WHAT IS THE ROLE OF HHV 8 IN ETIOPATHOGENESIS OF KAPOSI'S SARCOMA OCCURRED AFTER KIDNEY TRANSPLANTATION?

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) LANA is an 1,162-amino-acid protein that tethers terminal repeat (TR) DNA to mitotic chromosomes to mediate episome persistence in dividing cells. C-terminal LANA self-associates to bind TR DNA. LANA contains independent N- and C-terminal chromosome binding regions. N-terminal LANA binds histones H2A/H2B to attach to chromosomes, and this binding is essential for episome persistence. We now investigate the role of C-terminal chromosome binding in LANA function. Alanine substitutions for LANA residues 1068LKK1070 and 1125SHP1127 severely impaired chromosome binding but did not reduce the other C-terminal LANA functions of self-association or DNA binding. The 1068LKK1070 and 1125SHP1127 substitutions did not reduce LANA's inhibition of RB1-induced growth arrest, transactivation of the CDK2 promoter, or C-terminal LANA's inhibition of p53 activation of the BAX promoter. When N-terminal LANA was wild type, the 1068LKK1070 and 1125SHP1127 substitutions also did not reduce LANA chromosome association or episome persistence. However, when N-terminal LANA binding to chromosomes was modestly diminished, the substitutions in 1068LKK1070 and 1125SHP1127 dramatically reduced both LANA chromosome association and episome persistence. These data suggest a model in which N- and C-terminal LANA cooperatively associates with chromosomes to mediate full-length LANA chromosome binding and viral persistence.

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Role of Radiotherapy in Kaposi’s Sarcoma: Review of the Literature

Turkish Journal of Oncology ◽

10.5505/tjo.2021.2563 ◽

2021 ◽

Author(s):

ipek pınar aral

Keyword(s):

Kaposi's Sarcoma ◽

Kaposi’S Sarcoma ◽

Review Of The Literature

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Reactivation and role of HHV-8 in Kaposi's sarcoma initiation

Advances in Cancer Research ◽

10.1016/s0065-230x(01)81005-8 ◽

2001 ◽

pp. 161-200 ◽

Cited By ~ 54

Author(s):

Barbara Ensoli ◽

Michael Stürzl ◽

Paolo Monini

Keyword(s):

Kaposi's Sarcoma ◽

Kaposi’S Sarcoma

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Kaposi's Sarcoma in Young Patients Treated with Orthovoltage Irradiation and Having a Minimum Follow-Up of Forty-Six Years

Tumori Journal ◽

10.1177/030089160909500309 ◽

2009 ◽

Vol 95 (3) ◽

pp. 325-328 ◽

Cited By ~ 1

Author(s):

Stefano Pergolizzi ◽

Anna Santacaterina ◽

Michele Gaeta ◽

Alfredo Blandino

Keyword(s):

Renal Failure ◽

Radiation Therapy ◽

Chronic Renal Failure ◽

Clinical Outcome ◽

Kaposi's Sarcoma ◽

Young Patients ◽

Kaposi’S Sarcoma ◽

Orthovoltage Radiotherapy

Purpose To describe the clinical outcome and to evaluate the role of orthovoltage radiotherapy in the treatment of young (less than 30 years old) Mediterranean men with Kaposi's sarcoma. Patients and methods We reviewed the records of 198 consecutive patients with Kaposi's sarcoma treated with orthovoltage radiation therapy at our department between January 1920 and December 1987. Result We found three young shepherds, aged less than 30 years, with an available follow-up ranging from 45 to 67 years. One patient died at the age of 84 years of chronic renal failure while suffering from cutaneous Kaposi's sarcoma; two patients are still alive with recurrent Kaposi's sarcoma. Conclusions We presume that an indolent form of Kaposi's sarcoma may occur in young men. This very indolent form can be controlled for the duration of the patient's life by judiciously applied radiation therapy.

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Treatment of Kaposi's sarcoma after solid organ transplantation.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.6.2371 ◽

1997 ◽

Vol 15 (6) ◽

pp. 2371-2377 ◽

Cited By ~ 79

Author(s):

F A Shepherd ◽

E Maher ◽

C Cardella ◽

E Cole ◽

P Greig ◽

...

Keyword(s):

Kidney Transplantation ◽

Organ Transplantation ◽

Combination Chemotherapy ◽

Kaposi's Sarcoma ◽

Solid Organ Transplantation ◽

Kaposi’S Sarcoma ◽

Skin Toxicity ◽

Solid Organ ◽

Duration Of Response ◽

Italian Origin

PURPOSE This retrospective review of all patients who developed Kaposi's sarcoma (KS) after solid organ transplantation at a single institution was undertaken to define the clinical presentation of this malignancy in the setting of iatrogenic immunodeficiency, and to determine the most appropriate treatment for patients in this clinical setting. MATERIALS AND METHODS The records of 2,099 patients who underwent heart, lung, liver, or kidney transplantation at The Toronto Hospital between January 1, 1981 and June 30, 1995, were reviewed. Twelve patients were identified who developed biopsy-proven KS in the posttransplantation period. Five patients who had disseminated KS who had not responded to either reduction or withdrawal of immunosuppression or to local radiotherapy were treated with combination chemotherapy consisting of doxorubicin 20 to 30 mg/m2, bleomycin 10 mg/m2, and vincristine 2 mg (ABV) administered intravenously every 3 weeks. RESULTS Eight of 12 patients were male and nine were of Italian origin. KS was limited to a localized area of the skin for only six patients, all after kidney transplantation. Visceral KS was present in three patients. Four of five patients responded to ABV chemotherapy (two complete and two partial remissions). The fifth patient responded to second-line etoposide and cisplatin. The median duration of response was in excess of 13 months (range, 8+ to 45+ months). Toxicity was limited to grade 1 neurotoxicity and grade 1 skin toxicity. CONCLUSION KS is an uncommon but recognized complication of solid organ transplantation. Combination chemotherapy is a safe and effective treatment for patients with disseminated or visceral KS that fails to respond to changes in immunosuppression.

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