Tuesday, December 30, 2008

The malignant potential of HIV-associated Kaposi sarcoma.

The malignant potential of HIV-associated Kaposi sarcoma.

Cancer Cell Int. 2008

Wood NH, Feller L.

ABSTRACT: Human herpesvirus (HHV)-8 associated oncogenesis, a state of immune impairment, a local inflammatory environment, angiogenesis and HIV infection occurring concurrently are important factors for the development of HIV-associated Kaposi sarcoma (KS). Activation of the interleukin (IL)-6 receptor signalling pathway and constitutive signalling of viral G protein-coupled receptor (vGPCR) play an important role in the activation, proliferation and transformation of HHV-8 infected endothelial cells thus contributing to the initiation and progression of KS. HIV-tat protein, HIV-induced immune suppression and a hyperinflammatory state facilitate the oncogenic activity of HHV-8. In this article we reviewed some aspects of HIV-KS pathogenesis and tried to establish, according to the available information in the literature, whether HIV-KS is a monoclonal neoplasm or a benign angioproliferative disorder. From the data of this review it is evident that most of the HIV-KS lesions are oligoclonal in origin. It remains to be demonstrated whether these multiple monoclonal populations of cells are neoplastic, harbouring specific cytogenetic alterations such as mutations, rearrangements and amplifications, or are, as the current evidence shows, the result of HHV-8 induced intracellular signalling pathways that modulate the expression of cellular genes associated with cell cycle regulation, apoptosis, inflammatory response and angiogenesis, and represent a reactive angioproliferative disorder.

Cancer Cell International

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

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

Med Oral Patol Oral Cir Bucal. 2008 Nov

Campo-Trapero J, Del Romero-Guerrero J, Cano-Sánchez J, Rodríguez-Martín C, Martínez-González JM, Bascones-Martínez A.
Departamento de Medicina y Cirugía Bucofacial, Facultad de Odontología, UCM. Avda Complutense s/n, 28080 Madrid, Spain.

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.

Oral Medicine

Imaging techniques for Kaposi's sarcoma.

Imaging techniques for Kaposi's sarcoma.
J HIV Ther. 2008 Sept

O'Mahony D, Gandjbakche A, Hassan M, Vogel A, Yarchoan R.
HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD, USA.

Kaposi[']s sarcoma (KS) is a multicentric tumour that most frequently involves the skin but can involve other tissues as well. Clinicians treating patients with KS or conducting clinical trials in this disease can benefit from imaging studies to document the extent of disease, to document changes with therapy, and to assess the extent of visceral and lymphatic involvement. A number of conventional techniques can be of use in meeting these needs, such as conventional light photography to assess skin or mucosal lesions, computed tomography of the chest to assess pulmonary disease, and magnetic resonance imaging. In addition, a number of techniques are being developed with the goals of providing improved differentiation of KS from other diseases or providing information about the degree of angiogenesis in the lesions and other physiological factors. We present here an overview of both established and experimental modalities of imaging in KS.

PMID: 19039297 [PubMed - in process]

Imiquimod 5% cream for treatment of HIV-negative Kaposi's sarcoma skin lesions: A phase I to II, open-label trial in 17 patients.

Imiquimod 5% cream for treatment of HIV-negative Kaposi's sarcoma skin lesions: A phase I to II, open-label trial in 17 patients.
J Am Acad Dermatol. 2008 Apr
Célestin Schartz NE, Chevret S, Paz C, Kerob D, Verola O, Morel P, Lebbé C.
Department of Dermatology 2, Hôpital Saint Louis AP-HP, Paris, France.

BACKGROUND: Kaposi's sarcoma (KS), a virus-associated neoplasm, can be treated locally or systemically with interferon alfa. Therefore, imiquimod, an immune response modifier able to induce interferon-alpha secretion in situ, could prove a good local treatment for KS skin lesions.

OBJECTIVE: We sought to determine the efficacy and safety of imiquimod 5% cream for the topical treatment of classic or endemic KS skin lesions in patients who are HIV negative.

METHODS: We conducted a prospective, open-label, single center, phase II clinical trial. Imiquimod cream was applied under occlusion 3 times a week for 24 weeks. The main efficacy end points were the safety of topical imiquimod and the overall clinical response in patients evaluated on the basis of modified AIDS Clinical Trials Group criteria at 36 weeks. The statistical analysis was based on the intent-to-treat data set.

RESULTS: Seventeen patients were enrolled. Eight (47%) presented objective overall clinical response (2 complete and 6 partial responses). Tumor progression was noted in 6 patients. The most frequent side effects were local itching and erythema, seen in 9 patients (53%).

LIMITATIONS: This was not a randomized placebo-controlled study and was restricted to a small number of patients.

CONCLUSION: Topical imiquimod 5% cream had antitumor activity in about half the patients with classic and endemic KS and was generally well tolerated.

Journal of American Academy of Dermatology

Classic Kaposi Sarcoma in the United States over the last two decades:

Classic Kaposi Sarcoma in the United States over the last two decades: a clinicopathologic and molecular study of 438 non-HIV-related Kaposi Sarcoma patients with comparison to HIV-related Kaposi Sarcoma.
Mod Pathol. 2008
Hiatt KM, Nelson AM, Lichy JH, Fanburg-Smith JC.
1Dermatopathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

Classic Kaposi sarcoma is rare and occurs predominantly in Mediterranean and Middle Eastern men. Since the emergence of acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma, the incidence, clinicopathologic features, and molecular human herpesvirus 8 (HHV-8) association of American Classic Kaposi Sarcoma has not been fully explored. This study compares Classic Kaposi Sarcoma to AIDS-related Kaposi Sarcoma over the same two decade time period. There were 438 histologically and clinically confirmed Classic Kaposi Sarcoma patients. The ethnic/racial distribution included Caucasian/American (56%), Mediterranean (22%), South American Hispanic (18%), Black (10%), western European (4%), Middle East (4%), Scandinavian (2%), and other (2%). Classic Kaposi Sarcoma was more common in men, 7:1, with a mean age of 74 years. The lesions presented in the lower extremity (69%), in the nodular stage (83%), and HHV-8 was detected by PCR in 40/41 randomly selected cases. A second, non-Classic Kaposi Sarcoma, malignancy was present in 42% (n=45) of the 108 Classic Kaposi Sarcoma patients with complete clinical information, 73% (33 patients) with a higher incidence over the general population. Follow-up of <1-19> revealed that 24% of patients died of second malignancy, 22% died of other medical conditions, 2% died of treatment-related complications, and 2% patients died of widespread disease. Thirty-five percent are alive with no evidence of disease and 15% with persistent disease. Human immunodeficiency virus-related Kaposi Sarcoma was observed in 354 cases. There was a male predominance and more aggressive behavior, with higher rates of visceral and disseminated disease. While Classic Kaposi Sarcoma in the United States is an indolent disease and rarely accounts for patient demise, predominantly affecting Caucasian/American males on the lower extremity in the nodular phase, it more importantly may denote an underlying other malignancy. Current PCR probes detect HHV-8 in 98% of Classic Kaposi Sarcoma cases. In comparison, AIDS-related Kaposi Sarcoma is predominately multicentric, visceral, and disseminated, with more aggressive behavior.


Linking the Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8) to Human Malignancies.

Linking the Kaposi's Sarcoma-Associated Herpesvirus (KSHV/HHV-8) to Human Malignancies.

Methods Mol Biol. 2009
Kalt I, Masa SR, Sarid R.
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.

In 1994, the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) was identified as the etiologic agent of Kaposi's sarcoma (KS). KSHV has since been associated with two additional malignancies: primary effusion lymphoma and multicentric Castleman's disease. In this chapter, we describe the current understanding of the pathogenesis, transmission, and prevalence of KSHV, and its association mainly with KS. We describe evidence demonstrating that KSHV is a causative agent for KS, and we present other factors that possibly contribute to the incidence of KS. We compare worldwide data on the prevalence of KS and of KSHV infection. Specific viral genes that may induce KS tumors or enable their growth also are described. Finally, we discuss the implications of the transmission modes and epidemiology of this virus on recommendations for KSHV screening of tissues and blood products before transplantation or transfusion.

Springer Link