROCK1 is an Hrs-mediated event. Interaction between Hrs and ROCK1 is essential for the ROCK1-induced phosphorylation of NHE1 (Na(+)/H(+)exchanger 1), which is involved in the regulation of intracellular pH. Thus, our studies demonstrate the plasma membrane association of ESCRT protein Hrs during macropinocytosis and suggest that KSHV entry requires both Hrs- and ROCK1-dependent mechanisms and that ROCK1-mediated phosphorylation of NHE1 and pH change is an essential event required for the macropinocytosis of KSHV. Macropinocytosis is the major entry pathway of KSHV in human dermal microvascular endothelial cells, the natural target cells of KSHV

  14. Interaction of c-Cbl with myosin IIA regulates Bleb associated macropinocytosis of Kaposi's sarcoma-associated herpesvirus.

    Science.gov (United States)

    Valiya Veettil, Mohanan; Sadagopan, Sathish; Kerur, Nagaraj; Chakraborty, Sayan; Chandran, Bala

    2010-12-23

    KSHV is etiologically associated with Kaposi's sarcoma (KS), an angioproliferative endothelial cell malignancy. Macropinocytosis is the predominant mode of in vitro entry of KSHV into its natural target cells, human dermal microvascular endothelial (HMVEC-d) cells. Although macropinocytosis is known to be a major route of entry for many viruses, the molecule(s) involved in the recruitment and integration of signaling early during macropinosome formation is less well studied. Here we demonstrate that tyrosine phosphorylation of the adaptor protein c-Cbl is required for KSHV induced membrane blebbing and macropinocytosis. KSHV induced the tyrosine phosphorylation of c-Cbl as early as 1 min post-infection and was recruited to the sites of bleb formation. Infection also led to an increase in the interaction of c-Cbl with PI3-K p85 in a time dependent manner. c-Cbl shRNA decreased the formation of KSHV induced membrane blebs and macropinocytosis as well as virus entry. Immunoprecipitation of c-Cbl followed by mass spectrometry identified the interaction of c-Cbl with a novel molecular partner, non-muscle myosin heavy chain IIA (myosin IIA), in bleb associated macropinocytosis. Phosphorylated c-Cbl colocalized with phospho-myosin light chain II in the interior of blebs of infected cells and this interaction was abolished by c-Cbl shRNA. Studies with the myosin II inhibitor blebbistatin demonstrated that myosin IIA is a biologically significant component of the c-Cbl signaling pathway and c-Cbl plays a new role in the recruitment of myosin IIA to the blebs during KSHV infection. Myosin II associates with actin in KSHV induced blebs and the absence of actin and myosin ubiquitination in c-Cbl ShRNA cells suggested that c-Cbl is also responsible for the ubiquitination of these proteins in the infected cells. This is the first study demonstrating the role of c-Cbl in viral entry as well as macropinocytosis, and provides the evidence that a signaling complex containing c

  15. Interaction of c-Cbl with myosin IIA regulates Bleb associated macropinocytosis of Kaposi's sarcoma-associated herpesvirus.

    Directory of Open Access Journals (Sweden)

    Mohanan Valiya Veettil

    2010-12-01

    Full Text Available KSHV is etiologically associated with Kaposi's sarcoma (KS, an angioproliferative endothelial cell malignancy. Macropinocytosis is the predominant mode of in vitro entry of KSHV into its natural target cells, human dermal microvascular endothelial (HMVEC-d cells. Although macropinocytosis is known to be a major route of entry for many viruses, the molecule(s involved in the recruitment and integration of signaling early during macropinosome formation is less well studied. Here we demonstrate that tyrosine phosphorylation of the adaptor protein c-Cbl is required for KSHV induced membrane blebbing and macropinocytosis. KSHV induced the tyrosine phosphorylation of c-Cbl as early as 1 min post-infection and was recruited to the sites of bleb formation. Infection also led to an increase in the interaction of c-Cbl with PI3-K p85 in a time dependent manner. c-Cbl shRNA decreased the formation of KSHV induced membrane blebs and macropinocytosis as well as virus entry. Immunoprecipitation of c-Cbl followed by mass spectrometry identified the interaction of c-Cbl with a novel molecular partner, non-muscle myosin heavy chain IIA (myosin IIA, in bleb associated macropinocytosis. Phosphorylated c-Cbl colocalized with phospho-myosin light chain II in the interior of blebs of infected cells and this interaction was abolished by c-Cbl shRNA. Studies with the myosin II inhibitor blebbistatin demonstrated that myosin IIA is a biologically significant component of the c-Cbl signaling pathway and c-Cbl plays a new role in the recruitment of myosin IIA to the blebs during KSHV infection. Myosin II associates with actin in KSHV induced blebs and the absence of actin and myosin ubiquitination in c-Cbl ShRNA cells suggested that c-Cbl is also responsible for the ubiquitination of these proteins in the infected cells. This is the first study demonstrating the role of c-Cbl in viral entry as well as macropinocytosis, and provides the evidence that a signaling complex

  16. Treatment response and mortality among patients starting antiretroviral therapy with and without Kaposi sarcoma: a cohort study.

    Directory of Open Access Journals (Sweden)

    Mhairi Maskew

    Full Text Available BACKGROUND: Improved survival among HIV-infected individuals on antiretroviral therapy (ART has focused attention on AIDS-related cancers including Kaposi sarcoma (KS. However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART. METHODS: We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment. RESULTS: Between January 2001-January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2% were similar to those without KS (n = 13600,98% with respect to age (35 vs. 35yrs, presenting CD4 count (74 vs. 85cells/mm³ and proportion on TB treatment (37% vs. 30%. In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71-4.84 than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95-5.55 and attenuated thereafter (HR: 2.30; 95% CI: 1.08-4.89. Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7-52cells/mm³ and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99-2.06 within the first 6-months of treatment. CONCLUSIONS: HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS

  17. Kaposi’s sarcoma in Brazilian AIDS patients: a study of 144 cases Sarcoma de Kaposi em pacientes com AIDS: estudo de 144 casos

    Directory of Open Access Journals (Sweden)

    Esther G. BIRMAN

    2000-12-01

    Full Text Available One hundred and forty-four Brazilian AIDS patients presenting with Kaposi’s sarcoma (KS were evaluated with respect to the frequency of oral neoplasms and their clinical features. The majority of the patients were young male adults (age range: 21-40 years old, from which 11.1 % presented with oral KS (OKS exclusively. Oral and skin lesions were associated in 25% of the cases, while only four patients showed association between oral and visceral KS; 49.3% of the cases were exclusively dermatological. The hard palate was the main site affected, followed by the oropharynx. The localization of KS was found to be similarly frequent in the tongue, gingiva and other sites of the oral mucosa. Candidosis was the prevailing fungal disease; in 20% of the cases it was restricted to the oral mucosa and in 80% it was systemic. No high frequency of paracoccidioidomicosis and cryptococcosis was detected. The prevailing bacterial disease was Tuberculosis and there was only one case of syphilis. Among the viral diseases, the most frequently detected was herpes simplex, followed by molusco contagiosum, condiloma acuminatum and cytomegaloviroses at lower frequencies. Pneumonia caused by Pneumocystes carinii and toxoplasmosis were also identified. The authors emphasise the importance of oral examination in HIV-infected patients bearing in mind several aspects related especially to KS, and stress the need for an interdisciplinary team in the management of these patients, in order to provide better quality of life as well as rapid diagnosis and treatment.Foram estudados pacientes brasileiros portadores de SIDA apresentando sarcoma de Kaposi (SK. O perfil de idade mostrou um grupo com média de idade entre 21 e 40 anos, sendo que 11,1% da amostra apresentava SK exclusivamente na cavidade bucal, observando-se em 25% da amostra uma associação de lesões bucais e na pele. Somente quatro pacientes apresentaram associação de lesões bucais e viscerais, enquanto 49

  18. The Gammaherpesviruses Kaposi's Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus 68 Modulate the Toll-Like Receptor-Induced Proinflammatory Cytokine Response

    Science.gov (United States)

    Bussey, Kendra A.; Reimer, Elisa; Todt, Helene; Denker, Brigitte; Gallo, Antonio; Konrad, Andreas; Ottinger, Matthias; Adler, Heiko; Stürzl, Michael; Brune, Wolfram

    2014-01-01

    ABSTRACT The human pathogen Kaposi's sarcoma-associated herpesvirus (KSHV), the etiological agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease, establishes lifelong latency upon infection. Murine gammaherpesvirus 68 (MHV68) is a well-established model for KSHV. Toll-like receptors (TLRs) play a crucial role for the innate immune response to pathogens. Although KSHV and MHV68 are detected by TLRs, studies suggest they modulate TLR4 and TLR9 signaling, respectively. In this study, we show that in bone marrow-derived macrophages (BMDMs), MHV68 did not induce a detectable proinflammatory cytokine response. Furthermore, MHV68 abrogated the response to TLR2, -4, -7, and -9 agonists in BMDMs. Similarly to observations with MHV68, infection with KSHV efficiently inhibited TLR2 signaling in THP-1 monocytes. Using a KSHV open reading frame (ORF) library, we found that K4.2, ORF21, ORF31, and the replication and transcription activator protein (RTA)/ORF50 inhibited TLR2-dependent nuclear factor kappa B (NF-κB) activation in HEK293 TLR2-yellow fluorescent protein (YFP)- and Flag-TLR2-transfected HEK293T cells. Of the identified ORFs, RTA/ORF50 strongly downregulated TLR2 and TLR4 signaling by reducing TLR2 and TLR4 protein expression. Confocal microscopy revealed that TLR2 and TLR4 were no longer localized to the plasma membrane in cells expressing RTA/ORF50. In this study, we have shown that the gammaherpesviruses MHV68 and KSHV efficiently downmodulate TLR signaling in macrophages and have identified a novel function of RTA/ORF50 in modulation of the innate immune response. IMPORTANCE The Toll-like receptors (TLRs) are an important class of pattern recognition receptors of the innate immune system. They induce a potent proinflammatory cytokine response upon detection of a variety of pathogens. In this study, we found that the gammaherpesviruses murine gammaherpesvirus 68 (MHV68) and Kaposi's sarcoma-associated herpesvirus (KSHV

  19. DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Seho [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Lim, Chunghun [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Lee, Jae Young [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Song, Yoon-Jae [Department of Life Science, Kyungwon University, Seongnam-Si, Kyeonggi-Do 461-701 (Korea, Republic of); Park, Junsoo [Division of Biological Science and Technology, Yonsei University, Wonju 220-100 (Korea, Republic of); Choe, Joonho [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Seo, Taegun, E-mail: tseo@dongguk.edu [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of)

    2010-04-16

    During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

  20. Human Herpesvirus-8 Infection Associated with Kaposi Sarcoma, Multicentric Castleman's Disease, and Plasmablastic Microlymphoma in a Man with AIDS: A Case Report with Review of Pathophysiologic Processes

    Directory of Open Access Journals (Sweden)

    Christian Eaton

    2011-01-01

    Full Text Available Kaposi sarcoma (KS, multicentric Castleman's disease (MCD, and plasmablastic microlymphoma, are all linked to human herpesvirus-8 (HHV-8 infection and HIV-induced immunodeficiency. Herein, we describe the case of a Kenyan man diagnosed with HIV in 2000. He deferred highly active antiretroviral therapy (HAART and remained in good health until his CD4+ count declined in 2006. He was hospitalized with bacterial pneumonia in 2008, after which he agreed to take HAART but did so sporadically. In 2010, he was hospitalized with fever, lymphadenopathy, pancytopenia, and an elevated HHV-8 viral load. A lymph node biopsy showed findings consistent with KS, MCD, and plasmablastic microlymphoma. Eight months after starting liposomal doxorubicin, Rituximab, and a new HAART regimen, he has improved clinically, and his HIV and HHV-8 viral loads are suppressed. These three conditions, found in the same lymph node, underscore the inflammatory and malignant potential of HHV-8, particularly in the milieu of HIV-induced immunodeficiency.

  1. Kaposi Sarcoma Risk in HIV-Infected Children and Adolescents on Combination Antiretroviral Therapy From Sub-Saharan Africa, Europe, and Asia

    DEFF Research Database (Denmark)

    Rohner, Eliane; Schmidlin, Kurt; Zwahlen, Marcel

    2016-01-01

    BACKGROUND:  The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS:  We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS...... and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged HIV/AIDS stage at cART initiation......HR, 3.4; 95% CI, 1.2-10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8-7.3) at cART initiation. CONCLUSIONS:  HIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might...

  2. Kaposi's sarcoma herpesvirus K15 protein contributes to virus-induced angiogenesis by recruiting PLCγ1 and activating NFAT1-dependent RCAN1 expression.

    Science.gov (United States)

    Bala, Kiran; Bosco, Raffaella; Gramolelli, Silvia; Haas, Darya A; Kati, Semra; Pietrek, Marcel; Hävemeier, Anika; Yakushko, Yuri; Singh, Vivek Vikram; Dittrich-Breiholz, Oliver; Kracht, Michael; Schulz, Thomas F

    2012-09-01

    Kaposi's Sarcoma (KS), caused by Kaposi's Sarcoma Herpesvirus (KSHV), is a highly vascularised angiogenic tumor of endothelial cells, characterized by latently KSHV-infected spindle cells and a pronounced inflammatory infiltrate. Several KSHV proteins, including LANA-1 (ORF73), vCyclin (ORF72), vGPCR (ORF74), vIL6 (ORF-K2), vCCL-1 (ORF-K6), vCCL-2 (ORF-K4) and K1 have been shown to exert effects that can lead to the proliferation and atypical differentiation of endothelial cells and/or the secretion of cytokines with angiogenic and inflammatory properties (VEGF, bFGF, IL6, IL8, GROα, and TNFβ). To investigate a role of the KSHV K15 protein in KSHV-mediated angiogenesis, we carried out a genome wide gene expression analysis on primary endothelial cells infected with KSHV wildtype (KSHVwt) and a KSHV K15 deletion mutant (KSHVΔK15). We found RCAN1/DSCR1 (Regulator of Calcineurin 1/Down Syndrome critical region 1), a cellular gene involved in angiogenesis, to be differentially expressed in KSHVwt- vs KSHVΔK15-infected cells. During physiological angiogenesis, expression of RCAN1 in endothelial cells is regulated by VEGF (vascular endothelial growth factor) through a pathway involving the activation of PLCγ1, Calcineurin and NFAT1. We found that K15 directly recruits PLCγ1, and thereby activates Calcineurin/NFAT1-dependent RCAN1 expression which results in the formation of angiogenic tubes. Primary endothelial cells infected with KSHVwt form angiogenic tubes upon activation of the lytic replication cycle. This effect is abrogated when K15 is deleted (KSHVΔK15) or silenced by an siRNA targeting the K15 expression. Our study establishes K15 as one of the KSHV proteins that contribute to KSHV-induced angiogenesis.

  3. p53 Tumor Suppressor Protein Stability and Transcriptional Activity Are Targeted by Kaposi's Sarcoma-Associated Herpesvirus-Encoded Viral Interferon Regulatory Factor 3

    Science.gov (United States)

    Baresova, Petra; Musilova, Jana; Pitha, Paula M.

    2014-01-01

    Viruses have developed numerous strategies to counteract the host cell defense. Kaposi's sarcoma-associated herpesvirus (KSHV) is a DNA tumor virus linked to the development of Kaposi's sarcoma, Castleman's disease, and primary effusion lymphoma (PEL). The virus-encoded viral interferon regulatory factor 3 (vIRF-3) gene is a latent gene which is involved in the regulation of apoptosis, cell cycle, antiviral immunity, and tumorigenesis. vIRF-3 was shown to interact with p53 and inhibit p53-mediated apoptosis. However, the molecular mechanism underlying this phenomenon has not been established. Here, we show that vIRF-3 associates with the DNA-binding domain of p53, inhibits p53 phosphorylation on serine residues S15 and S20, and antagonizes p53 oligomerization and the DNA-binding affinity. Furthermore, vIRF-3 destabilizes p53 protein by increasing the levels of p53 polyubiquitination and targeting p53 for proteasome-mediated degradation. Consequently, vIRF-3 attenuates p53-mediated transcription of the growth-regulatory p21 gene. These effects of vIRF-3 are of biological relevance since the knockdown of vIRF-3 expression in KSHV-positive BC-3 cells, derived from PEL, leads to an increase in p53 phosphorylation, enhancement of p53 stability, and activation of p21 gene transcription. Collectively, these data suggest that KSHV evolved an efficient mechanism to downregulate p53 function and thus facilitate uncontrolled cell proliferation and tumor growth. PMID:24248600

  4. CTCF and Rad21 act as host cell restriction factors for Kaposi's sarcoma-associated herpesvirus (KSHV lytic replication by modulating viral gene transcription.

    Directory of Open Access Journals (Sweden)

    Da-Jiang Li

    2014-01-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is a human herpesvirus that causes Kaposi's sarcoma and is associated with the development of lymphoproliferative diseases. KSHV reactivation from latency and virion production is dependent on efficient transcription of over eighty lytic cycle genes and viral DNA replication. CTCF and cohesin, cellular proteins that cooperatively regulate gene expression and mediate long-range DNA interactions, have been shown to bind at specific sites in herpesvirus genomes. CTCF and cohesin regulate KSHV gene expression during latency and may also control lytic reactivation, although their role in lytic gene expression remains incompletely characterized. Here, we analyze the dynamic changes in CTCF and cohesin binding that occur during the process of KSHV viral reactivation and virion production by high resolution chromatin immunoprecipitation and deep sequencing (ChIP-Seq and show that both proteins dissociate from viral genomes in kinetically and spatially distinct patterns. By utilizing siRNAs to specifically deplete CTCF and Rad21, a cohesin component, we demonstrate that both proteins are potent restriction factors for KSHV replication, with cohesin knockdown leading to hundred-fold increases in viral yield. High-throughput RNA sequencing was used to characterize the transcriptional effects of CTCF and cohesin depletion, and demonstrated that both proteins have complex and global effects on KSHV lytic transcription. Specifically, both proteins act as positive factors for viral transcription initially but subsequently inhibit KSHV lytic transcription, such that their net effect is to limit KSHV RNA accumulation. Cohesin is a more potent inhibitor of KSHV transcription than CTCF but both proteins are also required for efficient transcription of a subset of KSHV genes. These data reveal novel effects of CTCF and cohesin on transcription from a relatively small genome that resemble their effects on the cellular

  5. Kaposi's sarcoma herpesvirus K15 protein contributes to virus-induced angiogenesis by recruiting PLCγ1 and activating NFAT1-dependent RCAN1 expression.

    Directory of Open Access Journals (Sweden)

    Kiran Bala

    2012-09-01

    Full Text Available Kaposi's Sarcoma (KS, caused by Kaposi's Sarcoma Herpesvirus (KSHV, is a highly vascularised angiogenic tumor of endothelial cells, characterized by latently KSHV-infected spindle cells and a pronounced inflammatory infiltrate. Several KSHV proteins, including LANA-1 (ORF73, vCyclin (ORF72, vGPCR (ORF74, vIL6 (ORF-K2, vCCL-1 (ORF-K6, vCCL-2 (ORF-K4 and K1 have been shown to exert effects that can lead to the proliferation and atypical differentiation of endothelial cells and/or the secretion of cytokines with angiogenic and inflammatory properties (VEGF, bFGF, IL6, IL8, GROα, and TNFβ. To investigate a role of the KSHV K15 protein in KSHV-mediated angiogenesis, we carried out a genome wide gene expression analysis on primary endothelial cells infected with KSHV wildtype (KSHVwt and a KSHV K15 deletion mutant (KSHVΔK15. We found RCAN1/DSCR1 (Regulator of Calcineurin 1/Down Syndrome critical region 1, a cellular gene involved in angiogenesis, to be differentially expressed in KSHVwt- vs KSHVΔK15-infected cells. During physiological angiogenesis, expression of RCAN1 in endothelial cells is regulated by VEGF (vascular endothelial growth factor through a pathway involving the activation of PLCγ1, Calcineurin and NFAT1. We found that K15 directly recruits PLCγ1, and thereby activates Calcineurin/NFAT1-dependent RCAN1 expression which results in the formation of angiogenic tubes. Primary endothelial cells infected with KSHVwt form angiogenic tubes upon activation of the lytic replication cycle. This effect is abrogated when K15 is deleted (KSHVΔK15 or silenced by an siRNA targeting the K15 expression. Our study establishes K15 as one of the KSHV proteins that contribute to KSHV-induced angiogenesis.

  6. Ex-vivo recognition of late-lytic CD8 epitopes specific for Kaposi's sarcoma-associated herpesvirus (KSHV) by HIV/KSHV-coinfected individuals.

    Science.gov (United States)

    Robey, Rebecca C; Mletzko, Salvinia; Bower, Mark; Meys, Rhonda; Boffito, Marta; Nelson, Mark; Bunker, Christopher B; Gotch, Frances M

    2011-06-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), the most common cancer in individuals with untreated HIV/AIDS. Host control of KSHV infection and KS oncogenesis by CD8 T cells remains underexplored. Although KSHV CD8 epitopes have been identified, the responses they elicit are weak and little is known about their relative importance. We sought to make a direct comparison of the recognition of a selection of the best-described known epitopes by a cohort of KSHV-seropositive, HIV-co-infected individuals, in order to assess the relative dominance of these epitopes. We further sought to identify novel epitopes from within a candidate immunogenic protein encoded by KSHV ORF28. MHC binding and denaturation assays identified putative novel A*0201-restricted epitopes from within the late-lytic glycoprotein ORF28. Recognition of these candidate epitopes was tested in a cohort of KSHV-seropositive, HIV-1-seropositive, A*0201-positive individuals by ex vivo ELISPOT, and compared with recognition of nine previously described epitopes. One novel late-lytic epitope from ORF28 was recognized by 7.1% of individuals, and was used for further investigation of KSHV-specific T cells using multimer technology. One known late-lytic epitope from the glycoprotein-encoding K8.1 was recognized by 71.4% of individuals, and represented an immunodominant KSHV epitope, but was too hydrophobic for multimer synthesis. This study identifies two KSHV CD8 epitopes derived from late-lytic antigens that are recognized by KSHV-seropositive, HIV co-infected individuals, and will be useful in future immunological studies into the CD8 response against KSHV in similar patient cohorts.

  7. Latency-Associated Nuclear Antigen Encoded by Kaposi's Sarcoma-Associated Herpesvirus Interacts with Tat and Activates the Long Terminal Repeat of Human Immunodeficiency Virus Type 1 in Human Cells

    OpenAIRE

    Hyun, Teresa S.; Subramanian, Chitra; Cotter, Murray A.; Robert A. Thomas; Robertson, Erle S.

    2001-01-01

    The latency-associated nuclear antigen (LANA) is constitutively expressed in cells infected with the Kaposi's sarcoma (KS) herpesvirus (KSHV), also referred to as human herpesvirus 8. KSHV is tightly associated with body cavity-based lymphomas (BCBLs) in immunocompromised patients infected with human immunodeficiency virus (HIV). LANA, encoded by open reading frame 73 of KSHV, is one of a small subset of proteins expressed during latent infection and was shown to be important in tethering the...

  8. Kaposi's Sarcoma-Associated Herpesvirus MicroRNAs Target GADD45B To Protect Infected Cells from Cell Cycle Arrest and Apoptosis.

    Science.gov (United States)

    Liu, Xiaoyan; Happel, Christine; Ziegelbauer, Joseph M

    2017-02-01

    Kaposi's sarcoma is one of the most common malignancies in HIV-infected individuals. The responsible agent, Kaposi's sarcoma-associated herpesvirus (KSHV; HHV8), expresses multiple microRNAs (miRNAs), but the targets and functions of these miRNAs are not completely understood. After infection in primary endothelial cells with KSHV, growth arrest DNA damage-inducible gene 45 beta (GADD45B) is one of the most repressed genes using genomic expression profiling. GADD45B was also repressed in mRNA expression profiling experiments when KSHV miRNAs were introduced to uninfected cells. We hypothesized that KSHV miRNAs target human GADD45B to protect cells from consequences of DNA damage, which can be triggered by viral infection. Expression of GADD45B protein is induced by the p53 activator, Nutlin-3, and KSHV miRNA-K9 inhibits this induction. In addition, Nutlin-3 increased apoptosis and cell cycle arrest based on flow cytometry assays. KSHV miR-K9 protected primary endothelial cells from apoptosis and cell cycle arrest following Nutlin-3 treatment. Similar protective phenotypes were seen for targeting GADD45B with short interfering RNAs (siRNAs), as with miR-K9. KSHV miR-K9 also decreased the protein levels of cleaved caspase-3, cleaved caspase-7, and cleaved poly(ADP-ribose) polymerase (PARP). In B lymphocytes latently infected with KSHV, specific inhibitors of KSHV miR-K9 led to increased GADD45B expression and apoptosis, indicating that miR-K9 is important for reducing apoptosis in infected cells. Furthermore, ectopic expression of GADD45B in KSHV-infected cells promoted apoptosis. Together, these results identify a new miRNA target and demonstrate that KSHV miRNAs are important for protecting infected cells from DNA damage responses. Kaposi's sarcoma-associated herpesvirus is a leading cause of cancers in individuals with AIDS. Promoting survival of infected cells is essential for maintaining viral infections. A virus needs to combat various cellular defense

  9. The CD8 and CD4 T-cell response against Kaposi's sarcoma-associated herpesvirus is skewed towards early and late lytic antigens.

    Directory of Open Access Journals (Sweden)

    Rebecca C Robey

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is causally related to Kaposi's sarcoma (KS, the most common malignancy in untreated individuals with HIV/AIDS. The adaptive T-cell immune response against KSHV has not been fully characterized. To achieve a better understanding of the antigenic repertoire of the CD8 and CD4 T-cell responses against KSHV, we constructed a library of lentiviral expression vectors each coding for one of 31 individual KSHV open reading frames (ORFs. We used these to transduce monocyte-derived dendritic cells (moDCs isolated from 14 KSHV-seropositive (12 HIV-positive and 7 KSHV-seronegative (4 HIV-positive individuals. moDCs were transduced with up to 3 KSHV ORFs simultaneously (ORFs grouped according to their expression during the viral life cycle. Transduced moDCs naturally process the KSHV genes and present the resulting antigens in the context of MHC class I and II. Transduced moDCs were cultured with purified autologous T cells and the CD8 and CD4 T-cell proliferative responses to each KSHV ORF (or group was assessed using a CFSE dye-based assay. Two pools of early lytic KSHV genes ([ORF8/ORF49/ORF61] and [ORF59/ORF65/K4.1] were frequently-recognized targets of both CD8 and CD4 T cells from KSHV seropositive individuals. One pool of late lytic KSHV genes ([ORF28/ORF36/ORF37] was a frequently-recognized CD8 target and another pool of late genes ([ORF33/K1/K8.1] was a frequently-recognized CD4 target. We report that both the CD8 and CD4 T-cell responses against KSHV are skewed towards genes expressed in the early and late phases of the viral lytic cycle, and identify some previously unknown targets of these responses. This knowledge will be important to future immunological investigations into KSHV and may eventually lead to the development of better immunotherapies for KSHV-related diseases.

  10. Prevalence and predictors of kaposi sarcoma herpes virus seropositivity: a cross-sectional analysis of HIV-infected adults initiating ART in Johannesburg, South Africa

    Directory of Open Access Journals (Sweden)

    Maskew Mhairi

    2011-11-01

    Full Text Available Abstract Background Kaposi sarcoma (KS is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV. Results We analyzed cross-sectional data collected from 404 HIV-infected treatment-naïve adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48% tested positive for KSHV at ART initiation; with 76 (39% reactive to lytic K8.1, 35 (18% to latent Orf73 and 82 (42% to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm3 and CD4 (90 vs. 80 cells/mm3 counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19, however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom

  11. HITS-CLIP analysis uncovers a link between the Kaposi's sarcoma-associated herpesvirus ORF57 protein and host pre-mRNA metabolism.

    Directory of Open Access Journals (Sweden)

    Emi Sei

    2015-02-01

    Full Text Available The Kaposi's sarcoma associated herpesvirus (KSHV is an oncogenic virus that causes Kaposi's sarcoma, primary effusion lymphoma (PEL, and some forms of multicentric Castleman's disease. The KSHV ORF57 protein is a conserved posttranscriptional regulator of gene expression that is essential for virus replication. ORF57 is multifunctional, but most of its activities are directly linked to its ability to bind RNA. We globally identified virus and host RNAs bound by ORF57 during lytic reactivation in PEL cells using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP. As expected, ORF57-bound RNA fragments mapped throughout the KSHV genome, including the known ORF57 ligand PAN RNA. In agreement with previously published ChIP results, we observed that ORF57 bound RNAs near the oriLyt regions of the genome. Examination of the host RNA fragments revealed that a subset of the ORF57-bound RNAs was derived from transcript 5' ends. The position of these 5'-bound fragments correlated closely with the 5'-most exon-intron junction of the pre-mRNA. We selected four candidates (BTG1, EGR1, ZFP36, and TNFSF9 and analyzed their pre-mRNA and mRNA levels during lytic phase. Analysis of both steady-state and newly made RNAs revealed that these candidate ORF57-bound pre-mRNAs persisted for longer periods of time throughout infection than control RNAs, consistent with a role for ORF57 in pre-mRNA metabolism. In addition, exogenous expression of ORF57 was sufficient to increase the pre-mRNA levels and, in one case, the mRNA levels of the putative ORF57 targets. These results demonstrate that ORF57 interacts with specific host pre-mRNAs during lytic reactivation and alters their processing, likely by stabilizing pre-mRNAs. These data suggest that ORF57 is involved in modulating host gene expression in addition to KSHV gene expression during lytic reactivation.

  12. Kaposi sarcoma herpes virus latency associated nuclear antigen protein release the G2/M cell cycle blocks by modulating ATM/ATR mediated checkpoint pathway.

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    Amit Kumar

    Full Text Available The Kaposi's sarcoma-associated herpesvirus infects the human population and maintains latency stage of viral life cycle in a variety of cell types including cells of epithelial, mesenchymal and endothelial origin. The establishment of latent infection by KSHV requires the expression of an unique repertoire of genes among which latency associated nuclear antigen (LANA plays a critical role in the replication of the viral genome. LANA regulates the transcription of a number of viral and cellular genes essential for the survival of the virus in the host cell. The present study demonstrates the disruption of the host G2/M cell cycle checkpoint regulation as an associated function of LANA. DNA profile of LANA expressing human B-cells demonstrated the ability of this nuclear antigen in relieving the drug (Nocodazole induced G2/M checkpoint arrest. Caffeine suppressed nocodazole induced G2/M arrest indicating involvement of the ATM/ATR. Notably, we have also shown the direct interaction of LANA with Chk2, the ATM/ATR signalling effector and is responsible for the release of the G2/M cell cycle block.

  13. Chromatin Immunoprecipitation and Microarray Analysis Suggest Functional Cooperation between Kaposi's Sarcoma-Associated Herpesvirus ORF57 and K-bZIP

    Science.gov (United States)

    Hunter, Olga V.; Sei, Emi; Richardson, R. Blake

    2013-01-01

    The Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 57 (ORF57)-encoded protein (Mta) is a multifunctional regulator of viral gene expression. ORF57 is essential for viral replication, so elucidation of its molecular mechanisms is important for understanding KSHV infection. ORF57 has been implicated in nearly every aspect of viral gene expression, including transcription, RNA stability, splicing, export, and translation. Here we demonstrate that ORF57 interacts with the KSHV K-bZIP protein in vitro and in cell extracts from lytically reactivated infected cells. To further test the biological relevance of the interaction, we performed a chromatin immunoprecipitation and microarray (ChIP-chip) analysis using anti-ORF57 antibodies and a KSHV tiling array. The results revealed four specific areas of enrichment, including the ORF4 and K8 (K-bZIP) promoters, as well as oriLyt, all of which interact with K-bZIP. In addition, ORF57 associated with DNA corresponding to the PAN RNA transcribed region, a known posttranscriptional target of ORF57. All of the peaks were RNase insensitive, demonstrating that ORF57 association with the viral genome is unlikely to be mediated exclusively by an RNA tether. Our data demonstrate that ORF57 associates with the viral genome by using at least two modes of recruitment, and they suggest that ORF57 and K-bZIP coregulate viral gene expression during lytic infection. PMID:23365430

  14. KSHV 2.0: a comprehensive annotation of the Kaposi's sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features.

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    Carolina Arias

    2014-01-01

    Full Text Available Productive herpesvirus infection requires a profound, time-controlled remodeling of the viral transcriptome and proteome. To gain insights into the genomic architecture and gene expression control in Kaposi's sarcoma-associated herpesvirus (KSHV, we performed a systematic genome-wide survey of viral transcriptional and translational activity throughout the lytic cycle. Using mRNA-sequencing and ribosome profiling, we found that transcripts encoding lytic genes are promptly bound by ribosomes upon lytic reactivation, suggesting their regulation is mainly transcriptional. Our approach also uncovered new genomic features such as ribosome occupancy of viral non-coding RNAs, numerous upstream and small open reading frames (ORFs, and unusual strategies to expand the virus coding repertoire that include alternative splicing, dynamic viral mRNA editing, and the use of alternative translation initiation codons. Furthermore, we provide a refined and expanded annotation of transcription start sites, polyadenylation sites, splice junctions, and initiation/termination codons of known and new viral features in the KSHV genomic space which we have termed KSHV 2.0. Our results represent a comprehensive genome-scale image of gene regulation during lytic KSHV infection that substantially expands our understanding of the genomic architecture and coding capacity of the virus.

  15. Task Shifting and Skin Punch for the Histologic Diagnosis of Kaposi's Sarcoma in Sub-Saharan Africa: A Public Health Solution to a Public Health Problem.

    Science.gov (United States)

    Laker-Oketta, Miriam O; Wenger, Megan; Semeere, Aggrey; Castelnuovo, Barbara; Kambugu, Andrew; Lukande, Robert; Asirwa, F Chite; Busakhala, Naftali; Buziba, Nathan; Diero, Lameck; Wools-Kaloustian, Kara; Strother, Robert Matthew; Bwana, Mwebesa; Muyindike, Winnie; Amerson, Erin; Mbidde, Edward; Maurer, Toby; Martin, Jeffrey

    2015-01-01

    Fueled by HIV, sub-Saharan Africa has the highest incidence of Kaposi's sarcoma (KS) in the world. Despite this, KS diagnosis in the region is based mostly on clinical grounds. Where biopsy is available, it has traditionally been excisional and performed by surgeons, resulting in multiple appointments, follow-up visits for suture removal, and substantial costs. We hypothesized that a simpler approach - skin punch biopsy - would make histologic diagnosis more accessible. To address this, we provided training and equipment for skin punch biopsy of suspected KS to three HIV clinics in East Africa. The procedure consisted of local anesthesia followed by a disposable cylindrical punch blade to obtain specimens. Hemostasis is facilitated by Gelfoam®. Patients removed the dressing after 4 days. From 2007 to 2013, 2,799 biopsies were performed. Although originally targeted to be used by physicians, biopsies were performed predominantly by nurses (62%), followed by physicians (15%), clinical officers (12%) and technicians (11%). There were no reports of recurrent bleeding or infection. After minimal training and provision of inexpensive equipment (USD 3.06 per biopsy), HIV clinics in East Africa can integrate same-day skin punch biopsy for suspected KS. Task shifting from physician to non-physician greatly increases access. Skin punch biopsy should be part of any HIV clinic's essential procedures. This example of task shifting may also be applicable to the diagnosis of other cancers (e.g., breast) in resource-limited settings.

  16. Asynchronous progression through the lytic cascade and variations in intracellular viral loads revealed by high-throughput single-cell analysis of Kaposi's sarcoma-associated herpesvirus infection.

    Science.gov (United States)

    Adang, Laura A; Parsons, Christopher H; Kedes, Dean H

    2006-10-01

    Kaposi's sarcoma-associated herpesvirus (KSHV or human herpesvirus-8) is frequently tumorigenic in immunocompromised patients. The average intracellular viral copy number within infected cells, however, varies markedly by tumor type. Since the KSHV-encoded latency-associated nuclear antigen (LANA) tethers viral episomes to host heterochromatin and displays a punctate pattern by fluorescence microscopy, we investigated whether accurate quantification of individual LANA dots is predictive of intracellular viral genome load. Using a novel technology that integrates single-cell imaging with flow cytometry, we found that both the number and the summed immunofluorescence of individual LANA dots are directly proportional to the amount of intracellular viral DNA. Moreover, combining viral (immediate early lytic replication and transcription activator [RTA] and late lytic K8.1) and cellular (syndecan-1) staining with image-based flow cytometry, we were also able to rapidly and simultaneously distinguish among cells supporting latent, immediate early lytic, early lytic, late lytic, and a potential fourth "delayed late" category of lytic replication. Applying image-based flow cytometry to KSHV culture models, we found that de novo infection results in highly varied levels of intracellular viral load and that lytic induction of latently infected cells likewise leads to a heterogeneous population at various stages of reactivation. These findings additionally underscore the potential advantages of studying KSHV biology with high-throughput analysis of individual cells.

  17. Programmed death ligand 1 (PD-L1) expression influences the immune-tolerogenic microenvironment in antiretroviral therapy-refractory Kaposi's sarcoma: A pilot study.

    Science.gov (United States)

    Mletzko, Salvinia; Pinato, David J; Robey, Rebecca C; Dalla Pria, Alessia; Benson, Peter; Imami, Nesrina; Bower, Mark

    2017-01-01

    Upregulation of programmed death ligand 1 (PD-L1) is a mechanism of immune escape utilized by a variety of tumors. PD-L1 expression in tumor cells or in the surrounding infiltrate correlates with clinical responsiveness to novel therapies targeting the PD-1/PD-L1 immune checkpoint. In the context of HIV-1 infection, Kaposi's sarcoma (KS) is largely responsive to restoration of immunity following combination antiretroviral therapy (cART), but there is a subset that is not. We hypothesized that this subset of cART-refractory KS may utilize the PD-L1 pathway of immune escape. We found that PD-L1 expressing KS had a denser CD8+ T cell (p = 0.03) and PD-L1 positive macrophage peritumoral infiltrate (p = 0.04) to suggest the involvement of PD-L1 in shaping an immune-tolerogenic microenvironment in cART-refractory KS. The presence of PD-L1 expression in association with immune-infiltrating cells provides rationale for the clinical development PD-1/PD-L1-targeted checkpoint inhibitors in cART-refractory KS.

  18. KSHV 2.0: a comprehensive annotation of the Kaposi's sarcoma-associated herpesvirus genome using next-generation sequencing reveals novel genomic and functional features.

    Science.gov (United States)

    Arias, Carolina; Weisburd, Ben; Stern-Ginossar, Noam; Mercier, Alexandre; Madrid, Alexis S; Bellare, Priya; Holdorf, Meghan; Weissman, Jonathan S; Ganem, Don

    2014-01-01

    Productive herpesvirus infection requires a profound, time-controlled remodeling of the viral transcriptome and proteome. To gain insights into the genomic architecture and gene expression control in Kaposi's sarcoma-associated herpesvirus (KSHV), we performed a systematic genome-wide survey of viral transcriptional and translational activity throughout the lytic cycle. Using mRNA-sequencing and ribosome profiling, we found that transcripts encoding lytic genes are promptly bound by ribosomes upon lytic reactivation, suggesting their regulation is mainly transcriptional. Our approach also uncovered new genomic features such as ribosome occupancy of viral non-coding RNAs, numerous upstream and small open reading frames (ORFs), and unusual strategies to expand the virus coding repertoire that include alternative splicing, dynamic viral mRNA editing, and the use of alternative translation initiation codons. Furthermore, we provide a refined and expanded annotation of transcription start sites, polyadenylation sites, splice junctions, and initiation/termination codons of known and new viral features in the KSHV genomic space which we have termed KSHV 2.0. Our results represent a comprehensive genome-scale image of gene regulation during lytic KSHV infection that substantially expands our understanding of the genomic architecture and coding capacity of the virus.

  19. Lymphatic Reprogramming by Kaposi Sarcoma Herpes Virus Promotes the Oncogenic Activity of the Virus-Encoded G-protein Coupled Receptor

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    Aguilar, Berenice; Choi, Inho; Choi, Dongwon; Chung, Hee Kyoung; Lee, Sunju; Yoo, Jaehyuk; Lee, Yong Suk; Maeng, Yong Sun; Lee, Ha Neul; Park, Eunkyung; Kim, Kyu Eui; Kim, Nam Yoon; Baik, Jae Myung; Jung, Jae U.; Koh, Chester J.; Hong, Young-Kwon

    2012-01-01

    Kaposi sarcoma (KS), the most common cancer in HIV-positive individuals, is caused by endothelial transformation mediated by the KS herpes virus (KSHV)-encoded G-protein coupled receptor (vGPCR). Infection of blood vascular endothelial cells (BECs) by KSHV reactivates an otherwise silenced embryonic program of lymphatic differentiation. Thus, KS tumors express numerous lymphatic endothelial cell (LEC)-signature genes. A key unanswered question is how lymphatic reprogramming by the virus promotes tumorigenesis leading to KS formation. In this study, we present evidence that this process creates an environment needed to license the oncogenic activity of vGPCR. We found that the G-protein regulator RGS4 is an inhibitor of vGPCR that is expressed in BECs, but not in LECs. RGS4 was downregulated by the master regulator of LEC differentiation PROX1, which is upregulated by KSHV and directs KSHV-induced lymphatic reprogramming. Moreover, we found that KSHV upregulates the nuclear receptor LRH1, which physically interacts with PROX1 and synergizes with it to mediate repression of RGS4 expression. Mechanistic investigations revealed that RGS4 reduced vGPCR-enhanced cell proliferation, migration, VEGF expression and Akt activation and to suppress tumor formation induced by vGPCR. Our findings resolve long-standing questions about the pathological impact of KSHV-induced reprogramming of host cell identity, and they offer biological and mechanistic insights supporting the hypothesis that a lymphatic microenvironment is more favorable for KS tumorigenesis. PMID:22942256

  20. Opposing regulation of PROX1 by interleukin-3 receptor and NOTCH directs differential host cell fate reprogramming by Kaposi sarcoma herpes virus.

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    Jaehyuk Yoo

    Full Text Available Lymphatic endothelial cells (LECs are differentiated from blood vascular endothelial cells (BECs during embryogenesis and this physiological cell fate specification is controlled by PROX1, the master regulator for lymphatic development. When Kaposi sarcoma herpes virus (KSHV infects host cells, it activates the otherwise silenced embryonic endothelial differentiation program and reprograms their cell fates. Interestingly, previous studies demonstrated that KSHV drives BECs to acquire a partial lymphatic phenotype by upregulating PROX1 (forward reprogramming, but stimulates LECs to regain some BEC-signature genes by downregulating PROX1 (reverse reprogramming. Despite the significance of this KSHV-induced bidirectional cell fate reprogramming in KS pathogenesis, its underlying molecular mechanism remains undefined. Here, we report that IL3 receptor alpha (IL3Rα and NOTCH play integral roles in the host cell type-specific regulation of PROX1 by KSHV. In BECs, KSHV upregulates IL3Rα and phosphorylates STAT5, which binds and activates the PROX1 promoter. In LECs, however, PROX1 was rather downregulated by KSHV-induced NOTCH signal via HEY1, which binds and represses the PROX1 promoter. Moreover, PROX1 was found to be required to maintain HEY1 expression in LECs, establishing a reciprocal regulation between PROX1 and HEY1. Upon co-activation of IL3Rα and NOTCH, PROX1 was upregulated in BECs, but downregulated in LECs. Together, our study provides the molecular mechanism underlying the cell type-specific endothelial fate reprogramming by KSHV.

  1. Kaposi's-sarcoma-associated-herpesvirus-activated dendritic cells promote HIV-1 trans-infection and suppress CD4{sup +} T cell proliferation

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    Liu, Wan; Qin, Yan; Bai, Lei [Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, the Chinese Academy of Sciences, Shanghai (China); Graduate School of the Chinese Academy of Sciences, Beijing (China); Lan, Ke [Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, the Chinese Academy of Sciences, Shanghai (China); Wang, Jian-Hua, E-mail: Jh_wang@sibs.ac.cn [Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, the Chinese Academy of Sciences, Shanghai (China)

    2013-06-05

    Infection of Kaposi's sarcoma-associated herpesvirus (KSHV) is commonly occurred in AIDS patients. KSHV and HIV-1 act cooperatively in regulating infection with each other and in human carcinogenesis. Dendritic cells (DCs), as the pivotal cells in host immunity, may be modulated by both viruses, for immunoevasion and dissemination, therefore, the interaction between DCs and each virus has been a prior focus for pathogenesis elucidation. Here, we assessed the potential effect of KSHV on DC–HIV-1 interaction. We found that KSHV stimulation could promote maturation of monocyte-derived DCs (MDDCs) and impaired the ability of MDDCs to drive proliferation of resting CD4{sup +} T cells, demonstrating the immunosuppression induced by KSHV. More importantly, KSHV-stimulated MDDCs could capture more HIV-1 and efficiently transferred these infectious viruses to Hut/CCR5 T cell line. Our results reveal the novel modulation of DC-mediated HIV-1 dissemination by KSHV, and highlight the importance of studying DC–HIV-1 interaction to elucidate HIV/AIDS pathogenesis. - Highlights: ► KSHV impaired the ability of MDDCs to drive proliferation of resting CD4{sup +} T cells. ► KSHV stimulation matured MDDCs and enhanced HIV-1 endocytosis. ► KSHV stimulated MDDCs increased ICAM-1 expression and tighten contact with T cells. ► KSHV-stimulated MDDCs promoted HIV-1 trans-infection of CD4{sup +} T cells.

  2. The impact of Kaposi sarcoma and non-Hodgkin lymphoma on mortality of people with AIDS in the highly active antiretroviral therapies era.

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    Serraino, Diego; De Paoli, Angela; Zucchetto, Antonella; Pennazza, Simona; Bruzzone, Silvia; Spina, Michele; De Paoli, Paolo; Rezza, Giovanni; Dal Maso, Luigino; Suligoi, Barbara

    2010-06-01

    Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) have strongly diminished in the HAART era, but their impact on life expectancy of people with AIDS (PWA) needs to be monitored. We aimed at quantifying the burden of KS and NHL on mortality of PWA in the HAART period in Italy. Death certificates of 3209 PWA diagnosed in 1999-2006 who died as of December 2006 were reviewed to identify those deaths in which KS or NHL was the underlying cause. Standardized mortality ratios (SMR) were computed. KS or NHL appeared in 4.3% and 14.6% death certificates, respectively; they were the underlying cause of death in 3.1% and 13.4% of cases. SMR were 8698-fold higher for KS and 349-fold higher for NHL, and tended to decline over the study period. KS and NHL caused about 16% of deaths of PWA in the HAART era, with 100-fold higher risks of death compared to the Italian general population also in recent years. Clinicians and public health officials should be aware of the persisting negative impact of these cancers on life expectancy of PWA. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  3. The clinical characteristics of 80 cases of acquired immunodeficiency syndrome-associated Kaposi's sarcoma in Xinjiang Autonomous Region and the effect of different treatments on the prognosis.

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    Yang, Tongtong; He, Li; Wan, Xuefeng; Maimaitiaili, Wubuli; Song, Yuxia; Zhang, Yuexin; Lu, Xiaobo

    2015-01-01

    To analyze the clinical features of AIDS-related Kaposi's sarcoma (AIDS-KS) patients in Xinjiang Autonomous Region and the impact of CD4 (+)T lymphocyte count, highly active antiretroviral therapy (HAART) and systemic chemotherapy on the prognosis. The clinical information of 80 AIDS-KS patients admitted in Sixth People's Hospital of Xinjiang Autonomous Region from January 2008 to August 2014 was retrospectively reviewed. Population characteristics, extent of lesions, KS progress, CD4 (+)T lymphocyte count, combined opportunistic infections, treatment and prognosis of these patients were analyzed. The 80 patients were divided into five groups according to treatment methods, including HAART, HAART + chemotherapy, chemotherapy + HAART, chemotherapy, and untreated groups. The efficacy and prognosis of the five groups were compared. Among the 80 patients, 74 (92.50%) patients were Uygur. The average age was 39.5±9.9 years and male-to-female ratio was 3:1. The median of baseline CD4 (+)T lymphocyte count was 152.5 cells/μL and the interquartile was 233.25 cells/μL. CD4 (+)T lymphocyte counts were significantly increased after treatment in HAART, HAART + chemotherapy, and chemotherapy + HAART groups (P AIDS-KS is high in young Uygur male people. HAART followed by chemotherapy has ideal efficacy, reduces the incidence of KS-IRIS and improves the prognosis.

  4. Effect of extremely low frequency electromagnetic fields (ELF-EMF) on Kaposi's sarcoma-associated herpes virus in BCBL-1 cells.

    Science.gov (United States)

    Pica, Francesca; Serafino, Annalucia; Divizia, Maurizio; Donia, Domenica; Fraschetti, Marzia; Sinibaldi-Salimei, Paola; Giganti, Maria Gabriella; Volpi, Antonio

    2006-04-01

    Association between extremely low frequency electromagnetic fields (ELF-EMF) and human cancers is controversial, and few studies have been conducted on their influence on oncogenic viruses. We studied the effects of 1 mT, 50 Hz sine waves, applied for 24-72 h, on Kaposi's sarcoma (KS)-associated herpesvirus (KSHV or HHV-8) in BCBL-1, a latently infected primary effusion lymphoma (PEL) cell line. ELF-EMF exposure did not affect the growth and viability of BCBL-1 cells, either stimulated or not with TPA. The total amount of KSHV DNA detected in ELF-EMF exposed cultures not stimulated with TPA did not differ from that of the unexposed controls (P = ns). However, in the presence of TPA stimulation, total KSHV DNA content was found higher in ELF-EMF exposed than in control BCBL-1 cultures (P = .024) at 72 h exposure, but not earlier. Viral DNA increase significantly correlated with increased mean fluorescence intensity/cell for the lytic antigen gp K8.1A/B (P EMF exposure consisted mainly of defective viral particles. (c) 2005 Wiley-Liss, Inc.

  5. A Prospective Study Assessing Tumour Response, Survival, and Palliative Care Outcomes in Patients with HIV-Related Kaposi's Sarcoma at Queen Elizabeth Central Hospital, Blantyre, Malawi

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    H. Francis

    2012-01-01

    Full Text Available Background. Human-Immunodeficiency-Virus- (HIV- related Kaposi's sarcoma (KS has a high prevalence in Africa; however, there is minimal published data on treatment and outcomes in this population. Objective and Design. This was a prospective study of 50 patients, aiming to assess the impact of vincristine therapy on tumour response and survival and to assess palliative care outcomes in patients with HIV-related KS. Methods. 50 consecutive patients were recruited during 2008. Vincristine therapy and highly active antiretroviral therapy (HAART were given. Tumour response, survival, and chemotherapy-related toxicities were documented. Palliative care outcomes were assessed using the African Palliative Care Association (APCA Palliative Outcome Scale (POS. Results. The majority of patients were male, and the median age was 33 years. At baseline assessment, the median CD4 T-cell count was 263, and 50% patients had evidence of peripheral neuropathy. The overall response rate was 64% at 6 weeks, and median progression-free survival was 30 weeks. Treatment was generally well tolerated, with peripheral neuropathy the main dose-limiting toxicity. Conclusion. The combination of vincristine and HAART is feasible and effective in a low resource setting, although peripheral neuropathy is a dose-limiting factor. This patient group carries a high mortality and as such adequate access to palliative care is crucial.

  6. Phosphorylation of Kaposi's Sarcoma-Associated Herpesvirus Processivity Factor ORF59 by a Viral Kinase Modulates Its Ability To Associate with RTA and oriLyt

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    McDowell, Maria E.; Purushothaman, Pravinkumar; Rossetto, Cyprian C.; Pari, Gregory S.

    2013-01-01

    ORF59 of Kaposi's sarcoma-associated herpesvirus (KSHV) plays an essential role in viral lytic replication by providing DNA processivity activity to the viral DNA polymerase (ORF9). ORF59 forms a homodimer in the cytoplasm and binds and translocates ORF9 into the nucleus, where it secures ORF9 to the origin of lytic DNA replication (oriLyt) in order to synthesize long DNA fragments during replication. ORF59 binds to oriLyt through an immediate early protein, replication and transcription activator (RTA). Here, we show that viral kinase (ORF36) phosphorylates serines between amino acids 376 and 379 of ORF59 and replacement of the Ser378 residue with alanine significantly impairs phosphorylation. Although mutating these serine residues had no effect on binding between ORF59 and ORF9, viral polymerase, or ORF36, the viral kinase, it significantly reduced the ability of ORF59 to bind to RTA. The results for the mutant in which Ser376 to Ser379 were replaced by alanine showed that both Ser378 and Ser379 contribute to binding to RTA. Additionally, the Ser376, Ser378, and Ser379 residues were found to be critical for binding of ORF59 to oriLyt and its processivity function. Ablation of these phosphorylation sites reduced the production of virion particles, suggesting that phosphorylation is critical for ORF59 activity and viral DNA synthesis. PMID:23678174

  7. Kaposi’s sarcoma in Brazilian AIDS patients: a study of 144 cases Sarcoma de Kaposi em pacientes com AIDS: estudo de 144 casos

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    Birman, Esther G.; SILVEIRA, Fernando R. X.; GODOY, Luzia F.; Catalina R. COSTA

    2000-01-01

    One hundred and forty-four Brazilian AIDS patients presenting with Kaposi’s sarcoma (KS) were evaluated with respect to the frequency of oral neoplasms and their clinical features. The majority of the patients were young male adults (age range: 21-40 years old), from which 11.1 % presented with oral KS (OKS) exclusively. Oral and skin lesions were associated in 25% of the cases, while only four patients showed association between oral and visceral KS; 49.3% of the cases were exclusively derma...

  8. p130Cas scaffolds the signalosome to direct adaptor-effector cross talk during Kaposi's sarcoma-associated herpesvirus trafficking in human microvascular dermal endothelial cells.

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    Bandyopadhyay, Chirosree; Veettil, Mohanan Valiya; Dutta, Sujoy; Chandran, Bala

    2014-12-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with cell surface receptors, such as heparan sulfate, integrins (α3β1, αVβ3, and αVβ5), and EphrinA2 (EphA2), and activates focal adhesion kinase (FAK), Src, phosphoinositol 3-kinase (PI3-K), c-Cbl, and RhoA GTPase signal molecules early during lipid raft (LR)-dependent productive macropinocytic entry into human dermal microvascular endothelial cells. Our recent studies have identified CIB1 as a signal amplifier facilitating EphA2 phosphorylation and subsequent cytoskeletal cross talk during KSHV macropinocytosis. Although CIB1 lacks an enzymatic activity and traditional adaptor domain or known interacting sequence, it associated with the KSHV entry signal complex and the CIB1-KSHV association was sustained over 30 min postinfection. To identify factors scaffolding the EphA2-CIB1 signal axis, the role of major cellular scaffold protein p130Cas (Crk-associated substrate of Src) was investigated. Inhibitor and small interfering RNA (siRNA) studies demonstrated that KSHV induced p130Cas in an EphA2-, CIB1-, and Src-dependent manner. p130Cas and Crk were associated with KSHV, LRs, EphA2, and CIB1 early during infection. Live-cell microscopy and biochemical studies demonstrated that p130Cas knockdown did not affect KSHV entry but significantly reduced productive nuclear trafficking of viral DNA and routed KSHV to lysosomal degradation. p130Cas aided in scaffolding adaptor Crk to downstream guanine nucleotide exchange factor phospho-C3G possibly to coordinate GTPase signaling during KSHV trafficking. Collectively, these studies demonstrate that p130Cas acts as a bridging molecule between the KSHV-induced entry signal complex and the downstream trafficking signalosome in endothelial cells and suggest that simultaneous targeting of KSHV entry receptors with p130Cas would be an attractive potential avenue for therapeutic intervention in KSHV infection. Eukaryotic cell adaptor molecules, without any intrinsic

  9. The Kaposi Sarcoma Herpesvirus Latency-associated Nuclear Antigen DNA Binding Domain Dorsal Positive Electrostatic Patch Facilitates DNA Replication and Episome Persistence.

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    Li, Shijun; Tan, Min; Juillard, Franceline; Ponnusamy, Rajesh; Correia, Bruno; Simas, J Pedro; Carrondo, Maria A; McVey, Colin E; Kaye, Kenneth M

    2015-11-20

    Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA binding surface, which is the site of BET protein binding. Here we investigate the functional role of the positive patch in LANA-mediated episome persistence. As expected, LANA mutants with alanine or glutamate substitutions in the central, peripheral, or lateral portions of the positive patch maintained the ability to bind DNA by EMSA. However, all of the substitution mutants were deficient for LANA DNA replication and episome maintenance. Mutation of the peripheral region generated the largest deficiencies. Despite these deficiencies, all positive patch mutants concentrated to dots along mitotic chromosomes in cells containing episomes, similar to LANA. The central and peripheral mutants, but not the lateral mutants, were reduced for BET protein interaction as assessed by co-immunoprecipitation. However, defects in BET protein binding were independent of episome maintenance function. Overall, the reductions in episome maintenance closely correlated with DNA replication deficiencies, suggesting that the replication defects account for the reduced episome persistence. Therefore, the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence and may act through a host cell partner(s) other than a BET protein or by inducing specific structures or complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Kaposi's sarcoma associated herpesvirus encoded viral FLICE inhibitory protein K13 activates NF-κB pathway independent of TRAF6, TAK1 and LUBAC.

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    Hittu Matta

    Full Text Available Kaposi's sarcoma associated herpesvirus encoded viral FLICE inhibitory protein (vFLIP K13 activates the NF-κB pathway by binding to the NEMO/IKKγ subunit of the IκB kinase (IKK complex. However, it has remained enigmatic how K13-NEMO interaction results in the activation of the IKK complex. Recent studies have implicated TRAF6, TAK1 and linear ubiquitin chains assembled by a linear ubiquitin chain assembly complex (LUBAC consisting of HOIL-1, HOIP and SHARPIN in IKK activation by proinflammatory cytokines.Here we demonstrate that K13-induced NF-κB DNA binding and transcriptional activities are not impaired in cells derived from mice with targeted disruption of TRAF6, TAK1 and HOIL-1 genes and in cells derived from mice with chronic proliferative dermatitis (cpdm, which have mutation in the Sharpin gene (Sharpin(cpdm/cpdm. Furthermore, reconstitution of NEMO-deficient murine embryonic fibroblast cells with NEMO mutants that are incapable of binding to linear ubiquitin chains supported K13-induced NF-κB activity. K13-induced NF-κB activity was not blocked by CYLD, a deubiquitylating enzyme that can cleave linear and Lys63-linked ubiquitin chains. On the other hand, NEMO was required for interaction of K13 with IKK1/IKKα and IKK2/IKKβ, which resulted in their activation by "T Loop" phosphorylation.Our results demonstrate that K13 activates the NF-κB pathway by binding to NEMO which results in the recruitment of IKK1/IKKα and IKK2/IKKβ and their subsequent activation by phosphorylation. Thus, K13 activates NF-κB via a mechanism distinct from that utilized by inflammatory cytokines. These results have important implications for the development of therapeutic agents targeting K13-induced NF-κB for the treatment of KSHV-associated malignancies.

  11. Piracy of prostaglandin E2/EP receptor-mediated signaling by Kaposi's sarcoma-associated herpes virus (HHV-8) for latency gene expression: strategy of a successful pathogen.

    Science.gov (United States)

    George Paul, Arun; Sharma-Walia, Neelam; Kerur, Nagaraj; White, Carl; Chandran, Bala

    2010-05-01

    Kaposi's sarcoma-associated herpes virus (KSHV) is implicated in the pathogenesis of KS, a chronic inflammation-associated malignancy. Cyclooxygenase-2 (COX-2) and its metabolite prostaglandin E2 (PGE2), two pivotal proinflammatory/oncogeneic molecules, are proposed to play roles in the expression of major KSHV latency-associated nuclear antigen-1 (LANA-1). Microsomal PGE2 synthase, PGE2, and its receptors (EP1, EP2, EP3, and EP4) were detected in KS lesions with the distinct staining of EP2/EP4 in KS lesions. In latently infected endothelial TIVE-LTC cells, EP receptor antagonists downregulated LANA-1 expression as well as Ca(2+), p-Src, p-PI3K, p-PKCzeta/lambda, and p-NF-kappaB, which are also some of the signal molecules proposed to be important in KS pathogenesis. Exogenous PGE2 and EP receptor agonists induced the LANA-1 promoter in 293 cells, and YY1, Sp1, Oct-1, Oct-6, C/EBP, and c-Jun transcription factors seem to be involved in this induction. PGE2/EP receptor-induced LANA-1 promoter activity was downregulated significantly by the inhibition of Ca(2+), p-Src, p-PI3K, p-PKCzeta/lambda, and p-NF-kappaB. These findings implicate the inflammatory PGE2/EP receptors and the associated signal molecules in herpes virus latency and uncover a novel paradigm that shows the evolution of KSHV genome plasticity to use inflammatory response for its survival advantage of maintaining latent gene expression. These data also suggest that potential use of anti-COX-2 and anti-EP receptor therapy may not only ameliorate the chronic inflammation associated with KS but could also lead to elimination of the KSHV latent infection and the associated KS lesions. (c)2010 AACR.

  12. Human herpesvirus 8 (HHV-8 detected by nested polymerase chain reaction (PCR in HIV patients with or without Kaposi's sarcoma. An analytic cross-sectional study

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    Paula Renata Lima Machado

    Full Text Available CONTEXT AND OBJECTIVE: Kaposi's sarcoma (KS is a common neoplastic disease in AIDS patients. The aim of this study was to evaluate the frequency of human herpesvirus 8 (HHV-8 infection in human immunodeficiency virus (HIV-infected patients, with or without KS manifestations and correlate HHV-8 detection with KS staging. DESIGN AND SETTING: Analytic cross-sectional study conducted in a public tertiary-level university hospital in Ribeirão Preto, São Paulo, Brazil. METHODS: Antibodies against HHV-8 lytic-phase antigens were detected by means of the immunofluorescence assay. HHV-8 DNA was detected in the patient samples through a nested polymerase chain reaction (nested PCR that amplified a region of open reading frame (ORF-26 of HHV-8. RESULTS: Anti-HHV-8 antibodies were detected in 30% of non-KS patients and 100% of patients with KS. Furthermore, the HHV-8 DNA detection rates observed in HIV-positive patients with KS were 42.8% in serum, 95.4% in blood samples and 100% in skin biopsies; and in patients without KS, the detection rate was 4% in serum. Out of the 16 serum samples from patients with KS-AIDS who were classified as stage II, two were positive (12.5%; and out of the 33 samples from patients in stage IV, 19 (57.6% were positive. CONCLUSION: We observed an association between HHV-8 detection and disease staging, which was higher in the serum of patients in stage IV. This suggests that detection of HHV-8 DNA in serum could be very useful for clinical assessment of patients with KS and for monitoring disease progression.

  13. Critical appraisal of volumetric-modulated arc therapy compared with electrons for the radiotherapy of cutaneous Kaposi's sarcoma of lower extremities with bone sparing.

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    Nicolini, G; Abraham, S; Fogliata, A; Jordaan, A; Clivio, A; Vanetti, E; Cozzi, L

    2013-03-01

    To evaluate the use of volumetric-modulated arc therapy [VMAT, RapidArc® (RA); Varian Medical Systems, Palo Alto, CA] for the treatment of cutaneous Kaposi's sarcoma (KS) of lower extremities with adequate target coverage and high bone sparing, and to compare VMAT with electron beam therapy. 10 patients were planned with either RA or electron beams. The dose was prescribed to 30 Gy, 10 fractions, to mean the planning target volume (PTV), and significant maximum dose to bone was limited to 30 Gy. Plans were designed for 6-MV photon beams for RA and 6 MeV for electrons. Dose distributions were computed with AcurosXB® (Varian Medical Systems) for photons and with a Monte Carlo algorithm for electrons. V(90%) was 97.3±1.2 for RA plans and 78.2±2.6 for electrons; similarly, V(107%) was 2.5±2.2 and 37.7±3.4, respectively. RA met coverage criteria. Concerning bone sparing, D(2%) was 29.6±1.1 for RA and 31.0±2.4 for electrons. Although acceptable for bone involvement, pronounced target coverage violations were obtained for electron plans. Monitor units were similar for electrons and RA, although for the latter they increased when superior bone sparing was imposed. Delivery times were 12.1±4.0 min for electrons and 4.8±1.3 min for the most modulated RA plans. High plan quality was shown for KS in the lower extremities using VMAT, and this might simplify their management in comparison with the more conventional usage of electrons, particularly in institutes with limited staff resources and heavy workloads. VMAT is also dosimetrically extremely advantageous in a typology of treatments where electron beam therapy is mainly considered to be effective owing to the limited penetration of the beams.

  14. Treatment outcomes of AIDS-associated Kaposi's sarcoma under a routine antiretroviral therapy program in Lilongwe, Malawi: bleomycin/vincristine compared to vincristine monotherapy.

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    Albert A Mwafongo

    Full Text Available Despite Kaposi's sarcoma (KS being the most prevalent AIDS-associated cancer in resource limited settings, optimal treatment options remain unknown. We assessed whether bleomycin/vincristine compared to vincristine monotherapy was associated with improved treatment outcomes for AIDS-associated KS among patients initiating combination antiretroviral therapy (cART in Malawi.All patients initiating cART and chemotherapy for AIDS-related KS were identified from an electronic data system from the HIV Lighthouse Clinic from 2002 to 2011. Treatment responses were compared between patients receiving vincristine monotherapy and vincristine/bleomycin. Binomial regression models were implemented to assess probability of tumor improvement for patients receiving vincristine/bleomycin compared to vincristine monotherapy after a complete cycle of chemotherapy (9-10 months. A chi-squared test was used to compare changes in CD4 count after six months of chemotherapy.Of 449 patients with AIDS-associated KS on chemotherapy, 94% received vincristine monotherapy and 6% received bleomycin/vincristine. Distribution of treatment outcomes was different: 29% of patients on vincristine experienced tumor improvement compared to 53% of patients on bleomycin/vincristine. Patients receiving bleomycin/vincristine were 2.25 (95% CI: 1.47, 3.44 times as likely to experience tumor improvement as to those on vincristine monotherapy. This value changed little after adjustment for age and baseline CD4 count: 2.46 (95% CI: 1.57, 3.86. Change in CD4 count was similar for patients receiving vincristine monotherapy and bleomycin/vincristine (p = 0.6.Bleomycin/vincristine for the treatment of AIDS-associated KS was associated with better tumor response compared to vincristine monotherapy without impairing CD4 count recovery. Replication in larger datasets and randomized controlled trials is necessary.

  15. Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi's sarcoma.

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    Bruno C Jham

    2011-04-01

    Full Text Available Kaposi's sarcoma (KS is a vascular neoplasm characterized by the dysregulated expression of angiogenic and inflammatory cytokines. The driving force of the KS lesion, the KSHV-infected spindle cell, secretes elevated levels of vascular endothelial growth factor (VEGF, essential for KS development. However, the origin of VEGF in this tumor remains unclear.Here we report that the KSHV G protein-coupled receptor (vGPCR upregulates VEGF in KS through an intricate paracrine mechanism. The cytokines secreted by the few vGPCR-expressing tumor cells activate in neighboring cells multiple pathways (including AKT, ERK, p38 and IKKβ that, in turn, converge on TSC1/2, promoting mTOR activation, HIF upregulation, and VEGF secretion. Conditioned media from vGPCR-expressing cells lead to an mTOR-dependent increase in HIF-1α and HIF-2α protein levels and VEGF upregulation. In a mouse allograft model for KS, specific inhibition of the paracrine activation of mTOR in non-vGPCR-expressing cells was sufficient to inhibit HIF upregulation in these cells, and abolished the ability of the vGPCR-expressing cells to promote tumor formation in vivo. Similarly, pharmacologic inhibition of HIF in this model blocked VEGF secretion and also lead to tumor regression.Our findings provide a compelling explanation for how the few tumor cells expressing vGPCR can contribute to the dramatic amplification of VEGF secretion in KS, and further provide a molecular mechanism for how cytokine dysregulation in KS fuels angiogenesis and tumor development. These data further suggest that activation of HIF by vGPCR may be a vulnerable target for the treatment of patients with KS.

  16. Human herpesvirus-8 (HHV-8 antibodies in women from São Paulo, Brazil: association with behavioral factors and Kaposi's sarcoma

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    Caterino-de-Araujo Adele

    2003-01-01

    Full Text Available BACKGROUND: With the spread of AIDS, many HIV-infected women have been diagnosed with Kaposi's sarcoma (KS, especially in Africa. Since the discovery of a novel herpesvirus as the causative agent of KS (human herpesvirus 8 - HHV-8 several seroepidemiological studies have been conducted to identify groups at risk for KS. The risk for women in Brazil has not been studied. MATERIALS AND METHODS: We searched for HHV-8 antibodies in sera obtained from a bank made up of samples from 3 groups of individuals: Group I: 163 HIV-1-infected women attended at an ambulatory clinic in 1994; Group II: 108 children born to HIV-1-infected mothers from 1990 to 1992, their antibodies reflected maternal infection, and Group III: 630 HIV-1-seronegative, healthy women. In-house immunofluorescence and Western-Blot assays based on the BCBL-1 cell line were used to detect anti-latent and anti-lytic HHV-8 antibodies. RESULTS: Group I had an overall frequency of antibodies of 8.6%, with a 1.2% frequency of anti-latent antibodies and an 8.0% frequency of anti-lytic antibodies. Similar results were detected in Group II, i.e., no cases with anti-latent antibodies and a 7.4% frequency of anti-lytic antibodies. In contrast, prevalences of 1.1% anti-latent antibodies and 0.3% anti-lytic antibodies were observed in Group III. CONCLUSIONS: The epidemiologic pattern of HHV-8 in women from São Paulo varies according to behavioral factors, with emphasis on the sexual and blood routes of virus transmission/acquisition. Although HHV-8 anti-lytic antibodies were found in HIV-1-infected women, no case of KS was detected. Protective factors against KS are probably related to gender and/or to antiretroviral therapies introduced in Brazil since 1994.

  17. Human herpesvirus-8 (HHV-8 antibodies in women from São Paulo, Brazil: association with behavioral factors and Kaposi's sarcoma

    Directory of Open Access Journals (Sweden)

    Adele Caterino-de-Araujo

    Full Text Available BACKGROUND: With the spread of AIDS, many HIV-infected women have been diagnosed with Kaposi's sarcoma (KS, especially in Africa. Since the discovery of a novel herpesvirus as the causative agent of KS (human herpesvirus 8 - HHV-8 several seroepidemiological studies have been conducted to identify groups at risk for KS. The risk for women in Brazil has not been studied. MATERIALS AND METHODS: We searched for HHV-8 antibodies in sera obtained from a bank made up of samples from 3 groups of individuals: Group I: 163 HIV-1-infected women attended at an ambulatory clinic in 1994; Group II: 108 children born to HIV-1-infected mothers from 1990 to 1992, their antibodies reflected maternal infection, and Group III: 630 HIV-1-seronegative, healthy women. In-house immunofluorescence and Western-Blot assays based on the BCBL-1 cell line were used to detect anti-latent and anti-lytic HHV-8 antibodies. RESULTS: Group I had an overall frequency of antibodies of 8.6%, with a 1.2% frequency of anti-latent antibodies and an 8.0% frequency of anti-lytic antibodies. Similar results were detected in Group II, i.e., no cases with anti-latent antibodies and a 7.4% frequency of anti-lytic antibodies. In contrast, prevalences of 1.1% anti-latent antibodies and 0.3% anti-lytic antibodies were observed in Group III. CONCLUSIONS: The epidemiologic pattern of HHV-8 in women from São Paulo varies according to behavioral factors, with emphasis on the sexual and blood routes of virus transmission/acquisition. Although HHV-8 anti-lytic antibodies were found in HIV-1-infected women, no case of KS was detected. Protective factors against KS are probably related to gender and/or to antiretroviral therapies introduced in Brazil since 1994.

  18. Comparative Study of Kaposi's Sarcoma-Associated Herpesvirus Serological Assays Using Clinically and Serologically Defined Reference Standards and Latent Class Analysis▿

    Science.gov (United States)

    Nascimento, Maria Claudia; de Souza, Vanda Akico; Sumita, Laura Masami; Freire, Wilton; Munoz, Fernando; Kim, Joseph; Pannuti, Claudio S.; Mayaud, Philippe

    2007-01-01

    Accurate determination of infection with Kaposi's sarcoma-associated herpesvirus (KSHV) has been hindered by the lack of a “gold standard” for comparison of serological assays used to estimate KSHV prevalence in serosurveys conducted in different settings. We have evaluated the performance of five in-house (developed at University College London [UCL], United Kingdom, and at the virology laboratory of the Instituto de Medicine Tropical [IMT] in Sao Paulo, Brazil) and two commercial (ABI and DIAVIR) serological assays to detect antibodies to latency-associated nuclear antigen (LANA) and to lytic KSHV antigens. We used a variety of serum samples assembled to represent populations likely to be at high, intermediate, and low risk of KSHV infection in Brazil. Composite reference standard panels were prepared based on clinical and serological parameters, against which assay performances were assessed using conventional Bayesian statistics and latent class analysis (LCA). Against the clinical reference standard, in-house immunofluorescence assays to detect anti-LANA antibodies (IFA-LANA) produced at UCL and IMT had similar performances, with sensitivities of 61% (95% confidence interval [CI], 48% to 74%) and 72% (95% CI, 58% to 83%) and specificities of 99% (95% CI, 94% to 100%) and 100% (95% CI, 96% to 100%), respectively, and only the IMT IFA-LANA was included in LCA, together with the IMT IFA-lytic and four enzyme-linked immunosorbent assays (ELISAs). The LCA indicated that the IMT whole-virus ELISA performed best (sensitivity, 87% [95% CI, 81% to 91%]; and specificity, 100% [95% CI, 98% to 100%]), confirming the results obtained with the conventional statistical approach. Commercially available ELISA-based tests yielded the lowest specificities using a spectrum of serum samples. The evaluation of KSHV serological assays is warranted before planning serosurveys in various settings. PMID:17182752

  19. Role of radiotherapy in local control of non-AIDS associated Kaposi's sarcoma patients in Korea: a single institution experience

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    Chang, Ji Hyun; Kim, Il Han [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2012-12-15

    There has been no definite consensus on standard treatment, either local or systemic, for the Kaposi's sarcoma (KS). Radiotherapy (RT) can be a good local therapeutic choice especially in non-AIDS associated KS (NAKS) for its indolent behavior. Medical records of 17 KS patients treated with RT at the Seoul National University Hospital from February 1998 to January 2012 were retrospectively reviewed. One human immunodeficiency virus (HIV)+ patient with 3 lesions was excluded. The total number of the lesion was 23 among the 16 patients. The median follow-up period was 27.9 months. Correlation between response and variables was analyzed using the logistic regression model. Median age of the patients was 75 years. All the 23 lesions were located at the extremities. Fourteen (61%) of those had pain or local swelling as the initial presentation. Ten patients had possible causes of immunodeficiency and were regarded as iatrogenic, and other 6 were classic KS. Median dose of RT was 36 Gy. No KS-related death was observed. Excluding 2 with short-term follow-up only, complete response and partial response were obtained in 2 (9%) and 19 (73%) lesions, respectively. Of those, 3 lesions underwent local progression. Six had out-of-field recurrence after RT. Symptom improvement was achieved in 13 (93%) of 14 patients. Grade 2 skin toxicities were found in 9 lesions but all got improvement after treatment. When divided into responsive and progressive group, free from progression was not related to any of the possible variables. RT is effective in local control of NAKS resulting great response rate.

  20. Kaposi's sarcoma-associated herpesvirus noncoding polyadenylated nuclear RNA interacts with virus- and host cell-encoded proteins and suppresses expression of genes involved in immune modulation.

    Science.gov (United States)

    Rossetto, Cyprian C; Pari, Gregory S

    2011-12-01

    During lytic infection, Kaposi's sarcoma-associated herpesvirus (KSHV) expresses a polyadenylated nuclear RNA (PAN RNA). This noncoding RNA (ncRNA) is localized to the nucleus and is the most abundant viral RNA during lytic infection; however, to date, the role of PAN RNA in the virus life cycle is unknown. Many examples exist where ncRNAs have a defined key regulatory function controlling gene expression by various mechanisms. Our goal for this study was to identify putative binding partners for PAN RNA in an effort to elucidate a possible function for the transcript in KSHV infection. We employed an in vitro affinity protocol where PAN RNA was used as bait for factors present in BCBL-1 cell nuclear extract to show that PAN RNA interacts with several virus- and host cell-encoded factors, including histones H1 and H2A, mitochondrial and cellular single-stranded binding proteins (SSBPs), and interferon regulatory factor 4 (IRF4). RNA chromatin immunoprecipitation (ChIP) assays confirmed that PAN RNA interacted with these factors in the infected cell environment. A luciferase reporter assay showed that PAN RNA expression interfered with the ability of IRF4/PU.1 to activate the interleukin-4 (IL-4) promoter, strongly suggesting a role for PAN RNA in immune modulation. Since the proteomic screen and functional data suggested a role in immune responses, we investigated if constitutive PAN RNA expression could affect other genes involved in immune responses. PAN RNA expression decreased expression of gamma interferon, interleukin-18, alpha interferon 16, and RNase L. These data strongly suggest that PAN RNA interacts with viral and cellular proteins and can function as an immune modulator.

  1. Interaction of Kaposi's sarcoma-associated herpesvirus ORF59 with oriLyt is dependent on binding with K-Rta.

    Science.gov (United States)

    Rossetto, Cyprian C; Susilarini, Ni Ketut; Pari, Gregory S

    2011-04-01

    Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) displays two distinct life stages, latency and lytic reactivation. Progression through the lytic cycle and replication of the viral genome constitute an essential step toward the production of infectious virus and human disease. KSHV K-RTA has been shown to be the major transactivator required for the initiation of lytic reactivation. In the transient-cotransfection replication assay, K-Rta is the only noncore protein required for DNA synthesis. K-Rta was shown to interact with both C/EBPα binding motifs and the R response elements (RRE) within oriLyt. It is postulated that K-Rta acts in part to facilitate the recruitment of replication factors to oriLyt. In order to define the role of K-Rta in the initiation of lytic DNA synthesis, we show an interaction with ORF59, the DNA polymerase processivity factor (PF), one of the eight virally encoded proteins necessary for origin-dependent DNA replication. Using the chromatin immunoprecipitation (ChIP) assay, both K-Rta and ORF59 interact with the RRE and C/EBPα binding motifs within oriLyt in cells harboring the KSHV bacterial artificial chromosome (BAC). A transient-transfection ChIP assay demonstrated that the interaction of ORF59 with oriLyt is dependent on binding with K-Rta and that ORF59 fails to bind to oriLyt in the absence of K-Rta. Also, using the cotransfection replication assay, overexpression of the interaction domain of K-Rta with ORF59 has a dominant negative effect on oriLyt amplification, suggesting that the interaction of K-Rta with ORF59 is essential for DNA synthesis and supporting the hypothesis that K-Rta facilitates the formation of a replication complex at oriLyt.

  2. MANIFESTATIONS OF AGGRESSIVE ATYPICAL KAPOSI'S ...

    African Journals Online (AJOL)

    Infection by the human immunodeficiency virus (HIV) has since the mid-1980's been known to distinguish atypical, aggressive Kaposi's sarcoma (AAKS) from the endemic type in Africa (1). In our series at the University of Maiduguri Teaching Hospital, we recorded 44 patients with AAKS, 35 of them male and 9 female, giving ...

  3. Ser-634 and Ser-636 of Kaposi's Sarcoma-Associated Herpesvirus RTA are Involved in Transactivation and are Potential Cdk9 Phosphorylation Sites.

    Science.gov (United States)

    Tsai, Wan-Hua; Wang, Pei-Wen; Lin, Shu-Yu; Wu, I-Lin; Ko, Ying-Chieh; Chen, Yu-Lian; Li, Mengtao; Lin, Su-Fang

    2012-01-01

    The replication and transcription activator (RTA) of Kaposi's sarcoma-associated herpesvirus (KSHV), K-RTA, is a lytic switch protein that moderates the reactivation process of KSHV latency. By mass spectrometric analysis of affinity purified K-RTA, we showed that Thr-513 or Thr-514 was the primary in vivo phosphorylation site. Thr-513 and Thr-514 are proximal to the nuclear localization signal ((527)KKRK(530)) and were previously hypothesized to be target sites of Ser/Thr kinase hKFC. However, substitutions of Thr with Ala at 513 and 514 had no effect on K-RTA subcellular localization or transactivation activity. By contrast, replacement of Ser with Ala at Ser-634 and Ser-636 located in a Ser/Pro-rich region of K-RTA, designated as S634A/S636A, produced a polypeptide with ∼10 kDa shorter in molecular weight and reduced transactivation in a luciferase reporter assay relative to the wild type. In contrast to prediction, the decrease in molecular weight was not due to lack of phosphorylation because the overall Ser and Thr phosphorylation state in K-RTA and S634A/S636A were similar, excluding that Ser-634 or Ser-636 motif served as docking sites for consecutive phosphorylation. Interestingly, S634A/S636A lost ∼30% immuno-reactivity to MPM2, an antibody specific to pSer/pThr-Pro motif, indicating that (634)SPSP(637) motif was in vivo phosphorylated. By in vitro kinase assay, we showed that K-RTA is a substrate of CDK9, a Pro-directed Ser/Thr kinase central to transcriptional regulation. Importantly, the capability of K-RTA in associating with endogenous CDK9 was reduced in S634A/S636A, which suggested that Ser-634 and Ser-636 may be involved in CDK9 recruitment. In agreement, S634A/S636A mutant exhibited ∼25% reduction in KSHV lytic cycle reactivation relative to that by the wild type K-RTA. Taken together, our data propose that Ser-634 and Ser-636 of K-RTA are phosphorylated by host transcriptional kinase CDK9 and such a process contributes to a full

  4. Human Immunodeficiency Virus Type 1 Tat Accelerates Kaposi Sarcoma-Associated Herpesvirus Kaposin A-Mediated Tumorigenesis of Transformed Fibroblasts In Vitro as well as in Nude and Immunocompetent Mice

    Directory of Open Access Journals (Sweden)

    Xiuying Chen

    2009-12-01

    Full Text Available Kaposi sarcoma-associated herpesvirus (KSHV is necessary but not sufficient to cause Kaposi sarcoma (KS. Coinfection with human immunodeficiency virus type 1 (HIV-1, in the absence of antiretroviral suppressive therapy, drastically increases the risk of KS. Previously, we identified that HIV-1 transactivative transcription protein (Tat was an important cofactor that activated lytic cycle replication of KSHV. Here, we further investigated the potential of Tat to influence tumorigenesis induced by KSHV Kaposin A, a product of KSHV that was encoded by the open reading frame K12 (a KSHV-transforming gene. By using colony formation in soft agar, 3H-TdR incorporation, cell cycle, and microarray gene expression analyses, we demonstrated that Tat enhanced proliferation as well as mitogen-activated protein kinase, signal transducer and activator of transcription 3, and phosphatidylinositol 3-kinase/protein kinase B signaling induced by Kaposin A in NIH3T3 cells. Animal experiments further demonstrated that Tat accelerated tumorigenesis by Kaposin A in athymic nu/nu mice. Cells obtained from primary tumors of nude mice succeeded inducing tumors in immunocompetent mice. These data suggest that Tat can accelerate tumorigenesis induced by Kaposin A. Our data present the first line of evidence that Tat may participate in KS pathogenesis by collaborating with Kaposin A in acquired immunodeficiency syndrome (AIDS-related KS (AIDS-KS patients. Our data also suggest that the model for Kaposin and Tat-mediated oncogenesis will contribute to our understanding of the pathogenesis of AIDS-KS at the molecular level and may even be important in exploring a novel therapeutic method for AIDS-KS.

  5. Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's Sarcoma-associated herpesvirus by herpes simplex virus type 1

    Directory of Open Access Journals (Sweden)

    Lv Zhigang

    2011-10-01

    Full Text Available Abstract Background Kaposi's sarcoma-associated herpesvirus (KSHV is causally linked to several acquired immunodeficiency syndrome-related malignancies, including Kaposi's sarcoma (KS, primary effusion lymphoma (PEL and a subset of multicentric Castleman's disease. Regulation of viral lytic replication is critical to the initiation and progression of KS. Recently, we reported that herpes simplex virus type 1 (HSV-1 was an important cofactor that activated lytic cycle replication of KSHV. Here, we further investigated the possible signal pathways involved in HSV-1-induced reactivation of KSHV. Results By transfecting a series of dominant negative mutants and protein expressing constructs and using pharmacologic inhibitors, we found that either Janus kinase 1 (JAK1/signal transducer and activator of transcription 3 (STAT3 or JAK1/STAT6 signaling failed to regulate HSV-1-induced KSHV replication. However, HSV-1 infection of BCBL-1 cells activated phosphatidylinositol 3-kinase (PI3K/protein kinase B (PKB, also called AKT pathway and inactivated phosphatase and tensin homologue deleted on chromosome ten (PTEN and glycogen synthase kinase-3β (GSK-3β. PTEN/PI3K/AKT/GSK-3β pathway was found to be involved in HSV-1-induced KSHV reactivation. Additionally, extracellular signal-regulated protein kinase (ERK mitogen-activated protein kinase (MAPK pathway also partially contributed to HSV-1-induced KSHV replication. Conclusions HSV-1 infection stimulated PI3K/AKT and ERK MAPK signaling pathways that in turn contributed to KSHV reactivation, which provided further insights into the molecular mechanism controlling KSHV lytic replication, particularly in the context of HSV-1 and KSHV co-infection.

  6. HLA polymorphisms and detection of kaposi sarcoma-associated herpesvirus DNA in saliva and peripheral blood among children and their mothers in the uganda sickle cell anemia KSHV Study

    Directory of Open Access Journals (Sweden)

    Figueiredo Constança

    2010-11-01

    Full Text Available Abstract Kaposi sarcoma-associated herpesvirus (KSHV, also called Human herpesvirus 8 or HHV8 is a γ-2 herpesvirus that causes Kaposi sarcoma. KSHV seroprevalence rates vary geographically with variable rates recorded in different sub Sahara African countries, suggesting that effects of genetic and/or environmental factors may influence the risk of infection. One study conducted in South Africa, where KSHV seroprevalence is relatively low, found that carriage of human leukocyte antigen (HLA alleles HLA-A*6801, HLA-A*30, HLA-A*4301, and HLA-DRB1*04 was associated with increased shedding of KSHV DNA in saliva. Confirmation of those results would strengthen the hypothesis that genetic factors may influence KSHV distribution by modulating KSHV shedding in saliva. To explore these associations in another setting, we used high resolution HLA-A, B, and DRB1 typing on residual samples from the Uganda Sickle Cell Anemia KSHV study, conducted in a high KSHV seroprevalence region, to investigate associations between HLA and KSHV shedding in saliva or peripheral blood among 233 children and their mothers. HLA-A and HLA-DRB1 alleles were not associated with KSHV shedding in our study, but our study was small and was not adequately powered to exclude small associations. In exploratory analyses, we found marginal association of KSHV DNA shedding in saliva but not in peripheral blood among children carrying HLA- B*4415 and marginal association of KSHV DNA shedding in peripheral blood but not in saliva among children carrying HLA- B*0801 alleles. The contribution of individual HLA polymorphisms to KSHV shedding is important but it may vary in different populations. Larger population-based studies are needed to estimate the magnitude and direction of association of HLA with KSHV shedding and viral control.

  7. Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

    Science.gov (United States)

    2016-06-09

    Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

  8. AIDS-related cancer in the era of highly active antiretroviral therapy (HAART): a model of the interplay of the immune system, virus, and cancer. "On the offensive--the Trojan Horse is being destroyed"--Part A: Kaposi's sarcoma.

    Science.gov (United States)

    Cheung, Tony W

    2004-01-01

    The introduction of highly active antiretroviral therapy (HAART), aimed at controlling human immunodeficiency virus (HIV), has been associated with a dramatic decrease in the incidence of acquired immunodeficiency syndrome-Kaposi's sarcoma (AIDS-KS) and the clinical manifestations of KS appear to be less aggressive. The pathogenesis of AIDS-related KS is related to a system of cytokines (e.g., interleukin-6) driven by autocrine and paracrine loops. More recently, human herpesvirus 8 (HHV-8), was discovered to be the putative etiological agent of this disease. This virus encodes several unique open reading frames that are homologs of human cellular proteins involved in cellular regulations, cell proliferation, apoptosis, and immune regulation. The treatment of this disease depends on whether it is "limited" disease or "extensive" disease. For "limited" disease, local therapy or non-bone marrow suppressive agents should be used. For "extensive" disease, new chemotherapeutic agents, such as liposomal anthracycline, which are active and have little adverse reactions, are indicated. The control of HIV infection continues to be essential. Knowledge of the pathogenesis of the disease has led to the development of novel treatment strategies, aimed at the inflammatory or angiogenesis cytokines necessary for growth or at HHV-8 as the target of therapy.

  9. NEMO is essential for Kaposi's sarcoma-associated herpesvirus-encoded vFLIP K13-induced gene expression and protection against death receptor-induced cell death, and its N-terminal 251 residues are sufficient for this process.

    Science.gov (United States)

    Tolani, Bhairavi; Matta, Hittu; Gopalakrishnan, Ramakrishnan; Punj, Vasu; Chaudhary, Preet M

    2014-06-01

    Kaposi's sarcoma-associated herpesvirus-encoded viral FLICE inhibitory protein (vFLIP) K13 was originally believed to protect virally infected cells against death receptor-induced apoptosis by interfering with caspase 8/FLICE activation. Subsequent studies revealed that K13 also activates the NF-κB pathway by binding to the NEMO/inhibitor of NF-κB (IκB) kinase gamma (IKKγ) subunit of an IKK complex and uses this pathway to modulate the expression of genes involved in cellular survival, proliferation, and the inflammatory response. However, it is not clear if K13 can also induce gene expression independently of NEMO/IKKγ. The minimum region of NEMO that is sufficient for supporting K13-induced NF-κB has not been delineated. Furthermore, the contribution of NEMO and NF-κB to the protective effect of K13 against death receptor-induced apoptosis remains to be determined. In this study, we used microarray analysis on K13-expressing wild-type and NEMO-deficient cells to demonstrate that NEMO is required for modulation of K13-induced genes. Reconstitution of NEMO-null cells revealed that the N-terminal 251 amino acid residues of NEMO are sufficient for supporting K13-induced NF-κB but fail to support tumor necrosis factor alpha (TNF-α)-induced NF-κB. K13 failed to protect NEMO-null cells against TNF-α-induced cell death but protected those reconstituted with the NEMO mutant truncated to include only the N-terminal 251 amino acid residues [the NEMO(1-251) mutant]. Taken collectively, our results demonstrate that NEMO is required for modulation of K13-induced genes and the N-terminal 251 amino acids of NEMO are sufficient for supporting K13-induced NF-κB. Finally, the ability of K13 to protect against TNF-α-induced cell death is critically dependent on its ability to interact with NEMO and activate NF-κB. Kaposi's sarcoma-associated herpesvirus-encoded vFLIP K13 is believed to protect virally infected cells against death receptor-induced apoptosis and to

  10. Sarcoma of the head and neck at Kenyatta National Hospital ...

    African Journals Online (AJOL)

    The histopathological types of the neoplasms included Kaposi's sarcoma (39%), osteosarcoma (23%), rhabdomyosarcoma (21 %), fibrosarcoma (13%), chondrosarcoma (two per cent), malignant fibrous histiocytoma (one per cent) and dermatofibrosarcoma protuberans (one per cent). Conclusion: The results of this ...

  11. Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen and Angiogenin Interact with Common Host Proteins, Including Annexin A2, Which Is Essential for Survival of Latently Infected Cells

    Science.gov (United States)

    Paudel, Nitika; Sadagopan, Sathish; Balasubramanian, Sandhya

    2012-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) infection and latency-associated nuclear antigen (LANA-1) upregulate the multifunctional protein angiogenin (ANG). Our studies demonstrate that silencing ANG or inhibiting its nuclear translocation downregulates KSHV LANA-1 expression and ANG is necessary for KSHV latency, anti-apoptosis and angiogenesis (Sadagopan et al., J. Virol. 83:3342–3364, 2009; Sadagopan et al., J Virol. 85:2666–2685, 2011). Here we show that LANA-1 interacts with ANG and colocalizes in latently infected endothelial telomerase-immortalized human umbilical vein endothelial (TIVE-LTC) cells. Mass spectrometric analyses of TIVE-LTC proteins immunoprecipitated by anti-LANA-1 and ANG antibodies identified 28 common cellular proteins such as ribosomal proteins, structural proteins, tRNA synthetases, metabolic pathway enzymes, chaperons, transcription factors, antioxidants, and ubiquitin proteosome proteins. LANA-1 and ANG interaction with one of the proteins, annexin A2, was validated. Annexin A2 has been shown to play roles in cell proliferation, apoptosis, plasmin generation, exocytosis, endocytosis, and cytoskeleton reorganization. It is also known to associate with glycolytic enzyme 3-phosphoglyceratekinase in the primer recognition protein (PRP) complex that interacts with DNA polymerase α in the lagging strand of DNA during replication. A higher level of annexin A2 is expressed in KSHV+ but not in Epstein-Barr virus (EBV)+ B-lymphoma cell lines. Annexin A2 colocalized with several LANA-1 punctate spots in KSHV+ body cavity B-cell lymphoma (BCBL-1) cells. In triple-staining analyses, we observed annexin A2-ANG-LANA-1, annexin A2-ANG, and ANG-LANA-1 colocalizations. Annexin A2 appeared as punctate nuclear dots in LANA-1-positive TIVE-LTC cells. In LANA-1-negative TIVE-LTC cells, annexin A2 was detected predominately in the cytoplasm, with some nuclear spots, and colocalization with ANG was observed mostly in the cytoplasm. Annexin A2

  12. Sarcoma de Kaposi en paciente con SIDA

    OpenAIRE

    Jesús Ramón León Polanco; Tereza Rodríguez Feliz; Ángel Franco Yee

    2015-01-01

    Se presenta el caso de un paciente masculino de 33 años de edad, con antecedentes de VIH-SIDA desde hace 10 años, que se mantiene en tratamiento con antirretrovirales. Durante todo este tiempo ha presentado varios episodios de infecciones respiratorias, incluyendo tuberculosis pulmonar 5 años atrás. Acude a consulta refiriendo edemas en miembros inferiores acompañado de lesiones en piel de color violáceo de un año de evolución, previamente interpretado como linfangitis rebelde al tratamiento ...

  13. 103 Recurrent, massive Kaposi's sarcoma pericardial effusion ...

    African Journals Online (AJOL)

    Chen, Y., Brennessel, D., Walters, J., Johnson, M., Rosner, F., & Raza, M. (1999) Human immunodeficiency virus-associated pericardial effusion: report of 40 cases and review of the literature. American Heart Journal 137, 516-521. Chyu, K.Y., Birnbaum, Y., Naqvi, T., Fishbein, M.C. & Siegel, R.J. (1998) Echocardiographic.

  14. Kaposi's sarcoma in renal transplant recipients

    African Journals Online (AJOL)

    these patients. The present study retrospectively reviews our experi- ence with KS in renal transplant recipients followed up at the Renal Transplant Unit ... local radiotherapy; cyclophosphamide. Management. Azathioprine;. 8. Disseminated. Withdrawal; local. 15. Cyclosporin-A;. (skin, lymph radiotherapy; steroids nodes).

  15. MANAGEMENT OF EPIDEMIC KAPOSI'S SARCOMA: A RECENT ...

    African Journals Online (AJOL)

    . DENTISTRY. By: Dr. Jeff Luande, M.D.. Tanzania Tumor Centre. INTRODUCTION: ... skin and mucous membranes, however, oral presentation typi- cally remains ... telecobalt radiotherapy machine with the patient placed on the floor. Anterior ...

  16. Survival Following Resection for Soft Tissue Sarcomas | Igun ...

    African Journals Online (AJOL)

    For intermediate grade lesions, Kaposi's sarcoma carried the lowest mean survival time (MST) of 1 year, fibroblastic fibrosarcoma 2 years and undifferentiated sarcoma 3 years. The average MST for all high grade lesions was 2 years. Upper extremity lesions carried the worst prognosis with a MST of 1½ years, head, neck, ...

  17. Blood vessel growth blocker may treat AIDS-related Kaposi’s sarcoma

    Science.gov (United States)

    Patients with an AIDS-associated cancer, Kaposi's sarcoma (KS), showed improvement after receiving the combination of bevacizumab, a cancer drug that blocks the growth of new blood vessels, and highly active antiretroviral therapy (HAART).

  18. Synovial sarcoma

    Directory of Open Access Journals (Sweden)

    Sucari S.C. Vlok

    2014-12-01

    Full Text Available Synovial sarcoma is a malignant, predominantly juxta-articular, soft-tissue tumour representing approximately 10% of all soft-tissue sarcomas. Frequently initially incorrectly diagnosed as a benign lesion, it should be considered as a diagnosis when a young adult patient presents with a calcified juxta-articular soft-tissue mass of insidious onset.

  19. Case report: HIV negative isolated scrotal Kaposi's sarcoma

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    Hamid Ozmen

    2014-01-01

    CONCLUSION: Classical KS is generally observed in the lower extremities, it can rarely affect scrotal skin as isolated lesions. Therefore, a careful physical examination should also include scrotum for these patients.

  20. Managing AIDS-related Kaposi's sarcoma and pregnancy

    African Journals Online (AJOL)

    Division of Radiation and Clinical Oncology, Department of Medical Imaging and Clinical Oncology,. Stellenbosch University, Stellenbosch, South Africa. Corresponding author: P Barnardt (pieterb@sun.ac.za). A 24-year-old woman was referred to the. Division of Oncology at a large academic hospital. She had presented ...

  1. Survival of patients with Kaposi's sarcoma in the South African ...

    African Journals Online (AJOL)

    To evaluate survival and changes over time in AIDS-KS patients treated at a tertiary academic hospital oncology unit (the Steve Biko Academic Hospital medical oncology unit) in Pretoria, SA, in the context of ART availability in SA. Methods. We conducted a retrospective review of electronic and paper records of KS patients ...

  2. Commentary: Multifactorial etiology of Kaposi's sarcoma: a hypothesis

    Indian Academy of Sciences (India)

    2008-11-13

    Nov 13, 2008 ... Harry W Haverkos1 2. Captain US Public Health Service (Retired) Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA; 15328 Bitterroot Way, Rockville, MD 20853, USA ...

  3. Evaluation of 14 patients performed radiotherapy due to Kaposi sarcoma

    Directory of Open Access Journals (Sweden)

    Fatma Teke

    2015-09-01

    Full Text Available Methods: The patients undergoing radiotherapy (RT because of the KS between the years 2005-2012 in Radiation Oncology Department of Dicle University Hospital were included. All patients underwent RT with different dose-fractionation schemes to increase quality of life and to palliate the symptoms. Patients with lesions in multiple regions underwent RT in the same or different dates. Responses to radiotherapy were recorded as complete or partial response. Results: Fourteen patients received radiotherapy because of f KS were evaluated retrospectively. Twenty two different regions of 14 patients underwent RT . Only one patient (4.5% was performed RT to glans penis as a third region while performed to the two regions in six patients (27.3%. At irradiations, 6 MV and 10 MV photon energies with 6 MeV, 9 MeV and 12 MeV electron energy were used. Water phantom or bolus material was used to obtain a homogeneous dose distribution in the photon irradiation. RT dose administered to a total of 22 different regional was median 800 cGy (Range: 800-3000 cGy. Median number of RT fractions was 1 (Range: 1-10. When treatment response were evaluated stable disease was present in the 4 (18.1% regions. Partial response was achieved in eight (36.4% regions, complete response in 10 (45.5%. RT-related common lymphedema in the feet and legs was observed in the four (57.3% regions in the acute period. Complication of pain was present in two (28.7% regions. Conclusion: RT is an appropriate and effective treatment regimen in the palliative treatment of KS lesions. Excellent response rates of skin lesions may be obtained by RT. Lesions and symptoms such as itching may be lost after RT. Side effects such as edema and pain may be relieved by supportive treatment.

  4. Kaposi's sarcoma: Good outcome with doxorubicin, bleomycin and ...

    African Journals Online (AJOL)

    We prospectively treated 12 patients with an institutional review board-approved protocol consisting of four monthly courses of doxorubicin (Adriamycin), bleomycin and vincristine sulphate (ABV), with highly active antiretroviral therapy (HAART) plus co-trimoxazole prophylaxis for those who were HIV-positive, with ...

  5. HAART in hand: The change in Kaposi's sarcoma presentation in ...

    African Journals Online (AJOL)

    who were not chemotherapy or radiotherapy naïve. ... associations of HAART with age, gender, CD4 count, urban/rural residence, fungating lesions, ulceration and lymphoedema, and treatment delay ... Of 198 patients, 194 were documented as HIV-positive; 168 (86.6%) were on HAART at the time of their KS diagnosis.

  6. Managing AIDS-related Kaposi's sarcoma and pregnancy | Barnardt ...

    African Journals Online (AJOL)

    ... of AIDS in 30 - 40% of patients. Any organ may be involved, but the gastrointestinal tract and lung remain the most frequently involved locations. The case described here presented a clinical and ethical dilemma where visceral KS, pregnancy and medical complications required multi-disciplinary management.

  7. Kaposi's sarcoma, lymphoedema and gangrene in AIDS – a ...

    African Journals Online (AJOL)

    The manifestations of the HIV pandemic are manifold, affecting all organ systems. With respect to the vascular system, it is recognised that vasculitides constitute one of the less common but none the less challenging consequences of HIV infection.1 The HIV pandemic has also seen a dramatic increase in the prevalence of ...

  8. Chylothorax associated with non-endemic Kaposi's sarcoma

    African Journals Online (AJOL)

    In the setting of. HIV-associated KS, the underlying aetiology for bilateral chylothorax may include primary tumour (KS with involvement of pleura or .... Mayo Clin Proc 1980;55(11):700-704. 3. Varadarajalu L, Jahandardoost M, Pyreddy L, Diaz-Fuentes G. Non-traumatic chylothorax. International Journal of Pulmonary ...

  9. disseminated endemic kaposi's sarcoma in a young man without

    African Journals Online (AJOL)

    'Nggm H.A. 2rant 'Dogo D. 'Khalil MLA. 'nan-y 'r.o.. Departments of 1Histopathology, 2Surgery, “Medical Microbioloq University of Maiduguri Teaching Hospital. P.M.B. 1414 Maiduguri, Borno State, Nigeria. 2Department of Surgery University of Maiduguri Teaching. Hospital P.M.B. 1414 Maiduguri,. Borno State, Nigeria.

  10. Chylothorax associated with non-endemic Kaposi's sarcoma

    African Journals Online (AJOL)

    bleomycin and vincristine. After 6 months of ART, he was ... aetiologies of persistent bilateral pleural effusion aside from KS-induced scarring of the thoracic duct. Diagnostic ... Bilateral pleural effusion with consolidation of the right lower zone of the lung without any pulmonary nodules or lymphadenopathy. Sputum ...

  11. HIV/AIDS-associated Kaposi's sarcoma of the gastrointestinal tract ...

    African Journals Online (AJOL)

    Case reports. A 71-year-old man presented with a 2-month history of malaise, weakness, dizziness, loss of weight and diarrhoea. He had no significant past medical, surgical or social history. His retroviral disease status was unknown. On examination he was cachexic and pale with no other significant clinical findings. He.

  12. kaposi sarcoma:changing trend in calabar, south eastern nigeria

    African Journals Online (AJOL)

    Emmanuel Ameh

    était base sur la technique ELISA. Résultats: Notre étude comptait 11 patients (7 hommes et 4 femmes), avec un sexe ratio homme femme de 1,75. Il s'agissait de la tumeur maligne cutanée la plus fréquente (38%) suivi par le carcinome a cellule squameuses (34,5%). L'âge variait de 21 a 60 ans pour une moyenne de 42,9 ...

  13. HHV-8 prevalence, immunosuppression and Kaposi's sarcoma in South Italy.

    Science.gov (United States)

    Crispo, A; Tamburini, M; De Marco, M R; Ascierto, P; Silvestro, P; Ronga, D; Tridente, V; Desicato, S; Carbone, S; Fabbrocini, G; Spiteri, D; Montella, M

    2001-05-01

    The identification of HHV-8 has opened the way for numerous epidemiological studies aimed at determining both the prevalence of HHV-8 in various sub-groups of the population (affected or not by KS) and at identifying possible cofactors necessary for the development of KS. We set up a study to evaluate the prevalence of HHV-8 in the South of Italy in KS cases, hospital patients and blood donors and to verify the role of immunosuppression in KS. In KS patients the prevalence of lytic and latent antigens were both 91% (29 positive cases). Lytic and latent antigens have prevalence rates of 20% and 15% respectively in hospital patients. In the donor group the rates were 16% for lytic antigens and 2% for latent antigens. The most recurrent chronic pathology in KS patients was cardiopathy (5 cases). The pathological case histories report 4 cases of Herpes Zoster, 6 of diabetes, one case of hepatitis C who had also had gonorrea. There was also a case, negative to HHV-8, who had had malaria after residing for three years in Oristano in Sardinia (a zone with high endemic malaria). Our study confirms that in Southern Italy there are relatively high prevalences of HHV-8 both in the general population and in blood donors and that immunodysregulation may be involved in the pathogenesis of KS. Other studies are necessary to confirm the sexual transmission of the HHV-8 virus and to better understand the natural history of HHV-8 infection.

  14. Kaposi's sarcoma, a South African perspective: Demographic and ...

    African Journals Online (AJOL)

    of slit-like vascular spaces, extravasated red bood cells (Fig. 1), haemosiderin pigment, plasma cells and hyaline globules. Three histological stages, patch, plaque and nodular, are recognised based on the clinical appearance and increasing degree of spindle cell proliferation. Furthermore, special morphological variants ...

  15. Sarcoma Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Gouw, Launce G., E-mail: launce.gouw@hsc.utah.edu [Departments of Oncology, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Jones, Kevin B. [Departments of Orthopaedic Surgery, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Sharma, Sunil [Departments of Oncology, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Randall, R. Lor [Departments of Orthopaedic Surgery, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States)

    2011-11-10

    Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis.

  16. Sarcoma Immunotherapy

    Directory of Open Access Journals (Sweden)

    R. Lor Randall

    2011-11-01

    Full Text Available Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis.

  17. Targeted therapy for sarcomas

    Directory of Open Access Journals (Sweden)

    Forscher C

    2014-03-01

    Full Text Available Charles Forscher,1 Monica Mita,2 Robert Figlin3 1Sarcoma Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Academic Development Program, Samuel Oschin Comprehensive Cancer Institute, and Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing's sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing's sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. Keywords: sarcoma, targeted agents, tyrosine kinase inhibitors, mTor inhibition

  18. Breast sarcomas. Literature review

    Directory of Open Access Journals (Sweden)

    D. A. Ryabchikov

    2014-01-01

    Full Text Available The article presents an overview of the literature about breast sarcomas (nonepithelial malignances. Primary sarcomas are extremely rare, with less than 1 % of all malignant tumors of the breast. Breast carcinomas cause an increased interest of the scientists due to their unique clinical and pathological features and unpredictable prognosis.

  19. Trial of Dasatinib in Advanced Sarcomas

    Science.gov (United States)

    2017-03-20

    Rhabdomyosarcoma; Malignant Peripheral Nerve Sheath Tumors; Chondrosarcoma; Sarcoma, Ewing's; Sarcoma, Alveolar Soft Part; Chordoma; Epithelioid Sarcoma; Giant Cell Tumor of Bone; Hemangiopericytoma; Gastrointestinal Stromal Tumor (GIST)

  20. The Danish Sarcoma Database

    Directory of Open Access Journals (Sweden)

    Jorgensen PH

    2016-10-01

    Full Text Available Peter Holmberg Jørgensen,1 Gunnar Schwarz Lausten,2 Alma B Pedersen3 1Tumor Section, Department of Orthopedic Surgery, Aarhus University Hospital, Aarhus, 2Tumor Section, Department of Orthopedic Surgery, Rigshospitalet, Copenhagen, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Aim: The aim of the database is to gather information about sarcomas treated in Denmark in order to continuously monitor and improve the quality of sarcoma treatment in a local, a national, and an international perspective. Study population: Patients in Denmark diagnosed with a sarcoma, both skeletal and ekstraskeletal, are to be registered since 2009. Main variables: The database contains information about appearance of symptoms; date of receiving referral to a sarcoma center; date of first visit; whether surgery has been performed elsewhere before referral, diagnosis, and treatment; tumor characteristics such as location, size, malignancy grade, and growth pattern; details on treatment (kind of surgery, amount of radiation therapy, type and duration of chemotherapy; complications of treatment; local recurrence and metastases; and comorbidity. In addition, several quality indicators are registered in order to measure the quality of care provided by the hospitals and make comparisons between hospitals and with international standards. Descriptive data: Demographic patient-specific data such as age, sex, region of living, comorbidity, World Health Organization's International Classification of Diseases – tenth edition codes and TNM Classification of Malignant Tumours, and date of death (after yearly coupling to the Danish Civil Registration System. Data quality and completeness are currently secured. Conclusion: The Danish Sarcoma Database is population based and includes sarcomas occurring in Denmark since 2009. It is a valuable tool for monitoring sarcoma incidence and quality of treatment and its improvement, postoperative

  1. Cutaneous Metastatic Undifferentiated Pleomorphic Sarcoma from a Mediastinal Sarcoma.

    Science.gov (United States)

    Jeong, Do Seon; Park, Dong Hwa; Kim, Chi Yeon

    2015-06-01

    Undifferentiated pleomorphic sarcoma, known as malignant fibrous histiocytoma, is a malignant neoplasm that arises in both soft tissue and bones. In 2002, the World Health Organization declassified malignant fibrous histocytoma as a formal diagnostic entity and renamed it 'undifferentiated pleomorphic sarcoma not otherwise specified.' It most commonly occurs in the lower extremities and rarely metastasizes cutaneously. We report a case of cutaneous metastatic undifferentiated pleomorphic sarcoma of the buttocks occurring in a 73-year-old man diagnosed with mediastinal sarcoma 4 years previously. He first noticed the mass approximately 2 months previously. Histological findings with immunomarkers led to a final diagnosis of cutaneous metastatic sarcoma from mediastinal undifferentiated pleomorphic sarcoma.

  2. Primary renal synovial sarcoma

    Directory of Open Access Journals (Sweden)

    Girish D. Bakhshi

    2012-03-01

    Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

  3. Stages of Uterine Sarcoma

    Science.gov (United States)

    ... are abnormal. This procedure is also called a Pap smear. Because uterine sarcoma begins inside the uterus, this cancer may not show up on the Pap test. Enlarge Pap test. A speculum is inserted ...

  4. Spindle Cell Hemangioendothelioma of the Temporal Muscle Resected with Zygomatic Osteotomy: A Case Report of an Unusual Intramuscular Lesion Mimicking Sarcoma

    Directory of Open Access Journals (Sweden)

    Tomohiro Minagawa

    2011-01-01

    Full Text Available Spindle cell hemangioendothelioma (SCH was originally described by Weiss and Enzinger (1986 as a low-grade angiosarcoma resembling both cavernous hemangioma and Kaposi's sarcoma. Recent studies suggest that SCH is a benign neoplasm or reactive lesion accompanying a congenital or acquired vascular malformation. Most SCHs present as one or more nodules affecting the dermis or subcutis of the distal extremities. Few reports describe SCH of the head and neck region; even fewer note intramuscular SCH. Here, we describe a case of SCH involving the temporal muscle mimicking soft tissue sarcoma, who had a successful surgical treatment with a coronal approach and zygomatic osteotomy.

  5. Uterine sarcoma ? current perspectives

    OpenAIRE

    Benson C; Miah AB

    2017-01-01

    Charlotte Benson,1 Aisha B Miah1,2 1Sarcoma Unit, Royal Marsden Hospital, 2Department of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK Abstract: Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiom...

  6. Treatment Option Overview (Uterine Sarcoma)

    Science.gov (United States)

    ... Cancer Prevention Endometrial Cancer Screening Research Uterine Sarcoma Treatment (PDQ®)–Patient Version General Information About Uterine Sarcoma ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  7. aifes'e'ations 0f aggressive atypical kaposi's sarcoma hiv disease ...

    African Journals Online (AJOL)

    and 9 female, giving an M: F ratio approximately 4:1. ... clinical features manifested by the patients were fever (100%), weight loss (86.8%) skin nodules .... females. The upper limb accounted for 4 cases (9.1% of all sites) with no sex bias. Four cases of multiple sites were seen in only males. Three cases of lymph nodes (2-.

  8. Kaposi's sarcoma after alpha-interferon treatment for HIV-negative T ...

    African Journals Online (AJOL)

    Haematology/Oncology Unit and School ofPathology,. University of the Witwatersrand, Johannesburg .... of natural interferons,8 decreased 1\\.TK cell activity has also been described as well as more generalised immune suppression.9,10 The differences observed in various stud- ies may be dependent, among other factors, ...

  9. Epidemiology Of Oral Kaposi's Sarcoma In Zimbabwe 1988-1997: A ...

    African Journals Online (AJOL)

    Incident cases of OKS from the upper and lower lips, oral vestibule, retromolar area, floor of mouth, tongue, cheek mucosa, gums, hard and soft palate were accessed from the Zimbabwe National Cancer Registry (ZNCR). Cases from the skin, pharynx, larynx and the major salivary glands were excluded from the study.

  10. Kaposi's Sarcoma and Human Herpesvirus 8 in Cuba: evidence of subtype B expansion.

    Science.gov (United States)

    Kourí, Vivian; Martínez, Pedro A; Capó, Virginia; Blanco, Orestes; Rodríguez, María E; Jiménez, Narciso; Fleites, Gilberto; Caballero, Iraida; Dovigny, María C; Alemán, Yoan; Correa, Consuelo; Pérez, Lissette; Soto, Yudira; Cardellá, Lidia; Álvarez, Alina; Nambiar, Sandeep; Hengge, Ulrich

    2012-10-25

    To evaluate the temporal distribution (1991-2009) and associated variation of KSHV subtypes in Cuba. Phylogenetic characterization based on the KSHV K1 gene was performed using 90 KSHV positive samples. Molecular characterization confirmed the prevalence of a wide range of KSHV subtypes (A: n=48 [A5=12]; C: n=15; B: n=22; and E: n=5). In the current study, we observed a significant increase in HHV-8 subtype B after 2004 (p=0.0063). This Subtype B in Cuba was associated with: heterosexual behaviour (OR: 3.63, CI: 1,2-10,98; p=0.03), with the antecedent of acquiring HIV/KSHV in Africa (p=0.0003), with nodular stage of KS lesions (OR 4.2, CI: 1.1 to 15.7; p=0.04). Our study is the first to report KSHV Subtype B expansion in Cuba, that might be reflective of a change in human behavioural pattern. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Epidemiology Of Oral Kaposi's Sarcoma In Zimbabwe 1988-1997: A ...

    African Journals Online (AJOL)

    Sitwala

    Oral squamous cell carcinoma (OSCC) is a common oral malignancy that was used to assess the relative rate of increase of OKS. The accessed data for each case ... SCC. KS. 0.6%. Only one case of metastatic KS (0.2%) was recorded in the oral cavity. OKS mostly affected the palate (70.2%) followed by, in descending ...

  12. Immunotherapeutic Intervention against Sarcomas

    Directory of Open Access Journals (Sweden)

    Paolo Pedrazzoli, Simona Secondino, Vittorio Perfetti, Patrizia Comoli, Daniela Montagna

    2011-01-01

    Full Text Available Advances in systemic therapy for sarcoma have produced, over the last two decades, relatively short-term benefits for the majority of patient. Among the novel biologic therapeutics that will likely increase our ability to cure human cancer in the years to come, immunotherapy is one of the most promising approaches. While past attempts to use immunotherapy have failed to dramatically shift the paradigm of care for the treatment of patients with sarcoma, major advances in basic and translational research have resulted, in more recent years, in clinical trial activity that is now beginning to generate promising results. However, to move from “proof of principle” to large scale clinical applicability, we need well-designed, multi-institutional clinical trials, along with continuous laboratory research to explore further the immunological characteristics of individual sarcoma subtypes and the consequent tailoring of therapy.

  13. The Danish Sarcoma Database

    DEFF Research Database (Denmark)

    Jørgensen, Peter Holmberg; Lausten, Gunnar Schwarz; Pedersen, Alma B

    2016-01-01

    skeletal and ekstraskeletal, are to be registered since 2009. MAIN VARIABLES: The database contains information about appearance of symptoms; date of receiving referral to a sarcoma center; date of first visit; whether surgery has been performed elsewhere before referral, diagnosis, and treatment; tumor...... characteristics such as location, size, malignancy grade, and growth pattern; details on treatment (kind of surgery, amount of radiation therapy, type and duration of chemotherapy); complications of treatment; local recurrence and metastases; and comorbidity. In addition, several quality indicators are registered...... of Diseases - tenth edition codes and TNM Classification of Malignant Tumours, and date of death (after yearly coupling to the Danish Civil Registration System). Data quality and completeness are currently secured. CONCLUSION: The Danish Sarcoma Database is population based and includes sarcomas occurring...

  14. Multifocal Retroperitoneal Sarcoma

    Directory of Open Access Journals (Sweden)

    Theodosios Theodosopoulos

    2013-01-01

    Full Text Available Introduction. Retroperitoneal sarcomas comprise a small proportion of all soft tissue sarcomas, and multiple factors influence their clinical behavior. Histopathological type and grade as well as complete surgical resection especially on the first operative attempt are well recognized as the main prognostic factors. Multifocality is another prognostic factor, which compromises therapy and finally makes prognosis worse due to multiple adverse implications. Case Presentation. A rare case of a 65-year-old male patient suffering from a multifocal retroperitoneal liposarcoma successfully treated in our hospital is presented herein. Discussion. Also, general considerations for these tumors are discussed, and especially multifocality is underlined as an ominous sign of retroperitoneal sarcomas behavior. Despite multifocality, once again complete surgical excision remains the mainstay of treatment of these patients, as long as further systemic and local therapies do not provide durable results.

  15. The Danish Sarcoma Database

    DEFF Research Database (Denmark)

    Jørgensen, Peter Holmberg; Lausten, Gunnar Schwarz; Pedersen, Alma B

    2016-01-01

    in order to measure the quality of care provided by the hospitals and make comparisons between hospitals and with international standards. DESCRIPTIVE DATA: Demographic patient-specific data such as age, sex, region of living, comorbidity, World Health Organization's International Classification...... of Diseases - tenth edition codes and TNM Classification of Malignant Tumours, and date of death (after yearly coupling to the Danish Civil Registration System). Data quality and completeness are currently secured. CONCLUSION: The Danish Sarcoma Database is population based and includes sarcomas occurring...

  16. Microenvironmental targets in sarcoma

    Directory of Open Access Journals (Sweden)

    Monika eEhnman

    2015-11-01

    Full Text Available Sarcomas are rare malignant tumors affecting all age groups. They are typically classified according to their resemblance to corresponding normal tissue. Their heterogeneous features, for example in terms of disease-driving genetic aberrations and body location, complicate both disease classification and development of novel treatment regimens. Many years of failure of improved patient outcome in clinical trials has lead to the conclusion that novel targeted therapies are likely needed in combination with current multimodality regimens. Sarcomas have not, in contrast to the common carcinomas, been the subject for larger systematic studies on how tumor behavior relates to characteristics of the tumor microenvironment. There is consequently an urgent need for identifying suitable molecular targets, not only in tumor cells, but also in the tumor microenvironment. This review discusses preclinical and clinical data about potential molecular targets in sarcomas. Studies on targeted therapies involving the tumor microenvironment are prioritized. A greater understanding of the biological context is expected to facilitate more successful design of future clinical trials in sarcoma.

  17. Mathematical Modeling of the HIV/Kaposi’s Sarcoma Coinfection Dynamics in Areas of High HIV Prevalence

    Directory of Open Access Journals (Sweden)

    E. Lungu

    2013-01-01

    k to below unity should be the goal for disease eradication. Provision of HAART is shown to provide dual benefit of reducing HIV spread and the risk of acquiring another fatal disease for HIV/AIDS patients. By providing treatment to 10% of the HIV population, about 87% of the AIDS population acquire protection against coinfection with HIV and Kaposi's Sarcoma (KS. Most sub-Sahara African countries already have programmes in place to screen HIV. Our recommendation is that these programmes should be expanded to include testing for HHV-8 and KS counseling.

  18. Stages of Adult Soft Tissue Sarcoma

    Science.gov (United States)

    ... Tissue Sarcoma Treatment Childhood Vascular Tumors Treatment Research Adult Soft Tissue Sarcoma Treatment (PDQ®)–Patient Version General Information About Adult Soft Tissue Sarcoma Go to Health Professional Version ...

  19. Uterine sarcoma – current perspectives

    Directory of Open Access Journals (Sweden)

    Benson C

    2017-08-01

    Full Text Available Charlotte Benson,1 Aisha B Miah1,2 1Sarcoma Unit, Royal Marsden Hospital, 2Department of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK Abstract: Uterine sarcomas comprise a group of rare tumors with differing tumor biology, natural history and response to treatment. Diagnosis is often made following surgery for presumed benign disease. Currently, preoperative imaging does not reliably distinguish between benign leiomyomas and other malignant pathology. Uterine leiomyosarcoma is the most common sarcoma, but other subtypes include endometrial stromal sarcoma (low grade and high grade, undifferentiated uterine sarcoma and adenosarcoma. Clinical trials have shown no definite survival benefit of adjuvant radiotherapy or chemotherapy and have been hampered by the rarity and heterogeneity of these disease types. There is a role of adjuvant treatment in carefully selected cases following multidisciplinary discussion at sarcoma reference centers. In patients with metastatic disease, systemic chemotherapy can then be considered. There is activity of a number of agents, including doxorubicin, trabectedin, gemcitabine-based chemotherapy, eribulin and pazopanib. Patients should be considered for clinical trial entry where possible. Close international collaboration is important to allow progress in this group of diseases. Keywords: sarcoma, leiomyosarcoma, endometrial stromal sarcoma, undifferentiated uterine sarcoma, leiomyoma

  20. Doxorubicin With Upfront Dexrazoxane Plus Olaratumab for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma

    Science.gov (United States)

    2018-02-08

    Sarcoma, Soft Tissue; Soft Tissue Sarcoma; Undifferentiated Pleomorphic Sarcoma; Leiomyosarcoma; Liposarcoma; Synovial Sarcoma; Myxofibrosarcoma; Angiosarcoma; Fibrosarcoma; Malignant Peripheral Nerve Sheath Tumor; Epithelioid Sarcoma

  1. Genetics Home Reference: Ewing sarcoma

    Science.gov (United States)

    ... links) American Cancer Society: What is the Ewing Family of Tumors? Disease InfoSearch: Ewing's Sarcoma KidsHealth from Nemours MalaCards: ewing ... II: interactions between two members of the TET family, EWS and hTAFII68, and subunits of ... Park YK. Ewing sarcoma: a chronicle of molecular pathogenesis. Hum Pathol. 2016 May 28. ...

  2. Sarcoma risk after radiation exposure

    Directory of Open Access Journals (Sweden)

    Berrington de Gonzalez Amy

    2012-10-01

    Full Text Available Abstract Sarcomas were one of the first solid cancers to be linked to ionizing radiation exposure. We reviewed the current evidence on this relationship, focusing particularly on the studies that had individual estimates of radiation doses. There is clear evidence of an increased risk of both bone and soft tissue sarcomas after high-dose fractionated radiation exposure (10 + Gy in childhood, and the risk increases approximately linearly in dose, at least up to 40 Gy. There are few studies available of sarcoma after radiotherapy in adulthood for cancer, but data from cancer registries and studies of treatment for benign conditions confirm that the risk of sarcoma is also increased in this age-group after fractionated high-dose exposure. New findings from the long-term follow-up of the Japanese atomic bomb survivors suggest, for the first time, that sarcomas can be induced by acute lower-doses of radiation (

  3. Comparison between preoperative biopsy and post-excision histology results in sarcoma: experience at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.

    Science.gov (United States)

    Panda, Kitela Ghislain; Hale, Martin J; Kruger, Deirdre; Luvhengo, Thifhelimbilu Emmanuel

    2014-06-06

    Tumour size, grade and subtype are the main prognostic factors in adult patients presenting with soft-tissue sarcoma. Planning for appropriate management, including the need for additional staging investigations and neoadjuvant therapy, is dependent on reliable preoperative histopathological results. To determine whether there is agreement between preoperative and post-excision histological findings in patients presenting with soft-tissue sarcoma, and whether the agreement is influenced by the subtypes of sarcomas. Records of adult patients who had soft-tissue sarcomas excised were reviewed. Kaposi's sarcoma and gastrointestinal stromal tumours were excluded. Data were retrieved from the Department of Anatomical Pathology of the National Health Laboratory Service and theatre records at Chris Hani Baragwanath Academic Hospital, and included patient demography, tumour sites and size, HIV status, biopsy types and post-excision histological findings. Records of 153 patients were found (median age 44 years). The majority of the sarcomas were >5 cm in diameter, deep seated and localised in extremities. The commonest subtype, irrespective of HIV status, was dermatofibrosarcoma protuberans. Fine-needle aspiration biopsy (FNAB) results were inaccurate in determining the malignant nature, grade and subtype of sarcoma. Rates of accurate tumour subtype classification following core needle and incision biopsies when compared with post-excision histological findings were 73.1% and 78.3%, respectively. FNAB should not be used in the primary evaluation of soft-tissue tumours. A report of spindle cells on the FNAB smear should be followed by core needle or incision biopsy. Incision biopsy is superior to core needle biopsy in the classification of sarcomas by subtype.

  4. Cutaneous Metastatic Undifferentiated Pleomorphic Sarcoma from a Mediastinal Sarcoma

    OpenAIRE

    Jeong, Do Seon; Park, Dong Hwa; Kim, Chi Yeon

    2015-01-01

    Undifferentiated pleomorphic sarcoma, known as malignant fibrous histiocytoma, is a malignant neoplasm that arises in both soft tissue and bones. In 2002, the World Health Organization declassified malignant fibrous histocytoma as a formal diagnostic entity and renamed it 'undifferentiated pleomorphic sarcoma not otherwise specified.' It most commonly occurs in the lower extremities and rarely metastasizes cutaneously. We report a case of cutaneous metastatic undifferentiated pleomorphic sarc...

  5. Treatment Option Overview (Ewing Sarcoma)

    Science.gov (United States)

    ... providers who are experts in treating cancer in children. Treatment for Ewing sarcoma may cause side effects. Five types of standard treatment are used: Chemotherapy Radiation therapy Surgery Targeted therapy High-dose chemotherapy ...

  6. General Information about Ewing Sarcoma

    Science.gov (United States)

    ... providers who are experts in treating cancer in children. Treatment for Ewing sarcoma may cause side effects. Five types of standard treatment are used: Chemotherapy Radiation therapy Surgery Targeted therapy High-dose chemotherapy ...

  7. Kaposi’s sarcoma: An unusual penile lesion in a HIV negative patient

    Directory of Open Access Journals (Sweden)

    Aldo Franco De Rose

    2017-06-01

    Full Text Available Kaposi's sarcoma (KS of the penis is a very rare lesion and it is usually observed in HIV-infected patients. We introduce a case of KS of the penis in a 75 years old HIV negative patient with a peripheral T-cell lymphoma. He came to our attention with a painful ulcerated red lesion on the glans that stretched from the urethral meatus to the coronal skin. This lesion was found to be a KS balanopreputial in the classical variant. Penile KS must be included in the differential diagnosis of genital diseases especially when the clinical features of the lesion are aspecific and diagnosis can be made histologically by performing a biopsy.

  8. Trabectedin in Soft Tissue Sarcomas

    Directory of Open Access Journals (Sweden)

    Bradley J. Petek

    2015-02-01

    Full Text Available Soft tissue sarcomas are a group of rare tumors derived from mesenchymal tissue, accounting for about 1% of adult cancers. There are over 60 different histological subtypes, each with their own unique biological behavior and response to systemic therapy. The outcome for patients with metastatic soft tissue sarcoma is poor with few available systemic treatment options. For decades, the mainstay of management has consisted of doxorubicin with or without ifosfamide. Trabectedin is a synthetic agent derived from the Caribbean tunicate, Ecteinascidia turbinata. This drug has a number of potential mechanisms of action, including binding the DNA minor groove, interfering with DNA repair pathways and the cell cycle, as well as interacting with transcription factors. Several phase II trials have shown that trabectedin has activity in anthracycline and alkylating agent-resistant soft tissue sarcoma and suggest use in the second- and third-line setting. More recently, trabectedin has shown similar progression-free survival to doxorubicin in the first-line setting and significant activity in liposarcoma and leiomyosarcoma subtypes. Trabectedin has shown a favorable toxicity profile and has been approved in over 70 countries for the treatment of metastatic soft tissue sarcoma. This manuscript will review the development of trabectedin in soft tissue sarcomas.

  9. Radiological Findings of Primary Retroperitoneal Ewing Sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Ulusan, S.; Koc, Z.; Tuba Canpolat, E.; Colakoglu, T. [Depts. of Radiology, Pathology, and General Surgery, Baskent Univ. Faculty of Medicine, Adana (Turkey)

    2007-09-15

    Ewing sarcomas are most commonly located in bone, while extra skeletal involvement of the retroperitoneum is extremely rare. We describe the radiologic and pathological findings in an adult patient with retroperitoneal extra skeletal Ewing sarcoma. Keywords: Color Doppler ultrasound; computed tomography; extra skeletal Ewing sarcoma; magnetic resonance imaging; ultrasound.

  10. Epithelioid sarcoma of the tongue.

    Science.gov (United States)

    Leroy, X; Delobelle, A; Lefebvre, J L; Cabaret, V; Bloget, F; Vilain, M O

    1997-01-01

    A case of epithelioid sarcoma in the tongue is reported. The patient, a 35 year old woman, presented with a non-ulcerated painful lesion of the tongue. Microscopically, the tumour was characterised by multiple coalescent nodules with central geographic necrosis infiltrating the lingual muscle. The tumour cells were epithelioid with abundant eosinophilic cytoplasm and atypical nuclei. Immunohistochemically, the tumour cells stained for vimentin, keratin, and epithelial membrane antigen. These morphological and immunohistochemical appearances led to the diagnosis of epithelioid sarcoma of the tongue. Seven years later, the patient died with metastatic dissemination to the scalp, lungs, and brain. No case of epithelioid sarcoma arising in the tongue has been described previously. Images PMID:9462274

  11. Targeting Angiogenesis in Childhood Sarcomas

    Directory of Open Access Journals (Sweden)

    Hemant K. Bid

    2011-01-01

    Full Text Available Angiogenesis and vasculogenesis constitute two processes in the formation of new blood vessels and are essential for progression of solid tumors. Consequently, targeting angiogenesis, and to a lesser extent vasculogenesis, has become a major focus in cancer drug development. Angiogenesis inhibitors are now being tested in pediatric populations whereas inhibitors of vasculogenesis are in an earlier stage of development. Despite the initial enthusiasm for targeting angiogenesis for treatment of cancer, clinical trials have shown only incremental increases in survival, and agents have been largely cytostatic rather than inducing tumor regressions. Consequently, the role of such therapeutic approaches in the context of curative intent for childhood sarcomas is less clear. Here we review the literature on blood vessel formation in sarcomas with a focus on pediatric sarcomas and developments in targeting angiogenesis for treatment of these rare cancers.

  12. Testicular myeloid sarcoma: case report

    Directory of Open Access Journals (Sweden)

    Luzia Beatriz Ribeiro Zago

    2013-01-01

    Full Text Available Myeloid sarcomas are extramedullary solid tumors composed of immature granulocytic precursor cells. In association with acute myeloid leukemia and other myeloproliferative disorders, they may arise concurrently with compromised bone marrow related to acute myeloid leukemia, as a relapsed presentation, or occur as the first manifestation. The testicles are considered to be an uncommon site for myeloid sarcomas. No therapeutic strategy has been defined as best but may include chemotherapy, radiotherapy and/or hematopoietic stem cell transplantation. This study reports the evolution of a patient with testicular myeloid sarcoma as the first manifestation of acute myeloid leukemia. The patient initially refused medical treatment and died five months after the clinical condition started.

  13. Epidemiology and therapies for metastatic sarcoma

    Directory of Open Access Journals (Sweden)

    Amankwah EK

    2013-05-01

    Full Text Available Ernest K Amankwah,1 Anthony P Conley,2 Damon R Reed2 1Department of Cancer Epidemiology, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 2Sarcoma Department, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA Abstract: Sarcomas are cancers arising from the mesenchymal layer that affect children, adolescents, young adults, and adults. Although most sarcomas are localized, many display a remarkable predilection for metastasis to the lungs, liver, bones, subcutaneous tissue, and lymph nodes. Additionally, many sarcoma patients presenting initially with localized disease may relapse at metastatic sites. While localized sarcomas can often be cured through surgery and often radiation, controversies exist over optimal management of patients with metastatic sarcoma. Combinations of chemotherapy are the most effective in many settings, and many promising new agents are under active investigation or are being explored in preclinical models. Metastatic sarcomas are excellent candidates for novel approaches with additional agents as they have demonstrated chemosensitivity and affect a portion of the population that is motivated toward curative therapy. In this paper, we provide an overview on the common sarcomas of childhood (rhabdomyosarcoma, adolescence, and young adults (osteosarcoma, Ewing sarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumor and older adults (leiomyosarcoma, liposarcoma, and undifferentiated high grade sarcoma in terms of the epidemiology, current therapy, promising therapeutic directions and outcome with a focus on metastatic disease. Potential advances in terms of promising therapy and biologic insights may lead to more effective and safer therapies; however, more clinical trials and research are needed for patients with metastatic sarcoma. Keywords: chemotherapy, pediatric sarcoma, rhabdomyosarcoma, osteosarcoma, Ewing sarcoma, synovial sarcoma

  14. Crystalline inclusions in granulocytic sarcoma.

    Science.gov (United States)

    Strauchen, James A; Gordon, Ronald E

    2002-01-01

    Two cases of granulocytic sarcoma were found to contain numerous crystalline inclusions identified on hematoxylin-eosin-stained sections as clusters of pointed needlelike crystals present in foci of necrosis or within macrophages. The crystals were negative for chloroacetate esterase and myeloperoxidase. Electron microscopy demonstrated homogeneously dense, bipyramidal structures, indistinguishable from Charcot-Leyden crystals. Granulocytic sarcomas may contain crystalline inclusions similar to Charcot-Leyden crystals; these structures should be distinguished from crystalline immunoglobulin inclusions occurring in cases of plasma cell myeloma and lymphoplasmacytic lymphoma, which may have a similar appearance.

  15. Spinal Ewing sarcoma: Misleading appearances

    Energy Technology Data Exchange (ETDEWEB)

    Weinstein, J.B.; Siegel, M.J.; Griffith, R.C.

    1984-04-01

    The plain radiographic and computed tomographic (CT) findings in two unusual cases of spinal Ewing sarcoma are reported. Radiographic features resembling neuroblastoma in one case and aneurysmal bone cyst in the other were present. These findings may be misleading and distinguishing characteristics in each case are discussed.

  16. [Imaging diagnostics of bone sarcomas].

    Science.gov (United States)

    Krämer, J A; Gübitz, R; Beck, L; Heindel, W; Vieth, V

    2014-06-01

    Bone tumors and especially bone sarcomas are rare lesions of the skeletal system in comparison to the much more frequently occurring bone metastases. Despite the relative rarity they are important differential diagnoses of bone lesions. The aim of this article is to give the reader an insight into the fundamentals of the primary imaging of bone sarcomas and to illustrate this with the help of two examples (e.g. osteosarcoma and chondrosarcoma). The foundation of the imaging of bone sarcomas is the radiograph in two planes. This method delivers important information on bone tumors. This information should be analyzed with the help of the Lodwick classification, the configuration of periosteal reactions and a possible reaction of the cortex. A possible tumor matrix and the localization within the skeleton or within long bones also provide important information for differential diagnostic delimitation. Magnetic resonance imaging (MRI) with specific adapted bone tumor sequences allows an exact local staging of a bone sarcoma. In addition to local imaging a compartmental MRI which illustrates the entire extent of tumor-bearing bone and the adjacent joints should be performed to rule out possible skip lesions. The most common distant metastases of osteosarcoma and chondrosarcoma occur in the lungs; therefore, a computed tomography (CT) of the chest is part of staging. Other imaging methods, such as CT of the tumor, positron emission tomography CT (PET-CT), bone scan and whole body MRI supplement the imaging depending on tumor type.

  17. The human herpes virus 8-encoded chemokine receptor is required for angioproliferation in a murine model of Kaposi's sarcoma

    DEFF Research Database (Denmark)

    Jensen, Kristian K; Manfra, Denise J; Grisotto, Marcos G

    2005-01-01

    active G protein-coupled receptor known as vGPCR that binds CXC chemokines with high affinity. In this study, we show that conditional transgenic expression of vGPCR by cells of endothelial origin triggers an angiogenic program in vivo, leading to development of an angioproliferative disease...... that resembles KS. This angiogenic program consists partly in the expression of the angiogenic factors placental growth factor, platelet-derived growth factor B, and inducible NO synthase by the vGPCR-expressing cells. Finally, we show that continued vGPCR expression is essential for progression of the KS......-like phenotype and that down-regulation of vGPCR expression results in reduced expression of angiogenic factors and regression of the lesions. Together, these findings implicate vGPCR as a key element in KS pathogenesis and suggest that strategies to block its function may represent a novel approach...

  18. Perceived Life Changes in Adults with Acquired Immunodeficiency Syndrome and Kaposi’s Sarcoma Utilizing a Behavioral Systems Model.

    Science.gov (United States)

    1987-01-01

    Doctorate Degree 3 I.0 Sexual Orientation Heterosexual 0 0.0 * Homosexual 27 90.0 Bisexual 3 I0.0 55 . . .. TabLe I (ComtLimd) sple by Varia"aee (v...would have changes in this item in light of the "internalized homophobia " referred to in the literature (Christ & Wiener, 1985; Wolcott, et al., 1985... heterosexual culture, female patients, and those with other sources of HIV infection, would strengthen these findings. The potential theoretical implications

  19. Upper gastrointestinal Kaposi's sarcoma in HIV-infected patients: ten years of endoscopy observation at a single Brazilian center

    Directory of Open Access Journals (Sweden)

    Rosamar Eulira Fontes Rezende

    2015-10-01

    Conclusions: GI KS is an infrequent finding in patients with HIV infection. Among those with GI KS, 80% had concomitant skin lesions. Immunohistochemical methods for CD31, CD34, and LNA-1 were important tools in the diagnostic assessment of lesions suggestive of KS in the GI tract. Further studies are required to confirm these data, and the need for routine endoscopic investigation of the GI tract in HIV-infected patients with cutaneous KS should be assessed.

  20. Pazopanib in advanced vascular sarcomas: an EORTC Soft Tissue and Bone Sarcoma Group (STBSG) retrospective analysis

    NARCIS (Netherlands)

    Kollar, A.; Jones, R.L.; Stacchiotti, S.; Gelderblom, H.; Guida, M.; Grignani, G.; Steeghs, N.; Safwat, A.; Katz, D.; Duffaud, F.; Sleijfer, S.; Graaf, W.T. van der; Touati, N.; Litiere, S.; Marreaud, S.; Gronchi, A.; Kasper, B.

    2017-01-01

    BACKGROUND: Pazopanib is a multitargeted tyrosine kinase inhibitor approved for the treatment of patients with selective subtypes of advanced soft tissue sarcoma (STS) who have previously received standard chemotherapy including anthracyclines. Data on the efficacy in vascular sarcomas are limited.

  1. Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery

    Science.gov (United States)

    2017-10-31

    Metastatic Angiosarcoma; Metastatic Epithelioid Sarcoma; Metastatic Fibrosarcoma; Metastatic Leiomyosarcoma; Metastatic Liposarcoma; Metastatic Malignant Peripheral Nerve Sheath Tumor; Metastatic Synovial Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Pleomorphic Rhabdomyosarcoma; Stage III Soft Tissue Sarcoma; Stage IV Soft Tissue Sarcoma; Undifferentiated (Embryonal) Sarcoma

  2. Proton Radiotherapy for Pediatric Sarcoma

    Directory of Open Access Journals (Sweden)

    Matthew M. Ladra

    2014-01-01

    Full Text Available Pediatric sarcomas represent a distinct group of pathologies, with approximately 900 new cases per year in the United States alone. Radiotherapy plays an integral role in the local control of these tumors, which often arise adjacent to critical structures and growing organs. The physical properties of proton beam radiotherapy provide a distinct advantage over standard photon radiation by eliminating excess dose deposited beyond the target volume, thereby reducing both the dose of radiation delivered to non-target structures as well as the total radiation dose delivered to a patient. Dosimetric studies comparing proton plans to IMRT and 3D conformal radiation have demonstrated the superiority of protons in numerous pediatric malignancies and data on long-term clinical outcomes and toxicity is emerging. In this article, we review the existing clinical and dosimetric data regarding the use of proton beam radiation in malignant bone and soft tissue sarcomas.

  3. Adrenal Ewing's Sarcoma in an Elderly Man.

    Science.gov (United States)

    Toda, Kazuyoshi; Ishii, Sumiyasu; Yasuoka, Hidetoshi; Nishioka, Masaki; Kobayashi, Takayuki; Horiguchi, Kazuhiko; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Satoh, Tetsurou; Koshi, Hiromi; Segawa, Atsuki; Shimizu, Shin-Ichi; Oyama, Tetsunari; Yamada, Masanobu

    2018-02-15

    Ewing's sarcoma usually arises in the bones of children and adolescents. We herein report a 74-year-old man with Ewing's sarcoma in the adrenal gland. The diagnosis was confirmed by a genetic test, pathological studies, and several imaging studies. He already had multiple liver metastases when he was transferred to our hospital and died on the 37th day. The diagnosis was further confirmed by autopsy studies. Adrenal Ewing's sarcoma is very rare, and our patient was older than other reported cases. Ewing's sarcoma should be considered even in elderly patients with adrenal tumors.

  4. Olaratumab for soft tissue sarcoma.

    Science.gov (United States)

    Teyssonneau, Diego; Italiano, Antoine

    2017-08-01

    Soft tissue sarcomas (STS) are rare malignant tumors. Unfortunately, the first-line doxorubicin-based treatment has not been improved since the 1970s. Platelet-derived growth factor (PDGF) receptor alpha (PDGFR-α) and its ligands are co-expressed in many types of cancer, including sarcomas. They are involved in stimulating growth and regulating stromal-derived fibroblasts and angiogenesis. PDGFR-α and its ligand may play an important role in tumorigenesis and be a potential target in the treatment of sarcomas. Olaratumab is a fully human IgG1-type anti-PDGFR-α monoclonal antibody with a high affinity and a low 50% inhibitory concentration (IC50). Areas covered: The authors review the role of olaratumab in the treatment of STS by focusing on the recent, randomized Phase II JDGD trial that challenged patients with unresectable or metastatic STS with doxorubicin in the presence or absence of olaratumab. This trial showed a great improvement in overall survival (OS), with an increase in survival from 14.7 months to 26.5 months for patients in the experimental arm and showed acceptable toxicity. Expert opinion: Results seem promising. However, it must be qualified, as the study includes several uncertainties. These uncertainties should be addressed by the ongoing Phase 3 JGDJ confirmatory trial, for which the final efficacy analysis is expected by 2019.

  5. Talimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery

    Science.gov (United States)

    2017-11-14

    FNCLCC Sarcoma Grade 2; FNCLCC Sarcoma Grade 3; Leiomyosarcoma; Liposarcoma; Stage I Soft Tissue Sarcoma AJCC v7; Stage IA Soft Tissue Sarcoma AJCC v7; Stage IB Soft Tissue Sarcoma AJCC v7; Stage II Soft Tissue Sarcoma AJCC v7; Stage IIA Soft Tissue Sarcoma AJCC v7; Stage IIB Soft Tissue Sarcoma AJCC v7; Undifferentiated Pleomorphic Sarcoma

  6. [Radiotherapy of adult soft tissue sarcoma].

    Science.gov (United States)

    Le Péchoux, C; Moureau-Zabotto, L; Llacer, C; Ducassou, A; Sargos, P; Sunyach, M P; Thariat, J

    2016-09-01

    Incidence of soft tissue sarcoma is low and requires multidisciplinary treatment in specialized centers. The objective of this paper is to report the state of the art regarding indications and treatment techniques of main soft tissue sarcoma localisations. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  7. Sarcoma auricular izquierdo pleomórfico

    Directory of Open Access Journals (Sweden)

    Enrique Fulquet

    2006-07-01

    El estudio anatomopatológico muestra sarcoma de alto grado, áreas extensas de necrosis y un patrón variable de diferenciación. Se diagnostica sarcoma miofibroblástico con áreas diferenciadas de tumor de células gigantes (Fig. 2, izquierda y condrosarcoma (Fig. 2, derecha.

  8. AZD0530 in Treating Patients With Recurrent Locally Advanced or Metastatic Soft Tissue Sarcoma

    Science.gov (United States)

    2015-07-02

    Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Rhabdomyosarcoma; Dermatofibrosarcoma Protuberans; Endometrial Stromal Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Uterine Carcinosarcoma; Uterine Leiomyosarcoma

  9. Penile epithelioid sarcoma: MR imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Sirikci, A.; Bayram, M.; Demirci, M. [Department of Radiology, Faculty of Medicine, Gaziantep University, Kolejtepe, Gaziantep (Turkey); Bakir, K. [Department of Pathology, Faculty of Medicine, Gaziantep University, Kolejtepe, Gaziantep (Turkey); Sarica, K. [Department of Urology, Faculty of Medicine, Gaziantep University, Kolejtepe, Gaziantep (Turkey)

    1999-10-01

    Magnetic resonance imaging findings of a 38-year-old man with epithelioid sarcoma of the penis is presented. It started as a firm, painless and slowly growing nodule at the base of his penis 6 months previously which caused pain radiating to the testis during coitus. It has been well known that sarcomas may well mimic reactive processes. Initial presentation of epithelioid sarcoma may provoke considerable diagnostic difficulty, and its differentiation from benign lesions, such as Peyronie`s disease and chronic inflammation, may be a clinical problem. In our present report the MR findings are compared with those of the epithelioid sarcomas of various locations reported in the literature and differential diagnosis of the entity is discussed. To our knowledge, this is the first report regarding the MR findings of the epithelioid sarcoma of penis. (orig.) With 3 figs., 16 refs.

  10. Socioeconomic factors and the risk for sarcoma.

    Science.gov (United States)

    Hampras, Shalaka S; Moysich, Kirsten B; Marimuthu, Sathiya P; Ravi, Vinod; Jayaprakash, Vijayvel

    2014-11-01

    Sarcomas are a heterogeneous group of rare malignancies arising from mesenchymal tissue. Although several occupational exposures have been evaluated in association with sarcoma, little is known about the role of socioeconomic indicators such as education. Socioeconomic status has been found to be associated with risk of development of several types of cancers, primarily lung, gastric, and cervical cancers. We conducted a hospital-based case-control study to evaluate the association of socioeconomic level with the risk for sarcoma. A total of 371 incident cases of sarcoma were matched in terms of age, sex, and year of enrollment in the study with 742 cancer-free controls. Education and income levels were evaluated as the indicators of socioeconomic status. Higher education (college level) was associated with a significantly lower risk for sarcoma [odds ratio (OR)=0.48, 95% confidence interval (CI)=0.29-0.80], even after adjusting for important confounders. After stratifying by sex, significantly lower risk for sarcoma was observed among men who had college level education compared with men with a level of education of eighth grade or lower (OR=0.38, 95% CI=0.19-0.74). A significant association between education and the risk for sarcoma remained after stratifying by income (OR=0.49, 95% CI=0.28-0.86, among the low income group). When analyzed as a composite exposure, individuals with high education and high income status had significantly lower risk for sarcoma compared with those with low income and low education status (OR=0.41, 95% CI=0.23-0.71). Thus, socioeconomic factors may play a significant role in determining the risk for sarcoma and should be explored further to elucidate the underlying factors that may explain these sociodemographic inequalities related to sarcoma.

  11. Ewing's Sarcoma and Second Malignancies

    Directory of Open Access Journals (Sweden)

    Joshua D. Schiffman

    2011-01-01

    Full Text Available Ewing's sarcoma (ES is a rare tumor that is most common in children and young adults. Late effects of ES therapy include second cancers, a tragic outcome for survivors of such a young age. This paper will explore the frequencies and types of malignancies that occur after ES. Additionally, it will review how second malignancies have changed with the shift in treatment from high-dose radiation to chemotherapy regimens including alkylators and epipodophyllotoxins. The risk of additional cancers in ES survivors will also be compared to survivors of other childhood cancers. Finally, the possible genetic contribution to ES and second malignancies will be discussed.

  12. [Isolated myeloid sarcoma involving the mediastinum].

    Science.gov (United States)

    Jelić-Puskarić, Biljana; Kardum-Skelin, Ika; Sustercić, Dunja; Pazur, Marina; Vrhovac, Radovan; Radić-Kristo, Delfa; Gredelj-Simec, Njetocka; Kovacević, Dragica Obad; Plasćak, Jasmina; Gasparov, Slavko; Jaksić, Branimir

    2011-09-01

    Myeloid sarcoma is a rare extramedullary solid tumor consisting of immature myeloid cells and most commonly involving the bone, skin, lymph nodes, soft tissue, gastrointestinal tract and testis. Mediastinal myeloid sarcoma is very rare. There are two major types of myeloid sarcoma: granulocytic sarcoma and monoblastic sarcoma, according to immature cell type. Myeloid sarcoma is found in 2%-8% of patients with acute myeloid leukemia (AML). Myeloid sarcoma may develop before or concurrently with AML, or may be the initial manifestation of AML relapse in previously treated patients. Blast transformation of some form of myeloproliferative neoplasm or myelodysplastic syndrome may also manifest as myeloid sarcoma. A major differential diagnostic problem is isolated primary myeloid sarcoma without bone marrow and peripheral blood involvement, which may precede leukemic stage for months or years, and which is frequently misdiagnosed, mostly as malignant lymphoma. A case is presented of a 56-year-old female patient complaining of weakness, vertigo, dry cough and breathing difficulties. Clinical examination revealed enhanced vascular pattern on the right chest and right arm edema. Computed tomography (CT) of the thorax showed an expansive growth measuring 11 cm craniocaudally in the anterior mediastinum. Fine needle aspiration cytology of tumor mass yielded a scarcely cellular sample with individual atypical immature cells, fine chromatin structure and scarce cytoplasm with occasional granules and Auer rods. Considering the morphological, cytochemical and immunocytochemical characteristics of immature cells, the diagnosis of myeloid sarcoma was made and verified by histopathology of tumor biopsy sample. Immature cells were not found by analysis of bone marrow puncture sample, immunophenotyping of bone marrow cells and bone biopsy analysis. As immature cell proliferation was not detected in bone marrow and peripheral blood, while spread of the disease beyond the mediastinum

  13. Primary osteogenic sarcoma of the breast

    Directory of Open Access Journals (Sweden)

    Akang Effiong E

    2006-12-01

    Full Text Available Abstract Background Primary extra-osseous osteogenic sarcomas have been reported in many tissues of the body but their occurrence in the breast is extremely rare. It can arise as a result of osseous metaplasia in a pre-existing benign or malignant neoplasm of the breast or as non-phylloides sarcoma from the soft tissue of a previously normal breast. Case presentation A 40 year-old Nigerian woman was clinically diagnosed to have carcinoma of the left breast. The histology report of core-needle biopsy of the mass showed a malignant neoplasm comprising islands of chondroblastic and osteoblastic stromal cells. This report changed the diagnosis from carcinoma to osteogenic sarcoma of the breast. She had a left modified radical mastectomy, however there was significant post surgery skin deficit. A latissimus dorsi musculocutaneous flap was used to cover the anterior chest wall defect. Sections from the mastectomy specimen confirmed the diagnosis of osteogenic sarcoma. She died six months after mastectomy. Conclusion A diagnosis of osteogenic sarcoma of the breast was made based on histology report and after excluding an osteogenic sarcoma arising from underlying ribs and sternum. This is the second documented case of primary osteogenic sarcoma of the breast coming from Nigeria

  14. New diagnostic modalities in soft tissue sarcoma.

    Science.gov (United States)

    Singer, S

    1999-01-01

    Molecular and cytogenetic analysis of soft tissue sarcoma has provided a vast amount of new genetic information over the past 10 years. Recent advances in genetic technology, such as fluorescence in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and positional cloning techniques have greatly increased the rate of new discoveries and soon may bring cytogenetic and molecular analysis to standard pathology laboratories. Karotypic analysis of soft tissue tumors have demonstrated specific cytogenetic aberrations which have proved to be extremely useful diagnostically and have solidified and improved soft tissue tumor classification systems. Objective and reproducible prognostication in soft tissue sarcoma remains problematic. Presently, the grade and size of the sarcoma are the most important factors used to estimate risk of relapse and overall survival. Assigning a pathologic grade to an individual sarcoma as a means of predicting clinical behavior is often difficult with a 40% discordance rate even between expert sarcoma pathologists. There is mounting evidence that the composition of membrane phospholipid in tumor tissue is an important indicator of a tumor's cellularity, proliferative capacity, and differentiation state. However, there is a lack of information on the biochemical determinants of sarcoma proliferation and differentiation. To address these problems, novel quantitative ex vivo nuclear magnetic resonance (NMR) methods have been applied to determine the biochemical changes in tissue lipid for soft tissue sarcoma. The biochemical changes in tissue lipid have been found to correlate with sarcoma cellularity, growth rate, and differentiation. Continued prospective NMR analysis of tissue lipid biochemistry in soft tissue tumors will permit the development of a clinically relevant biochemical system of prognostic determinants for soft tissue sarcoma in the future.

  15. Primary clear cell sarcoma of rib

    Energy Technology Data Exchange (ETDEWEB)

    Hersekli, Murat Ali [Baskent University Medical Faculty, Department of Orthopedics and Traumatology, Adana (Turkey); Baskent University Medical Faculty, Adana Medical Center, Yuregir Adana (Turkey); Ozkoc, Gurkan; Akpinar, Sercan; Ozalay, Metin; Tandogan, Reha N. [Baskent University Medical Faculty, Department of Orthopedics and Traumatology, Adana (Turkey); Bircan, Sema [Suleyman Demirel University Medical Faculty, Department of Pathology, Adana (Turkey); Tuncer, Ilhan [Baskent University Medical Faculty, Department of Pathology, Adana (Turkey)

    2005-03-01

    Clear cell sarcoma (malignant melanoma of soft tissues) is a very rare soft tissue neoplasm. It generally arises in tendons and aponeuroses. Although metastasis of malignant melanoma to bone is not uncommon, primary clear cell sarcoma of bone is an extremely rare neoplasm. To our knowledge five cases have been reported in the English literature. We present a case of primary clear cell sarcoma of bone in a 28-year-old woman arising in the left ninth rib. We treated the patient with total excision of the mass and postoperative radiotherapy. The patient is alive and well without local recurrence or distant metastasis at 33 months after surgery. (orig.)

  16. Soft tissue sarcomas or intramuscular haematomas?

    Energy Technology Data Exchange (ETDEWEB)

    Taieb, Sophie [Department of Radiology, Centre Oscar Lambret, 03, rue Frederic Combemale, BP 307, 59020 Lille Cedex (France)], E-mail: s-taieb@o-lambret.fr; Penel, Nicolas [Department of Oncology, Centre Oscar Lambret, 03, rue Frederic Combemale, BP 307, 59020 Lille Cedex (France); Vanseymortier, Luc [Department of Surgery, Centre Oscar Lambret, 03, rue Frederic Combemale, BP 307, 59020 Lille Cedex (France); Ceugnart, Luc [Department of Radiology, Centre Oscar Lambret, 03, rue Frederic Combemale, BP 307, 59020 Lille Cedex (France)

    2009-10-15

    Haematomas are common and sarcomas are rare. However the absence of trauma or a light trauma should alert the clinician to the possibility that the abnormality may represent haemorrhage into a tumor and not just haematoma, even in a haemophilic patient. Clinical findings, sonography with Doppler assessment and magnetic resonance images with contrast administration will help in the differential diagnosis. The diagnosis of a high grade sarcoma must be considered in these patients and any doubt should be resolved with a biopsy to avoid tragic consequences of missed sarcoma.

  17. Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery

    Science.gov (United States)

    2017-09-01

    Bone Cancer; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma

  18. Chemotherapy in Ewing′s sarcoma

    Directory of Open Access Journals (Sweden)

    Jain Sandeep

    2010-01-01

    Full Text Available Ewing′s sarcoma constitutes three per cent of all pediatric malignancies. Ewing′s sarcoma has generally been more responsive to chemotherapy than adult-type sarcomas, and chemotherapy is now recommended for all patients with this disease. It is essential to integrate local control measures in the form of surgery and/or radiotherapy at the appropriate time, along with chemotherapy to eradicate the disease. This approach has improved the survival substantially to the tune of 70% in localized disease, although outcome for metastatic disease remains dismal. Newer therapeutic approaches are required to improve outcome for metastatic and recurrent or refractory Ewing′s sarcoma in organized co-operative group trials.

  19. Kaposi’s Sarcoma in Film

    Directory of Open Access Journals (Sweden)

    Richard F. WAGNER

    2016-04-01

    Full Text Available Kaposi’s sarcoma, a historically rare, indolent cutaneous malignancy of elderly men emerged as a frequent and easily recognizable cutaneous manifestation of Acquired Immunodeficiency Syndrome in the 1980s. Since these tumors were often visible to the public, Kaposi’s sarcoma quickly became a stigmatizing marker for those infected, and predicted the high mortality risk from comorbid opportunistic infections. English language films released from 1985-2008 are analyzed for their depictions of Kaposi’s sarcoma, and the role(s it played in these films. With the advent of highly active antiretroviral therapy for those with HIV infection, Kaposi’s sarcoma has once again become relatively rare.

  20. [Molecular biology for sarcoma: useful or necessary?].

    Science.gov (United States)

    Neuville, Agnès; Coindre, Jean-Michel; Chibon, Frédéric

    2015-01-01

    Sarcomas are a heterogeneous group of tumors. Their diagnosis is based on morphology and immunohistochemical profile, with categories of tumors according to the type of tissue that they resemble. Nevertheless, for several tumors, cellular origin is unknown. Molecular analysis performed in recent years allowed, combining histophenotype and genomics, better classifying such sarcomas, individualizing new entities and grouping some tumors. Simple and recurrent genetic alterations, such as translocation, mutation, amplification, can be identified in one of two sarcomas and appear as new diagnostic markers. Their identification in specialized laboratories in molecular pathology of sarcomas is often useful and sometimes necessary for a good diagnosis, leading to a heavy and multidisciplinary multi-step treatment. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. Dicty_cDB: SFH333 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Kaposi's sarcoma-associated herpes-lik... 39 2e-06 AF192756_1( AF192756 |pid:none) Kaposi's sarcoma-associated...Kaposi's sarcoma-associated herpesvir... 39 5e-05 AF305694_1( AF305694 |pid:none) Kaposi's sarcoma-associated

  2. Dicty_cDB: AFN381 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Kaposi's sarcoma-associated herpes... 82 6e-14 U93872_83( U93872 |pid:none) Kaposi's sarcoma-associated...Kaposi's sarcoma-associated herpes... 81 7e-14 U52064_1( U52064 |pid:none) Kaposi's sarcoma-associated

  3. Fibromyxoid sarcoma of the leg

    Directory of Open Access Journals (Sweden)

    Uwe Wollina

    2010-01-01

    Full Text Available A 48-year-old female with an atypical plaque-like lesion of the lower leg is presented in this article. Histologic investigation revealed a rare low-grade fibromyxoid sarcoma (pT1a cN0 cM0; stage Ia of suprafascial localization. Staging of the patient did not reveal metastatic spread. The tumor was surgically removed with wide safety margins. The defect was closed using a mesh graft transplant and vacuum-assisted closure. Healing was complete. Regular follow-up for at least 5 years is recommended. Besides the rareness of this tumor, this case is also remarkable because of the localization on the lower leg and the suprafascial soft tissue.

  4. Synovial sarcoma of the mandible

    Directory of Open Access Journals (Sweden)

    Maryam Khalili

    2012-01-01

    Full Text Available Synovial sarcoma (SS is a relatively common soft tissue tumor but only 6%-7% of cases are diagnosed in the head and neck region. It typically occurs in young adults and is slightly more common in males. The most common sites in the head and neck region are hypopharynx and parapharyngeal spaces. However, SS can also occur in tonsils, tongue, and orofacial soft tissues. It is not difficult to diagnose SS microscopically with its classic biphasic appearance, but the diagnosis of monophasic forms is more challenging especially in unusual locations. In this article, we report a rare case of monophasic SS of the mandible. The clinical, histopathological, and immunohistochemical features are discussed and compared with previously reported cases in the literature. To our knowledge, only six primary involvements have been reported in the jaws. Therefore, our case represents the seventh reported case of SS in the area.

  5. Synovial sarcoma of the mandible

    Science.gov (United States)

    Khalili, Maryam; Eshghyar, Nosratollah; Ensani, Fereshteh; Shakib, Pouyan Amini

    2012-01-01

    Synovial sarcoma (SS) is a relatively common soft tissue tumor but only 6%-7% of cases are diagnosed in the head and neck region. It typically occurs in young adults and is slightly more common in males. The most common sites in the head and neck region are hypopharynx and parapharyngeal spaces. However, SS can also occur in tonsils, tongue, and orofacial soft tissues. It is not difficult to diagnose SS microscopically with its classic biphasic appearance, but the diagnosis of monophasic forms is more challenging especially in unusual locations. In this article, we report a rare case of monophasic SS of the mandible. The clinical, histopathological, and immunohistochemical features are discussed and compared with previously reported cases in the literature. To our knowledge, only six primary involvements have been reported in the jaws. Therefore, our case represents the seventh reported case of SS in the area. PMID:23833586

  6. Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma

    Science.gov (United States)

    2017-05-18

    Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Adult Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  7. [Uterine sarcoma. Analytic study of 37 cases].

    Science.gov (United States)

    Cabra Zurita, R; Ruiz Moreno, J A; Kably Ambe, A

    1998-04-01

    The lack of uniformity in the nomenclature of the uterine sarcomas, it have contributed to a variety and variability of classifications. Fortunately the sarcomas of uterus are rare. The incidence of this tumor is of 3-5% of all the uterine cancers or of 1.7/100,000 women of 20 years or more. The clinical presentation of these tumors is diverse could come bleed uterine abnormal, abdominal pain, pelvic mass, discharge or cervix prominent mass. Clinical discoveries associated with exist the sarcomas how they are the obesity and high blood pressure in a 30% of the patients it are also observed antecedents of pelvic radiation in a 5-10% of the cases. The genomic alterations that is reported the chromosomes in the literature is associated with 1, 7 11 playing an important paper in the initiation or progression of the sarcomas. We was carried out a retrospective analysis of 37 cases of uterine sarcoma managed in the National Institute of Cancerology at one time of 5 years. Being that the leiomiosarcomas comes in the 51.3% of the cases, followed by the stromal sarcoma, bleed uterine abnormal it was the clinical fact of high importance, detecting these patients in Ia and IIa stadiums predominantly. We observed an increment in the incidence of the uterine sarcoma in patients of 40 years or more. 17 patients were managed exclusively with surgery, 17 patients with surgery and radiotherapy and 5 patients with surgery and chemotherapy (2 patients were managed with surgery + radiotherapy + chemotherapy). The index of failure was from the 45.1% to two years in general form, coming metastasic illness in lung, liver and breast mainly. In conclusion, the adjuvant radiotherapy and chemotherapy to the hysterectomy doesn't increase the index of survivor in the several subtype of uterine sarcomas.

  8. Endometrial Stromal Sarcoma Presenting As Puberty Menorrhagia

    Directory of Open Access Journals (Sweden)

    Rema Prabhakaran Nair

    2005-05-01

    Full Text Available Endometrial stromal sarcomas are rare uterine tumours usually seen in perimenopausal females. We report here a case of low grade malignant endometrial stromal sarcoma in an adolescent girl, presenting as puberty menorrhagia. She underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic node sampling. She also received adjuvant chemotherapy and radiotherapy. She is disease free at completion of one year of follow-up.

  9. SURGICAL TREATMENT OF THE RETROPERITONEAL SARCOMA

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    Darja Eržen

    2003-12-01

    Full Text Available Background. Retroperitoneal sarcomas are malignant tumors with an aggressive course of disease. Cause of death is local disease in 50% and disseminated disease in only 25%. We made a retrospective analysis of surgical treatment of retroperitoneal sarcomas in order assess the effect of this treatment modality on the course of the disease.In the years between 1975 and 2000, 155 patients were surgically treated for primary retroperotneal sarcoma at the Institute of Oncology in Ljubljana. Only 81 of 155 patients received the first treatment at our Institute, while other patients had been at least once operated on elsewhere before the admission to our Institute. Of these patients, 40 required a second surgery for the residual disease and 31 for recurrence. In 23 patients, metastatic spread was found at diagnosis. Our treatment approach was aggressive. We surgically removed the recurrent sarcomas and metastases wherever accessible. Operability at the first surgical treatment performed at the Institute of Oncology was 92%. Therefore, 44 patients underwent 3 or more surgeries for sarcoma. The highest number of operations performed in one patients was 9 (2 patients. In 127 patients, the tumor block resection involved at least one additional organ (up to 6.Results. Complications were not sparse; perioperative mortality was 8.4%. The survival depended upon the metastatic spread at diagnosis, tumor grade and oncologic surgery type.Conclusions. Despite complications, only complete resection without microscopic resuduum and contamination yields a long-term survival to the patients with retroperitoneal sarcoma.

  10. Isolated Limb Perfusion of Melphalan With or Without Tumor Necrosis Factor in Treating Patients With Soft Tissue Sarcoma of the Arm or Leg

    Science.gov (United States)

    2012-03-14

    Stage IVB Adult Soft Tissue Sarcoma; Stage IIB Adult Soft Tissue Sarcoma; Stage IIC Adult Soft Tissue Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Stage IVA Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma

  11. Oncopig soft-tissue sarcomas recapitulate key transcriptional features of human sarcomas

    NARCIS (Netherlands)

    Schachtschneider, Kyle M.; Liu, Yingkai; Makelainen, Suvi; Madsen, Ole; Rund, Laurie A.; Groenen, Martien A.M.; Schook, Lawrence B.

    2017-01-01

    Human soft-tissue sarcomas (STS) are rare mesenchymal tumors with a 5-year survival rate of 50%, highlighting the need for further STS research. Research has been hampered by limited human sarcoma cell line availability and the large number of STS subtypes, making development of STS cell lines

  12. Tyrosine kinase inhibitors in treating soft tissue sarcomas: sunitinib in non-GIST sarcomas.

    Science.gov (United States)

    Homet Moreno, Blanca; Garralda Cabanas, Elena; Hitt, Ricardo

    2010-07-01

    Sarcomas are uncommon malignancies that represent more than 50 different tumor types. Surgery remains the mainstay of treating localised disease. Anthracycline and ifosfamide-based chemotherapy is an option for advanced disease; however, effective treatment of advanced soft tissue sarcoma remains a challenge. Advances in understanding the genetic nature of cancer have led to the development of new treatment options for sarcoma. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor with antiangiogenic properties and promising activity in the treatment of GIST refractory to imatinib, however in either soft tissue sarcoma, experience with sunitinib is under development in different clinical trials. In this review we offer the experience with this small molecular target in non-GIST sarcomas.

  13. Maladie de Kaposi à localisation broncho-pulmonaire révélant une ...

    African Journals Online (AJOL)

    La maladie de Kaposi (MK) associée au VIH, forme dite épidémique, a été décrite la 1ère fois en 1981 par Hymmes. C'est l'affection maligne la plus fréquente au cours du SIDA. La MK est à l'origine de 10% des atteintes pleuropulmonaires au cours de l'infection par le VIH et 40% des pneumopathies en cas de MK ...

  14. Metastatic undifferentiated pleomorphic sarcoma causing intraoperative stroke.

    Science.gov (United States)

    Spaulding, Reed; Koumoundouros, Theodoros; Parker, Joseph C

    2013-01-01

    Malignant Fibrous Histiocytoma was historically the most commonly diagnosed soft tissue sarcoma of adults. In 2002, the World Health Organization declassified malignant fibrous histiocytoma as a formal diagnostic entity. They recommended renaming the disease "Pleomorphic Undifferentiated Sarcoma". Current thoughts about the origin of this tumor are being debated. We report a case of a dedifferentiated liposarcoma that metastasized to the lung within one year. The histologic morphology of the metastasis was more aggressive than the primary lesion, and was consistent with a pleomorphic undifferentiated sarcoma. Following surgical resection of the metastatic pulmonary lesion, the patient never fully regained consciousness. He expired the day following his surgery. At autopsy, the patient was found to have died from a massive hemorrhagic stroke involving almost the entire left cerebrum. Tumor emboli from the pulmonary metastasis were seen in the left middle cerebral artery, causing the cerebral infarct. The embolic lesion was consistent with a pleomorphic undifferentiated sarcoma. This case illustrates the evolution that soft tissue sarcomas can undergo as they metastasize and become increasingly undifferentiated, and confirms the surgical risk of resecting such lesions.

  15. Targeted Therapies in Sarcomas: Challenging the Challenge

    Directory of Open Access Journals (Sweden)

    Juan Martín Liberal

    2012-01-01

    Full Text Available Sarcomas are a heterogeneous group of mesenchymal malignancies that very often lead to death. Nowadays, chemotherapy is the only available treatment for most sarcomas but there are few active drugs and clinical results still remain very poor. Thus, there is an imperious need to find new therapeutic alternatives in order to improve sarcoma patient’s outcome. During the last years, there have been described a number of new molecular pathways that have allowed us to know more about cancer biology and tumorigenesis. Sarcomas are one of the tumors in which more advances have been made. Identification of specific chromosomal translocations, some important pathways characterization such as mTOR pathway or the insulin-like growth factor pathway, the stunning development in angiogenesis knowledge, and brand new agents like viruses have lead to the development of new therapeutic options with promising results. This paper makes an exhaustive review of preclinical and clinical evidence of the most recent targeted therapies in sarcomas and provides a future view of treatments that may lead to improve prognosis of patients affected with this disease.

  16. Immunotherapy for Bone and Soft Tissue Sarcomas

    Directory of Open Access Journals (Sweden)

    Takenori Uehara

    2015-01-01

    Full Text Available Although multimodal therapies including surgery, chemotherapy, and radiotherapy have improved clinical outcomes of patients with bone and soft tissue sarcomas, the prognosis of patients has plateaued over these 20 years. Immunotherapies have shown the effectiveness for several types of advanced tumors. Immunotherapies, such as cytokine therapies, vaccinations, and adoptive cell transfers, have also been investigated for bone and soft tissue sarcomas. Cytokine therapies with interleukin-2 or interferons have limited efficacy because of their cytotoxicities. Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE, an activator of the innate immune system, has been approved as adjuvant therapeutics in combination with conventional chemotherapy in Europe, which has improved the 5-year overall survival of patients. Vaccinations and transfer of T cells transduced to express chimeric antigen receptors have shown some efficacy for sarcomas. Ipilimumab and nivolumab are monoclonal antibodies designed to inhibit immune checkpoint mechanisms. These antibodies have recently been shown to be effective for patients with melanoma and also investigated for patients with sarcomas. In this review, we provide an overview of various trials of immunotherapies for bone and soft tissue sarcomas, and discuss their potential as adjuvant therapies in combination with conventional therapies.

  17. Microsatellite Instability in Sarcoma: Fact or Fiction?

    Science.gov (United States)

    Monument, Michael J.; Lessnick, Stephen L.; Schiffman, Joshua D.; Randall, Rl. Tx.

    2012-01-01

    Microsatellite instability (MSI) is a unique molecular abnormality, indicative of a deficient DNA mismatch repair (MMR) system. Described and characterized in the colorectal cancer literature, the MSI-positive phenotype is predictive of disease susceptibility, pathogenesis, and prognosis. The clinical relevance of MSI in colorectal cancer has inspired similar inquisition within the sarcoma literature, although unfortunately, with very heterogeneous results. Evolving detection techniques, ill-defined sarcoma-specific microsatellite loci and small study numbers have hampered succinct conclusions. The literature does suggest that MSI in sarcoma is observed at a frequency similar to that of sporadic colorectal cancers, although there is little evidence to suggest that MSI-positive tumors share distinct biological attributes. Emerging evidence in Ewing sarcoma has demonstrated an intriguing mechanistic role of microsatellite DNA in the activation of key EWS/FLI-target genes. These findings provide an alternative perspective to the biological implications of microsatellite instability in sarcoma and warrant further investigation using sophisticated detection techniques, sensitive microsatellite loci, and appropriately powered study designs. PMID:23401795

  18. Epithelioid sarcoma : Still an only surgically curable disease

    NARCIS (Netherlands)

    de Visscher, Sebastiaan A. H. J.; van Ginkel, Robbert J.; Wobbes, Theo; Veth, Rene P. H.; ten Heuvel, Suzanne E.; Suurmeijer, Albert J. H.; Hoekstra, Harad J.

    2006-01-01

    BACKGROUND. Epithelioid sarcoma is a rare soft tissue sarcoma with a known high propensity for locoregional recurrence and distant metastases. The clinical behavior and prognostic factors that influence the survival of patients with epithelioid sarcoma were studied. METHODS. Twenty-three patients,

  19. Granulocytic sarcoma (chloroma) of the sacrum: initial manifestation of leukemia.

    Science.gov (United States)

    Novick, S L; Nicol, T L; Fishman, E K

    1998-02-01

    We present an unusual case of a granulocytic sarcoma (chloroma) of the sacrum which predated the initial clinical manifestation of acute myelogenous leukemia. Although granulocytic sarcomas occur in up to 9.1% of cases of acute myelogenous leukemia they usually present concurrently with the leukemic presentation. Although granulocytic sarcomas can involve several different organ systems, bone is the most common site.

  20. Uterine sarcoma Part II—Uterine endometrial stromal sarcoma: The TAG systematic review

    Directory of Open Access Journals (Sweden)

    Huann-Cheng Horng

    2016-08-01

    Full Text Available Endometrial stromal tumors are rare uterine tumors (<1%. Four main categories include endometrial stromal nodule, low-grade endometrial stromal sarcoma (LG-ESS, high-grade endometrial stromal sarcoma (HG-ESS, and uterine undifferentiated sarcoma (UUS. This review is a series of articles discussing the uterine sarcomas. LG-ESS, a hormone-dependent tumor harboring chromosomal rearrangement, is an indolent tumor with a favorable prognosis, but characterized by late recurrences even in patients with Stage I disease, suggesting the requirement of a long-term follow-up. Patients with HG-ESS, based on the identification of YWHAE-NUTM2A/B (YWHAE-FAM22A/B gene fusion, typically present with advanced stage diseases and frequently have recurrences, usually within a few years after initial surgery. UUS is, a high-grade sarcoma, extremely rare, lacking a specific line of differentiation, which is a diagnosis of exclusion (the wastebasket category, which fails to fulfill the morphological and immunohistochemical criteria of translocation-positive ESS. Surgery is the main strategy in the management of uterine sarcoma. Due to rarity, complex biological characteristics, and unknown etiology and risk factors of uterine sarcomas, the role of adjuvant therapy is not clear. Only LG-ESS might respond to progestins or aromatase inhibitors.

  1. Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 2-Uncommon Sarcomas.

    Science.gov (United States)

    Levy, Angela D; Manning, Maria A; Miettinen, Markku M

    2017-01-01

    Soft-tissue sarcomas occurring in the abdomen and pelvis are an uncommon but important group of malignancies. Recent changes to the World Health Organization classification of soft-tissue tumors include the movement of gastrointestinal stromal tumors (GISTs) into the soft-tissue tumor classification. GIST is the most common intraperitoneal sarcoma. Liposarcoma is the most common retroperitoneal sarcoma, and leiomyosarcoma is the second most common. GIST, liposarcoma, and leiomyosarcoma account for the majority of sarcomas encountered in the abdomen and pelvis and are discussed in part 1 of this article. Undifferentiated pleomorphic sarcoma (previously called malignant fibrous histiocytoma), dermatofibrosarcoma protuberans, solitary fibrous tumor, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, extraskeletal chondro-osseous sarcomas, vascular sarcomas, and sarcomas of uncertain differentiation uncommonly arise in the abdomen and pelvis and the abdominal wall. Although these lesions are rare sarcomas and their imaging features overlap, familiarity with the locations where they occur and their imaging features is important so they can be diagnosed accurately. The anatomic location and clinical history are important factors in the differential diagnosis of these lesions because metastasis, more-common sarcomas, borderline fibroblastic proliferations (such as desmoid tumors), and endometriosis have imaging findings that overlap with those of these uncommon sarcomas. In this article, the clinical, pathologic, and imaging findings of uncommon soft-tissue sarcomas of the abdomen and pelvis and the abdominal wall are reviewed, with an emphasis on their differential diagnosis.

  2. Primary Pulmonary Synovial Sarcoma in Pregnancy

    Directory of Open Access Journals (Sweden)

    K. Bunch

    2012-01-01

    Full Text Available Background. Primary pulmonary synovial sarcoma is a rare malignancy with a poor prognosis. Surgical resection and postoperative management of these tumors has not been previously described in pregnancy. Case. A 38-year-old pregnant woman was admitted for evaluation of a right thoracic mass found on chest radiography at 26 weeks of gestation. A computed tomography-guided biopsy was subsequently completed and demonstrated a high-grade neoplasm. A right pneumonectomy was performed at 28 weeks of gestation due to pulmonary decompensation, and pathological examination revealed a pulmonary synovial sarcoma. The patient developed a postpartum pulmonary embolism and expired 6 weeks after delivery. Conclusion. Aggressive intervention for pulmonary malignancies during pregnancy may be necessary. Complete tumor resection is the most important prognostic factor in primary pulmonary synovial sarcoma.

  3. Generalized intramuscular granulocytic sarcoma mimicking polymyositis

    Energy Technology Data Exchange (ETDEWEB)

    Fritz, Jan; Claussen, Claus D.; Pereira, Philippe L.; Horger, Marius S. [Eberhard-Karls-University, Department of Diagnostic Radiology, Tuebingen (Germany); Vogel, Wichard [Eberhard-Karls-University, Department of Internal Medicine-Oncology, Tuebingen (Germany); Wehrmann, Martin [Eberhard-Karls-University, Department of Pathology, Tuebingen (Germany)

    2007-10-15

    We report a case of granulocytic sarcoma exclusively manifesting as diffuse intramuscular infiltration of the proximal upper and lower limb girdle and the torso muscles in a patient with previous history of acute myelogenous leukemia 5a. Whole-body CT showed widespread distribution of ill-defined intramuscular, homogeneously enhancing lesions. On whole-body MRI, lesions were homogeneously hyperintense on fat saturated T2-weighted images, isointense on T1-weighted images and strongly enhancing after intravenous gadolinium contrast administration. Histopathology revealed muscular infiltration of blast cells with identical immunochemistry to the initial manifestation of leukemia, diagnostic for an extramedullary relapse manifesting as granulocytic sarcoma. CT and MRI characteristics of this previously undocumented manifestation of granulocytic sarcoma should assist in the identification of such cases. (orig.)

  4. Gemcitabine Hydrochloride With or Without Pazopanib Hydrochloride in Treating Patients With Refractory Soft Tissue Sarcoma

    Science.gov (United States)

    2017-11-01

    Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated Pleomorphic Sarcoma; Malignant Adult Hemangiopericytoma; Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  5. Pulmonary metastasectomy for sarcoma-Essen experience.

    Science.gov (United States)

    Gafencu, Dumitrita Alina; Welter, Stefan; Cheufou, Danjouma Housmanou; Ploenes, Till; Stamatis, Georgios; Stuschke, Martin; Theegarten, Dirk; Taube, Christian; Bauer, Sebastian; Aigner, Clemens

    2017-10-01

    Pulmonary metastasectomy is an established treatment modality for patients with soft as well as bone tissue sarcomas. Aim of this study is to describe the Essen experience in the surgical management of patients with pulmonary sarcoma metastases. This is a retrospective single center analysis of perioperative outcome of patients undergoing pulmonary metastasectomy for sarcoma metastases from 1997-2017 and a summary of published papers on this topic. During the observation period 327 patients (49.23% female) underwent pulmonary metastasectomy for metastases of extrathoracic sarcomas in curative intent. The number of resected metastases was 1-3 in 283 cases (86.54%), 4-9 in 31 cases (9.48%) and 10 or more lesions in 14 cases (4.28%). Wedge resections or precision excisions with laser or electrocautery were performed in 278 cases (85.02%), anatomical segmental resections in 16 patients (4.89%) and lobectomies in 33 patients (10.09%). Bilateral procedures were performed in 98 cases (29.96%). Lymphadenectomy was performed in 122 patients. Positive lymph nodes were found only in 6 cases. All of these cases were patients with soft tissue sarcoma as primary tumor. Preoperative neoadjuvant treatment was performed in 79 patients (24.15%) with chemotherapy, in 54 patients (16.51%) with radiochemotherapy and in 10 patients (3.05%) with radiotherapy. Major postoperative complications were observed in 2.75% of all patients. Thirty-day mortality was 0%. Pulmonary metastasectomy in sarcoma patients is a feasible and safe treatment strategy even in patients with bilateral metastases and multiple lesions. Thoracic lymph node metastases are rare and did not influence survival in our cohort.

  6. Cellular immunotherapy for soft tissue sarcomas

    Science.gov (United States)

    Finkelstein, Steven Eric; Fishman, Mayer; Conley, Anthony P.; Gabrilovich, Dmitry; Antonia, Scott; Chiappori, Alberto

    2015-01-01

    SUMMARY Soft tissue sarcomas are rare neoplasms, with approximately 9,000 new cases in the United States every year. Unfortunately, there is little progress in the treatment of metastatic soft tissue sarcomas in the past two decades beyond the standard approaches of surgery, chemotherapy, and radiation. Immunotherapy is a modality complementary to conventional therapy,. It is appealing because functional anti-tumor activity could affect both local-regional and systemic disease and act over a prolonged period of time. In this report, we review immunotherapeutic investigative strategies being developed, including several tumor vaccine, antigen vaccine, and dendritic cell vaccine strategies. PMID:22401634

  7. Soft tissue sarcoma of the extremity.

    LENUS (Irish Health Repository)

    Cooper, T M

    2012-02-03

    A retrospective review of 33 cases of soft tissue sarcoma of the extremity presenting over a 10 year period was undertaken. The history, patterns of referral, diagnostic investigations, procedures undertaken and outcomes were studied. We found there was a frequent delay in diagnosis and sometimes misinterpretation of biopsy specimens. Patients were seen by a variety of specialists from disciplines such as general surgery, plastic surgery, orthopaedic surgery and rheumatology. Considerable progress has been made in the treatment of soft tissue sarcomas, often allowing local control of the tumour without amputation. We believe there should be early referral of patients having these tumours to a centre where a combined multidisciplinary approach can be undertaken.

  8. Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma

    Science.gov (United States)

    2017-09-07

    Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  9. Bone tumor and soft tissue sarcomas

    Directory of Open Access Journals (Sweden)

    Reynaldo Jesus Garcia Filho

    2008-03-01

    Full Text Available When we evaluate a rheumatologic patient we have to think aboutthe differential diagnosis among primary bone tunors, secondarybone tumors and soft tissue sarcomas. Muscle skeletal tumors,like rheumatologic diseases, have a predilection for old patients.Their knowledge is very important for a correct diagnosis andtreatment.

  10. The Value of Surgery for Retroperitoneal Sarcoma

    Directory of Open Access Journals (Sweden)

    Sepideh Gholami

    2009-01-01

    Full Text Available Introduction. Retroperitoneal sarcomas are uncommon large malignant tumors. Methods. Forty-one consecutive patients with localized retroperitoneal sarcoma were retrospectively studied. Results. Median age was 58 years (range 20–91 years. Median tumor size was 17.5 cm (range 4–41 cm. Only 2 tumors were <5 cm. Most were liposarcoma (44% and high-grade (59%. 59% were stage 3 and the rest was stage 1. Median followup was 10 months (range 1–106 months. Thirty-eight patients had an initial complete resection; 15 (37% developed recurrent sarcoma and 12 (80% had a second complete resection. Patients with an initial complete resection had a 5-year survival of 46%. For all patients, tumor grade affected overall survival (=.006. Complete surgical resection improved overall survival for high-grade tumors (=.03. Conclusions. Tumor grade/stage and complete surgical resection for high-grade tumors are important prognostic variables. Radiation therapy or chemotherapy had no significant impact on overall or recurrence-free survival. Complete surgical resection is the treatment of choice for patients with initial and locally recurrent retroperitoneal sarcoma.

  11. A case of clear cell sarcoma

    DEFF Research Database (Denmark)

    Juel, Jacob; Ibrahim, Rami Mossad

    2017-01-01

    INTRODUCTION: Clear cell sarcoma (CCS) is a rare tumour of the soft tissue often misdiagnosed, as it shares characteristics with malignant melanoma (MM). Previously, CCS has been characterised, as malignant melanoma of the soft tissue, contemporary immunohistochemical techniques, however, have ma...

  12. Sarcomas primitivos do pulmão

    Directory of Open Access Journals (Sweden)

    F. Caeiro

    1998-07-01

    Full Text Available RESUMO: Os sarcomas primitivos do pulmão são raros, representando 0.1 % de todas as neoplasias pulmonares malignas.No presente trabalho os autores reveem 5 casos clinicos diagnosticodos no periodo compreendido entre 1985 e 1997.A série inclui 4 doentes do sexo musculino e l do sexo femimino, com idades entre os 21 e os 73 anos. Apenas um doente era fumador.A sintomatologia mais frequente foi a toracalgia, a tosse seca. a dispneia e a expeetoração hemoptoica.O diagnóstieo hislopatológico foi feito em 3 casos através da peça operatória e cm 2 por biópsia brôm quica. Os tipos histológicos encontrados foram: 2 leiomiossarcomas, I rabdomiossarcoma, 1 careinos-sarcoma e 1 sarcoma poueo diferenciado.No que sc refere à terapêutica, todos os doentes tratados foram submetidos a cirurgia, tendo efectua-do cm 3 casos terapêutica adjuvante com quimiote-rapia ou quimioterapia+radioterapia.Após o dingnóstieo, os doentes sobreviveram entre 6 dias e 49 meses. Apesar da maioria ter sido submetida a cirurgia. apenas um doente sobreviveu para além dos 3 anos, o que está de acordu cum a agressividade destas neoplasias.REV PORT PNEUMOL 1998; IV (4: 403-412 ABSTRACT: Primary pulmonary sarcomas represent 0.1% of all primary lung neoplasms.In this work w e reviewed a consecutive serie of patients with this diagnosis, treated al our department between the period of 1985 and 1997.Four patients were males and I female, aged between 21 and 72 years old. Only one was a smoker.The most frequent symptoms were chest pain, cough, dyspnea and hemoptoic sputum.The diagnosis was obtained by surgery in 3 patients and by bronchial biopsy in 2 cases. The histologic types observed w ere 2 leiomyossareomas. 1 rabdomyossarcoma, I carcinossarcoma and I low diferentiated sarcoma.Four patients were treated with pulmonary surgery and in 3 cases plus thoracic irradiation and chemotherapy or simply chemotherapy.After the diagnosis, patients had survived between 6 days and

  13. Matrix metalloproteinase 1: role in sarcoma biology.

    Directory of Open Access Journals (Sweden)

    Muhammad Umar Jawad

    2010-12-01

    Full Text Available In carcinomas stromal cells participate in cancer progression by producing proteases such as MMPs. The expression MMP1 is a prognostic factor in human chondrosarcoma, however the role in tumor progression is unknown. Laser capture microdissection and In Situ hybridization were used to determine cellular origin of MMP1 in human sarcomas. A xenogenic model of tumor progression was then used and mice were divided in two groups: each harboring either the control or a stably MMP1 silenced cell line. Animals were sacrificed; the neovascularization, primary tumor volumes, and metastatic burden were assessed. LCM and RNA-ISH analysis revealed MMP1 expression was predominantly localized to the tumor cells in all samples of sarcoma (p = 0.05. The percentage lung metastatic volume at 5 weeks (p = 0.08 and number of spontaneous deaths secondary to systemic tumor burden were lower in MMP1 silenced cell bearing mice. Interestingly, this group also demonstrated a larger primary tumor size (p<0.04 and increased angiogenesis (p<0.01. These findings were found to be consistent when experiment was repeated using a second independent MMP1 silencing sequence. Prior clinical trials employing MMP1 inhibitors failed because of a poor understanding of the role of MMPs in tumor progression. The current findings indicating tumor cell production of MMP1 by sarcoma cells is novel and highlights the fundamental differences in MMP biology between carcinomas and sarcomas. The results also emphasize the complex roles of MMP in tumor progression of sarcomas. Not only does metastasis seem to be affected by MMP1 silencing, but also local tumor growth and angiogenesis are affected inversely.

  14. The Roles of Sox Family Genes in Sarcoma.

    Science.gov (United States)

    Li, Jingyuan; Shen, Jacson; Wang, Kunzheng; Hornicek, Francis; Duan, Zhenfeng

    2016-01-01

    Sox (SRY-related HMG-box) family genes are important regulators of cell development, homeostasis, and regeneration. Deregulation of certain members of the Sox gene family has been implicated in a number of human malignancies, including in sarcoma. Accumulating evidence suggests that Sox genes play crucial roles in sarcoma cell pathogenesis, growth, and proliferation. Here, we review the biological relevance of Sox2 and Sox9 genes in osteosarcoma, chondrosarcoma and chordoma; Sox2, Sox6, and Sox17 genes in Ewing's sarcoma; Sox2, Sox9, and Sox10 genes in synovial sarcoma; Sox2 gene in fibrosarcoma; and Sox21 gene in liposarcoma. These findings potentiate the targeting of Sox genes for novel therapeutic interventions in sarcoma and may also hold valuable clinical potential to improve the care of patients with sarcoma.

  15. Management of metastatic retroperitoneal sarcoma: a consensus approach from the Transatlantic Retroperitoneal Sarcoma Working Group (TARPSWG).

    Science.gov (United States)

    MacNeill, A J; Van Houdt, W J; Swallow, C J; Gronchi, A

    2018-02-07

    Retroperitoneal sarcoma (RPS) is a rare disease accounting for 0.1-0.2% of all malignancies. Management of RPS is complex and requires multidisciplinary, tailored treatment strategies at all stages, but especially in the context of metastatic or multifocal recurrent disease. Due to the rarity and heterogeneity of this family of diseases, the literature to guide management is limited. The Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG) is an international collaboration of sarcoma experts from all disciplines convened in an effort to overcome these limitations. The TARPSWG has compiled the available evidence surrounding metastatic and multifocally recurrent RPS along with expert opinion in an iterative process to generate a consensus document regarding the complex management of this disease. The objective of this document is to guide sarcoma specialists from all disciplines in the diagnosis and treatment of multifocal recurrent or metastatic RPS. All aspects of patient assessment, diagnostic processes, local and systemic treatments, and palliation are reviewed in this document, and consensus recommendations provided accordingly. Recommendations were guided by available evidence, in conjunction with expert opinion where evidence was lacking. This consensus document combines the available literature regarding the management of multifocally recurrent or metastastic RPS with the practical expertise of high-volume sarcoma centers from multiple countries. It is designed as a tool for decision-making in the complex multidisciplinary management of this condition and is expected to standardize management across centers, thereby ensuring that patients receive the highest quality care.

  16. Granulocytic sarcoma (chloroma) of the sacrum: initial manifestation of leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Novick, S.L.; Fishman, E.K. [Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, 600 N. Wolfe Street, Baltimore, MD 21287 (United States); Nicol, T.L. [Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland (United States)

    1998-02-01

    We present an unusual case of a granulocytic sarcoma (chloroma) of the sacrum which predated the initial clinical manifestation of acute myelogenous leukemia. Although granulocytic sarcomas occur in up to 9.1% of cases of acute myelogenous leukemia they usually present concurrently with the leukemic presentation. Although granulocytic sarcomas can involve several different organ systems, bone is the most common site. (orig.) With 2 figs., 6 refs.

  17. Significance of Circulating Tumor Cells in Soft Tissue Sarcoma

    OpenAIRE

    Chiara Nicolazzo; Angela Gradilone

    2015-01-01

    Circulating tumor cells can be detected from the peripheral blood of cancer patients. Their prognostic value has been established in the last 10 years for metastatic colorectal, breast, and prostate cancer. On the contrary their presence in patients affected by sarcomas has been poorly investigated. The discovery of EpCAM mRNA expression in different sarcoma cell lines and in a small cohort of metastatic sarcoma patients supports further investigations on these rare tumors to deepen the impor...

  18. Deep-seated sarcomas of the penis

    Directory of Open Access Journals (Sweden)

    Alberto A. Antunes

    2005-06-01

    Full Text Available Mesenchymal neoplasias represent 5% of tumors affecting the penis. Due to the rarity of such tumors, there is no agreement concerning the best method for staging and managing these patients. Sarcomas of the penis can be classified as deep-seated if they derive from the structures forming the spongy body and the cavernous bodies. Superficial lesions are usually low-grade and show a small tendency towards distant metastasis. In contrast, deep-seated lesions usually show behavior that is more aggressive and have poorer prognosis. The authors report 3 cases of deep-seated primary sarcomas of the penis and review the literature on this rare and aggressive neoplasia.

  19. Thyroid carcino-sarcoma in a dog

    Directory of Open Access Journals (Sweden)

    Antonio Giuliano

    2013-04-01

    Full Text Available An adult male greyhound was diagnosed with a thyroid carcino-sarcoma by means of histopathology and positive immuno-histochemistry staining for cytokeratin and vimentin. Surgery and radiotherapy of the area were successful in local tumour control. Adjuvant chemotherapy was recommended to treat and prevent further metastasis. The use of carboplatin, metronomic cyclophosphamide chemotherapy and toceranib failed to control the progression of distant metastasis. The survival time was seven months from the time of diagnosis. This is the eighth case of carcino-sarcoma of the thyroid documented in veterinary medicine and the first one treated with a multimodal approach based on surgery, radiotherapy and chemotherapy. As documented in human medicine, chemotherapy appeared to be ineffective to prevent or delay the progression of the metastatic disease in this case.

  20. Childhood Ewing Sarcoma of the Orbit.

    Science.gov (United States)

    Alfaar, Ahmad S; Zamzam, Manal; Abdalla, Badr; Magdi, Ranin; El-Kinaai, Naglaa

    2015-08-01

    In the span of the last 48 years, only 33 cases of children with orbital Ewing sarcoma have been reported. This study is to present 3 cases that were admitted to Children's Cancer Hospital Egypt 57357, during the period from 2009 to 2013. We have 2 cases treated using the hospital standard Ewing sarcoma treatment protocol, to completion, whereas the third discontinued treatment. All tumors have confirmed CD99 positivity, although translocation (11;22) was positive in 1 patient and negative in the third. With earlier diagnosis and adequate surgical resection and integration of chemotherapy and radiotherapy 1 patient survived for about 4 years, whereas the other 2 cases died due to disease progression or recurrence.

  1. Current Immunotherapies for Sarcoma: Clinical Trials and Rationale

    Directory of Open Access Journals (Sweden)

    Demytra Mitsis

    2016-01-01

    Full Text Available Sarcoma tumors are rare and heterogeneous, yet they possess many characteristics that may facilitate immunotherapeutic responses. Both active strategies including vaccines and passive strategies involving cellular adoptive immunotherapy have been applied clinically. Results of these clinical trials indicate a distinct benefit for select patients. The recent breakthrough of immunologic checkpoint inhibition is being rapidly introduced to a variety of tumor types including sarcoma. It is anticipated that these emerging immunotherapies will exhibit clinical efficacy for a variety of sarcomas. The increasing ability to tailor immunologic therapies to sarcoma patients will undoubtedly generate further enthusiasm and clinical research for this treatment modality.

  2. Primary Intimal Sarcoma of Thoracic Aorta Presenting as Hypertensive Crisis.

    Science.gov (United States)

    Lin, Shu-I; Su, Min-I; Tsai, Cheng-Ting

    2015-11-01

    We report a 45-year-old woman who presented to our facility in a hypertensive crisis. Computed tomography (CT) revealed a thoracic aortic tumor, and tissues obtained via endovascular biopsy revealed undifferentiated sarcoma. A final diagnosis of intimal sarcoma was made by intra-operative pathological examination. Despite undergoing surgical resection followed by adjuvant chemotherapy, the patient died from progressive multiple metastasis and severe sepsis. Although aortic sarcoma is rarely diagnosed, it should be considered a possible etiology of hypertensive crisis. Aortic tumor; Endovascular biopsy; Hypertension crisis; Intimal sarcoma.

  3. An Unusual Location of Extraosseous Ewing's Sarcoma

    Directory of Open Access Journals (Sweden)

    Lisanne Geens

    2013-05-01

    Full Text Available Ewing's sarcoma (ES is the second most common malignant bone tumor in children and young adults. ES also occurs as a primary soft tissue neoplasm without involvement of bone. We report the second case of extraosseous (EO ES emerging from the omentum and a review of the relevant literature. EO ES should be included in the differential diagnosis of soft tissue neoplasms in the abdomen.

  4. An Unusual Location of Extraosseous Ewing's Sarcoma

    Science.gov (United States)

    Geens, Lisanne; Robays, Johan Van; Geert, Verswijvel; der Speeten, Kurt Van

    2013-01-01

    Ewing's sarcoma (ES) is the second most common malignant bone tumor in children and young adults. ES also occurs as a primary soft tissue neoplasm without involvement of bone. We report the second case of extraosseous (EO) ES emerging from the omentum and a review of the relevant literature. EO ES should be included in the differential diagnosis of soft tissue neoplasms in the abdomen. PMID:23898272

  5. Multimodality Local Therapy for Retroperitoneal Sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Paryani, Nitesh N.; Zlotecki, Robert A.; Swanson, Erika L.; Morris, Christopher G. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Grobmyer, Stephen R.; Hochwald, Steven N. [Department of General Surgery, University of Florida College of Medicine, Gainesville, FL (United States); Marcus, Robert B. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

    2012-03-01

    Purpose: Soft-tissue sarcomas of the retroperitoneum are rare tumors comprising less than 1% of all malignancies. Although surgery continues as the mainstay of treatment, the large size of these tumors coupled with their proximity to critical structures make resection with wide margins difficult to achieve. The role and timing of radiotherapy are controversial. This study updates our institutional experience using multimodality local therapy for resectable retroperitoneal sarcoma and identifies prognostic factors impacting disease control and survival. Methods and Materials: Between 1974 and 2007, 58 patients with nonmetastatic retroperitoneal sarcoma were treated with surgery and radiation at University of Florida. The median age at radiotherapy was 57 years old (range, 18-80 years). Forty-two patients received preoperative radiotherapy and 16 received postoperative radiotherapy. Nineteen patients received 1.8 Gy once daily and 39 patients received 1.2 Gy twice daily. Variables analyzed for prognostic value included age, grade, kidney involvement, histology, de novo versus recurrent presentation, tumor diameter, margin status, radiotherapy sequencing (preoperative vs. postoperative), total radiation dose, fractionation scheme, and treatment era. Results: The 5-year overall survival, cause-specific survival, and local control rates were 49%, 58%, and 62%, respectively. Nearly two-thirds of disease failures involved a component of local progression. On multivariate analysis, only margin status was significantly associated with improved 5-year local control (85%, negative margins; 63%, microscopic positive margins; 0%, gross positive margins; p < 0.0001) and 5-year overall survival (64%, negative margins; 56%, microscopic positive margins; 13%, gross positive margins; p = 0.0012). Thirty-one Grade 3 or greater toxicities were observed in 22 patients, including two treatment-related deaths (3%). Conclusion: For retroperitoneal sarcoma, local control remains a

  6. Sarcomas: etiología y síntomas Sarcomas: etiology and symptoms

    Directory of Open Access Journals (Sweden)

    Roberto Gabriel Albín Cano

    2012-07-01

    Full Text Available Debido a la amplia diversidad de sarcomas, casi son inexistentes los textos que incluyen todas las variedades de este tipo de cáncer. Generalmente, su descripción y revisión se incluyen en las del sistema de órganos afectados específicamente, y la literatura que los aborda está muy fragmentada en las diferentes especialidades médicas. Se realiza una revisión bibliográfica sobre la etiología y síntomas de la mayor parte de los diferentes tipos de sarcomas. Es objetivo de esta revisión, lograr unir la información más actual disponible acerca de la etiología y síntomas de los sarcomas. Se han identificado diferentes factores de riesgo y factores etiológicos, tanto genéticos, infecciosos, como ambientales. Los grandes descubrimientos en relación con los mecanismos genéticos involucrados en los diferentes tipos de sarcoma, han abierto un camino de inestimable valor para introducir nuevos tratamientos, que incluyen ensayos con anticuerpos monoclonales y nuevos fármacos de terapia génica.

    Due to the wide diversity of sarcomas, almost no texts include all varieties of this type of cancer. Generally, their description and review is included in those of the specifically affected organ system, and the literature containing that information is very fragmented in different medical specialties. We performed a literature review on the etiology and symptoms of most types of sarcomas. It is aimed at achieving a recompilation of most current information available on the causes and symptoms of sarcomas. Different risks and etiologic factors have been identified regarding genetics, infections, and environment. The great discoveries regarding genetic mechanisms involved in different types of sarcomas, have opened an invaluable way to introduce new treatments, including monoclonal antibodies and new drugs of gene therapy.

  7. Kaposi's Sarcoma-Associated Herpesvirus K8 Is an RNA Binding Protein That Regulates Viral DNA Replication in Coordination with a Noncoding RNA.

    Science.gov (United States)

    Liu, Dongcheng; Wang, Yan; Yuan, Yan

    2018-01-10

    KSHV lytic replication and constant primary infection of fresh cells are crucial for viral tumorigenicity. Virus-encoded b-Zip family protein K8 plays an important role in viral DNA replication in both viral reactivation and de novo infection. The mechanism underlying the functional role of K8 in the viral life cycle is elusive. Here we report that K8 is a RNA binding protein, which also associates with many proteins including other RNA binding proteins. Many K8-involved protein-protein interactions are mediated by RNA. Using a crosslinking and immunoprecipitation (CLIP) procedure combined with high-throughput sequencing, RNAs that are associated with K8 in BCBL-1 cells were identified, that include both viral (PAN, T1.4, T0.7 and etc.) and cellular (MALAT-1, MRP, 7SK and etc.) RNAs. An RNA-binding motif in K8 was defined, and mutation of the motif abolished the ability of K8 binding to many noncoding RNAs as well as viral DNA replication during de novo infection, suggesting that the K8 functions in viral replication are carried out through RNA association. The function of K8 and associated T1.4 RNA was investigated in details and results showed that T1.4 mediates the binding of K8 with ori-Lyt DNA. T1.4-K8 complex physically bound to KSHV ori-Lyt DNA and recruited other proteins and cofactors to assemble replication complex. Depletion of T1.4 abolished the DNA replication in primary infection. These findings provide mechanistic insights into the role of K8 in coordination with T1.4 RNA in regulating KSHV DNA replication during de novo infection.ImportanceGenome wide analyses of the mammalian transcriptome revealed that a large proportion of sequence previously annotated as noncoding region are actually transcribed and give rise to stable RNAs. Emergence of a large number of noncoding RNAs suggests that functional RNA-protein complexes exampled by ribosome or spliceosome are not ancient relics of the last riboorganism but would be well adapted for regulatory role in biology. K8 has been puzzled by its unique characteristic such as multiple regulatory roles in gene expression and DNA replication without DNA binding capability. This study revealed the mechanism underlying its regulatory role by demonstrating that K8 is an RNA binding protein that binds to DNA and initiate DNA replication in coordination with a noncoding RNA. It is suggested that many of K8 functions, if not all, are carried out through its associated RNAs. Copyright © 2018 American Society for Microbiology.

  8. The interaction between smoking status and highly active antiretroviral therapy (HAART) use on the risk of Kaposi's sarcoma (KS) in a cohort of HIV-infected men.

    Science.gov (United States)

    Luu, H N; Amirian, E S; Scheurer, M E

    2013-03-19

    Although the independent effects of smoking status and HAART are reported as lower risks against KS, their combined effects have not been explored. We examined whether there is an interaction between smoking status and HAART use on the risk of KS development in an on-going US cohort of HIV-infected men. Cox proportional hazards regression was used to analyse a total sample of 2736 participants of the Multicenter AIDS Cohort Study (MACS). We identified 530 incident KS cases with a total follow-up time of 26 594 person-years (incidence rate: 2.00 out of 100 person-years). Current smoking status and HAART use were independently associated with a lower risk of KS development (hazard ratio - HR=0.56, 95% CI: 0.35-0.90, P=0.02 and HR=0.27, 95% CI: 0.16-0.48, Psmoking status and HAART use on KS risk (HR=2.14, 95% CI: 0.97-4.73, Pinteraction=0.06). Lower effect of smoking was only present among those not on HAART (HR=0.57, 95% CI: 0.35-0.92, P=0.02). The inverse association of cigarette smoking on KS risk may be limited to those not on HAART. The biological mechanism of smoking in KS carcinogenesis should be elucidated.

  9. CIB1 synergizes with EphrinA2 to regulate Kaposi's sarcoma-associated herpesvirus macropinocytic entry in human microvascular dermal endothelial cells.

    Directory of Open Access Journals (Sweden)

    Chirosree Bandyopadhyay

    2014-02-01

    Full Text Available KSHV envelope glycoproteins interact with cell surface heparan sulfate and integrins, and activate FAK, Src, PI3-K, c-Cbl, and Rho-GTPase signal molecules in human microvascular dermal endothelial (HMVEC-d cells. c-Cbl mediates the translocation of virus bound α3β1 and αVβ3 integrins into lipid rafts (LRs, where KSHV interacts and activates EphrinA2 (EphA2. EphA2 associates with c-Cbl-myosin IIA and augmented KSHV-induced Src and PI3-K signals in LRs, leading to bleb formation and macropinocytosis of KSHV. To identify the factor(s coordinating the EphA2-signal complex, the role of CIB1 (calcium and integrin binding protein-1 associated with integrin signaling was analyzed. CIB1 knockdown did not affect KSHV binding to HMVEC-d cells but significantly reduced its entry and gene expression. In contrast, CIB1 overexpression increased KSHV entry in 293 cells. Single virus particle infection and trafficking during HMVEC-d cell entry was examined by utilizing DiI (envelope and BrdU (viral DNA labeled virus. CIB1 was associated with KSHV in membrane blebs and in Rab5 positive macropinocytic vesicles. CIB1 knockdown abrogated virus induced blebs, macropinocytosis and virus association with the Rab5 macropinosome. Infection increased the association of CIB1 with LRs, and CIB1 was associated with EphA2 and KSHV entry associated signal molecules such as Src, PI3-K, and c-Cbl. CIB1 knockdown significantly reduced the infection induced EphA2, Src and Erk1/2 activation. Mass spectrometry revealed the simultaneous association of CIB1 and EphA2 with the actin cytoskeleton modulating myosin IIA and alpha-actinin 4 molecules, and CIB1 knockdown reduced EphA2's association with myosin IIA and alpha-actinin 4. Collectively, these studies revealed for the first time that CIB1 plays a role in virus entry and macropinocytosis, and suggested that KSHV utilizes CIB1 as one of the key molecule(s to coordinate and sustain the EphA2 mediated signaling involved in its entry, and CIB1 is an attractive therapeutic target to block KSHV infection.

  10. A Rare Case of Synovial Sarcoma of the Prostate

    African Journals Online (AJOL)

    AbStRACt. Prostatic synovial sarcomas are exceedingly rare. To our knowledge, only six primary cases have been reported so far. We herein describe a primary synovial sarcoma of the prostate seen in a 25- year-old male patient, the youngest patient seen with this disease to date. He was referred to our department with ...

  11. Adult Soft Tissue Sarcoma Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Soft tissue sarcomas can form almost anywhere in the body, but are most common in the head, neck, arms, legs, truck, and abdomen. Find out about risk and genetic factors, symptoms, tests to diagnose, prognosis, staging, and treatment for soft tissue sarcoma.

  12. (q24: q12) translocation is common in Ewing's sarcoma

    Indian Academy of Sciences (India)

    Unknown

    2005-06-09

    Jun 9, 2005 ... 5 and T RAJKUMAR. 1,. *. 1Department of Molecular Oncology, 2Department of Pathology, 3Department of Biochemistry, ... Ewing's sarcoma/peripheral neuroectodermal tumour in south Indian patients; J. Biosci. 30 371–376]. 1. ... traditionally describes a group of undifferentiated pediatric sarcomas that ...

  13. SARCOMAS OF THE HEAD AND NECK AT KENYATTA NATIONAL ...

    African Journals Online (AJOL)

    hi-tech

    2000-05-05

    May 5, 2000 ... Objective: To determine the pattern of occurrence of sarcomas afflicting the neck and craniofacial region. Design: A retrospective study (1982-1991). Setting: Cancer ... of most patients with a sarcoma of the head and neck region is due to its .... associated with the cheek, maxiliary sinus, pharynx, palate,.

  14. Tumor - host immune interactions in Ewing sarcoma : implications for therapy

    NARCIS (Netherlands)

    Berghuis, Dagmar

    2012-01-01

    In this thesis, we report on various aspects of tumor - host (immune) interactions in Ewing sarcoma patients with the aim to obtain leads for immunotherapeutic or targeted treatment strategies. We demonstrate a key role for interferon gamma (IFNg) in enhancing both Ewing sarcoma immunogenicity and

  15. Variations of Surveillance Practice for Patients with Bone Sarcoma: A Survey of Australian Sarcoma Clinicians

    Directory of Open Access Journals (Sweden)

    Jeremy Lewin

    2017-01-01

    Full Text Available Introduction. After treatment, bone sarcoma patients carry a high chance of relapse and late effects from multimodal therapy. We hypothesize that significant variation in surveillance practice exists between pediatric medical oncology (PO and nonpediatric medical oncology (NP sarcoma disciplines. Methods. Australian sarcoma clinicians were approached to do a web based survey that assessed radiologic surveillance (RS strategies, late toxicity assessment, and posttreatment psychosocial interventions. Results. In total, 51 clinicians responded. No differences were identified in local disease RS. In metastatic disease response assessment, 100% of POs (23/23 and 93% of NPs (24/26 conducted CT chest. However, this was more likely to occur for NPs in the context of a CT chest/abdomen/pelvis (NP: 10/26; PO: 1/23; p=0.006. POs were more likely to use CXR for RS (p=0.006. POs showed more prescriptive intensity in assessment of heart function (p=0.001, hearing (p<0.001, and fertility (p=0.02. POs were more likely to deliver written information for health maintenance/treatment summary (p=0.04. The majority of respondents described enquiring about psychosocial aspects of health (n=33/37, 89%, but a routine formal psychosocial screen was only used by 23% (n=6/26. Conclusion. There is high variability in bone sarcoma surveillance between PO and NP clinicians. Efforts to harmonize approaches would allow early and late effects recognition/intervention and facilitate improved patient care/transition and research.

  16. Mesenchymal Stem Cells and the Origin of Ewing's Sarcoma

    Directory of Open Access Journals (Sweden)

    Patrick P. Lin

    2011-01-01

    Full Text Available The origin of Ewing's sarcoma is a subject of much debate. Once thought to be derived from primitive neuroectodermal cells, many now believe it to arise from a mesenchymal stem cell (MSC. Expression of the EWS-FLI1 fusion gene in MSCs changes cell morphology to resemble Ewing's sarcoma and induces expression of neuroectodermal markers. In murine cells, transformation to sarcomas can occur. In knockdown experiments, Ewing's sarcoma cells develop characteristics of MSCs and the ability to differentiate into mesodermal lineages. However, it cannot be concluded that MSCs are the cell of origin. The concept of an MSC still needs to be rigorously defined, and there may be different subpopulations of mesenchymal pluripotential cells. Furthermore, EWS-FLI1 by itself does not transform human cells, and cooperating mutations appear to be necessary. Therefore, while it is possible that Ewing's sarcoma may originate from a primitive mesenchymal cell, the idea needs to be refined further.

  17. Oesophageal sarcomas in dogs: histological and clinical evaluation.

    Science.gov (United States)

    Ranen, Eyal; Dank, Gillian; Lavy, Eran; Perl, Samuel; Lahav, Dan; Orgad, Uri

    2008-10-01

    A histological grading system of oesophageal sarcomas has not been established. Thirty-two cases of oesophageal sarcomas have been reviewed for tumour characteristics and clinical outcome. Nineteen dogs underwent surgical intervention to remove oesophageal tumours; ten of them survived (median 278 days). Primary tumour types included osteosarcoma (47%), osteosarcoma with tumour giant cells (7%), fibroblastic osteosarcoma (13%), chondroblastic osteosarcoma (7%) fibrosarcoma (23%) and undifferentiated sarcoma (3%). Histological grade evaluation revealed 33% grade 1 sarcoma, 50% grade 2 and 17% grade 3. No correlation could be found between survival and signalment, duration of clinical signs, tumour type, tumour grade and chemotherapy. Chemotherapy was found to reduce lung metastases' histological scores in three cases (P=0.0007). Surgery seems to be the treatment of choice but the effect of chemotherapy warrants further investigation. Additional research of cases should be performed in order to further define prognostic factors of oesophageal sarcomas.

  18. The roles and implications of exosomes in sarcoma

    Science.gov (United States)

    Min, Li; Shen, Jacson; Tu, Chongqi; Hornicek, Francis; Duan, Zhenfeng

    2016-01-01

    Better diagnostic biomarkers and therapeutic options are still necessary for patients with sarcomas due to the current limitations of diagnosis and treatment. Exosomes are small extracellular membrane vesicles that are released by various cells and are found in most body fluids. Tumor-derived exosomes have been proven to mediate tumorigenesis, intercellular communication, microenvironment modulation, and metastasis in different cancers, including in sarcomas. Recently, exosomes have been considered as potential biomarkers for sarcoma diagnosis, prognosis, and possible targets for sarcoma therapy. Moreover, due to their specific cell-tropism and bioavailability, exosomes can also be engineered as vehicles for drug delivery. In this review, we discuss recent advances in the roles of tumor-derived exosomes in sarcoma and their potential clinical applications. PMID:27342745

  19. Granulocytic Sarcoma of the Stomach Presenting as Dysphagia during Pregnancy

    Directory of Open Access Journals (Sweden)

    Anuradha Sekaran

    2011-01-01

    Full Text Available Granulocytic sarcoma also known as extramedullary myeloid sarcoma or chloroma is an uncommon manifestation of leukemia and presents as a deposit of leukemic cells outside the bone marrow. We report a case of a twenty-five-year-old pregnant woman who presented with progressive dysphagia and recurrent postprandial vomiting. Upper GI endoscopy had shown large flat laterally spread nodular lesions in the cardia and proximal body of stomach. Biopsies from the gastric lesion showed granulocytic sarcoma of the stomach. Concurrent peripheral and bone marrow picture was suggestive of acute myeloid leukemia (AML–M4. There is limited reported literature on granulocytic sarcoma of the stomach. Concurrent gastric granulocytic sarcoma involving cardia and AML in pregnancy has not been reported till date.

  20. [A case of proximal type epithelioid sarcoma of the perineum].

    Science.gov (United States)

    Murashima, Takaya; Kamibeppu, Toyoharu; Hiromasa, Tukino; Mukai, Syoichiro; Kamoto, Toshiyuki

    2013-11-01

    Epithelioid sarcomas are rare soft tissue neoplasms which occur more often in young people. They tend to relapse, metastatize and show poor prognosis. Proximal-type epithelioid sarcomas arise from the more proximal part of body and are more malignant than distal-type epithelioid sarcomas. We present a case of proximal-type epithelioid sarcoma which occurred in the perineum. A 24-year-old male visited our hospital with the chief complaint of pain in the perineum. Computed tomography and magnetic resonance imaging showed a tumor 30×23×17 mm in diameter in the perineal region. The tumor was excised regionally and the pathological examination with immunohistochemical staining revealed that the tumor was proximal-type epithelioid sarcoma. The patient is free of recurrence and metastasis one year after local excision.

  1. Significance of Circulating Tumor Cells in Soft Tissue Sarcoma

    Directory of Open Access Journals (Sweden)

    Chiara Nicolazzo

    2015-01-01

    Full Text Available Circulating tumor cells can be detected from the peripheral blood of cancer patients. Their prognostic value has been established in the last 10 years for metastatic colorectal, breast, and prostate cancer. On the contrary their presence in patients affected by sarcomas has been poorly investigated. The discovery of EpCAM mRNA expression in different sarcoma cell lines and in a small cohort of metastatic sarcoma patients supports further investigations on these rare tumors to deepen the importance of CTC isolation. Although it is not clear whether EpCAM expression might be originally present on tumor sarcoma cells or acquired during the mesenchymal-epithelial transition, the discovery of EpCAM on circulating sarcoma cells opens a new scenario in CTC detection in patients affected by a rare mesenchymal tumor.

  2. Significance of Circulating Tumor Cells in Soft Tissue Sarcoma

    Science.gov (United States)

    Nicolazzo, Chiara; Gradilone, Angela

    2015-01-01

    Circulating tumor cells can be detected from the peripheral blood of cancer patients. Their prognostic value has been established in the last 10 years for metastatic colorectal, breast, and prostate cancer. On the contrary their presence in patients affected by sarcomas has been poorly investigated. The discovery of EpCAM mRNA expression in different sarcoma cell lines and in a small cohort of metastatic sarcoma patients supports further investigations on these rare tumors to deepen the importance of CTC isolation. Although it is not clear whether EpCAM expression might be originally present on tumor sarcoma cells or acquired during the mesenchymal-epithelial transition, the discovery of EpCAM on circulating sarcoma cells opens a new scenario in CTC detection in patients affected by a rare mesenchymal tumor. PMID:26167450

  3. Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, Elizabeth H., E-mail: ebaldini@partners.org [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Bosch, Walter [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Roberge, David [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Haas, Rick L.M. [Department of Radiotherapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Catton, Charles N. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Indelicato, Daniel J. [Department of Radiation Oncology, University of Florida Medical Center, Jacksonville, Florida (United States); Olsen, Jeffrey R. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Deville, Curtiland [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Chen, Yen-Lin [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Finkelstein, Steven E. [Translational Research Consortium, 21st Century Oncology, Scottsdale, Arizona (United States); DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Wang, Dian [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States)

    2015-08-01

    Purpose: The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials: Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions: For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.

  4. Current state of pediatric sarcoma biology and opportunities for future discovery: A report from the sarcoma translational research workshop.

    Science.gov (United States)

    Hingorani, Pooja; Janeway, Katherine; Crompton, Brian D; Kadoch, Cigall; Mackall, Crystal L; Khan, Javed; Shern, Jack F; Schiffman, Joshua; Mirabello, Lisa; Savage, Sharon A; Ladanyi, Marc; Meltzer, Paul; Bult, Carol J; Adamson, Peter C; Lupo, Philip J; Mody, Rajen; DuBois, Steven G; Parsons, D Williams; Khanna, Chand; Lau, Ching; Hawkins, Douglas S; Randall, R Lor; Smith, Malcolm; Sorensen, Poul H; Plon, Sharon E; Skapek, Stephen X; Lessnick, Stephen; Gorlick, Richard; Reed, Damon R

    2016-05-01

    Sarcomas are a rare subgroup of pediatric cancers comprised of a variety of bone and soft-tissue tumors. While significant advances have been made in improving outcomes of patients with localized pediatric sarcomas since the addition of systemic chemotherapy to local control many decades ago, outcomes for patients with metastatic and relapsed sarcoma remain poor with few novel therapeutics identified to date. With the advent of new technologies to study cancer genomes, transcriptomes and epigenomes, our understanding of sarcoma biology has improved tremendously in a relatively short period of time. However, much remains to be accomplished in this arena especially with regard to translating all of this new knowledge to the bedside. To this end, a meeting was convened in Philadelphia, PA, on April 18, 2015 sponsored by the QuadW foundation, Children's Oncology Group and CureSearch for Children's Cancer that brought together sarcoma clinicians and scientists from North America to review the current state of pediatric sarcoma biology and ongoing/planned genomics based clinical trials in an effort to identify and bridge knowledge gaps that continue to exist at present. At the conclusion of the workshop, three key objectives that would significantly further our understanding of sarcoma were identified and a proposal was put forward to develop an all-encompassing pediatric sarcoma biology protocol that would address these specific needs. This review summarizes the proceedings of the workshop. Copyright © 2016. Published by Elsevier Inc.

  5. [Venereal undifferentiated hematosarcoma of Canidae (Sticker's sarcoma): trial of a single electron therapy treatment].

    Science.gov (United States)

    Zarrouk, K

    1979-09-01

    After symptology's description of "Sticker sarcoma" the author gives a light on the origin of this néoplasm. He then indicates a new modality of treatment by electrontherapy in one time only, and proposes to give up histopathologic denomination "Reticulo Sarcoma" and replace it with "Sticker sarcoma" " Veneral non différentiated hematasarcoma" "Sticker sarcoma"

  6. Outcome analysis in patients with uterine sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Yu, To Sol; Kim, Hak Jae; Wu, Hong Gyun; Ha, Sung Whan; Song, Yong Sang; Park, Noh Hyun; Kim, Jae Won [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-03-15

    To analyze the prognostic factors for survivals and to evaluate the impact of postoperative whole pelvic radiotherapy (WPRT) on pelvic failure in patients with uterine sarcoma treated with radical surgery. We retrospectively analyzed 75 patients with uterine sarcoma who underwent radical surgery with (n = 22) or without (n = 53) radiotherapy between 1990 and 2010. There were 23 and 52 patients with carcinosarcoma and non-carcinosarcoma (leiomyosarcoma, 22; endometrial stromal sarcoma, 25; others, 5), respectively. The median follow-up period was 64 months (range, 17 to 269 months). The 5-year overall survival (OS) and pelvic failure-free survival (PFFS) of total patients was 64.2% and 83.4%, respectively. Multivariate analysis revealed that mitotic count (p = 0.006) was a significant predictor of OS. However, factors were not found to be associated with PFFS. On analyzing each of the histologic subtypes separately, postoperative WPRT significantly reduced pelvic failure in patients with carcinosarcoma (10.0% vs. 53.7%; p = 0.046), but not in patients with non-carcinosarcoma (12.5% vs. 9.9%; p = 0.866). Among the patients with carcinosarcoma, 4 patients (17%) had recurrence within the pelvis and 3 patients (13%) had recurrence in other sites as an initial failure, whereas among the patients with non-carcinosarcoma, 3 patients (6%) experienced pelvic failure and 13 patients (25%) experienced distant failure. The most significant predictor of OS was mitotic count. Based on the improved PFFS after postoperative WPRT only in patients with carcinosarcoma and the difference in patterns of failure between histologic subtypes, optimal adjuvant treatment options should be offered to patients based on the risk of recurrence patterns.

  7. Neoadjuvant treatment of soft tissue sarcoma.

    Science.gov (United States)

    Greto, Daniela; Livi, Lorenzo; Saieva, Calogero; Bonomo, Pierluigi; Meattini, Icro; Loi, Mauro; Di Brina, Lucia; Beltrami, Giovanni; Campanacci, Domenico; Scoccianti, Guido; Capanna, Rodolfo; Mangoni, Monica; Paiar, Fabiola; Franchi, Alessandro; Biti, Giampaolo

    2014-03-01

    The aim of this study was to evaluate disease-free survival (DFS), overall survival and toxicity of patients who underwent preoperative therapy for soft tissue sarcoma. The data of 38 consecutive patients affected by soft tissue sarcoma were retrospectively analysed. Six (15.8 %) patients were treated only with neoadjuvant radiotherapy, and 32 (84.2 %) with neoadjuvant chemo-radiation therapy. Surgery was performed within 4-6 weeks after the completion of neoadjuvant treatment. Median follow-up was 4.9 years (range 1-13.7 years). All patients received preoperative external beam radiotherapy (RT). Most patients (84.2 %) underwent neoadjuvant chemotherapy treatment associated with radiotherapy. After neoadjuvant treatment, the majority of patients underwent wide excision (32 out of 38) and five patients had marginal surgery; only one patient underwent amputation. Local recurrence was observed in only two patients (5.2 %). Fourteen (36.8 %) patients experienced metastatic relapse. At the time of our analysis 13 patients (34.2 %) had died due to metastatic spread of the disease. In our series, DFS in relation to distant metastases (DM) showed a significant result for lower limb involvement (p = 0.038) and marginal excision (p = 0.024), both predictors of a worse DFS, histology was statistically significant although it was not possible to evaluate the risk for specific histology due to the small number of events in the different subtypes. The results obtained from our study are encouraging with regard to the feasibility and efficacy of preoperative RT in the treatment of soft tissue sarcoma in view of the results obtained in terms of local control, limb sparing and safety.

  8. Granulocytic sarcoma: a rare cause of sciatica.

    Science.gov (United States)

    Valsamis, Epaminondas Markos; Glover, Thomas Edward

    2017-02-15

    We describe a case report of a man aged 56 years with a 4-month history of right-sided sciatica-type pain with subclinical disc prolapse evident on MRI. Worsening pain together with the appearance of a tender mass in his right buttock prompted further imaging, which demonstrated an infiltrative mass engulfing the lumbosacral plexus. This was later shown to be a granulocytic sarcoma on biopsy. Intervertebral disc herniation can be an incidental finding and is not always the cause of sciatica. 2017 BMJ Publishing Group Ltd.

  9. Alveolar soft part sarcoma: A rare diagnosis

    Directory of Open Access Journals (Sweden)

    Priyanka Sarkar

    2013-01-01

    Full Text Available Alveolar soft-part sarcoma (ASPS is an extremely rare disease arising from connective tissues with a propensity for recurrence and metastasis. Clinically, it can be confused with hemangioma or arterio-venous malformations. Thus, a high index of suspicion and histopathological examination are required to make a definitive diagnosis. We report a case of recurrent ASPS in a young female with multiple sites involvement without any features of metastasis who has been treated with excision of the symptomatic lesions followed by chemotherapy.

  10. Ewing's sarcoma mimicking a meningioma in radiological findings: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hee Jin; Choi, Sun Seob [College of Medicine, Dong-A University, Busan (Korea, Republic of)

    2007-10-15

    Ewing's sarcoma is an uncommon primary bone tumor. Primary Ewing's sarcoma of the cranium is extremely rare and constitutes only 1% of all Ewing's sarcoma cases. Usually, primary Ewing's sarcoma of the carnium manifests as an expansile osteolytic malignant bone tumor with or without intracranial extension. We report here the radiological findings of a case of Ewing's sarcoma mimicking a meningioma in an 18-year-old man.

  11. Multiple granulocytic sarcomas in essential thrombocythemia.

    Science.gov (United States)

    Tanaka, Yasuhiro; Nagai, Yuya; Mori, Minako; Fujita, Haruyuki; Togami, Katsuhiro; Kurata, Masayuki; Matsushita, Akiko; Maeda, Akinori; Nagai, Kenichi; Tanaka, Kyoko; Takahashi, Takayuki

    2006-12-01

    A 59-year-old woman was diagnosed with essential thrombocythemia in 1988 and had been treated with hydroxyurea, mitobronitol, busulfan, and ranimustine, in that order. Hepatosplenomegaly, low-grade fever, and body weight loss manifested, and a few blasts were noted in the peripheral blood studied in March 2002. A biopsied specimen of the bone marrow showed myelofibrosis but not a leukemia in August 2004. An abnormal karyotype with der(1; 13) appeared for the first time. She was treated with low-dose prednisolone. In January 2005, she experienced left hip joint pain, and magnetic resonance scanning showed a tumoral lesion in the femoral head. Histological diagnosis of the biopsied mass revealed that it was a granulocytic sarcoma, and radiotherapy was performed. In April 2005, bone scintigraphy showed multiple lesions. She became febrile and red blood cell transfusion-dependent with hepatosplenomegaly and a small number of circulating blasts. Intravenous cytarabine (low dose) and etoposide relieved the fever and hepatosplenomegaly; however, she developed a pathologic fracture of the right humerus. An additional karyotypic abnormality (7q22 deletion) was noted. She subsequently died of infection. Granulocytic sarcoma is very rare in essential thrombocythemia, and this patient may be the first reported case of essential thrombocythemia that developed multiple lesions and a pathologic fracture without transformation to overt leukemia.

  12. Limb salvage treatment vs. amputation in sarcoma

    Directory of Open Access Journals (Sweden)

    Motamedi M

    1993-05-01

    Full Text Available Many years ago the treatment of sarcoma was radiotherapy up to 2000-4000 rad. This treatment was very complicated, due to producing neoplasm after radiotherapy. By this method of treatment of osteosarcoma, the rate of survival became about 20% (two years. The second method of treatment was chemotherapy for a period of 2-5 weeks that amputation was performed afterwards. By chemotherapy, the rate of being alive reached up to 25-27% (five years. Right now, the best treatment for sarcoma is limb salvage. In our report, the chance of being alive in chondrosarcoma was about four years. This was nearly the same as that of the other institutes in the world especially in America, Europe, and Japan. The rate of recurrence was also more than that from different parts of the world. The survival rate in osteosarcomatic patients was about two years less for males the females, and it was more in tall people than short ones. The survival rate of the patients with giant cell tumor was more than osteosarcoma up to five years, and it has no recurrence or metastasis

  13. Primary fibro sarcoma of the heart.

    Science.gov (United States)

    Kabashi, Serbeze; Hoxha, Naim; Gashi, Shkelzen; Ahmegjekaj, Ilir; Bejta, Ilir; Sadiku, Muharrem; Ymeri, Halit; Kabashi, Antigona; Bicaj, Xhavit; Mucaj, Sefedin

    2013-01-01

    Primary malignant heart tumors represent rare entities where fibro sarcoma represents about 3% of all. Introducing the patient: A 15 years old patient with cardiac insufficiency (heart failure) symptoms, such as weakness, cyanosis, palpitations and breathing difficulties; enlargement of upper mediastinum and pleural effusion. Through echocardiography a pericardial effusion and intracavitary thrombus in atrium was diagnosed. With computed tomography is diagnosed a tumoral mass in right atrium which is also spread in the right ventricle of the heart. Tumor is completely removed; pat histology result showed primary fibro sarcoma of the heart. At that time no metastasis was found. Conclusion. Primary malignant heart tumors may manifest like cardiac insufficiency or like systemic diseases. Fibrosarcomas are rare and have bad prognosis. On average patients can live around six months after initial symptoms appeared and diagnosis of the tumor was done. In the case of cardiac insufficiency with differential diagnosis we should also think of heart tumors, which could certainly be proved for or eliminated by echocardiography.

  14. [Alveolar soft part sarcoma in pediatric patients].

    Science.gov (United States)

    Paillard, Catherine; Coulomb, Aurore; Helfre, Sylvie; Orbach, Daniel

    2015-09-01

    Alveolar soft part sarcoma, ASPS, is a rare malignant tumor, with preferential primary localization in limbs, usually occurring in adolescents and young adults. This sarcoma, well defined histologically and at molecular level, has an indolent course, but a high potential metastatic pulmonary and cerebral evolution, sometimes late. ASPS is characterized by an almost specific translocation t(X, 17)(p11;25) which creates a fusion protein, APSL-TFE3, acting as an aberrant transcription factor. An in-bloc resection of the primary tumor is the treatment of choice in cases of localized disease. Conventional chemotherapy is generally ineffective. The role of radiotherapy is discussed in case of micro- or macroscopical incomplete residue. It seems to reduce local recurrence, but did not influence overall survival. The 5 years survival rate in children, adolescents and young adults is close to 80% in case of localized disease but poorer in presence of metastases. Recently, systemic anti-tumoral treatments have been focused on the use of targeted therapies. Anti-angiogenic drugs and tyrosine kinase inhibitors are the most promising approaches, but require further study. Prognostic risk factors in the literature are age (>10Y), tumor size (>5cm) and presence of metastases. This article reviews the clinical manifestations, diagnosis modalities, radiographic characteristics and therapeutic strategy of this disease in the pediatric population. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  15. Considerations for the long term treatment of pediatric sarcoma survivors

    Directory of Open Access Journals (Sweden)

    Kurt R Weiss

    2018-01-01

    Full Text Available Sarcomas are primary malignancies of the connective tissues. They are exceedingly rare in adults, but much more common in children. The historically recent advent of cytotoxic chemotherapy for pediatric sarcomas has revolutionized the treatment of these diseases and dramatically improved their prognoses. There is thus a population of pediatric sarcoma survivors that are “coming of age” as adults. However, this progress is not without consequences. Due to aggressive treatment protocols that include various combinations of surgery, chemotherapy, and radiation therapy, pediatric sarcoma survivors are at risk of myriad physical, medical, and psychological difficulties as they enter adulthood. These include but are not limited to physical disabilities, chemotherapy-induced cardiac issues, second malignancies, and anxiety. These patients pose unique challenges to their adult primary care physicians. One possible solution to these challenges is multidisciplinary sarcoma survivorship clinics. By paying greater attention to the unique issues of pediatric sarcoma survivors, involved physicians can maximize the physical and emotional health of pediatric sarcoma survivors.

  16. Quantitative morphology in canine cutaneous soft tissue sarcomas.

    Science.gov (United States)

    Simeonov, R; Ananiev, J; Gulubova, M

    2015-12-01

    Stained cytological specimens from 24 dogs with spontaneous soft tissue sarcomas [fibrosarcoma (n = 8), liposarcoma (n = 8) and haemangiopericytoma (n = 8)], and 24 dogs with reactive connective tissue lesions [granulation tissue (n = 12) and dermal fibrosis (n = 12)] were analysed by computer-assisted nuclear morphometry. The studied morphometric parameters were: mean nuclear area (MNA; µm(2)), mean nuclear perimeter (MNP; µm), mean nuclear diameter (MND mean; µm), minimum nuclear diameter (Dmin; µm) and maximum nuclear diameter (Dmax; µm). The study aimed to evaluate (1) possibility for quantitative differentiation of soft tissue sarcomas from reactive connective tissue lesions and (2) by using cytomorphometry, to differentiate the various histopathological soft tissue sarcomas subtypes in dogs. The mean values of all nuclear cytomorphometric parameters (except for Dmax) were statistically significantly higher in reactive connective tissue processes than in soft tissue sarcomas. At the same time, however, there were no considerable differences among the different sarcoma subtypes. The results demonstrated that the quantitative differentiation of reactive connective tissue processes from soft tissue sarcomas in dogs is possible, but the same was not true for the different canine soft tissue sarcoma subtypes. Further investigations on this topic are necessary for thorough explication of the role of quantitative morphology in the diagnostics of mesenchymal neoplasms and tumour-like fibrous lesions in dogs. © 2014 John Wiley & Sons Ltd.

  17. Ewing sarcoma versus osteomyelitis: differential diagnosis with magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Henninger, B.; Glodny, B.; Rudisch, A.; Trieb, T.; Loizides, A.; Judmaier, W.; Schocke, M.F. [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria); Putzer, D. [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria)

    2013-08-15

    To find and evaluate characteristic magnetic resonance imaging (MRI) patterns for the differentiation between Ewing sarcoma and osteomyelitis. We identified 28 consecutive patients referred to our department for MRI (1.5 T) of an unclear bone lesion with clinical symptoms suggestive of Ewing sarcoma or osteomyelitis. MRI scans were re-evaluated by two experienced radiologists, typical MR imaging features were documented and a diagnostic decision between Ewing sarcoma and osteomyelitis was made. Statistical significance of the association between MRI features and the biopsy-based diagnosis was assessed using Fisher's exact test. The most clear-cut pattern for determining the correct diagnosis was the presence of a sharp and defined margin of the bone lesion, which was found in all patients with Ewing sarcoma, but in none of the patients with osteomyelitis (P < 0.0001). Contrast enhancing soft tissue was present in all cases with Ewing sarcoma and absent in 4 patients with osteomyelitis (P = 0.0103). Cortical destruction was found in all patients with Ewing sarcoma, 4 patients with osteomyelitis did not present any cortical reaction (P = 0.0103). Cystic or necrotic areas were identified in 13 patients with Ewing sarcoma and in 1 patient with osteomyelitis (P = 0.004). Interobserver reliability was very good (kappa = 1) in Ewing sarcoma and moderate (kappa = 0.6) in patients with osteomyelitis. A sharp and defined margin, optimally visualized on T1-weighted images in comparison to short tau inversion recovery (STIR) images, is the most significant feature of Ewing sarcoma in differentiating from osteomyelitis. (orig.)

  18. Maladie de Kaposi à localisation broncho-pulmonaire révélant une infection VIH

    Science.gov (United States)

    Sebbar, Amal; Zaghba, Nahid; Benjelloun, Hanane; Bakhatar, Abdelaziz; Yassine, Najiba

    2015-01-01

    La maladie de Kaposi (MK) associée au VIH, forme dite épidémique, a été décrite la 1ère fois en 1981 par Hymmes. C'est l'affection maligne la plus fréquente au cours du SIDA. La MK est à l'origine de 10% des atteintes pleuropulmonaires au cours de l'infection par le VIH et 40% des pneumopathies en cas de MK cutanéomuqueuse. Les localisations pulmonaires occupent la deuxième place des atteintes viscérales après la forme digestive. Le diagnostic repose sur des arguments épidémiologiques, cliniques, radiologiques, biologiques, endoscopiques et histologiques. Nous rapportons un cas de MK broncho-pulmonaire compliquant une infection VIH chez un patient présentant une maladie de Kaposi cutanée de découverte fortuite au cours de l'atteinte pulmonaire. Le diagnostic a été retenu après avoir éliminé les maladies opportunistes à tropisme pulmonaire. Le Kaposi pulmonaire constitue l'atteinte la plus grave de la MK-sida et la survie après le diagnostic est courte malgré les thérapeutiques agressives. PMID:26958142

  19. Granulocytic sarcoma masquerading as Ewing′s sarcoma: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Haresh Kunhi

    2008-01-01

    Full Text Available An eleven-year-old boy presented with a swelling in his left elbow. Radiologically the features were that of an Ewing′s sarcoma involving the ulna. Histopathology showed small round cell tumor strongly positive for Monoclonal Imperial Cancer research fund 2 (MIC2 antigen. Similar cells in the bone marrow were involved with MIC2 positivity. The patient developed skin lesions, which on biopsy were found to be chloromas. The initial biopsies were reevaluated with special stains revealing granulocytic sarcomas in acute myeloid leukemia masquerading as Ewing′s due to its MIC2 positivity. The possibility of myeloid neoplasms should be considered routinely with known MIC2 positive round cell tumors.

  20. Spindle cell sarcoma in Bothrops leucurus Sarcoma fusocelular em jararaca - Bothrops leucurus

    Directory of Open Access Journals (Sweden)

    H. B. Marcello Jr.

    2002-06-01

    Full Text Available O presente relato descreve os achados anatomopatológicos de uma neoplasia maligna em jararaca (Bothrops leucurus, mantida em cativeiro durante sete anos. O animal apresentava massa nodular subcutânea localizada no lado direito do terço anterior. O exame histológico revelou tratar-se de neoplasia mesenquimal maligna, permitindo o diagnóstico de sarcoma fusocelular.

  1. Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas.

    Science.gov (United States)

    Schachtschneider, Kyle M; Liu, Yingkai; Mäkeläinen, Suvi; Madsen, Ole; Rund, Laurie A; Groenen, Martien A M; Schook, Lawrence B

    2017-06-01

    Human soft-tissue sarcomas (STS) are rare mesenchymal tumors with a 5-year survival rate of 50%, highlighting the need for further STS research. Research has been hampered by limited human sarcoma cell line availability and the large number of STS subtypes, making development of STS cell lines and animal models representative of the diverse human STS subtypes critical. Pigs represent ideal human disease models due to their similar size, anatomy, metabolism, and genetics compared to humans. The Oncopig encodes inducible KRAS (G12D) and TP53 (R167H) transgenes, allowing for STS modeling in a spatial and temporal manner. This study utilized Oncopig STS cell line (fibroblast) and tumor (leiomyosarcoma) RNA-seq data to compare Oncopig and human STS expression profiles. Altered expression of 3,360 and 7,652 genes was identified in Oncopig STS cell lines and leiomyosarcomas, respectively. Transcriptional hallmarks of human STS were observed in Oncopig STS, including altered TP53 signaling, Wnt signaling activation, and evidence of epigenetic reprogramming. Furthermore, master regulators of Oncopig STS expression were identified, including FOSL1, which was previously identified as a potential human STS therapeutic target. These results demonstrate the Oncopig STS model's ability to mimic human STS transcriptional profiles, providing a valuable resource for sarcoma research and cell line development.

  2. Breast sarcoma. A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Nuria Li

    2016-01-01

    Conclusion: Surgery represents the only potentially curative therapy for breast sarcoma. Tumor size and adequate resection margin are the most important prognostic factors. Approximately 80% of recurrences appear in the first two years.

  3. The (epi)genetics of human synovial sarcoma

    NARCIS (Netherlands)

    Bruijn, de D.R.H.; Nap, J.P.H.; Kessel, A.G.

    2007-01-01

    Human synovial sarcomas are aggressive soft tissue tumors with relatively high rates of recurrences and metastases. They display a variable response to common treatment protocols such as radiation and chemotherapy. For the development of novel diagnostic, prognostic, and therapeutic approaches,

  4. Primary low-grade endometrial stromal sarcoma of the omentum

    OpenAIRE

    Kiran Clair; Juliet Wolford; Sonia Veran-Taguibao; Grace Kim; Eskander, Ramez N.

    2017-01-01

    Highlights ? Extra-uterine endometrial stromal sarcoma may arise in endometriosis. ? Abdominal exploration for extra pelvic endometriosis is warranted. ? Representative endometriotic implants should be resected and/or biopsied if clinically suspicious.

  5. A Comparative Study between Carcinoma and Sarcoma Using Raman Spectroscopy

    Science.gov (United States)

    Dehghani-Bidgoli, Z.; Baygi, M. H. Miran; Kabir, E.; Malekfar, R.

    2014-01-01

    The purpose of this study was to find discriminating Raman spectral features between two major types of cancer, i.e., carcinoma and sarcoma. To this end, Raman spectra from adenocarcinoma, liposarcoma and fibrosarcoma samples were compared. A Raman system was used for the tissue Raman spectroscopic measurements at 785-nm laser excitation. After pre-processings, the Raman spectra were investigated, in major bands associated with protein and lipids, in the adenocarcinoma, liposarcoma, and fibrosarcoma groups. Principal component analysis and nonnegative matrix factorization were performed for finding most significant features in discriminating the spectra of carcinoma from those of sarcoma samples. The findings of this study show that the lipid content in the sarcoma samples decreases compared with the carcinoma samples. The achieved accuracy in discriminating carcinoma from sarcoma by linear discriminant analysis is 93.75 % and 90.63 % using the first nine principal components and nonnegative matrix factorization analysis, respectively.

  6. Myeloid sarcoma of the rib: An atypical isolated chest finding

    Directory of Open Access Journals (Sweden)

    Antonio Raucci

    2015-03-01

    Systemic treatment was administered and currently neither systemic nor local relapse has been identified. Our experience suggests surgical resection could be a valid treatment in isolated myeloid sarcoma patients.

  7. Sarcoma cutáneo mixto radioinducido Radiation-induced mixed cutaneous sarcoma

    Directory of Open Access Journals (Sweden)

    Isidoro Rubio-Correa

    2012-06-01

    Full Text Available Introducción: Los sarcomas son tumores malignos poco frecuentes, siendo raros en cabeza y cuello. En su etiología se involucran factores como agentes químicos, radiación, inmunosupresión y síndromes y anomalías genéticas. Caso clínico: Varón de 64 años, que presenta lesión en piel de mejilla derecha de un año de evolución, localización en la que presentó hace veinte años un carcinoma basocelular tratado con radioterapia. Tras descartar existencia de metástasis, se realizó exéresis de la lesión con márgenes de seguridad y reconstrucción con colgajo de Mustardé. Se complementó el tratamiento con radioterapia. Discusión: El diagnóstico es anatomopatológico, siendo fundamental descartar afectación metastásica. Para mejorar la supervivencia y disminuir su elevada tasa de recidiva, deberían tratarse de forma multidisciplinar (cirugía, radioterapia y/o quimioterapia. Conclusión: A pesar de su baja frecuencia, los sarcomas deben estar presentes en el diagnóstico diferencial de toda lesión que aparezca en zonas radiadas previamente, especialmente en la piel facial.Introduction: Sarcomas are malignant tumors that are infrequent, being rare in the head and neck. Factors such as chemical agents, radiation, immunosuppression, and genetic syndromes and abnormalities are involved in their etiology. Case report: A 64-year-old man developed a skin lesion on the right cheek one year earlier at the site where he had presented a basal cell carcinoma 20 years earlier that was treated with radiation therapy. After ruling out the existence of metastasis, the lesion was treated by surgical resection with safety margins and reconstruction with the Mustardé flap. Treatment was supplemented with radiation therapy. Discussion: The diagnosis of sarcomas is histopathologic and it is essential to rule out metastasis. To improve survival and reduce the high rate of recurrence, a multidisciplinary approach to treatment should be used (surgery

  8. Epithelioid sarcoma with unusual radiological findings

    Energy Technology Data Exchange (ETDEWEB)

    Yamato, M.; Nishimura, G. [Department of Radiology, Dokkyo University School of Medicine, Tochigi (Japan); Yamaguchi, Takehiko [Department of Pathology, Dokkyo University School of Medicine, Tochigi (Japan); Tamai, Kazuya; Saotome, Koichi [Department of Orthopaedic Surgery, Dokkyo University School of Medicine, Tochigi (Japan)

    1997-10-01

    The case of a patient with epithelioid sarcoma in the right arm is reported. The diagnosis was delayed because of misinterpretation arising from complexity in the MR findings, including a honeycomb pattern in the subcutaneous fat simulating lymphedema, and an intramuscular diffuse high signal intensity on T2-weighted images without a discrete mass lesion. The histological findings revealed that the diffuse muscular abnormality mainly resulted from denervation of the muscles due to perineural invasion by the tumor, and subcutaneous edema from lymphedema secondary to lymphatic tumor spread concurrent with lymphatic fibrosis. Multiple foci of cortical erosions in the humerus, a rare manifestation of this tumor, were detected 6 months later. (orig.) 11 refs.

  9. Bilateral clear cell sarcoma of the kidney

    Directory of Open Access Journals (Sweden)

    Wael Zekri

    2015-06-01

    Full Text Available Clear cell sarcoma of the kidney (CCSK accounts for 2–5% of all pediatric renal malignancies, and is known for its propensity to metastasize to bone and other sites. We are reporting two cases with bilateral CCSK that were diagnosed at our institution. One patient initially presented with bilateral renal masses, as well as pulmonary, hepatic and bone metastasis; while other present only with bilateral masses with no evident distant metastasis. Both patients received aggressive neo-adjuvant chemotherapy to decrease tumor size. One patient completed his designated treatment and initially showed complete remission (CR; eventually suffering from relapse. The other patient’s tumor progressed during the course of chemotherapy. Both cases manifested brain dissemination at the time of relapse or progression. This emphasizes the importance of staging stratification in CCSK. This also illustrates CCSK’s ability to metastasize to bone and other sites including the brain (a primary relapse site in our cases.

  10. Small soft tissue sarcomas do metastasize

    DEFF Research Database (Denmark)

    Styring, Emelie; Hartman, Linda; Nilbert, Mef

    2014-01-01

    BACKGROUND: Small (≤ 5 cm) soft tissue sarcomas (STS) of the extremities and the trunk wall generally have a favorable prognosis. However, 1 of 10 patients do develop metastases, and we therefore aimed to determine predictors of metastasis in a population-based cohort of patients with small STSs...... necrosis and vascular invasion were the major predictors of metastatic disease in this subset. Tumors with both these risk factors metastasized in 8 of 18 patients, which corresponds to a 12-fold increased risk of metastasis. These findings suggest that although small STS generally are linked to a good...... prognosis, necrosis and vascular invasion are features indicating biologically aggressive tumors for which treatment and surveillance should equal that for larger tumors....

  11. Dicty_cDB: SFD486 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 2e-07 AF192756_1( AF192756 |pid:none) Kaposi's sarcoma-associated herpes... 54 4e-06 BT036468_1( BT036468...Kaposi's sarcoma-associated herpes-lik... 51 3e-05 AF305694_1( AF305694 |pid:none) Kaposi's sarcoma-associated...51 3e-05 U93872_83( U93872 |pid:none) Kaposi's sarcoma-associated herpesvir... 50 4e-05 CP001071_1748(

  12. Dicty_cDB: SFL145 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 54 2e-06 U93872_83( U93872 |pid:none) Kaposi's sarcoma-associated herpesvir... 54 2e-06 AF360120_1( AF360120...Kaposi's sarcoma-associated herpes... 54 3e-06 AF305694_1( AF305694 |pid:none) Kaposi's sarcoma-associated...52 1e-05 U52064_1( U52064 |pid:none) Kaposi's sarcoma-associated herpes-lik... 52 1e-05 CP001454_12(

  13. Dicty_cDB: SFJ367 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Kaposi's sarcoma-associated herpes... 45 0.007 AF192756_1( AF192756 |pid:none) Kaposi's sarcoma-associated...44 0.009 U52064_1( U52064 |pid:none) Kaposi's sarcoma-associated herpes-lik... 44 0.012 AF148805_82(...43 0.026 U93872_83( U93872 |pid:none) Kaposi's sarcoma-associated herpesvir... 41 0.077 AF360120_1( AF360120

  14. Dicty_cDB: SFC806 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available e-143 AF305694_1( AF305694 |pid:none) Kaposi's sarcoma-associated herpes... 52 4e-05 AF148805_82( AF148805...Kaposi's sarcoma-associated herpes... 50 2e-04 U52064_1( U52064 |pid:none) Kaposi's sarcoma-associated...48 6e-04 U93872_83( U93872 |pid:none) Kaposi's sarcoma-associated herpesvir... 48 7e-04 AF360120_1( AF360120

  15. Dicty_cDB: SFB257 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Kaposi's sarcoma-associated herpes... 49 4e-04 AF192756_1( AF192756 |pid:none) Kaposi's sarcoma-associated...45 0.005 U52064_1( U52064 |pid:none) Kaposi's sarcoma-associated herpes-lik... 44 0.008 AL844506_105(...43 0.022 U93872_83( U93872 |pid:none) Kaposi's sarcoma-associated herpesvir... 42 0.029 AF360120_1( AF360120

  16. Dicty_cDB: SSJ719 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Value AF305694_1( AF305694 |pid:none) Kaposi's sarcoma-associated herpes... 50 1e-04 AF148805_82( AF148805...49 2e-04 U93872_83( U93872 |pid:none) Kaposi's sarcoma-associated herpesvir... 49 2e-04 AF360120_1( AF360120...Kaposi's sarcoma-associated herpes... 48 4e-04 U52064_1( U52064 |pid:none) Kaposi's sarcoma-associated

  17. Dicty_cDB: CHC546 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available e-103 AF305694_1( AF305694 |pid:none) Kaposi's sarcoma-associated herpes... 47 2e-04 CR940347_653( CR940347...Kaposi's sarcoma-associated herpes-lik... 45 4e-04 U93872_83( U93872 |pid:none) Kaposi's sarcoma-associated...5e-04 AF192756_1( AF192756 |pid:none) Kaposi's sarcoma-associated herpes... 45 5e-04 (Q54VY3) RecName:

  18. Hepatic Involvement of Histiocytic Sarcoma: CT and MRI Findings

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, Takatoshi [Department of Radiology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8654 (Japan); Kiryu, Shigeru; Akai, Hiroyuki [Department of Radiology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan); Ota, Yasunori [Department of Pathology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan); Tojo, Arinobu [Department of Hematology and Oncology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan); Yoshida, Hideo [Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo 150-8935 (Japan); Kato, Naoya [Advanced Medical Science, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan); Nakano, Yoshiyasu [Department of Radiology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639 (Japan); Ohtomo, Kuni [Department of Radiology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8654 (Japan)

    2016-11-01

    Histiocytic sarcoma in the liver is an extremely rare hematological malignancy. Herein, we reported the case of a 68-year-old woman who presented with characteristic wedge-shaped abnormality bounded by hepatic veins on computed tomography and magnetic resonance imaging of the liver. In the wedge-shaped area, decreased portal flow and the deposition of iron were observed. These imaging findings are consistent with intrasinusoidal tumor cell infiltration. A liver biopsy was performed, and histiocytic sarcoma was confirmed histopathologically.

  19. Hepatic involvement of histiocytic sarcoma: CT and MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, Takatosh; Ohtomo, Kuni [Graduate School of Medicine, University of Tokyo, Tokyo (Japan); Kiryu, Shigeru; Akai, Hiroyuki; Ora, Yasunori; Tojo, Arinobu; Yoshida, Hideo; Kato, Naoya; Nakano, Yoshiyasu [Institute of Medical Science, University of Tokyo, Tokyo (Japan)

    2016-09-15

    Histiocytic sarcoma in the liver is an extremely rare hematological malignancy. Herein, we reported the case of a 68-year-old woman who presented with characteristic wedge-shaped abnormality bounded by hepatic veins on computed tomography and magnetic resonance imaging of the liver. In the wedge-shaped area, decreased portal flow and the deposition of iron were observed. These imaging findings are consistent with intrasinusoidal tumor cell infiltration. A liver biopsy was performed, and histiocytic sarcoma was confirmed histopathologically.

  20. Giant primary synovial sarcoma of the anterior mediastinum: A case ...

    African Journals Online (AJOL)

    2015-06-11

    Jun 11, 2015 ... Posterior mediastinal biphasic synovial sarcoma in a 12 year‑old boy: A case report and review of literature. J Cancer. Res Ther 2010;6:564‑6. 4. Kwon OY, Lee SK, Cho MK, Kim YJ. A case of biphasic synovial sarcoma of frontal bone in an elderly patient. J Korean Neurosurg Soc 2007;42:67‑70. 5. Korula ...

  1. Recent Progress in the Management of Retroperitoneal Sarcoma

    Directory of Open Access Journals (Sweden)

    Rona Cheifetz

    2001-01-01

    Full Text Available Retroperitoneal sarcomas (RPS are rare tumours that typically present late and carry a poor prognosis even following grossly complete resection. In an attempt to improve the outlook for patients with RPS, sarcoma specialists have employed various adjuvant therapies, including extermal beam radiation, intraoperative radiation, brachyradiation and systemic chemotherapy. This article reviews the presentation and prognosis of RPS, and focuses on the results of new treatment strategies compared with conventional management.

  2. Induction of histiocytic sarcoma in mouse skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Jianing Liu

    Full Text Available Myeloid sarcomas are extramedullary accumulations of immature myeloid cells that may present with or without evidence of pathologic involvement of the bone marrow or peripheral blood, and often coincide with or precede a diagnosis of acute myeloid leukemia (AML. A dearth of experimental models has hampered the study of myeloid sarcomas and led us to establish a new system in which tumor induction can be evaluated in an easily accessible non-hematopoietic tissue compartment. Using ex-vivo transduction of oncogenic Kras(G12V into p16/p19(-/- bone marrow cells, we generated transplantable leukemia-initiating cells that rapidly induced tumor formation in the skeletal muscle of immunocompromised NOD.SCID mice. In this model, murine histiocytic sarcomas, equivalent to human myeloid sarcomas, emerged at the injection site 30-50 days after cell implantation and consisted of tightly packed monotypic cells that were CD48+, CD47+ and Mac1+, with low or absent expression of other hematopoietic lineage markers. Tumor cells also infiltrated the bone marrow, spleen and other non-hematopoietic organs of tumor-bearing animals, leading to systemic illness (leukemia within two weeks of tumor detection. P16/p19(-/-; Kras(G12V myeloid sarcomas were multi-clonal, with dominant clones selected during secondary transplantation. The systemic leukemic phenotypes exhibited by histiocytic sarcoma-bearing mice were nearly identical to those of animals in which leukemia was introduced by intravenous transplantation of the same donor cells. Moreover, murine histiocytic sarcoma could be similarly induced by intramuscular injection of MLL-AF9 leukemia cells. This study establishes a novel, transplantable model of murine histiocytic/myeloid sarcoma that recapitulates the natural progression of these malignancies to systemic disease and indicates a cell autonomous leukemogenic mechanism.

  3. Kaposi’s Sarcoma Herpesvirus Genome Persistence

    Directory of Open Access Journals (Sweden)

    Franceline Juillard

    2016-08-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV has an etiologic role in Kaposi’s sarcoma, primary effusion lymphoma and multicentric Castleman’s disease. These diseases are most common in immunocompromised individuals, especially those with AIDS. Similar to all herpesviruses, KSHV infection is lifelong. KSHV infection in tumor cells is primarily latent, with only a small subset of cells undergoing lytic infection. During latency, the KSHV genome persists as a multiple copy, extrachromosomal episome in the nucleus. In order to persist in proliferating tumor cells, the viral genome replicates once per cell cycle and then segregates to daughter cell nuclei. KSHV only expresses several genes during latent infection. Prominent among these genes, is the latency-associated nuclear antigen (LANA. LANA is responsible for KSHV genome persistence and also exerts transcriptional regulatory effects. LANA mediates KSHV DNA replication and in addition, is responsible for segregation of replicated genomes to daughter nuclei. LANA serves as a molecular tether, bridging the viral genome to mitotic chromosomes to ensure that KSHV DNA reaches progeny nuclei. N-terminal LANA attaches to mitotic chromosomes by binding histones H2A/H2B at the surface of the nucleosome. C-terminal LANA binds specific KSHV DNA sequence and also has a role in chromosome attachment. In addition to the essential roles of N- and C-terminal LANA in genome persistence, internal LANA sequence is also critical for efficient episome maintenance. LANA’s role as an essential mediator of virus persistence makes it an attractive target for inhibition in order to prevent or treat KSHV infection and disease.

  4. Clear cell sarcoma: the Roswell Park experience.

    Science.gov (United States)

    Finley, J W; Hanypsiak, B; McGrath, B; Kraybill, W; Gibbs, J F

    2001-05-01

    Clear cell sarcoma of the tendons and aponeuroses (CCSTA) is an aggressive, rare soft-tissue tumor with approximately 300 reported cases. Although it appears to be histogenetically related to melanoma, its clinical behavior resembles soft tissue sarcoma with a propensity for lymph node metastases. We report our experience at a tertiary cancer center. Eight cases of CCSTA evaluated at Roswell Park Cancer Institute between 1970 and 1998 were reviewed retrospectively. Patient data analyzed included patient age, gender, anatomic location, size of tumor, development of local, regional and distant recurrence, and patient status at last follow up. Six of eight patients were alive at 2 years, while three of seven patients were alive at 5 years. Of the patients alive with no evidence of recurrence, two had tumors of less than 2 cm, and the remaining patient had incomplete information regarding tumor size. Five patients recurred within 2 years of definitive surgical management. Four had tumors > 5 cm. All five patients progressed to metastatic disease at a median follow up of 20 months (range 1-108 months) following definitive surgical management and all eventually died of their disease at a median of 3 months (range 0-24 months) from presentation with metastatic disease. Four of five patients with lesions > 5 cm received adjuvant chemotherapy with intent to cure, but all eventually died of disease at 4, 22, 34, and 41 months from initial presentation. CCSTA is an aggressive tumor of the soft tissues. Early recognition and management are associated with an excellent long-term prognosis. Tumors greater than 5 cm warrant aggressive surgical management and treatment, and are at high risk of the development of distant disease. Aggressive multiagent chemotherapy appeared to have no impact on outcome. Other adjuvant therapeutic options including immunotherapy should be investigated. Copyright 2001 Wiley-Liss, Inc.

  5. Treatment of early uterine sarcomas: disentangling adjuvant modalities

    Directory of Open Access Journals (Sweden)

    Kouloulias Vassilios

    2009-04-01

    Full Text Available Abstract Uterine sarcomas are a rare group of neoplasms with aggressive clinical course and poor prognosis. They are classified into four main histological subtypes in order of decreasing incidence: carcinosarcomas, leiomyosarcomas, endometrial stromal sarcomas and "other" sarcomas. The pathological subtype demands a tailored approach. Surgical resection is regarded as the mainstay of treatment. Total abdominal hysterectomy and bilateral salpingo-oophorectomy represents the standard treatment of uterine sarcomas. Pelvic and para-aortic lymph node dissection in carcinosarcomas is recommended, given their high incidence of lymph node metastases, and may have a role in endometrial stromal sarcomas. Adjuvant radiation therapy has historically been of little survival value, but it appears to improve local control and may delay recurrence. Regarding adjuvant chemotherapy, there is little evidence in the literature supporting its use except for carcinosarcomas. However, more trials are needed to address these issues, especially, their sequential application. Patients with uterine sarcomas should be referred to large academic centers for participation in clinical trials.

  6. Adherence to Guidelines for Adult (Non-GIST) Soft Tissue Sarcoma in the Netherlands : A Plea for Dedicated Sarcoma Centers

    NARCIS (Netherlands)

    Hoekstra, Harald J; Haas, Rick L M; Verhoef, Cornelis; Suurmeijer, Albert J H; van Rijswijk, Carla S P; Bongers, Ben G H; van der Graaf, Winette T; Ho, Vincent K Y

    2017-01-01

    INTRODUCTION: Optimal management of soft tissue sarcoma (STS) remains a challenge. A nationwide survey assessed the quality of STS care in the Netherlands, thereby aiming to identify potentialities for improvement through more centralized disease management. METHODS: From the Netherlands Cancer

  7. Wiki-based clinical practice guidelines for the management of adult onset sarcoma: a new paradigm in sarcoma evidence.

    Science.gov (United States)

    Neuhaus, S J; Thomas, D; Desai, J; Vuletich, C; von Dincklage, J; Olver, I

    2015-01-01

    In 2013 Australia introduced Wiki-based Clinical Practice Guidelines for the Management of Adult Onset Sarcoma. These guidelines utilized a customized MediaWiki software application for guideline development and are the first evidence-based guidelines for clinical management of sarcoma. This paper presents our experience with developing and implementing web-based interactive guidelines and reviews some of the challenges and lessons from adopting an evidence-based (rather than consensus-based) approach to clinical sarcoma guidelines. Digital guidelines can be easily updated with new evidence, continuously reviewed and widely disseminated. They provide an accessible method of enabling clinicians and consumers to access evidence-based clinical practice recommendations and, as evidenced by over 2000 views in the first four months after release, with 49% of those visits being from countries outside of Australia. The lessons learned have relevance to other rare cancers in addition to the international sarcoma community.

  8. [Positron emission tomography with fluorine-deoxyglucose in sarcomas and non-sarcoma non-epithelial tumors].

    Science.gov (United States)

    Massardo, Teresa; Jofré, María Josefina; Sierralta, María Paulina; Canessa, José; Castro, Gabriel; Berrocal, Isabel; Gallegos, Iván

    2012-09-01

    The usefulness of positron emission tomography (PET) with fluorine-deoxyglucose (FDG) in sarcomas and non-sarcoma non-epithelial (NSNE) tumors is not clearly defined. To report a Chilean experience with NSNE tumors evaluated using PET with FDG. Retrospective review of the database of a PET laboratory. Demographic data, indications and metabolic findings were compared with conventional imaging in 88 adults and children with diverse bone and soft tissue sarcomas as well as 24 gastrointestinal stromal tumors (GIST), 6 pleural malignant mesotheliomas in adults, and 9 medulloblastomas in children. FDG showed good concordance with conventional imaging in NSNE tumors. It was helpful for staging, restaging, follow-up after treatment and for the detection of new not previously suspected lesions. PET with FDG could have a prognostic role and help in patient management, mainly in musculoskeletal and high grade or less differentiated sarcomas. In GIST, it was a good tool for immunotherapy control.

  9. period 1993 to 1999 By SIJAONA A. and KIKWILU EN

    African Journals Online (AJOL)

    Abstract. Kaposi's sarcoma has been strongly linked with. HIV/AIDS epidemic in many countries. Data on. Kaposi's sarcoma in Tanzania that has been published up to 1992 indicate a strong link with. HIV/AIDS. No published reports on Kaposi's sarcoma for the period 1993 to date were available at the time of commencing ...

  10. Dicty_cDB: SHH340 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Kaposi's sarcoma-associated herpes... 65 5e-09 U93872_83( U93872 |pid:none) Kaposi's sarcoma-associated...9e-08 AF192756_1( AF192756 |pid:none) Kaposi's sarcoma-associated herpes... 60 1e-07 ( O76329 ) RecName:

  11. Dicty_cDB: CHQ337 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Kaposi's sarcoma-associated herpes... 44 0.005 U52064_1( U52064 |pid:none) Kaposi's sarcoma-associated...0.008 AF192756_1( AF192756 |pid:none) Kaposi's sarcoma-associated herpes... 44 0.008 AL034558_21( AL034558

  12. Dicty_cDB: SFJ814 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 3e-05 AF305694_1( AF305694 |pid:none) Kaposi's sarcoma-associated herpes... 48 3e-04 CR855913_1( CR855913...Kaposi's sarcoma-associated herpes-lik... 47 5e-04 AF192756_1( AF192756 |pid:none) Kaposi's sarcoma-associated

  13. Dicty_cDB: SFH310 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 0.002 AF305694_1( AF305694 |pid:none) Kaposi's sarcoma-associated herpes... 46 0.003 BT036468_1( BT036468...Kaposi's sarcoma-associated herpes-lik... 44 0.006 AF192756_1( AF192756 |pid:none) Kaposi's sarcoma-associated

  14. Dicty_cDB: SFF501 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Kaposi's sarcoma-associated herpes... 45 0.006 AF192756_1( AF192756 |pid:none) Kaposi's sarcoma-associated...44 0.010 U52064_1( U52064 |pid:none) Kaposi's sarcoma-associated herpes-lik... 44 0.014 CR855913_1( CR855913

  15. Feline injection-site sarcoma / Sarcoma de aplicação felino

    Directory of Open Access Journals (Sweden)

    Julia Maria Matera

    2008-08-01

    Full Text Available The feline injection-site sarcoma (FIS is a challenge for the veterinarian and the affected cat’s owner. The injectable applications (vaccines, medications seems to be the reason for that neoplasia, more specifically, the inflammation caused by injury of given drugs or antigens to the health tissue. Generally the FIS presents a more aggressive behavior when compared to sarcoma not associated to application. The most effective treatment has not been established yet, but it is believed that a multimodality of therapies, surgery, radiotherapy, and chemotherapy would be the most indicated option. The knowledge of the illness in all of its aspects will supply to professionals colleges subsidies in relation to the best way to approach its diagnosis and treatment.O sarcoma de aplicação felino (SAF é atualmente um grande desafio para o médico veterinário e também para o proprietário do felino acometido. Aplicações injetáveis por via subcutânea ou intramuscular, como vacinas e medicações, aparecem como iniciadoras do processo de neogênese dessa neoplasia, mais precisamente a inflamação persistente, causada pela lesão ao tecido sadio decorrente do fármaco ou antígeno administrado. Geralmente o SAF apresenta comportamento mais agressivo quando comparado ao sarcoma não associado à aplicação. O tratamento mais eficaz ainda não está estabelecido, mas acredita-se que a multimodalidade de terapias, cirurgia, radioterapia e quimioterapia seja a opção mais indicada. O conhecimento da afecção em todos os seus aspectos irá fornecer aos colegas profissionais subsídios em relação a melhor maneira de abordá-la em termos de diagnóstico, tratamento e prevenção.

  16. Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas

    DEFF Research Database (Denmark)

    Silveira, Sara Martoreli; Villacis, Rolando Andre Rios; Marchi, Fabio Albuquerque

    2013-01-01

    Undifferentiated high-grade pleomorphic sarcomas (UPSs) display aggressive clinical behavior and frequently develop local recurrence and distant metastasis. Because these sarcomas often share similar morphological patterns with other tumors, particularly leiomyosarcomas (LMSs), classification...

  17. Advances in chromosomal translocations and fusion genes in sarcomas and potential therapeutic applications.

    Science.gov (United States)

    Xiao, Xin; Garbutt, Cassandra C; Hornicek, Francis; Guo, Zheng; Duan, Zhenfeng

    2018-02-01

    Chromosomal translocations and fusion genes are very common in human cancer especially in subtypes of sarcomas, such as rhabdomyosarcoma, Ewing's sarcoma, synovial sarcoma and liposarcoma. The discovery of novel chromosomal translocations and fusion genes in different tumors are due to the advancement of next-generation sequencing (NGS) technologies such as whole genome sequencing. Recently, many novel chromosomal translocations and gene fusions have been identified in different types of sarcoma through NGS approaches. In addition to previously known sarcoma fusion genes, these novel specific fusion genes and associated molecular events represent important targets for novel therapeutic approaches in the treatment of sarcomas. This review focuses on recent advances in chromosomal translocations and fusion genes in sarcomas and their potential therapeutic applications in the treatment of sarcomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Dual Pten/Tp53 Suppression Promotes Sarcoma Progression by Activating Notch Signaling

    OpenAIRE

    Guijarro, Maria V.; Dahiya, Sonika; Danielson, Laura S.; Miguel F. Segura; Vales-Lara, Frances M.; Menendez, Silvia; Popiolek, Dorota; Mittal, Khushbakhat; Wei, Jian Jun; Zavadil, Jiri; Cordon-Cardo, Carlos; Pandolfi, Pier Paolo; Hernando, Eva

    2013-01-01

    Soft tissue sarcomas are a heterogeneous group of tumors associated with poor clinical outcome. Although a subset of soft tissue sarcomas is characterized by simple karyotypes and recurrent chromosomal translocations, the mechanisms driving cytogenetically complex sarcomas are largely unknown. Clinical evidence led us to partially inactivate Pten and Tp53 in the smooth muscle lineage of mice, which developed high-grade undifferentiated pleomorphic sarcomas, leiomyosarcomas, and carcinosarcoma...

  19. Like or Dislike? Impact of Facebook on Ewing Sarcoma Treatment.

    Science.gov (United States)

    Ruckenstuhl, Paul; Schippinger, Michael; Liebmann, Paul; Leithner, Andreas; Bernhardt, Gerwin

    2016-08-25

    An increasing number of patients are raising their voices in online forums to exchange health-related information. Facebook is the leading social media platform with more than 1 billion international daily users recorded in the summer of 2015. Facebook has a dynamic audience and is utilized in a number of ways, discussing medical issues being one of them. Ewing sarcoma mainly affects teenagers and young adults. Additionally, many individuals within this age group are regular users of Facebook. However, little is known about the impact of this modern way of communication via Web-based platforms on patients with Ewing sarcoma and their social environment. The aim of this study was to analyze and compare Ewing sarcoma patients' and relatives' behavior on Facebook to draw conclusions regarding the impact of Facebook on Ewing sarcoma treatment. We examined a Facebook group named "Ewing Sarcoma Awareness" that is used to exchange information for both patients and relatives regarding Ewing sarcoma. A self-designed questionnaire was used to compare patients' and relatives' answers. Additionally, we analyzed all processes (posts, likes, threads, links) in the group for 6 consecutive months. A total of 65 members of the Facebook group (26 patients, 39 relatives) out of 2227 international group members participated in our study. More than 70% (46/65) of all participants reported that they use the group Ewing Sarcoma Awareness as a source of information about Ewing sarcoma. Of the participants, 89% (58/65) agreed on our scale from a little to a lot that being in contact with other affected people through the group makes it easier to handle the diagnosis. In this study, 20% (13/65) of all participants reported that the group affected their choice of treatment and 15% (10/65) of participants were influenced in the selection of their specialist. Regarding the recommendation of the Facebook group toward other people, significant differences (P=.003) were found comparing patients

  20. Feasibility of chemosensitivity testing in soft tissue sarcomas

    Directory of Open Access Journals (Sweden)

    Steinstraesser Lars

    2005-04-01

    Full Text Available Abstract Background Soft tissue sarcomas comprise less than 1% of all solid malignancies. The presentation and behavior of these tumors differs depending on location and histological characteristics. Standard therapy consists of complete surgical resection in combination with adjuvant radiotherapy. The role of chemotherapy is not clearly defined and is largely restricted to clinical trials. Only a limited number of agents have proved to be effective in soft tissue sarcomas. The use of doxorubicin, epirubicin and ifosfamide allowed response rates of more than 20%. In addition, recent chemotherapy trials did not demonstrate any significant differences in efficacy for various histological subtypes. Methods The objective of this study was to gain additional information about the chemosensitivity of soft tissue sarcomas to seven 7 different chemotherapy agents as single drugs and 4 combinations. Therefore we used an established ATP based in-vitro testing system and examined 50 soft tissue sarcomas. Chemosensitivity was assessed using a luciferin-luciferase-based luminescence assay providing individual chemosensitivity indices for each agent tested. Results The sensitivity varied widely according to the histological subtypes. The tumors state of cellular dedifferentiation played a crucial role for the efficiency of the chemotherapeutic agents. The sensitivity also depended on the presentation of the sarcoma as a primary or recurrent tumor. The highest sensitivity was demonstrated for actinomycin D as a single agent, with 74% of the tumor samples exhibiting a high-grade sensitivity (20% low sensitivity, no resistance. The combination of actinomycin D and ifosfamide yielded a high sensitivity in 76% (2% resistance. Doxorubicin as a mono-therapy or in combination with ifosfamide achieved high sensitivity in 70% and 72%, respectively, and resistance in 6% of the samples. Conclusion Chemosensitivity testing is feasible in soft tissue sarcomas. It can be

  1. Osteogenic Sarcoma: A 21st Century Review.

    Science.gov (United States)

    Osasan, Stephen; Zhang, Mingyong; Shen, Fan; Paul, Paulose J; Persad, Sujata; Sergi, Consolato

    2016-09-01

    Compared to other bone tumors, bone osteogenic sarcoma (BOS) continues to confer a much grimmer prognosis as the survival benefit of traditional chemotherapy treatment regimens is still unsatisfactory. Chemotherapy was demonstrated to be effective in eradicating both primary tumor and pulmonary metastases in the last century, with effective agents used in various combination regimens having changed the survival rate from less than 10% to 75%. The most common primary bone cancer, BOS is conventionally a primary intramedullary high-grade malignant tumor characterized by malignant cells forming immature bone or osteoid. BOS is a disease with diverse morphological presentations. The treatment of all morphological variants seem to have been the same for over 30 years. The introduction of antiproliferative agents such as insulin growth factor-binding protein 3 hold promise of a potentially veritable therapeutic target. In this review, we highlight recent data on osteosarcoma to consolidate a platform able to connect bench and bedside. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. Myeloid Sarcoma: The Clinician's Point of View

    Directory of Open Access Journals (Sweden)

    M. Malagola

    2011-01-01

    Full Text Available Myeloid Sarcoma may occur in patients with an acute or chronic myeloproliferative disorder as well as de novo, with no apparent sign or symptom of concomitant haematological disease. The patients are preferentially young male and the site of disease localization may vary from central nervous system to pleura and thorax, with a common involvement of the reticuloendothelial system. The disease often shows chromosomal rearrangements, involving chromosomes 7, 8 and 3 and sometimes a complex karyotype (more than 3 abnormalities is detected at diagnosis. The prognosis of this disease is dismal and only high-dose chemotherapy with autologous or allogeneic stem cells transplantation (auto or allo-SCT may be potentially curative. In the absence of definitive elements that can define the prognosis of extra-medullary localization of “standard risk” AML, Clinicians should pursue the collection of data from different Centres and design of homogeneous treatment strategies, that could integrate standard chemotherapy with specific approaches, such as radiotherapy, transplant procedures or, in selected cases (such as those displaying molecular abnormalities involving protein tyrosine-kinases, molecularly targeted therapies.

  3. Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, Hirofumi; Araki, Nobuhito [Department of Orthopedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-Ku, 537-8511, Osaka (Japan); Sawai, Yuka [Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Kudawara, Ikuo [Department of Orthopedic Surgery, Osaka National Hospital, Osaka (Japan); Mano, Masayuki; Ishiguro, Shingo [Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Ueda, Takafumi; Yoshikawa, Hideki [Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka (Japan)

    2003-12-01

    To characterize the radiological and clinicopathologic features of cystic synovial sarcoma. Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed. CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma. All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging. (orig.)

  4. Targeting the p53 Pathway in Ewing Sarcoma

    Directory of Open Access Journals (Sweden)

    Paul M. Neilsen

    2011-01-01

    Full Text Available The p53 tumour suppressor plays a pivotal role in the prevention of oncogenic transformation. Cancers frequently evade the potent antitumour surveillance mechanisms of p53 through mutation of the TP53 gene, with approximately 50% of all human malignancies expressing dysfunctional, mutated p53 proteins. Interestingly, genetic lesions in the TP53 gene are only observed in 10% of Ewing Sarcomas, with the majority of these sarcomas expressing a functional wild-type p53. In addition, the p53 downstream signaling pathways and DNA-damage cell cycle checkpoints remain functionally intact in these sarcomas. This paper summarizes recent insights into the functional capabilities and regulation of p53 in Ewing Sarcoma, with a particular focus on the cross-talk between p53 and the EWS-FLI1 gene rearrangement frequently associated with this disease. The development of several activators of p53 is discussed, with recent evidence demonstrating the potential of small molecule p53 activators as a promising systemic therapeutic approach for the treatment of Ewing Sarcomas with wild-type p53.

  5. Low-grade fibromyxoid sarcoma: case report and immunohistochemical study.

    Science.gov (United States)

    Nichols, G E; Cooper, P H

    1994-08-01

    A case is presented of low-grade fibromyxoid sarcoma involving the arm of a 52-year-old man. Low-grade fibromyxoid sarcoma is a recently described neoplasm of the deep and subcutaneous soft tissue which demonstrates a spectrum of histologic images. The current case demonstrated the typical patterns of intermixed, sweeping bands of fibrous and myxoid tissue, homogeneous foci of fibrous and myxoid tissue, focal areas of storiforming, and concentric perivascular cuffs of slender spindle cells, all lacking the nuclear anaplasia, mitotic activity, and necrosis generally associated with sarcoma. Immunohistochemical analysis performed on paraffin-embedded sections demonstrated strong labeling of the tumor cells by anti-CD34 antibody, moderate labeling for vimentin, and rare, focal positivity for muscle-specific actin. Tumor cells were negative for markers of epithelial, muscular, neural, histiocytic, melanocytic, and vascular differentiation. The constellation of histopathologic features described in this and previous reports is characteristic of low-grade fibromyxoid sarcoma. Based on this case, it appears that the immunohistochemical features of low-grade fibromyxoid sarcoma can help to exclude many cutaneous and deep soft tissue tumors from the differential diagnosis. The findings support the interpretation that the neoplasm is essentially fibroblastic in nature.

  6. Primary Occipital Ewing’s Sarcoma with Subsequent Spinal Seeding

    Directory of Open Access Journals (Sweden)

    Ali Alqahtani

    2017-01-01

    Full Text Available Ewing’s sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing’s sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI showed cerebrospinal fluid (CSF seeding from the L5 to the S4 vertebrae. Primary cranial Ewing’s sarcoma is considered in the differential diagnosis of children with extra-axial posterior fossa mass associated with destructive permeative bone lesions. Although primary cranial Ewing’s sarcoma typically has good prognosis, our patient developed metastasis in the lower spine. Therefore, with CNS Ewing’s sarcoma, screening of the entire neural axis should be taken into consideration for early detection of CSF seeding metastasis in order to decrease the associated morbidity and mortality.

  7. Immediate versus Delayed Sarcoma Reconstruction: Impact on Outcomes

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    Kyle J. Sanniec

    2016-01-01

    Full Text Available Background. Sarcoma is a rare malignancy, and more recent management algorithms emphasize a multidisciplinary approach and limb salvage, which has resulted in an increase in overall survival and limb preservation. However, limb salvage has resulted in a higher rate of wound complications. Objective. To compare the complications between immediate and delayed (>three weeks reconstruction in the multidisciplinary limb salvage sarcoma patient population. Methods. A ten-year retrospective review of patients who underwent sarcoma resection was performed. The outcome of interest was wound complication in the postoperative period based on timing of reconstruction. We defined infection as any infection requiring intravenous antibiotics, partial flap failure as any flap requiring a debridement or revision, hematoma/seroma as any hematoma/seroma requiring drainage, and wound dehiscence as a wound that was not completely intact by three weeks postoperatively. Results. 70 (17 delayed, 53 immediate patients who underwent sarcoma resection and reconstruction met the inclusion criteria. Delayed reconstruction significantly increased the incidence of postoperative wound infection and wound dehiscence. There was no difference in partial or total flap loss, hematoma, or seroma between the two groups. Discussion and Conclusion. Immediate reconstruction results in decreased wound complications may reduce the morbidity associated with multidisciplinary treatment in the limb salvage sarcoma patient.

  8. Epithelioid sarcoma with muscle metastasis detected by positron emission tomography

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    Oya Masafumi

    2008-08-01

    Full Text Available Abstract Background Epithelioid sarcoma is an uncommon high-grade sarcoma, mostly involving the extremities. Case presentation A 33-year-old man was referred to our institute with a diagnosis of Volkmann's contracture with the symptom of flexion contracture of the fingers associated with swelling in his left forearm. Magnetic resonance imaging (MRI showed abnormal signal intensity, comprising iso-signal intensity on T1- and high-signal intensity on T2-weighted images surrounding the flexor tendons in the forearm. Diagnosis of epithelioid sarcoma was made by open biopsy, and amputation at the upper arm was then undertaken. [18F]-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET detected multiple lesions with an increased uptake in the right neck, the bilateral upper arms and the right thigh, as well as in the left axillary lymph nodes, with maximum standardized uptake value (SUVmax ranging from 2.0 to 5.5 g/ml. Magnetic resonance imaging confirmed that there was a lesion within the right thigh muscle which was suggestive of metastasis, even though the lesion was occult clinically. Conclusion Increased uptake on FDG-PET might be representative of epithelioid sarcoma, and for this reason FDG-PET may be useful for detecting metastasis. Muscle metastasis is not well documented in epithelioid sarcoma. Accordingly, the frequency of muscle metastasis, including occult metastasis, needs to be further analyzed.

  9. Uterine sarcomas-Recent progress and future challenges

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    Seddon, Beatrice M., E-mail: beatrice.seddon@uclh.nhs.uk [London Sarcoma Service, Department of Oncology, University College Hospital, 1st Floor Central, 250 Euston Road, London, NW1 2PG (United Kingdom); Davda, Reena [London Sarcoma Service, Department of Oncology, University College Hospital, 1st Floor Central, 250 Euston Road, London, NW1 2PG (United Kingdom)

    2011-04-15

    Uterine sarcomas are a group of rare tumours that provide considerable challenges in their treatment. Radiological diagnosis prior to hysterectomy is difficult, with the diagnosis frequently made post-operatively. Current staging systems have been unsatisfactory, although a new FIGO staging system specifically for uterine sarcomas has now been introduced, and may allow better grouping of patients according to expected prognosis. While the mainstay of treatment of early disease is a total abdominal hysterectomy, it is less clear whether routine oophorectomy or lymphadenectomy is necessary. Adjuvant pelvic radiotherapy may improve local tumour control in high risk patients, but is not associated with an overall survival benefit. Similarly there is no good evidence for the routine use of adjuvant chemotherapy. For advanced leiomyosarcoma, newer chemotherapy agents including gemcitabine and docetaxel, and trabectedin, offer some promise, while hormonal therapies appear to be more useful in endometrial stromal sarcoma. Novel targeted agents are now being introduced for sarcomas, and uterine sarcomas, and show some indications of activity. Non-pharmacological treatments, including surgical metastatectomy, radiofrequency ablation, and CyberKnife radiotherapy, are important additions to systemic therapy for advanced metastatic disease.

  10. Imaging of the most frequent superficial soft-tissue sarcomas

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    Morel, Melanie; Taieb, Sophie; Ceugnart, Luc [Centre Oscar Lambret, Department of Radiology, Lille (France); Penel, Nicolas [Centre Oscar Lambret, Department of Oncology, Lille (France); Mortier, Laurent [Centre Hospitalier Universitaire de Lille, Department of Dermatology, Hopital Claude Huriez, Lille (France); Vanseymortier, Luc [Centre Oscar Lambret, Department of Surgery, Lille (France); Robin, Y.M. [Centre Oscar Lambret, Departement of Pathology, Lille (France); Gosset, Pierre [Groupement Hospitalier de l' Institut Catholique-Faculte Libre de Medecine de Lille, Department of Pathology, Hopital Saint-Philibert, Lomme (France); Cotten, Anne [Centre Hospitalier Universitaire de Lille, Department of Musculoskeletal Radiology, Centre Hopital Roger Salengro, Lille (France)

    2011-03-15

    Superficial soft-tissue sarcomas are malignant mesenchymal tumors located within the cutaneous and/or subcutaneous layers. Most superficial soft-tissue sarcomas are low-grade tumors; yet, the risk of local recurrence is high, and initial wide surgery is the main prognostic factor. Some of these superficial sarcomas may grow, following an infiltrative pattern, and their real extent may be underestimated clinically. Imaging techniques are useful to determine precisely the real margins of the tumor, especially in cases of clinically doubtful or recurrent or large superficial lesions. Imaging tools enable one to determine the relationship with the superficial fascia separating the subcutaneous layer from the underlying muscle. In our institution ultrasonographic examination is followed by magnetic resonance (MR) imaging when the size of the lesion exceeds 3-5 cm. Imaging assessment is performed prior to biopsy, enabling optimal surgical management. Imaging features of the main superficial sarcomas are detailed in the following article, according to their major locations: those arising in the epidermis and/or dermis, which are most often diagnosed by dermatologists, and the subcutaneous sarcomas. (orig.)

  11. Periductal stromal sarcoma in a child: a case report

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    Kebdani Tayeb

    2011-06-01

    Full Text Available Abstract Introduction Periductal stromal sarcoma is an extremely rare malignant fibroepithelial tumor of the breast which is characterized by its biphasic histology with benign ductal elements and a sarcomatous stroma made of spindle cells and lacking phyllodes architecture. Its therapeutic management is based on wide surgery with free margins. Adjuvant therapies are not needed. Periductal stromal sarcoma may evolve into a phyllodes tumor with time, as well as a specific soft-tissue sarcoma. To the best of our knowledge, this tumor has never been described in a child. Case presentation A 14-year-old Arabic boy was presented to our hospital one year ago with a nodule of the right breast that was gradually increasing in size without signs of inflammation. The histological examination after lumpectomy revealed a periductal stromal sarcoma with free surgical margins. No adjuvant treatment was given. At 50 months of close follow-up, no recurrence was observed. Conclusion Periductal stromal sarcoma in a child is a very rare disease which has the same indolent behavior as it does in adults. Therefore, close follow-up is required.

  12. Primary synovial sarcoma of the abdominal wall: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Alsaif H Saif

    2008-01-01

    Full Text Available Synovial sarcoma is a malignant mesenchymal neoplasm which commonly occurs in the extremities of adults, in close association with joint capsules, tendon sheaths, bursae and fascial structures. Only a few cases of synovial sarcoma occurring in the abdominal wall have been reported. A case of a primary synovial sarcoma arising from the anterior abdominal wall fascial aponeurosis is presented.

  13. NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma.

    Science.gov (United States)

    Sugita, Shintaro; Arai, Yasuhito; Aoyama, Tomoyuki; Asanuma, Hiroko; Mukai, Wakako; Hama, Natsuko; Emori, Makoto; Shibata, Tatsuhiro; Hasegawa, Tadashi

    2017-07-01

    CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion. Copyright © 2017. Published by Elsevier Inc.

  14. Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities

    DEFF Research Database (Denmark)

    Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B.

    2017-01-01

    associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents...... including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong...... and IGF1R inhibitors. The mechanism of the drug synergy between these inhibitors is different from the sum of the mechanisms of the single agents. The combination effectively inhibited pathway crosstalk and averted feedback loop repression, in EWS-FLI1-dependent manner. Mol Cancer Ther; 16(1); 88...

  15. Synovial sarcoma of the temporomandibular joint and infratemporal fossa.

    Science.gov (United States)

    Nomura, Fuminori; Kishimoto, Seiji

    2014-12-01

    Synovial sarcoma in the head and neck region is rare, and is difficult to resect with adequate safety margins because of its anatomical complexity. We herein report our experiences with synovial sarcoma in this region, and review the literature regarding the management of such cases. We retrospectively examined four cases of synovial sarcoma arising from the temporomandibular joint (TMJ) area and infratemporal fossa. Only one patient remains alive without disease, while the other three patients have died. The local control of these tumors has improved because of the progress in the surgical operation methods, while it is expected that there is still a high rate of deaths due to distant metastasis increase. The development of strong chemotherapy is needed for the use after the initial treatment and surgery. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Adult Intramedullary Ewing Sarcoma of the Proximal Hip

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    Preetam Gongidi

    2014-01-01

    Full Text Available Ewing sarcoma of bone is classically a permeative lesion in the diaphysis of long bones in children. While they occur primarily in children and adolescents, they can be seen in young adults in their 20s, but these are typically seen in flat bones. The permeative nature of the lesion can elicit new bone formation creating a partially sclerotic appearance, cortical expansion presenting as a “Codman triangle,” or have an “onion-skin” type of aggressive periosteal reaction/periostitis. Ewing sarcoma is rarely seen without an associated soft-tissue mass and is even rarer to just have benign-appearing periostitis (e.g., thick, uniform, or wavy cortex. We present such a case of Ewing sarcoma in a young adult confined to just the medullary metadiaphysis without cortical erosion or soft-tissue mass. To the best of our knowledge, this is the first case to be reported in the radiology literature.

  17. Epithelioid Sarcoma: Opportunities for Biology-driven Targeted Therapy

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    Jonathan eNoujaim

    2015-08-01

    Full Text Available Epithelioid sarcoma is a soft tissue sarcoma of children and young adults for which the preferred treatment for localised disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review we will summarize clinically-relevant biomarkers (e.g., SMARCB1, CA125, dysadherin and others with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR and polykinase inhibitors (e.g., sunitinib in the management of local and disseminated disease. Towards building a consortium of pharmaceutical, academic and non-profit collaborators, we will discuss the state of resources for investigating epithelioid sarcoma with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed towards effective biology-driven therapies.

  18. Targeting glutathione S-transferase M4 in Ewing sarcoma

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    Rupeng eZhuo

    2014-08-01

    Full Text Available Ewing sarcoma is a malignant pediatric bone and soft tissue tumor. Although the 5-year survival rate of localized disease approaches 75%, the prognosis of metastatic and/or therapy-resistant disease remains dismal despite the wide use of aggressive therapeutic strategies. We previously reported that high expression of glutathione S-transferase M4 (GSTM4 in primary tumors correlates with poor patient outcomes. GSTM4 is required for oncogenic transformation and mediates resistance to chemotherapeutic drugs in Ewing sarcoma cells. Here, we performed RNA-sequencing analyses of Ewing sarcoma cells and combined our results with publicly-available datasets to demonstrate that GSTM4 is a major GST specifically expressed in Ewing sarcoma. Pharmacological inhibition of GSTM4 activity using a pan GST inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio hexanol (NBDHEX, significantly limited cellular proliferation and oncogenic transformation of Ewing sarcoma cells. Moreover, combined use of NBDHEX and etoposide synergistically increased cytotoxicity, suggesting a role for GSTM4 as an inhibitor of apoptosis. Mechanistic studies revealed that GSTM4 limits apoptosis owing to its ability to interact with Apoptosis Signal-regulating Kinase 1 (ASK1 and inhibit signaling via the c-Jun N-terminal Kinase axis. To exploit our observation that GSTM4 expression is specifically up-regulated in Ewing sarcoma, we tested the effect of a GSTM4-activated anti-cancer agent, O2-(2,4-dinitrophenyl 1-[(4-ethoxycarbonylpiperazin-1-yl]diazen-1-ium-1,2-diolate or JS-K, on tumor growth and survival. We found that JS-K robustly decreased Ewing sarcoma cell viability and xenograft tumor growth, and improved overall survival of xenograft mice. Our data suggest that GSTM4 is a novel therapeutic target for the treatment of high GSTM4-expressing Ewing sarcoma. Strategies that combine standard chemotherapy with agents that inhibit GSTM4, or that are activated by GSTM4, or that block GSTM4

  19. Ewing Sarcoma of the Kidney: A Rare Entity

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    Maria Fernanda Arruda Almeida

    2014-01-01

    Full Text Available Ewing sarcoma and primitive peripheral neuroectodermal tumor (PNET are high-grade malignant tumors typically found in children and adolescents. These tumors belong to the family of small round cell tumors and are of neuroectodermal origin. Primary Ewing sarcoma of the kidney is rare and because of that is an infrequent differential diagnosis in urologic malignancies. Renal PNET mostly presents with nonspecific symptoms such as hematuria and abdominal pain. The imaging findings are uncharacteristic. The diagnosis is based on the histology, immunohistochemistry, and molecular pathologic findings. Once PNET has been diagnosed, multimodal treatment is indicated. Despite all treatment options, the prognosis of those with metastatic disease is poor.

  20. SARC: Development and Support of a Sarcoma Research Consortium Infrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Arkison, Jim

    2007-10-29

    SARC is a non-for-profit organization whose mission and vision is to advocate for the collaboration on the design of clinical trials on sarcoma, to further the knowledge regarding the diagnosis and treatment of sarcoma and provide accurate and up to date information to physicians, patients and families. The objectives are to assist in the development of the infrastructure for the continued growth and spectrum of clinical research, to facilitate biannual meeting of investigators, and to develop a preclinical research base that would design and conduct research that would improve the process of drug treatments selected for clinical research trials.

  1. Orbital granulocytic sarcoma: an unusual presentation of acute myelocytic leukemia

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    Stein-Wexler, Rebecca; Wootton-Gorges, Sandra L. [University of California, Davis Medical Center, Davis Children' s Hospital, Sacramento, CA 95817 (United States); West, Daniel C. [Department of Pediatrics, University of California, Davis Medical Center, Davis Children' s Hospital, Sacramento, CA 95817 (United States)

    2003-02-01

    Granulocytic sarcoma is an unusual manifestation of acute myelogenous leukemia in children and presents a diagnostic dilemma when it precedes the development of systemic disease. We present CT and MRI findings of an extraconal mass proven to be granulocytic sarcoma in a 6-year-old otherwise healthy boy with several months' history of worsening unilateral proptosis. This case is unique in providing exquisite CT and MRI correlation and in demonstrating rapid response to therapy. Further, as cytogenetics were positive for the t(8,21) translocation, this case provides opportunity for discussion of the associated incidence of this translocation and concomitant better prognosis. (orig.)

  2. Flap reconstruction and interstitial brachytherapy in nonextremity soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Goel Vineeta

    2007-01-01

    Full Text Available Radiotherapy is an integral component of management of high-grade soft tissue sarcomas. Interstitial brachytherapy is used to deliver a boost or radical dose with several advantages over external beam radiotherapy. There has always been a concern to use brachytherapy with flap reconstruction of skin defects after wide excision. We preset our initial experience with interstitial brachytherapy in two patients of recurrent high-grade non-extremity sarcomas treated with surgical excision and soft tissue reconstruction of surgical defect.

  3. Sarcomas as a mise en abyme of mesenchymal stem cells

    DEFF Research Database (Denmark)

    Burns, Jorge S.; Safwat, Akmal Ahmed; Grisendi, Giulia

    2012-01-01

    Mise en abyme meaning "placed into abyss or infinite recurrence" is an apt paradigm for the relentless growth of sarcoma cells. Its alternative meaning, "self-reflexive embedding" fits the central role attributed to cancer stem cells (CSCs). Diversely sourced and defined, mesenchymal stem cells...... (MSCs) may be the cells of sarcoma origin, evolve a CSC phenotype and/or contribute to tumor growth through inherent qualities for homing, neovascularization, paracrine cross-feeding, microvesicle secretion, cell fusion, entosis and immune modulation. Exploiting these qualities, MSC expressing modified...

  4. Alveolar soft part sarcoma of the retro peritoneum

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    Xin Fan

    2010-01-01

    Full Text Available Alveolar Soft Part Sarcoma (ASPS, also called Alveolar Soft-Tissue Sarcoma, is a rare type of soft-tissue neoplasm with a poor long term prognosis. Such tumors originating in the retro peritoneal space are extremely rare. In this article we discuss a 34-year-old woman who was referred to our hospital with an increasing mass in her left lower abdomen. Ultrasonography and conventional Computed Tomography revealed a large hard mass occupying the left retroperitoneal space with a clear border. The pathological diagnosis was ASPS.

  5. Primary renal undifferentiated sarcoma as an infiltrative mass in a 12 year old boy

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    Kim, Yong Hee; Kim, Myung Joon; Lee, Mi Jung [Dept. of Radiology and Research Institute of Radiological Science, Severance Children' s Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Se Hwa [Dept. of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-09-15

    Undifferentiated sarcomas are rare tumors not classified into any sarcoma subtype. Due to their rarity, imaging findings of undifferentiated sarcomas are poorly characterized. The purpose of this report was to present imaging findings of a pathologically confirmed undifferentiated sarcoma originated from the left kidney of a 12-year-old boy. The mass was infiltrative involving the renal pelvis. It mimicked massive hilar lymphadenopathy with a preserved renal contour visible by both ultrasonography and CT. Renal vein thrombosis was also observed. Although undifferentiated sarcomas are rare, they should be considered in differential diagnosis of infiltrative renal masses with renal pelvis invasion in children.

  6. Meningeal chloroma (granulocytic sarcoma) in acute lymphoblastic leukemia mimicking a falx meningioma.

    Science.gov (United States)

    Ahn, Jung Yong; Kwon, Seong Oh; Shin, Moon Soo; Kang, Shin Heh; Kim, Young Rae

    2002-10-01

    Isolated chloromas (granulocytic sarcomas) are rare tumors. Chloromas are masses composed of immature granulocytic cells. Granulocytic sarcoma occurs primarily in patients with acute myelogenous leukemia and may also arise in patients with other myeloproliferative disorders, but rarely in patients with acute lymphoblastic leukemia (ALL). When dural-based, granulocytic sarcoma may be indistinguishable from meningioma radiologically. We now describe one patient affected by ALL with isolated granulocytic sarcoma mimicking a falx meningioma as initial CNS relapses. These unusual clinical manifestation and radiological finding in ALL should be considered as recurrence of leukemia. Early detection and antileukemic treatment of granulocytic sarcoma are necessarily important for favorable prognosis.

  7. Pediatric rhabdomyosarcomas and nonrhabdomyosarcoma soft tissue sarcoma

    Directory of Open Access Journals (Sweden)

    Agarwala Sandeep

    2006-01-01

    Full Text Available Tumors arising from the soft tissues are uncommon in children, accounting for about 6% of all childhood malignancies. More than half (53% of these originate from the striated muscles and are called rhabdomyosarcomas (RMS the remaining are nonrhabdomyosarcoma soft tissue sarcomas (NRSTS. Almost two-thirds of RMS cases are diagnosed in children < 6 years of age. They can arise at varied locations like the head and neck region, genitourinary tract, extremities, trunk and retroperitoneum. Pathologically RMS is now classified as superior, intermediate and poor outcome histologies. For stratification of treatment and also comparison of results the RMS are now staged both by the clinical grouping and the TNM staging systems. The ultimate outcome depends on the site, extent of disease and histology. Currently, approximately 70% of the patients survive for 5 years or more and are probably cured. This is credited to the use of multi-modal, risk-adapted therapy, refinements in tumor grouping and better supportive care which has emerged out of cooperative studies like Intergroup Rhabdomyosarcoma Study (IRS and the International Society of Pediatric Oncology studies (SIOP. The treatment involves chemotherapy, radiotherapy and organ/function preserving surgery. The gold standard chemotherapy is still vincristine, actinomycin D and cyclophosphamide (VAC regime with high doses of intensity bone marrow rescue with colony stimulating factors. The NRSTS are rare and of heterogenous histologies and so it has been difficult to arrive at a treatment strategy for these. What is definitely understood is that these are usually immature and poorly differentiated tumors that respond poorly to chemotherapy and so surgical resection forms the mainstay of treatment with adjuvant radiotherapy and chemotherapy to prevent local recurrences. In all likelihood, the molecular analysis of RMS will further refine current classification schemes and knowledge of genetic features of

  8. Cediranib for Metastatic Alveolar Soft Part Sarcoma

    Science.gov (United States)

    Kummar, Shivaani; Allen, Deborah; Monks, Anne; Polley, Eric C.; Hose, Curtis D.; Ivy, S. Percy; Turkbey, Ismail B.; Lawrence, Scott; Kinders, Robert J.; Choyke, Peter; Simon, Richard; Steinberg, Seth M.; Doroshow, James H.; Helman, Lee

    2013-01-01

    Purpose Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs). Patients and Methods We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging. Results Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis. Conclusion In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib. PMID:23630200

  9. Sarcoma granulocítico em órbita: relato de caso Orbital granulocytic sarcoma: case report

    Directory of Open Access Journals (Sweden)

    Nilson Lopes da Fonseca Junior

    2005-08-01

    Full Text Available O sarcoma granulocítico é tumor que freqüentemente aparece em pacientes portadores de leucemia mielóide aguda, podendo aparecer em diferentes regiões do corpo, incluindo a órbita. Nesta última localização, é mais freqüente em crianças e adultos jovens, com discreta predominância em pacientes do sexo masculino. Este é um caso de sarcoma granulocítico orbitário de evolução rápida, sem manifestação sistêmica associada em uma paciente de 33 anos de idade, o que o torna incomum. O surgimento do sarcoma granulocítico orbitário sem acometimento leucêmico pode ocorrer em cerca de 88% dos pacientes com acometimento orbitário. A maioria dos pacientes apresenta evidências hematológicas de comprometimento sistêmico em 2 meses após a manifestação orbitária. Neste relato de caso, a paciente não apresenta acometimento sistêmico, apesar da manifestação orbitária estar presente há 30 meses. Os principais diagnósticos diferenciais do sarcoma granulocítico orbitário são o linfoma, o rabdomiossarcoma e o neuroblastoma. O diagnóstico pode ser dificultado, principalmente nos casos sem acometimento sistêmico, nos quais os exames de imagem e as manifestações clínicas pouco diferem de outras doenças. Para o diagnóstico deve-se realizar uma biópsia da lesão orbitária para análise anatomopatológica e imuno-histoquímica. O tratamento nos casos de sarcoma granulocítico orbitário sem acometimento sistêmico não é padronizado. A hipótese diagnóstica de sarcoma granulocítico orbitário deve ser aventada em casos de pacientes com tumoração orbitária mesmo que não apresentem sinais ou sintomas sistêmicos e independentes da faixa etária.Orbital granulocytic sarcoma is a localized tumor consisting of malignant cells of myeloid origin. This tumor may present in association with acute myelogenous leukemia. Granulocytic sarcoma may be found in a variety of locations throughout the body including the orbit and

  10. Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 1-Common Sarcomas: From the Radiologic Pathology Archives.

    Science.gov (United States)

    Levy, Angela D; Manning, Maria A; Al-Refaie, Waddah B; Miettinen, Markku M

    2017-01-01

    Soft-tissue sarcomas are a diverse group of rare mesenchymal malignancies that can arise at any location in the body and affect all age groups. These sarcomas are most common in the extremities, trunk wall, retroperitoneum, and head and neck. In the adult population, soft-tissue sarcomas arising in the abdomen and pelvis are often large masses at the time of diagnosis because they are usually clinically silent or cause vague or mild symptoms until they invade or compress vital organs. In contrast, soft-tissue sarcomas arising from the abdominal wall come to clinical attention earlier in the course of disease because they cause a palpable mass, abdominal wall deformity, or pain that is more clinically apparent. The imaging features of abdominal and pelvic sarcomas and abdominal wall sarcomas can be nonspecific and overlap with more common pathologic conditions, making diagnosis difficult or, in some cases, delaying diagnosis. Liposarcoma (well-differentiated and dedifferentiated liposarcomas), leiomyosarcoma, and gastrointestinal stromal tumor (GIST) are the most common intra-abdominal primary sarcomas. Any soft-tissue sarcoma can arise in the abdominal wall. Knowledge of the classification and pathologic features of soft-tissue sarcomas, the anatomic locations where they occur, and their cross-sectional imaging features helps the radiologist establish the diagnosis or differential diagnosis so that patients with soft-tissue sarcomas can receive optimal treatment and management. In part 1 of this article, the most common soft-tissue sarcomas (liposarcoma, leiomyosarcoma, and GIST) are reviewed, with a discussion on anatomic locations, classification, clinical considerations, and differential diagnosis. Part 2 will focus on the remainder of the soft-tissue sarcomas occurring in the abdomen and pelvis.

  11. Comprehensive Surgical Treatment as the Mainstay of Management in Retroperitoneal Sarcomas: Retrospective Study from Two Non-sarcoma Specialist Centers.

    Science.gov (United States)

    Petrou, Athanasios; Constantinidou, Anastasia; Kontos, Michael; Papalampros, Alexandros; Moris, Demetrios; Bakoyiannis, Chris; Neofytou, Kyriakos; Kourounis, George; Felekouras, Evangelos

    2017-04-01

    Complete resection, surgical expertise and individualization of patient management in comprehensive oncology centres result in better clinical outcomes in patients presenting with retroperitoneal sarcomas. Clinical outcomes of primary and recurrent retroperitoneal sarcoma resections performed between January 2002 and December 2016 in two large surgical oncology, but non-sarcoma specialist centers, were reviewed to determine the efficacy of complete surgical resection as the principle instrument for treatment. The histological type, tumor size and grade, as well as organ resection, were recorded and subsequently reviewed. Our study included 108 cases of sarcoma resection (60 first-time, 38 second-time and 10 third-time laparotomies) in 60 patients (35 males and 25 females). Most patients had complete resection: 57 had a macroscopically complete (R0/R1) resection and three had R2 resection. The 90-day mortality rate was zero and morbidity was minimal. Five- and 10-year overall survival (OS) rates were 88% and 79%, respectively, whereas the corresponding disease-free survival (DFS) rates were 65% and 59%, respectively. High-grade tumors were associated with decreased DFS (hazard ratio(HR)=3.35; 95% confidence interval(CI)=1.23-9.10; p=0.018) and decreased OS (HR=7.18; 95% CI=1.50-34.22; p=0.013). Complete surgical resection of retroperitoneal sarcomas combined with individualized patient management when offered by experienced surgical oncology teams, adhering to international guidelines, can succeed in providing patients with good long-term outcomes, comparable to those achieved at sarcoma-specialist centers. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Sarcoma indiferenciado primário no sistema nervoso central Primary undifferentiated sarcoma of the central nervous system

    Directory of Open Access Journals (Sweden)

    Milton Marcio Machota Junior

    2012-04-01

    Full Text Available INTRODUÇÃO: O sarcoma de sistema nervoso central (SNC é uma neoplasia rara, com incidência de 0,1% a 4,3% dos tumores intracranianos. São tumores agressivos com prognóstico reservado e a maioria é tratada com ressecção radical. RELATO: Homem, 29 anos, com episódios de crises convulsivas e diagnóstico de hemorragia intraparenquimatosa. Durante a cirurgia, foi identificada lesão bem delimitada. A histologia demonstrou neoplasia fusocelular com atipias e numerosas mitoses. Os únicos marcadores imuno-histoquímicos positivos foram vimentina e S-100. O diagnóstico foi de sarcoma indiferenciado de alto grau. CONCLUSÃO: No diagnóstico diferencial de sarcomas de SNC, devem-se excluir lesões metastáticas e gliossarcoma.INTRODUCTION: The central nervous system (CNS sarcoma is a rare neoplasm with an incidence of 0.1% to 4.3% in intracranial tumors. They are aggressive with poor prognosis, and mostly treated with radical resection. REPORT: 29 year-old male patient with episodes of seizures and diagnosed with intraparenchymal hemorrhage. During the surgery a well-defined lesion was identified. Histology showed a spindle cell neoplasm with atypia and numerous mitoses. The immunohistochemical markers were positive only for vimentin and S-100. The diagnosis was high-grade undifferentiated sarcoma. CONCLUSION: Metastatic lesions and gliosarcoma should be excluded in the differential diagnosis of CNS sarcomas.

  13. Three-dimensional (3D) culture in sarcoma research and the clinical significance.

    Science.gov (United States)

    Gao, Songtao; Shen, Jacson; Hornicek, Francis; Duan, Zhenfeng

    2017-08-03

    Sarcomas are rare malignant tumors that arise from transformed cells of mesenchymal origin. Despite the progress in diagnosis and treatment, sarcomas have a high mortality rate due to local recurrence, metastasis, and the development of drug resistance to chemotherapy. New models for sarcoma research are required to further understand the disease and to develop new therapies. In vitro sarcoma modeling is challenging because of significant genetic heterogeneities, diverse pathological, and overlapping clinical characteristics. Studies on the mechanisms of recurrence, metastasis, and drug resistance in sarcoma have resulted in the generation of novel three-dimensional (3D) culture models for sarcoma research. 3D culture models aim to recapitulate the tumor microenvironment that plays a critical role in the pathogenesis of sarcoma using biomaterial scaffolds of natural biological materials and artificial polymers. An ideal 3D culture model can properly mimic not only the microenvironment, oncogenesis, and maintenance of sarcoma cell growth, but also imitate the interactions between cells and to the extracellular matrix. More recently, 3D cell culture has been used to research the biological behavior and mechanism of chemotherapy and radiotherapy resistance in different sarcoma models. Ultimately, findings using 3D models that more accurately reflect human sarcoma biology are likely to translate into improved clinical outcomes. In this review, we discuss the most recent advances of 3D culture technologies in sarcoma research and emerging clinical applications.

  14. Indian data on bone and soft tissue sarcomas: A summary of published study results

    Directory of Open Access Journals (Sweden)

    Anant Ramaswamy

    2016-01-01

    Full Text Available Bone sarcomas are rare tumors, approximating 0.2% of all cancers, with osteosarcoma (OGS, chondrosarcoma, and Ewing sarcoma being the most common cancers in this subset. The formation of disease management groups/clinics focused on sarcomas has resulted in better understanding and management of these uncommon tumors. Multiple large-scale retrospective data from Tata Memorial Hospital (TMH and All India Institute of Medical Sciences have reported outcomes comparable to Western data in the field of OGS and Ewing sarcoma, with interesting prognostic factors identified for further evaluation. Soft tissue sarcomas are a rare heterogeneous group of tumors, more than 50 different tumor entities. The common subtypes identified in India include Ewing sarcoma and synovial sarcoma. Valuable work regarding brachytherapy has been done by radiation oncologists from the TMH, especially in pediatric patients.

  15. Potentials of Long Noncoding RNAs (LncRNAs in Sarcoma: From Biomarkers to Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Li Min

    2017-03-01

    Full Text Available Sarcoma includes some of the most heterogeneous tumors, which make the diagnosis, prognosis and treatment of these rare yet diverse neoplasms especially challenging. Long noncoding RNAs (lncRNAs are important regulators of cancer initiation and progression, which implies their potential as neoteric prognostic and diagnostic markers in cancer, including sarcoma. A relationship between lncRNAs and sarcoma pathogenesis and progression is emerging. Recent studies demonstrate that lncRNAs influence sarcoma cell proliferation, metastasis, and drug resistance. Additionally, lncRNA expression profiles are predictive of sarcoma prognosis. In this review, we summarize contemporary advances in the research of lncRNA biogenesis and functions in sarcoma. We also highlight the potential for lncRNAs to become innovative diagnostic and prognostic biomarkers as well as therapeutic targets in sarcoma.

  16. Characterization of three newly established rat sarcoma cell clones

    Czech Academy of Sciences Publication Activity Database

    Holubová, Monika; Leba, M.; Sedmíková, M.; Vannucci, Luca; Horák, Vratislav

    2012-01-01

    Roč. 48, č. 10 (2012), s. 610-618 ISSN 1071-2690 R&D Projects: GA MŠk 2B08063 Institutional support: RVO:67985904 Keywords : sarcoma * cell clones * lewis rat Subject RIV: FD - Oncology ; Hematology Impact factor: 1.289, year: 2012

  17. Synovial Sarcoma-A Rare Tumor of the Larynx

    Directory of Open Access Journals (Sweden)

    Ghodrat Mohammadi

    2016-05-01

    Full Text Available Introduction: Malignant mesenchymal tumors of the larynx are rare. One type of malignant mesenchymal tumor is synovial sarcoma with unknown histogenesis, which occurs predominantly in the lower extremities of young adults. The head and neck region is a relatively rare location. There are few cases of malignant mesenchymal tumors with laryngeal localization in literature.  Case Report: In this report, a new case in a 23-year-old man, which was referred with increasing hoarseness for eight months, and dysphagia, odynophagia, and dyspnea since nearly one year ago, is reported. Indirect laryngoscopy revealed a laryngeal submucosal mass. The patient was operated and the histopathological diagnosis of synovial sarcoma was confirmed by IHC (Immunohistochemisry.  Conclusion:  Synovial sarcoma occurs predominantly in the lower extremities of young adults. Because very few cases of laryngeal synovial sarcoma are reported, every new case will bring some new information about diagnosis and therapy. It is of utmost importance to get to know new aspects and therapeutical modalities of this rare tumor.

  18. PRIMARY BREAST SARCOMA: CASE REPORT S. HASSAN and G ...

    African Journals Online (AJOL)

    hi-tech

    2004-07-07

    Jul 7, 2004 ... EAST AFRICAN MEDICAL JOURNAL. 377. In only one of 39 axillary dissections in a French study and two of 22 dissections at Mayo clinic(1,2) were nodes histologically involved. Mastectomy is not superior to wide resection in sarcoma if the margins are clear. Recurrence rates and overall survival are not.

  19. PRIMARY BREAST SARCOMA: CASE REPORT S. HASSAN and G ...

    African Journals Online (AJOL)

    hi-tech

    East African Medical Journal Vol. 81 No. 7 July 2004. PRIMARY BREAST SARCOMA: CASE REPORT. S. Hassan, BSc., MBChB, MMed, (Surg) FCS, Consultant Surgeon, Nairobi Womens Hospital Breast Center and Senior Lecturer, Department of Human Anatomy,. College of Health Sciences, University of Nairobi, P.O. ...

  20. Copy Number Alterations and Methylation in Ewing's Sarcoma

    Directory of Open Access Journals (Sweden)

    Mona S. Jahromi

    2011-01-01

    Full Text Available Ewing's sarcoma is the second most common bone malignancy affecting children and young adults. The prognosis is especially poor in metastatic or relapsed disease. The cell of origin remains elusive, but the EWS-FLI1 fusion oncoprotein is present in the majority of cases. The understanding of the molecular basis of Ewing's sarcoma continues to progress slowly. EWS-FLI1 affects gene expression, but other factors must also be at work such as mutations, gene copy number alterations, and promoter methylation. This paper explores in depth two molecular aspects of Ewing's sarcoma: copy number alterations (CNAs and methylation. While CNAs consistently have been reported in Ewing's sarcoma, their clinical significance has been variable, most likely due to small sample size and tumor heterogeneity. Methylation is thought to be important in oncogenesis and balanced karyotype cancers such as Ewing's, yet it has received only minimal attention in prior studies. Future CNA and methylation studies will help to understand the molecular basis of this disease.

  1. Pathogenetic studies of sarcoma development in retriever breeds

    NARCIS (Netherlands)

    Boerkamp, K.M.

    2014-01-01

    In the Dutch population of Golden retrievers, a predisposition for the development of cancer in general and certain types of cancer (such as mast cell tumours and possibly also soft tissue sarcomas (STS)) was shown to exist. In addition, age, location and incidence of various tumours differed as

  2. Functional Reconstruction of Sarcoma Defects Utilising Innervated Free Flaps

    Directory of Open Access Journals (Sweden)

    Damien Grinsell

    2012-01-01

    Full Text Available Soft-tissue reconstruction following preoperative radiotherapy and wide resection of soft tissue sarcoma remains a challenge. Pedicled and free tissue transfers are an essential part of limb sparing surgery. We report 22 cases of sarcoma treated with radiotherapy and wide excision followed by one-stage innervated free or pedicled musculocutaneous flap transfers. The resection involved the upper limb in 3 cases, the lower limb in 17, and the abdominal wall in 2. The flaps used for the reconstruction were mainly latissimus dorsi and gracilis. The range of motion was restored fully in 14 patients. The muscle strength of the compartment reconstructed was of grades 4 and 5 in all patients except one. The overall function was excellent in all the cases with functional scores of 71.2% in the upper limb and 84% in the lower limb. The only 2 major complications were flap necrosis, both revised with another flap, one of which was innervated with restoration of function. Innervated flaps are valuable alternatives for reconstruction after sarcoma resection in the extremity and in the abdominal wall. The excellent functional results are encouraging, and we believe that innervated muscle reconstruction should be encouraged in the treatment of sarcoma after radiotherapy and wide resection.

  3. Microsatellites with Macro-Influence in Ewing Sarcoma

    Directory of Open Access Journals (Sweden)

    Stephen L. Lessnick

    2012-07-01

    Full Text Available Numerous molecular abnormalities contribute to the genetic derangements involved in tumorigenesis. Chromosomal translocations are a frequent source of these derangements, producing unique fusion proteins with novel oncogenic properties. EWS/ETS fusions in Ewing sarcoma are a prime example of this, resulting in potent chimeric oncoproteins with novel biological properties and a unique transcriptional signature essential for oncogenesis. Recent evidence demonstrates that EWS/FLI, the most common EWS/ETS fusion in Ewing sarcoma, upregulates gene expression using a GGAA microsatellite response element dispersed throughout the human genome. These GGAA microsatellites function as enhancer elements, are sites of epigenetic regulation and are necessary for EWS/FLI DNA binding and upregulation of principal oncogenic targets. An increasing number of GGAA motifs appear to substantially enhance EWS/FLI-mediated gene expression, which has compelling biological implications as these GGAA microsatellites are highly polymorphic within and between ethnically distinct populations. Historically regarded as junk DNA, this emerging evidence clearly demonstrates that microsatellite DNA plays an instrumental role in EWS/FLI-mediated transcriptional regulation and oncogenesis in Ewing sarcoma. This unprecedented role of GGAA microsatellite DNA in Ewing sarcoma provides a unique opportunity to expand our mechanistic understanding of how EWS/ETS fusions influence cancer susceptibility, prognosis and transcriptional regulation.

  4. Ewing′s sarcoma in mandibular similar to dental abscess

    Directory of Open Access Journals (Sweden)

    Forouz Keshani

    2014-01-01

    This case report deals with a 16-year-old patient wrongly diagnosed with odontogenic infection and abscess, and hospitalized. As the symptoms did not remit, biopsy was carried out and the patient was operated on with Ewing′s sarcoma diagnosis.

  5. Advances in the Treatment of Pediatric Bone Sarcomas.

    Science.gov (United States)

    Grohar, Patrick J; Janeway, Katherine A; Mase, Luke D; Schiffman, Joshua D

    2017-01-01

    Bone tumors make up a significant portion of noncentral nervous system solid tumor diagnoses in pediatric oncology patients. Ewing sarcoma and osteosarcoma, both with distinct clinical and pathologic features, are the two most commonly encountered bone cancers in pediatrics. Although mutations in the germline have classically been more associated with osteosarcoma, there is recent evidence germline alterations in patients with Ewing sarcoma also play a significant role in pathogenesis. Treatment advances in this patient population have lagged behind that of other pediatric malignancies, particularly targeted interventions directed at the biologic underpinnings of disease. Recent advances in biologic and genomic understanding of these two cancers has expanded the potential for therapeutic advancement and prevention. In Ewing sarcoma, directed focus on inhibition of EWSR1-FLI1 and its effectors has produced promising results. In osteosarcoma, instead of a concentrated focus on one particular change, largely due to tumor heterogeneity, a more diversified approach has been adopted including investigations of growth factors inhibitors, signaling pathway inhibitors, and immune modulation. Continuing recently made treatment advances relies on clinical trial design and enrollment. Clinical trials should include incorporation of biological findings; specifically, for Ewing sarcoma, assessment of alternative fusions and, for osteosarcoma, stratification utilizing biomarkers. Expanded cancer genomics knowledge, particularly with solid tumors, as it relates to heritability and incorporation of family history has led to early identification of patients with cancer predisposition. In these patients through application of cost-effective evidence-based screening techniques the ultimate goal of cancer prevention is becoming a realization.

  6. Giant primary synovial sarcoma of the anterior mediastinum: A case ...

    African Journals Online (AJOL)

    ... histologic and immunohistochemical analyses confirmed a diagnosis of monophasic synovial sarcoma. However, 10 months postoperation she represented with chest pain, productive cough and a repeat CXR showed multiple left pulmonary nodules. She received two cycles of docetaxel and gemcitabine chemotherapy, ...

  7. Synovial sarcoma mimicking benign peripheral nerve sheath tumor

    Energy Technology Data Exchange (ETDEWEB)

    Larque, Ana B.; Nielsen, G.P.; Chebib, Ivan [Massachusetts General Hospital and Harvard Medical School, Department of Pathology, Boston, MA (United States); Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2017-11-15

    To assess the radiographic and clinicopathologic features of synovial sarcoma of the nerve that were clinically or radiologically interpreted as benign peripheral nerve sheath tumor. Five patients with synovial sarcoma arising from the peripheral nerve and interpreted clinically and radiologically as peripheral nerve sheath tumors were identified. Clinicopathologic and imaging features were evaluated. There were three females and two males, ranging in age from 28 to 50 (mean 35.8) years. Most patients (4/5) complained of a mass, discomfort or pain. MR images demonstrated a heterogeneous, enhancing, soft tissue mass contiguous with the neurovascular bundle. On histologic examination, most tumors were monophasic synovial sarcoma (4/5). At the time of surgery, all tumors were noted to arise along or within a peripheral nerve. All patients were alive with no evidence of disease with median follow-up of 44 (range 32-237) months. For comparison, approximately 775 benign peripheral nerve sheath tumors of the extremities were identified during the same time period. Primary synovial sarcoma of the nerve can mimic peripheral nerve sheath tumors clinically and on imaging and should be included in the differential diagnosis for tumors arising from peripheral nerves. (orig.)

  8. Primary breast sarcoma: case report | Hassan | East African Medical ...

    African Journals Online (AJOL)

    Primary breast sarcoma is a rare entity occurring in 0.5% of women with breast malignancy. Like in breast carcinoma, delay in its diagnosis has important clinical and treatment implications. The subject of this report presented at our breast unit with advanced breast lesion months after she noticed a small lump in her right ...

  9. Sarcomas: etiología y síntomas

    Directory of Open Access Journals (Sweden)

    Roberto Gabriel Albín Cano

    2012-05-01

    Full Text Available Debido a la amplia diversidad de sarcomas, casi son inexistentes los textos que incluyen todas las variedades de este tipo de cáncer. Generalmente, su descripción y revisión se incluyen en las del sistema de órganos afectados específicamente, y la literatura que los aborda está muy fragmentada en las diferentes especialidades médicas. Se realiza una revisión bibliográfica sobre la etiología y síntomas de la mayor parte de los diferentes tipos de sarcomas. Es objetivo de esta revisión, lograr unir la información más actual disponible acerca de la etiología y síntomas de los sarcomas. Se han identificado diferentes factores de riesgo y factores etiológicos, tanto genéticos, infecciosos, como ambientales. Los grandes descubrimientos en relación con los mecanismos genéticos involucrados en los diferentes tipos de sarcoma, han abierto un camino de inestimable valor para introducir nuevos tratamientos, que incluyen ensayos con anticuerpos monoclonales y nuevos fármacos de terapia génica.

  10. The First European Interdisciplinary Ewing Sarcoma Research Summit

    Directory of Open Access Journals (Sweden)

    Heinrich eKovar

    2012-05-01

    Full Text Available The European Network for Cancer Research in Children and Adolescents (ENCCA provides an interaction platform for stakeholders in research and care of children with cancer. Among ENCCA aims is the establishment of biology-based prioritization mechanisms for the selection of innovative targets, drugs, and prognostic markers for validation in clinical trials. Specifically for sarcomas, there is a burning need for novel treatment options since current chemotherapeutic treatment protocols have met their limits. This is most obvious for metastatic Ewing sarcoma, where long term survival rates are still below 20%. Despite significant progress in our understanding of Ewing sarcoma biology, clinical translation of promising laboratory results has not taken place due to fragmentation of research and lack of an institutionalized discussion forum. To fill this gap, ENCCA assembled 30 European expert scientists and 5 North American opinion leaders in December 2011 to exchange and critically discuss the state of the art in Ewing sarcoma research and latest results from the bench, and to propose biological studies and novel promising therapeutics for the upcoming European EWING2008 and EWING2012 clinical trials.

  11. Adult prostatic sarcoma: A contemporary multicenter Rare Cancer Network study

    NARCIS (Netherlands)

    Bari, B. De; Stish, B.; Ball, M.W.; Habboush, Y.; Sargos, P.; Krengli, M.; Bossi, A.; Stabile, A.; Pesutic, C. Sole; Lestrade, L.; Smeenk, R.J.; Jereczek-Fossa, B.A.; Zilli, T.; Crehange, G.; Alongi, F.; Zaorsky, N.; Ozsahin, M.

    2017-01-01

    INTRODUCTION: Adult prostatic sarcoma (PS) is a rare disease. While surgery is considered the standard approach, the role of other therapies is not completely established. We report results of the largest multicentric contemporary cohort of PS patients. MATERIALS AND METHODS: This study included 61

  12. Occupational factors and risk of adult bone sarcomas

    DEFF Research Database (Denmark)

    Merletti, Franco; Richiardi, Lorenzo; Bertoni, Franco

    2006-01-01

    sarcoma (68 chondrosarcomas and 28 osteosarcomas) were compared to 2,632 population (68%) or colon cancer (32%) controls. Subjects were interviewed to obtain information on occupational, medical and reproductive history, smoking and alcohol consumption and selected exposures including use of pesticides...

  13. Amputation risk after the revascularization procedures in sarcoma resections

    Directory of Open Access Journals (Sweden)

    Luiz Eduardo Moreira Teixeira

    Full Text Available ABSTRACT OBJECTIVE: The objective of this study is to evaluate the efficacy of vascular reconstructive surgery after resection of bone and soft tissue tumors in extremities and the risk of progression to amputation. METHODS: This is a retrospective, observational data collection from medical records of patients who underwent resection of bone and soft tissue tumors in the period of 2002-2015. Thirteen patients met the inclusion criteria, which evaluated the correlations between certain factors (gender, tumor type, location, reconstruction, revascularization and patency, infection with amputation in the postoperative period. RESULTS: In this study, of the 13 patients undergoing reconstruction, five (38.46% evolved to amputation. All patients who progressed to amputation had the following in common: presence of bone sarcoma (p = 0.005, having undergone reconstruction with an orthopedic prosthesis (p = 0.005, lack of vascular patency in the revascularization site in the postoperative period (p = 0.032, and surgical site infection (p = 0.001. None of the patients with soft tissue sarcoma underwent amputation, and the only patient with bone sarcoma who did not undergo amputation had no infection and maintained vascular patency of the graft. CONCLUSION: The occurrence of infection appears to be one of the main risk factors for failure of revascularization, especially in cases of bone sarcoma in which vascular reconstruction is performed with placement of a non-conventional joint prosthesis.

  14. Histiocytic sarcoma with bladder involvement: Case report and literature review.

    Science.gov (United States)

    Fernández-Aceñero, Mª Jesús; Pérez Alonso, Pablo; Díaz Del Arco, Cristina

    We report an unusual case of histiocytic sarcoma with bladder involvement. An 80 year-old man with a previous history of diffuse large B-cell malignant lymphoma presented with hematuria and back pain. Serial urine cytologies revealed no urothelial malignant cells, but cystoscopy showed a large intravesical mass. The patient underwent transurethral resection (TUR) of the tumor. The bladder TUR specimen showed a widely infiltrating epithelioid neoplasm, with intense immunohistochemical positivity for CD45 and histiocytic markers (CD68, lysozime and fascin). Histopathological diagnosis was histiocytic sarcoma. As the patient's condition was progressively deteriorating, only palliative care was indicated and he died one month after TUR. Although histiocytic sarcoma can often be widespread at the time of diagnosis, to our knowledge, this is the first report of a case presenting with urinary symptoms. Histiocytic sarcoma can mimic many other malignant lesions, and only immunohistochemistry can define the tumor cells, allowing correct therapy. We discuss the differential diagnosis and possible associations. Copyright © 2017 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Myeloid sarcoma developing in pre-existing pyoderma gangrenosum

    DEFF Research Database (Denmark)

    Kristensen, Ida Bruun; Møller, Hanne; Kjaerskov, Mette Wanscher

    2009-01-01

    We report here a case of pyoderma gangrenosum in a patient with myelodysplastic syndrome developing into myeloid sarcoma as a sign of transformation to acute leukaemia. The patient was treated successfully with intensive chemotherapy and achieved complete remission, and her otherwise expanding...

  16. Stem-Like Cells in Bone Sarcomas: Implications for Tumorigenesis

    Directory of Open Access Journals (Sweden)

    C. Parker Gibbs

    2005-11-01

    Full Text Available Bone sarcomas are a clinically and molecularly heterogeneous group of malignancies characterized by varying degrees of mesenchymal differentiation. Despite advances in medical and surgical management, survival rates for high-grade tumors have remained static at 50% to 70%. Tumor stem cells have been recently implicated in the pathogenesis of other heterogeneous, highly malignant tumors. We demonstrate here the existence of a small subpopulation of self-renewing bone sarcoma cells that are capable of forming suspended spherical, clonal colonies, also called “sarcospheres,” in anchorage-independent, serum-starved conditions. These bone sarcoma cells as well as tissue specimens express activated STAT3 and the marker genes of pluripotent embryonic stem (ES cells, Oct 3/4 and Nanog. Expression levels of Oct 3/4 and Nanog are greater in sarcospheres than in adherent cultures. A subset of bone sarcoma cells displays several surface markers of mesenchymal stem cells (Stro-1, CD105, and CD44 as well as attributes of mesodermal, ectodermal, and endodermal differentiation. Although previously documented in brain and breast tumors, our results support the extension of the cancer stem cell hypothesis to include tumors of mesenchymal lineage. Furthermore, they suggest the participation of ES cell homeobox proteins in non-germ cell tumorigenesis.

  17. Cancer incidence after retinoblastoma - Radiation dose and sarcoma risk

    NARCIS (Netherlands)

    Wong, FL; Boice, JD; Abramson, DH; Tarone, RE; Kleinerman, RA; Stovall, M; Goldman, MB; Seddon, JM; Tarbell, N; Fraumeni, JF; Li, FP

    1997-01-01

    Context.-There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy. Objective.-To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development.

  18. Poorly Differentiated Uterine or Cervical Sarcoma in a Young Dog

    Directory of Open Access Journals (Sweden)

    Michelle C. Cora

    2011-01-01

    Full Text Available A 1.5 year old, female, spayed, Labrador retriever with a history of three abdominal surgeries within the previous two months presented to the North Carolina State University Veterinary Teaching Hospital for evaluation of a pelvic inlet mass causing fecal tenesmus, obstipation, and dysuria. Abdominal ultrasound revealed a caudal abdominal mass extending into the pelvic cavity. Cytologic evaluation of the mass showed a pleomorphic round to fusiform cell population with histiocytic and suppurative inflammation. The primary differential was neoplasia, but inflammation with cellular pleomorphism could not be excluded. Via histopathology and immunohistochemistry, a diagnosis of poorly differentiated sarcoma originating from the uterus or cervix with widespread intra-abdominal dissemination and metastasis was made. Sarcomas of any type are rare in young dogs with only sporadic cases of poorly or undifferentiated sarcomas reported. This case is a unique presentation of an aggressive, poorly differentiated sarcoma arising from the cervix or uterus in a young dog and illustrates the importance of histologic evaluation of surgically resected tissues that are abnormal in appearance.

  19. A case of clear cell sarcoma-A rare malignancy

    DEFF Research Database (Denmark)

    Juel, Jacob; Ibrahim, Rami Mossad

    2017-01-01

    INTRODUCTION: Clear cell sarcoma (CCS) is a rare tumour of the soft tissue often misdiagnosed, as it shares characteristics with malignant melanoma (MM). Previously, CCS has been characterised, as malignant melanoma of the soft tissue, contemporary immunohistochemical techniques, however, have made...

  20. Carcinoma or Sarcoma of the Breast | Patnayak | Journal of Basic ...

    African Journals Online (AJOL)

    Carcinoma or Sarcoma of the Breast. ... She was a 62-year-old female who presented with complaint of pain and lump in left breast of 6 months duration. There was a discharging ulcer measuring 4 ×6 cm ... The IDC was estrogen and progesterone receptor negative and Human Epidermal Growth Factor -2 receptor positive.