Targeted therapy for Kaposi sarcoma.
BioDrugs. 2009
Sullivan RJ, Pantanowitz L, Dezube BJ.
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Kaposi sarcoma (KS) occurs as a result of Kaposi sarcoma-associated herpesvirus (KSHV) infection, typically in the context of one of several immunodeficient states. In the US, patients with KS may either be co-infected with HIV or receiving immunosuppressant therapy following solid-organ transplantation. Systemic treatment of KS has traditionally involved one of several chemotherapeutic agents administered either in combination or as single agents, which typically provide reasonable response rates and short-term control. However, recurrence of KS is common, and progression-free intervals are under 1 year. For these reasons, new therapies have been sought and with the elucidation of novel pathogenic mechanisms of KS infection, rational therapeutic targets have been identified. These include KSHV replication, restoration of immune competence, and signal transduction pathways utilized by KSHV in the propagation of KS. This review focuses on these emerging targets in the treatment of patients with KS and also highlights important clinicopathologic characteristics.
PubMed
Monday, June 8, 2009
Tuesday, May 19, 2009
Kaposi's sarcoma-associated herpesvirus transmission and primary infection
Kaposi's sarcoma-associated herpesvirus transmission and primary infection
Curr Opin HIV AIDS. 2009 Jan
Bagni R, Whitby D.
Viral Oncology Section, AIDS and Cancer Virus Program, SAIC-Frederick, NCI-Frederick, Frederick, Maryland 21702, USA.
PURPOSE OF REVIEW: Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, is the causal agent of Kaposi's sarcoma, one of the commonest cancers in HIV-infected individuals. Transmission and risk factors for infection by KSHV are not fully understood. The purpose of this review is to highlight recent advances in our understanding of KSHV transmission in various settings.
RECENT FINDINGS: KSHV and HIV are both common in southern Africa where KSHV infection occurs during childhood via saliva. HIV infection is a major risk factor for KSHV infection. In developed countries, KSHV transmission among men who have sex with men is related to sexual risk factors such as number of sexual partners and to sexual practices involving saliva. KSHV can be transmitted by transfusion of infected blood, but storage of blood products diminishes the risk.
SUMMARY: Recent reports have provided much additional insight into KSHV transmission in different populations, but have also provided a number of important questions for the research and public health communities. Most critically, the role of HIV in increasing risk for KSHV infection and the possible effects on KSHV prevalence, and consequently the incidence of Kaposi's sarcoma warrants urgent further study.
Lippincott, Williams & Wilkins
Curr Opin HIV AIDS. 2009 Jan
Bagni R, Whitby D.
Viral Oncology Section, AIDS and Cancer Virus Program, SAIC-Frederick, NCI-Frederick, Frederick, Maryland 21702, USA.
PURPOSE OF REVIEW: Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, is the causal agent of Kaposi's sarcoma, one of the commonest cancers in HIV-infected individuals. Transmission and risk factors for infection by KSHV are not fully understood. The purpose of this review is to highlight recent advances in our understanding of KSHV transmission in various settings.
RECENT FINDINGS: KSHV and HIV are both common in southern Africa where KSHV infection occurs during childhood via saliva. HIV infection is a major risk factor for KSHV infection. In developed countries, KSHV transmission among men who have sex with men is related to sexual risk factors such as number of sexual partners and to sexual practices involving saliva. KSHV can be transmitted by transfusion of infected blood, but storage of blood products diminishes the risk.
SUMMARY: Recent reports have provided much additional insight into KSHV transmission in different populations, but have also provided a number of important questions for the research and public health communities. Most critically, the role of HIV in increasing risk for KSHV infection and the possible effects on KSHV prevalence, and consequently the incidence of Kaposi's sarcoma warrants urgent further study.
Lippincott, Williams & Wilkins
Dermoscopy of Kaposi's sarcoma: Areas exhibiting the multicoloured 'rainbow pattern'
Dermoscopy of Kaposi's sarcoma: Areas exhibiting the multicoloured 'rainbow pattern'
J Eur Acad Dermatol Venereol. 2009 Apr 10
Hu SC, Ke CL, Lee CH, Wu CS, Chen GS, Cheng ST.
Department of Dermatology.
Abstract Background Kaposi's sarcoma is a vascular tumour characterized by a proliferation of spindle cells and endothelial cells to form closely arranged slit-like vascular spaces. Currently, the definitive diagnosis of Kaposi's sarcoma relies on histology. The dermoscopic features of Kaposi's sarcoma are not clearly defined in the scientific literature. Objectives We seek to evaluate the dermoscopic features of Kaposi's sarcoma and compare them with other vascular tumours. Methods One hundred forty-one lesions from seven patients with histologically proven Kaposi's sarcoma were evaluated using polarized light dermoscopy for the presence of various dermoscopic features. Twenty patients with other vascular tumours were also examined. Results Dermoscopic examination revealed bluish-reddish coloration (84% of lesions), multicoloured areas showing various colours of the rainbow spectrum (36%), scaly surface (29%), and small brown globules (15%). The 'rainbow pattern' was found in six out of seven patients with Kaposi's sarcoma and was not observed in other vascular tumours. In addition, there was an absence of dermoscopic features specific for other vascular and non-vascular skin tumours, such as well-defined lacunae or structured vascular pattern, in most of the Kaposi's sarcoma lesions. Conclusions The most frequent dermoscopic patterns in Kaposi's sarcoma were found to be bluish-reddish coloration, the 'rainbow pattern', and scaly surface. The rainbow pattern is a dermoscopic feature which has not been previously described. We propose that dermoscopy, as an adjunct to clinical examination, may enhance accuracy in the preoperative diagnosis of Kaposi's sarcoma.
Conflicts of interest None declared
Wiley InterScience
J Eur Acad Dermatol Venereol. 2009 Apr 10
Hu SC, Ke CL, Lee CH, Wu CS, Chen GS, Cheng ST.
Department of Dermatology.
Abstract Background Kaposi's sarcoma is a vascular tumour characterized by a proliferation of spindle cells and endothelial cells to form closely arranged slit-like vascular spaces. Currently, the definitive diagnosis of Kaposi's sarcoma relies on histology. The dermoscopic features of Kaposi's sarcoma are not clearly defined in the scientific literature. Objectives We seek to evaluate the dermoscopic features of Kaposi's sarcoma and compare them with other vascular tumours. Methods One hundred forty-one lesions from seven patients with histologically proven Kaposi's sarcoma were evaluated using polarized light dermoscopy for the presence of various dermoscopic features. Twenty patients with other vascular tumours were also examined. Results Dermoscopic examination revealed bluish-reddish coloration (84% of lesions), multicoloured areas showing various colours of the rainbow spectrum (36%), scaly surface (29%), and small brown globules (15%). The 'rainbow pattern' was found in six out of seven patients with Kaposi's sarcoma and was not observed in other vascular tumours. In addition, there was an absence of dermoscopic features specific for other vascular and non-vascular skin tumours, such as well-defined lacunae or structured vascular pattern, in most of the Kaposi's sarcoma lesions. Conclusions The most frequent dermoscopic patterns in Kaposi's sarcoma were found to be bluish-reddish coloration, the 'rainbow pattern', and scaly surface. The rainbow pattern is a dermoscopic feature which has not been previously described. We propose that dermoscopy, as an adjunct to clinical examination, may enhance accuracy in the preoperative diagnosis of Kaposi's sarcoma.
Conflicts of interest None declared
Wiley InterScience
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. jcampo@odon.ucm.es
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
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. jcampo@odon.ucm.es
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]
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. noel.schartz@noos.fr
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
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. noel.schartz@noos.fr
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
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