mTOR inhibitors block Kaposi sarcoma growth by inhibiting essential autocrine growth factors and tumor angiogenesis.

Feb 2013

Roy D, Sin SH, Lucas AS, Venkataramanan R, Wang L, Eason A, Chavakula V, Tamburro KM, Hilton IB, Damania B,Dittmer DP.

Source

Lineberger Comprehensive Cancer Center, UNC Chapel Hill.

Abstract

Kaposi's Sarcoma (KS) originates from endothelial cells and it is one of the most overt angiogenic tumors. In Sub-Saharan Africa, where HIV and the Kaposi Sarcoma-associated Herpes Virus (KSHV) are endemic, KS is the most common cancer overall, but model systems for disease study are insufficient. Here we report the development of a novel mouse model of KS where KSHV is retained stably and tumors are elicited rapidly. Tumor growth was sensitive to specific allosteric inhibitors (rapamycin, CCI-779, RAD001) of the pivotal cell growth regulator mTOR. Inhibition of tumor growth was durable up to 130 days and reversible. mTOR blockade reduced VEGF secretion and formation of tumor vasculature. Together, the results demonstrated that mTOR inhibitors exert a direct anti-KS effect by inhibiting angiogenesis and paracrine effectors, suggesting their application as a new treatment modality for KS and other cancers of endothelial origin.

Full Text

Cancer Research

Do we still need chemotherapy for AIDS-associated Kaposi's sarcoma?

Feb 2013

Pria AD, Hayward K, Bower M.

Source

National Centre for HIV Malignancy, Chelsea & Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.

Abstract

The widespread introduction of effective combination antiretroviral therapy (cART) has had a major influence on the epidemiology and natural history of AIDS-associated Kaposi's sarcoma (AIDS-KS). cART has reduced the incidence of AIDS-KS, and it has been shown to be an effective treatment for early-stage KS. So with the widespread availability of cART, is systemic chemotherapy still required for AIDS-KS? Two indications appear to remain: advanced-stage AIDS-KS and patients who have progressive KS despite effective cART including immune reconstitution inflammatory syndrome KS.

Expert Reviews

Kaposi sarcoma.

Radu O, Pantanowitz L.

Source

From the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Abstract

Kaposi sarcoma (KS) is a low-grade vascular tumor associated with Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8) infection. Kaposi sarcoma lesions predominantly present at mucocutaneous sites, but may involve all organs and anatomic locations. Recognized epidemiologic-clinical forms of KS include classic, African (endemic), AIDS-associated (epidemic), and iatrogenic KS. New clinical manifestations have been described, such as antiretroviral therapy-related KS regression or flares. Kaposi sarcoma lesions evolve from early (patch stage) macules into plaques (plaque stage) that grow into larger nodules (tumor stage). Newer histologic variants include anaplastic, hyperkeratotic, lymphangioma-like, bullous, telangiectatic, ecchymotic, keloidal, pyogenic granuloma-like, micronodular, intravascular, glomeruloid and pigmented KS, as well as KS with sarcoidlike granulomas and KS with myoid nodules. Latency-associated nuclear antigen (HHV8) is the most specific immunohistochemical marker available to help distinguish KS from its mimics. Since KS remains one of the most common AIDS-defining malignancies, it is important that pathologists be able to recognize KS and its contemporary manifestations.

Archives of Pathology and Laboratory Medicine

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

2013

Kaasinen E, Aavikko M, Vahteristo P, Patama T, Li Y, Saarinen S, Kilpivaara O, Pitkänen E, Knekt P, Laaksonen M, Artama M, Lehtonen R, Aaltonen LA, Pukkala E.

Source

Genome-Scale Biology Research Program, and Department of Medical Genetics, Faculty of Medicine, University of Helsinki, Helsinki, Finland ; Haartman Institute, University of Helsinki, Helsinki, Finland.

Abstract

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. 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 found in this study. 

PubMed

Late post transplant HIV infection with BK viremia and allograft tuberculosis in a renal transplant recipient with Kaposi sarcoma.

Sep 2012

Viswanathan V, Kandasamy V, Reddy YN, Reddy YN, Kurien A, Mathew M, Abraham G.

Source

Department of Medicine and Tanker Foundation, Madras Medical Mission, Chennai, India.

Abstract

In this report, we discuss a case of a 51-year-old African renal transplant who presented with metastatic Kaposi sarcoma1 year after transplant. The Kaposi sarcoma was treated with a switch of immunosuppressants and chemotherapy. Six years after transplant, he presented with chronic allograft nephropathy, allograft tuberculosis, BK viremia, and was diagnosed to have contracted HIV infection.

Full text with images now available

PubMedCentral - Indian Journal of Nephrology

Microscopic diversity in oral Kaposi sarcoma.

Feb 2013

Bunn BK, Carvalho Mde V, Louw M, Vargas PA, van Heerden WF.

Source

Oral Pathologist, Department of Oral Pathology and Oral Biology, School of Dentistry, Faculty of Health Sciences, University of Pretoria, South Africa.

Abstract

Kaposi sarcoma is the most common HIV-associated neoplasm, frequently presenting with oral mucosal involvement. This retrospective study aimed to assess and highlight the histomorphological spectrum of oral Kaposi sarcoma. A total of 135 cases diagnosed between 1990 and 2011 were retrieved from the archives of the Oral and Dental Hospital of the University of Pretoria, South Africa. Following histologic review, each case was placed into 1 of 7 categories based on the predominant pattern of growth. These histologic divisions included lesions designated as solid, lymphangioma-like, telangiectatic, desmoplastic, lymphangiectatic, ecchymotic, and anaplastic. The presence of coexistent pathology was identified in 25 cases, largely represented by superimposed candidiasis. Concomitant cytomegalovirus and non-necrotizing granulomatous inflammation were also observed. Although the prognostic significance of these variants is yet to be determined, the appreciation and recognition of such morphologic diversity remains essential in distinguishing these lesions from possible mimickers.

Science Direct

Complete Response to Second Line Paclitaxel Every 2 Weeks of Eyelid Kaposi Sarcoma: A Case Report.

Dec 2012

Brunetti AE, Attilio G, Vito L, Carla M, Angela S, Ilaria M, Nicola S.

Source

*Scientific Direction, †Hematology Unit, ‡Medical and Experimental Oncology Unit, Cancer Institute "Giovanni Paolo II", Bari, Italy.

Abstract

A 77-year-old male patient presented to our attention with violaceous nodular lesions on the skin of his hands and lower extremities. Clinical and histologic examination supported the diagnosis of Kaposi sarcoma. A first-line systemic chemotherapy based on liposomal doxorubicin at a dosage of 40 mg/m every 3 weeks for 5 cycles was carried out, resulting in partial resolution of skin lesions. However, 1 year later, a relapse of the disease in the lower limbs and a new lesion of the left eyelid were found, therefore the patient began a second-line therapy with 100 mg/m paclitaxel every 2 weeks. After 8 cycles of therapy, we observed a complete remission of eyelid tumor and a partial response of lower limbs lesions up to 6 months of follow up. In conclusion, eyelid Kaposi sarcoma was successfully treated with paclitaxel every 2 weeks, obtaining a complete response.

Lippincott