scholarly journals Lymphatic and vascular origin of Kaposi's sarcoma spindle cells during tumor development

2006 ◽  
Vol 119 (6) ◽  
pp. 1262-1267 ◽  
Author(s):  
Pawan Pyakurel ◽  
Fatemeh Pak ◽  
Amos. R. Mwakigonja ◽  
Ephata Kaaya ◽  
Thomas Heiden ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Tumor Development ◽  
Kaposi’S Sarcoma ◽  
Spindle Cells ◽  
Vascular Origin

scholarly journals 687. Iatrogenic Kaposi’s Sarcoma Following Treatment with Vedolizumab

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S397-S397
Author(s):  
Susanne O Ajao ◽  
Hamid Shaaban ◽  
Rajasingam Jayasingam
Keyword(s):  
Blood Cell ◽  
Cell Count ◽  
Kaposi's Sarcoma ◽  
Symptomatic Relief ◽  
Kaposi’S Sarcoma ◽  
Immunosuppressive Drugs ◽  
Lymph Node Biopsy ◽  
Human Herpes Virus 8 ◽  
Spindle Cells ◽  
Spindle Cell Proliferation

Abstract Background Kaposi’s sarcoma (KS) is a vascular tumor caused by human herpes virus-8 infection (HHV-8) commonly involving the skin. We report a case of a patient with controlled HIV who developed Kaposi’s sarcoma on vedolizumab. Darkened hyperkeratotic plaque on his left medial foot Methods A 39-year-old homosexual male with a history of Ulcerative Colitis (UC), Hodgkin’s lymphoma in remission and HIV presented with complaints of abdominal pain and bloody diarrhea. He had new tender lesions on his left foot which was absent at his previous admission a month ago. The lesions started as macules and later progressed to tender lesions. Mesalamine and oral corticosteroids were previously prescribed without symptomatic relief and he was started on vedolizumab 2 months ago. On physical exam he had abdominal tenderness, tender cervical and inguinal lymph nodes, and dark macules on his feet. Digital rectal exam revealed bloody mucoid stool. Laboratory showed white blood cell count of 12,600/mm3, ESR of 132 mm/hr and CRP of 4.6 mg/dL. His CD4 T-cell count was 873 cells/mm3 and viral load was 50 copies per milliliter. Cervical lymph node biopsy showed polymorphous population of lymphocytes but was negative for malignant cells. Biopsy of the foot plaques showed atypical intradermal vascular and spindle cell proliferation positive for HHV-8 and for vascular marker CD34. The results were consistent with the diagnosis of KS. Serology was also positive for HHV-8 with high viral titers of 74 copies/mL. Colonoscopy showed severe proctitis with deep ulcerations in a continuous pattern in the rectum with a normal sigmoid colon. Follow up colonoscopy showed improved proctitis and he was started on doxorubicin to treat KS with improvement of the foot lesion a month later following treatment. Dark macules on the sole of both feet Figure 3a: Spindle cells with irregular small vessel proliferation and red blood cell extravasation between tumor cells Figure 3b: Immunohistochemical stain showing HHV-8 expression of spindle cells Improvement of the foot lesion Results Vedolizumab is a monoclonal antibody that prevents the recruitment of lymphocytes to the inflamed tissue. It is approved for the treatment of IBD and has shown efficacy and safety. The iatrogenic form of Kaposi’s sarcoma occurs in patients on immunosuppressive therapy, as this patient. Conclusion Patients with IBD on immunosuppressive drugs should be followed up closely and screened for latent viral infections prior to initiating therapy. As in the patient, HHV-8 should be recognized as a likely underlying opportunistic infection in immunocompromised patients with IBD. Disclosures All Authors: No reported disclosures

scholarly journals Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Prolongs the Life Span of Primary Human Umbilical Vein Endothelial Cells

2003 ◽  
Vol 77 (11) ◽  
pp. 6188-6196 ◽  
Author(s):  
Takahiro Watanabe ◽  
Makoto Sugaya ◽  
April M. Atkins ◽  
Elisabeth A. Aquilino ◽  
Aparche Yang ◽  
...  
Keyword(s):  
Life Span ◽  
Kaposi's Sarcoma ◽  
Umbilical Vein ◽  
Kaposi’S Sarcoma ◽  
Nuclear Antigen ◽  
3T3 Cells ◽  
Spindle Cells ◽  
Umbilical Vein Endothelial Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT Tumor spindle cells in all clinical types of Kaposi's sarcoma (KS) are infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Although KSHV contains more than 80 genes, only a few are expressed in tumor spindle cells, including latency-associated nuclear antigen (LANA) and k-cyclin (kCYC). To assess the oncogenic potential of LANA and kCYC, primary human umbilical vein endothelial cells (HUVEC) and murine NIH 3T3 cells were stably transduced by using recombinant retroviruses expressing these genes or the known viral oncogene simian virus 40 large T antigen (LTAg). Interestingly, LANA-transduced HUVEC proliferated faster and demonstrated a greatly prolonged life span (mean ± standard deviation, 38.3 ± 11.0 passages) than untransduced cells and vector-transduced cells (<20 passages). By contrast, kCYC-transduced HUVEC did not proliferate faster or live longer than control cells. LANA- and kCYC-transduced HUVEC, but not LTAg-transduced HUVEC, retained the ability to form normal vessel-like structures in an in vitro model of angiogenesis. In cellular assays of transformation, LANA- and kCYC-transduced NIH 3T3 cells demonstrated minimal or no anchorage-independent growth in soft agar and no tumorigenicity when injected into nude mice, unlike LTAg-transduced NIH 3T3 cells. Lastly, gene expression profiling revealed down-regulation, or silencing, of a number of genes within LANA-transduced HUVEC. Taken together, these results suggest that KSHV LANA is capable of inducing prolonged life span, but not transformation, in primary human cells. These findings may explain why LANA-expressing spindle cells proliferate within KS tumors, yet most often do not demonstrate biologic characteristics of transformation or true malignant conversion.

scholarly journals Differential Expression of Viral Bcl-2 Encoded by Kaposi's Sarcoma-Associated Herpesvirus and Human Bcl-2 in Primary Effusion Lymphoma Cells and Kaposi's Sarcoma Lesions

2002 ◽  
Vol 76 (5) ◽  
pp. 2551-2556 ◽  
Author(s):  
Isabelle Widmer ◽  
Marion Wernli ◽  
Felix Bachmann ◽  
Fred Gudat ◽  
Gieri Cathomas ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Mononuclear Cells ◽  
Primary Effusion Lymphoma ◽  
Human Herpesvirus ◽  
Kaposi’S Sarcoma ◽  
Human Herpesvirus 8 ◽  
Lymphoma Cells ◽  
Herpesvirus 8 ◽  
Primary Effusion Lymphoma Cell ◽  
Spindle Cells

ABSTRACT Expression of human herpesvirus 8 viral Bcl-2 protein was demonstrated in spindle cells of late-stage Kaposi's sarcoma lesions but not in primary effusion lymphoma cell lines. In contrast, strong expression of human Bcl-2 was found in stimulated primary effusion lymphoma cells, whereas in Kaposi's sarcoma lesions preferential mononuclear cells, and to a lesser extent spindle cells, stained positive.

Expression of the fibroblast/macrophage marker 1B10 by spindle cells in Kaposi's sarcoma lesions and by Kaposi's sarcoma-derived tumor cells

2002 ◽  
Vol 29 (2) ◽  
pp. 72-78 ◽  
Author(s):  
◽  
Chantale Degraef ◽  
Michel Heenen ◽  
Philippe Hermans ◽  
Jean-Paul Van Vooren ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Macrophage Marker ◽  
Spindle Cells

scholarly journals Expression of Human Herpesvirus 8-Encoded Cyclin D in Kaposi's Sarcoma Spindle Cells

1997 ◽  
Vol 89 (24) ◽  
pp. 1868-1874 ◽  
Author(s):  
M. A. Davis ◽  
S. R. Opalenik ◽  
P. J. Browning ◽  
M. Sturzl ◽  
C. Blasig ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Human Herpesvirus ◽  
Kaposi’S Sarcoma ◽  
Human Herpesvirus 8 ◽  
Cyclin D ◽  
Herpesvirus 8 ◽  
Spindle Cells

scholarly journals Expression of HHV-8 latency-associated T0.7 RNA in spindle cells and endothelial cells of AIDS-associated, classical and African Kaposi's sarcoma

1997 ◽  
Vol 72 (1) ◽  
pp. 68-71 ◽  
Author(s):  
Michael Stürzl ◽  
Cornelia Blasig ◽  
Anneliese Schreier ◽  
Frank Neipel ◽  
Christine Hohenadl ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Spindle Cells

The Potential Role of Delta(9)-Tetrahydrocannabinol in the Pathogenesis of Kaposi’s Sarcoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1429-1429
Author(s):  
Xuefeng Zhang ◽  
Jian Feng Wang ◽  
George Kunos ◽  
Jerome E. Groopman
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
The United States ◽  
Calcium Flux ◽  
Inhibitory Effects ◽  
Kshv Infection ◽  
Spindle Cells ◽  
Low Concentrations ◽  
Cb2 Receptors ◽  
Cb1 And Cb2 Receptors

Abstract Kaposi’s sarcoma (KS) is a frequent neoplastic manifestation of immuno-compromised conditions such as AIDS and organ transplantation. The etiologic agent of the tumor is the KS-associated herpesvirus (KSHV), also known as human herpesvirus 8. Other factors, including HIV-1 Tat protein, may also contribute to the development and progression of KS in people with AIDS. Marijuana is the most commonly used illicit drug in the United States. In addition, its major active component, THC (Tetrahydrocannabinol), is prescribed for medicinal use. This includes treatment of HIV-related cachexia as well as pain and wasting in other immuno-compromised patients. However, relatively limited knowledge exists about the effects of cannabinoids on KS growth and spread. To investigate how cannabinoids may affect KS from the initiation of KSHV infection to proliferation of KS spindle cells, we first assessed whether KS spindle cells expressed cannabinoid receptors. The CB1 and CB2 receptors were detected on KS cells by flow cytometry. These receptors were found to be functional based on calcium flux upon ligand stimulation. We then sought to determine whether cannabinoids modulated viral entry. KSHV infection was quantitated in primary microvascular endothelial cells in the presence of a dose range of THC. We observed that low concentrations of Δ9-THC (less than 1 ng/ml) increased KSHV infection by about 30%. Higher concentrations of Δ9-THC induced significant cell death following KSHV exposure. Blocking of the CB1 and CB2 receptors had no effect on THC-modulated KSHV infection. We then studied the functional and biochemical changes in KS spindle cells after exposure to cannabinoids. We observed a dose-dependent inhibition of growth in these spindle cells in the presence of Δ9-THC. To elucidate the molecular mechanism of growth inhibition, we assayed signaling molecules involved in cell survival and proliferation. We found that Δ9-THC activated ERK1/2 MAP kinase and Akt, as well as VEGFR-2 and EGFR in KS spindle cells. High concentrations of Δ9-THC significantly inhibited VEGF-C and VEGF-D secretion but not VEGF-A production. Since KS is a vascular neoplasm and blockade of the CB1 and CB2 receptors did not antagonize the effects of Δ9-THC in KS, we investigated the activity of abn-cbd [(−)-4-(3-3, 4-trans-p-menthadien-[1, 8]-yl)-olivetol], a novel selective cannabinoid-like agonist specific for endothelium. Similar inhibitory effects in response to abn-cbd were observed in the KS spindle cells. These inhibitory effects were reversed by ARA-S (N-Arachidonoyl Serine) and O-1918 [(−)-4-(3-3, 4-trans-p-menthadien-(1, 8)-yl)-orcinol], specific antagonists of abn-cbd. These antagonists also reversed the reduction in VEGF-C and VEGF-D production. Taken together, our study indicates a biphasic effect of Δ9-THC, in that the cannabinoid may enhance KSHV infection at low concentrations, but inhibit KS spindle cell growth at higher concentrations. This modulation of KS cell function may involve a third putative receptor other than CB1 and CB2. Further knowledge regarding cannabinoid modulation of KS biology should allow for a greater understanding of the appropriate use of marijuana and its active constituents in immuno-suppressed hosts at risk for KS.

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