Epidemiologic aspects of american kaposi's sarcoma

Laor, Yona; Schwartz, Robert A.

doi:10.1002/jso.2930120403

Cited by 56 publications

(24 citation statements)

References 8 publications

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“…Even though only two cases of KS were found among 5692 Scandinavian renal transplant recipients in a recent study (Birkeland et al, 1995), iatrogenic immune suppression, such as in organ transplant recipients, remains a well-established risk factor for KS (Kinlen, 1982;Penn, 1983;Quibini et al, 1988). Similarly, systemic corticosteroid treatment has been suggested to confer an increased risk of KS in non-transplant recipients (Klepp et al, 1978 (Laor and Schwartz, 1979;Friedman-Birnbaum et al, 1990;Kaldor et al, 1994;Grulich et al, 1992;DiGiovanna and Safai, 1981). Although an excess of immigrants has been observed among Danish patients with non-AIDS-related KS in the period (Hjalgrim et al, 1996), less than 5% of the Swedish and Norwegian cases of KS were diagnosed in persons of foreign descents (Dictor and Attewell, 1988;Harvei et al, 1990).…”

Section: Resultsmentioning

confidence: 99%

Epidemiology of Kaposi's sarcoma in the Nordic countries before the AIDS epidemic

Hjalgrim

Melbye²,

Pukkala³

et al. 1996

Br J Cancer

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Summary Based on data from the Nordic cancer registries, time-related trends in incidence of Kaposi's sarcoma (KS) were analysed in four ethnically similar populations before the AIDS epidemic. Data were available for different time periods in Denmark (1970-79), Sweden (1958-79), Finland (1953 and Norway (1953-79). KS was more common among men than among women aged 60 years or more, whereas no differences were observed for younger persons. The incidence of KS differed significantly between the four countries (P=0.0001); Sweden having the highest and Denmark the lowest rates. Similarly, regional differences in incidence were observed within Sweden, rates being higher in the northern than in the southern areas (Ptrend = 0.002). Overall, in Nordic men the world standardised incidence rose from 0.5/1 000 000 person -years in the period 1953-57 to 1.8/1 000 000 person-years in 1978-79; in Nordic women, the corresponding rates were 0.2/1 000 000 person-years and 0.8/1 000 000 person-years respectively. The rate of increase was similar in Sweden, Finland and Norway (P=0.14), whereas the short period of observation in Denmark precluded precise assessment of time-related incidence trends. These observations cannot be explained by registrational procedures or known risk factors for KS, and argue that environmental factors play an important role in the development of the disease.

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Section: Resultsmentioning

confidence: 99%

Epidemiology of Kaposi's sarcoma in the Nordic countries before the AIDS epidemic

Hjalgrim

Melbye²,

Pukkala³

et al. 1996

Br J Cancer

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“…Classic KS, which appears in the apparent absence of immunosuppression, occurs predominantly on the lower extremities of elderly men, a common site of poor circulation in the elderly. There is also an association of KS with diabetes, which is known to cause circulatory problems (19,33). In addition, KS occurs on the skin, another site where hypoxic conditions have been measured (2), and KS has been described at the site of a surgical wound, yet another hypoxic tissue (62).…”

Section: Discussionmentioning

confidence: 99%

Latent Kaposi's Sarcoma-Associated Herpesvirus Infection of Endothelial Cells Activates Hypoxia-Induced Factors

Carroll¹,

Kenerson

Yeung

et al. 2006

J Virol

102

113

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Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) is the etiological agent of Kaposi's sarcoma, a highly vascularized, endothelial-derived tumor. A direct role for KSHV-mediated induction of angiogenesis has been proposed based upon the nature of the neoplasia and various KSHV gene overexpression and infection model systems. We have found that KSHV infection of endothelial cells induces mRNA of hypoxia-induced factor 1␣ (HIF1␣) and HIF2␣, two homologous alpha subunits of the heterodimeric transcription factor HIF. HIF is a master regulator of both developmental and pathological angiogenesis, composed of an oxygensensitive alpha subunit and a constitutively expressed beta subunit. HIF is classically activated posttranscriptionally with hypoxia, leading to increased protein stability of HIF1␣ and/or HIF2␣. However, we demonstrate that both alpha subunits are up-regulated at the transcript level by KSHV infection. The transcriptional activation of HIF leads to a functional increase in HIF activity under normoxic conditions, as demonstrated by both luciferase reporter assay and the increased expression of vascular endothelial growth factor receptor 1 (VEGFR1), an HIF-responsive gene. KSHV infection synergizes with hypoxia mimics and induces higher expression levels of HIF1␣ and HIF2␣ protein, and HIF1␣ is increased in a significant proportion of the latently infected endothelial cells. Src family kinases are required for the activation of HIF and the downstream gene VEGFR1 by KSHV. We also show that KS lesions, in vivo, express elevated levels of HIF1␣ and HIF2␣ proteins. Thus, KSHV stimulates the HIF pathway via transcriptional up-regulation of both HIF alphas, and this activation may play a role in KS formation, localization, and progression.

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“…Although there are reports that advanced KS may involve a monoclonal proliferation, 42 the best available evidence suggests that spindle cell proliferation induced directly and/or indirectly by KSHV-encoded genes plays an important role in the development and progression of this condition. [43][44][45] Hypoxia-induced KSHV reactivation may contribute to the increased prevalence of KS in patients with diabetes mellitus, 46,47 as this condition is often associated with vascular disease and poor circulation. It may also contribute to the tendency of KS to occur on the lower legs, especially in the elderly men who develop classic KS.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induces lytic replication of Kaposi sarcoma–associated herpesvirus

Davis

Rinderknecht

Zoeteweij

et al. 2001

Blood

227

195

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There is substantial evidence that Kaposi sarcoma-associated herpesvirus (KSHV) plays an important role in the pathogenesis of all forms of Kaposi sarcoma (KS). It has been noted that KS commonly occurs in locations, such as the feet, where tissue may be poorly oxygenated. On the basis of this observation, the potential role of hypoxia in the reactivation of KSHV replication was explored by studying 2 KSHV-infected primary effusion lymphoma B-cell lines (BC-3 and BCBL-1) latently infected with KSHV. Acute and chronic exposure of these cells to hypoxia (1% O 2 ) induced KSHV lytic replication, as indicated by an increase in intracellular lytic protein expression and detection of virus in cell supernatants by Western immunoblotting. In addition, hypoxia increased the levels of secreted viral interleukin-6. Moreover, hypoxia enhanced the lytic replication initiated by the viral inducer 12-O-tetradecanoylphorbol-13-acetate. Desferoxamine and cobalt chloride, 2 compounds that increase the intracellular levels of hypoxia-inducible factor 1, were also able to induce KSHV lytic replication. These studies suggest that hypoxia is an inducer of KSHV replication. This process may play an important role in the pathogenesis of KS. ( IntroductionKaposi sarcoma (KS) is a multifocal proliferative disease of vascular origin. KS lesions are characterized by proliferation and growth of spindle-shaped neoplastic cells that appear to be of lymphatic endothelial cell origin. [1][2][3] KS is the most common neoplasm in human immunodeficiency virus type 1-infected individuals. 1 Even before the advent of acquired immunodeficiency syndrome (AIDS), KS was known to be more prevalent in certain geographic areas and groups of patients (classic and endemic KS). A classic form of KS is described as occurring in elderly men in southern Italy and other Mediterranean countries, 4 and an endemic form of KS has been observed to occur in sub-Saharan Africa. 5,6 In addition, transplant recipients and other immunosuppressed patients are at risk for developing KS. 4 Since the discovery of Kaposi sarcoma-associated herpesvirus (KSHV), also called human herpesvirus-8 (HHV-8), in 1994, 7 substantial evidence has been accumulated that implicates it as an essential factor in the pathogenesis of all forms of KS. 8,9 It is also involved in the pathogenesis of primary effusion lymphoma (PEL) and certain cases of multicentric Castleman disease. 10 KSHV DNA is detected in nearly all KS lesions. 7,11,12 As with other human herpesviruses, infection with KSHV can be latent or lytic. Activation of viral replication in latently infected B cells, endothelial cells, or other target cells may be responsible for viral spread and contribute to the development of KS. 4 KSHV encodes for several cellular gene mimics that are produced during lytic replication and that have proangiogenic activity. [13][14][15][16] The virus also encodes several cellular protein mimics with oncogenic potential, such as v-cyc, a D-type cyclin, and a member of the interferon regulatory factor ...

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Epidemiologic aspects of american kaposi's sarcoma

Cited by 56 publications

References 8 publications

Epidemiology of Kaposi's sarcoma in the Nordic countries before the AIDS epidemic

Epidemiology of Kaposi's sarcoma in the Nordic countries before the AIDS epidemic

Latent Kaposi's Sarcoma-Associated Herpesvirus Infection of Endothelial Cells Activates Hypoxia-Induced Factors

Hypoxia induces lytic replication of Kaposi sarcoma–associated herpesvirus

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