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's sarcoma in pregnancy after initiation of highly active antiretroviral therapy: a manifestation of immune reconstitution syndrome.

Dec 2012

Adeyemo A, Wood C, Govind A.

Source

Department of Obstetrics and Gynaecology.

Abstract

A case of Kaposi's sarcoma (KS) presenting as an immune reconstitution inflammatory syndrome in pregnancy with conservative management is reported. Successful outcomes for mother and baby were achieved. HIV was diagnosed at antenatal booking and highly active antiretroviral therapy commenced at 20 weeks. Multiple lymphadenopathies developed two months later. Excision biopsy of a node confirmed KS. In the absence of advanced disease, she was managed conservatively until delivery. The placenta showed no evidence of KS or human herpes virus 8 (HHV-8). The baby had negative HIV and HHV-8 polymerase chain reaction tests at zero, six and 12 weeks of life. Six months postpartum, the KS had regressed and HHV-8 viral load was undetectable.

Full text

Int Journal of STD & AIDS

Kaposi's sarcoma: a computational approach through protein-protein interaction and gene regulatory networks analysis.

Dec 2012

Zaman A, Rahaman MH, Razzaque S.

Source

Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka, 1000, Bangladesh, aubhishek@gmail.com.

Abstract

Interactomic data for Kaposi's Sarcoma Associated Herpes virus (KSHV)-the causative agent of vascular origin tumor called Kaposi's sarcoma-is relatively modest to date. The objective of this study was to assign functions to the previously uncharacterized ORFs in the virus using computational approaches and subsequently fit them to the host interactome landscape on protein, gene, and cellular level. On the basis of expression data, predicted RNA interference data, reported experimental data, and sequence based functional annotation we also tried to hypothesize the ORFs role in lytic and latent cycle during viral infection. We studied 17 previously uncharacterized ORFs in KSHV and the host-virus interplay seems to work in three major functional pathways-cell division, transport, metabolic and enzymatic in general. Studying the host-virus crosstalk for lytic phase predicts ORF 10 and ORF 11 as a predicted virus hub whereas PCNA is predicted as a host hub. On the other hand, ORF31 has been predicted as a latent phase inducible protein. KSHV invests a lion's share of its coding potential to suppress host immune response; various inflammatory mediators such as IFN-γ, TNF, IL-6, and IL-8 are negatively regulated by the ORFs while Il-10 secretion is stimulated in contrast. Although, like any other computational prediction, the study requires further validation, keeping into account the reproducibility and vast sample size of the systems biology approach the study allows us to propose an integrated network for host-virus interaction with good confidence. We hope that the study, in the long run, would help us identify effective dug against potential molecular targets.

SpringerLink

Eosinophilic panniculitis presenting with Kaposi's sarcoma-like plaques in a patient who is human immunodeficiency virus positive: a case report.

Nov 2012

Ustuner P, Dilek N, Saral Y, Dilek AR, Bedir R.

Abstract

INTRODUCTION: Eosinophilic panniculitis is an unusual type of panniculitis characterized by a prominent infiltration of subcutaneous fat with eosinophils without an exact etiopathogenesis. To the best of our knowledge, up to now eosinophilic panniculitis has been described in only one previous case with human immunodeficiency virus disease in the literature.

CASE PRESENTATION:

Here we report the case of a 44-year-old Caucasian man, who is human immunodeficiency virus positive, diagnosed with eosinophilic panniculitis. A dermatological examination revealed multiple, confluent Kaposi's sarcoma-like purple colored, deep plaques and nodules on his right gluteal area and right thigh. The presence of the mixed inflammatory infiltrate of lymphocytes, macrophages, and numerous eosinophils involving both septa and lobules of the subcutis were noted on the histopathological examination. On the basis of all these clinical and histopathological findings the patient was diagnosed with eosinophilic panniculitis. He was given intravenous 60mg/day methylprednisolone for 3 consecutive days a week for 6 months. The lesions resolved almost completely after 6 months.

CONCLUSION:

The predominance of T helper-2 subset of T helper cells and the consequential increase in interleukin-5 cytokines accompanying peripheral eosinophilia and high serum immunoglobulin E levels may all be blamed for the development of eosinophilic panniculitis in our case study. As a result, we aim to emphasize that eosinophilic panniculitis should be kept in mind in the differential diagnosis of subcutaneous nodular lesions in patients who are human immunodeficiency virus positive. We also focus on the requirement of histopathological examination for the definitive diagnosis because the clinical features of eosinophilic panniculitis may easily be confused with Kaposi's sarcoma.

NIH/BioMed

Reactive Oxygen Species (ROS) are Induced by Kaposi's Sarcoma-Associated Herpesvirus Early During Primary Infection of Endothelial Cells to Promote Virus Entry.

Nov 2012

Bottero V, Chakraborty S, Chandran B.

Source

H. M. Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL.

Abstract

KSHV entry into human dermal microvascular endothelial cells (HMVEC-d), a natural in vivo target cell, via macropinocytosis is initiated through a multistep process involving binding of KSHV envelope glycoproteins with cell surface α3β1, αVβ3 and αVβ5 integrin molecules and tyrosine kinase EphrinA2 receptor followed by the activation of integrin-associated pre-existing signaling molecules such as FAK, Src, c-Cbl, PI3-K and Rho-GTPases. Many viruses, including KSHV, utilize cellular reactive oxygen species (ROS) for viral genomic replication and survival within host cells; however, the role of ROS on early events of viral entry and induction of signaling has not been elucidated. Here we show that KSHV induced ROS production very early during infection of HMVEC-d cells which was sustained over the observed 24 h post-infection. ROS induction was dependent on KSHV binding to the target cells since pretreatment of virus with heparin abolished ROS induction. Pretreatment of HMVEC-d cells with the antioxidant N-Acetyl-Cysteine (NAC) significantly inhibited KSHV entry and consequently gene expression without affecting virus binding. In contrast, H(2)O(2) treatment increased KSHV entry and infection. In addition, NAC inhibited KSHV infection induced translocation of αVβ3 integrin into lipid rafts, actin dependent membrane perturbations such as blebs observed during macropinocytosis and activation of EphrinA2 receptor, FAK, Src and Rac1 signal molecules. In contrast, H(2)O(2) treatment increased the activation of EphrinA2, FAK, Src and Rac1. These studies demonstrate that KSHV infection induces ROS very early during infection to amplify the signaling pathways necessary for its efficient entry via macropinocytosis in HMVEC-d cells.

PubMed

Fine-needle cytology of Kaposi's sarcoma in an intramammary lymphnode: report of one case.

Aug 2012

Fulciniti F, De Chiara A, Apice G, Petrillo A, Botti G, Feroce F, Mozzillo N.

Source

S.S.D. di Citopatologia, A.F. di Anatomia Patologica e Citopatologia, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy. f.fulciniti@istitutotumori.na.it

Abstract

Kaposi's sarcoma (KS) is the most common human immunodeficiency virus (HIV) infection disease-associated malignancy. It consists of an angiosarcomatous change of the epithelial and mucous membrane-associated connective tissue not only in various sites, for example, skin, gastrointestinal system, lungs, and so on, but may also involve nonepithelial organs, such as lymph nodes. An unusual localization of KS to an intramammary lymphnode is reported here. The patient, an HIV-negative 69-year-old woman with a clinical history of rheumatoid arthritis treated with hydrocortisone, had an 8-month pathological history of biopsy-proven Kaposi sarcoma of the skin with visceral extension (stomach and duodenum). The appearance of a well-defined 23 × 20 mm(2) breast nodule during chemotherapy elicited fine-needle cytology to exclude breast carcinoma. Surgical excision confirmed the cytopathological diagnosis of Kaposis's sarcoma.

Wiley Online Library

miRNAs and usRNAs Discovered in Kaposi's Sarcoma-associated Herpesvirus Virions.

Sept 2012

Lin X, Li X, Liang D, Lan K.

Source

Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.

Abstract

It is widely held that any given virus uses only one type of nucleic acids for genetic information storage. However, this consensus has been challenged a little bit by several recent studies showing that many RNA species are present within a range of DNA viruses that include Kaposi's sarcoma-associated herpesvirus (KSHV). RNAs extracted from purified DNA virus particles exhibit great diversity in terms of length, abundance, temporal expression, cellular localization, and coding capacity during viral infection. In addition to known RNA species, the current study showed that small regulatory RNAs were present in KSHV virion. A large number of viral and cellular miRNAs, as well as unusual small RNAs (usRNAs), were detected in KSHV virion by using deep sequencing. Both viral and host miRNAs detected in small RNAs extracted from KSHV virions were further shown to co-localize with KSHV virion directly by in situ hybridization (ISH)-electron microscopy (EM) (ISH-EM). Some of these miRNAs were differentially present in the host cells and KSHV virions, suggesting that they are not randomly present in KSHV virions. The virional miRNAs could be transported into host cells and they are biologically functional during de novo viral infection. Our study revealed miRNAs and usRNAs as a novel group of component in KSHV virion.

Journal of Virology

Myasthenia gravis developing in an HIV-negative patient with Kaposi's sarcoma.

Sept 2012

Mantero V, Mascolo M, Bandettini di Poggio M, Caponnetto C, Pardini M.

Source

Department of Neurosciences, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162, Milan, Italy, vittorio.mantero@ospedaleniguarda.it.

Abstract

Myasthenia gravis is a disorder of neuromuscular transmission caused by autoimmune mechanisms. We reported a possible association between seropositive myasthenia gravis and Kaposi's sarcoma in a HIV-negative subject and the observed interactions between the treatment regimen for these two conditions. A 62-year-old man came to our attention for ocular myasthenia gravis. He suffered from a classic form of Kaposi's sarcoma since about 1 year. When myasthenic symptoms worsened, the patient was started on prednisone and azathioprine. The patient had a significant worsening of Kaposi's sarcoma, so prednisone and azathioprine were reduced and he was treated with vinblastine, with improvement both in dermatologic than in neurological symptomatology. We propose some considerations: the potential correlation betweenKaposi's sarcoma and myasthenia gravis through immunological mechanism; myasthenia gravis as a paraneoplastic manifestation of Kaposi's sarcoma, and the role of an antitumoral agent as a treatment for both the conditions.

Springerlink

Non-HIV Kaposi's sarcoma: a review and therapeutic perspectives.

Sept 2012

Akasbi Y, Awada A, Arifi S, Mellas N, El Mesbahi O.

Source

Hassan II University Hospital, Medical Oncology Department, 19, rue Jebel Zalagh 2 Narjiss C, 30000 Fez, Morocco, University Libre of Brussels, Institut Jules-Bordet, Medical Oncology Clinic, Brussels, Belgium.

Abstract

"Classic" Kaposi's sarcoma (CKS) not related to HIV is a multifocal angioproliferative neoplasm that is linked to human herpesvirus. CKS is a cutaneous cancer frequently occurring with an indolent course. However, it can compromise the quality of life by causing pain, disfigurement and functional disability. For this reason, the main treatment goals are not only to reduce the cutaneous lesions but also to alleviate organ involvement and psychological stress by delaying disease progression and ultimately cure. This report summarizes systemic treatment options of CKS, including chemotherapy, immunotherapy and anti-HHV8 therapy. In addition, this review will focus on the recent understanding of carcinogenesis and consequently highlight potential "targeted" therapeutic interventions.

John Libbey Eurotext

Instigation of Notch signaling in the pathogenesis of Kaposi's sarcoma-associated herpesvirus and other human tumor viruses.

Oct 2012

Cheng F, Pekkonen P, Ojala PM.

Source

Institute of Biotechnology & Research Programs Unit, Genome-Scale Biology, University of Helsinki, PO Box 56 (Viikinkaari 9), 00014 University of Helsinki, Helsinki, Finland.

Abstract

The Notch pathway is a highly conserved signaling circuit with a critical role in cell-fate determination and tumor initiation. Notch is reported to regulate various key events in tumor progression, such as angiogenesis, maintenance of cancer stem cells, resistance to therapeutic agents and metastasis. This review describes the intimate interplay of human tumor viruses with the Notch signaling pathway. Special attention is paid to Kaposi's sarcoma-associated herpesvirus, the etiological agent of Kaposi's sarcoma and rare lymphoproliferative disorders. The past decade of active research has led to significant advances in understanding how Kaposi's sarcoma-associated herpesvirus exploits the Notch pathway to regulate its replication phase and to modulate the host cellular microenvironment to make it more favorable for viral persistence and spreading.

Future Medicine

Dermoscopic Rainbow Pattern in Kaposi's Sarcoma Lesions: Our Experience

Oct 2012

Rosanna Satta, MD; Leonardo Fresi, MD; Francesca Cottoni, PhD

Arch Dermatol. 2012;148(10):1207-1208. doi:10.1001/archdermatol.2012.2204.

Cheng et al were the first to define the multicolored areas in some Kaposi's sarcoma (KS) lesions observed under polarized-light dermoscopy as rainbow pattern and to describe this dermoscopic feature as specific but not sensitive for the diagnosis of KS. Their observation prompted several interesting discussions in the dermoscopic literature. In our clinical practice, we have observed a high number of classic KS (CKS) cases. Dermoscopic examination of all the KS lesions in a group of patients with CKS was performed to evaluate the sensitivity of the rainbow pattern feature observed in the different clinical types of KS lesions.

Archives of Dermatology

The Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein and Its Multiple Roles in mRNA Biogenesis.

Jackson BR, Noerenberg M, Whitehouse A.

Source

Institute of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds Leeds, UK.

Abstract

Post-transcriptional events which regulate mRNA biogenesis are fundamental to the control of gene expression. A nascent mRNA is therefore steered through multimeric RNA-protein complexes that mediate its capping, splicing, polyadenylation, nuclear export, and ultimately its translation. Kaposi's sarcoma-associated herpesvirus (KSHV) mRNA transport and accumulation protein, or ORF57, is a functionally conserved protein found in all herpesviruses which plays a pivotal role in enhancing viral gene expression at a post-transcriptional level. As such, ORF57 has been implicated in multiple steps of RNA biogenesis, including augmenting viral splicing, protecting viral RNAs from degradation to enhancing viral mRNA nuclear export and translation. In this review, we highlight the multiple roles of KSHV ORF57 in regulating the post-transcriptional events which are fundamental to the control of virus gene expression.

Frontier in Virology

Simultaneous Breast Cancer and Kaposi's Sarcoma Complicating Rheumatoid Arthritis.

Sept 2011

Barak F, Reitblat T.

Source

Oncology Institute, Barzilai Medical Center, Ashkelon, Affiliated to the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.

Abstract

Key Words: Secondary cancers, Rheumatoid arthritis, Methotrexate, Vinorelbine, Kaposi's sarcoma

For a number of years we have been following the medical literature to find a relationship between chronic treatment with methotrexate and breast cancer occurrence, because we had had in our clinic a female patient who had had two consecutive cancers following methotrexate treatment for rheumatoid arthritis (RA). We were much surprised to find in some papers that breast cancer incidence is low in women with RA. Since then, we have found several papers explaining the low incidence of breast cancer among women being under NSAIDs, but those papers are not univocal. Methotrexate is a known antifolate agent and it has been demonstrated that dietary shortage of folate is a risk factor for breast cancer development.

PubMed - Karger

Kaposi's sarcoma: case report and treatment options.

Oct 2011

Tan WC, Chan LC.

Source

Department of Dermatology, Hospital Pulau Pinang, Penang, Malaysia. tanwooichiang@yahoo.com

Abstract

Kaposi's sarcoma (KS) is strongly associated with Human Herpes Virus 8 (HHV8) and Human Immunodeficiency Virus infection (HIV). It was the first malignancy to be linked with Acquired Immunodeficiency Syndrome (AIDS). We report a case of Kaposi's sarcoma in a newly diagnosed retroviral homosexual patient with CD4 count of 21. He had multiple firm discrete violaceous plaques and nodules scattered over the face, scalp, hard palate, trunk and genitalia. Biopsy of a skin nodule over the trunk and a biopsy of a lesion from the gastric mucosa confirmed Kaposi's sarcoma. He was started on Highly Active Antiretroviral Therapy (HAART) and cryotherapy (liquid nitrogen) was given for the lesions over the skin. He responded well to treatment. Liquid nitrogen is a useful adjuvant treatment for Kaposi's sarcoma.

PubMed

Kaposi's Sarcoma Associated Herpesvirus Entry into Target Cells.

2012

Chakraborty S, Veettil MV, Chandran B.

Source

H. M. Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science North Chicago, IL, USA.

Abstract

Herpesvirus infection of target cells is a complex process involving multiple host cell surface molecules (receptors) and multiple viral envelope glycoproteins. Kaposi's sarcoma associated herpesvirus (KSHV or HHV-8) infects a variety of in vivo target cells such as endothelial cells, B cells, monocytes, epithelial cells, and keratinocytes. KSHV also infects a diversity of in vitro target cells and establishes in vitro latency in many of these cell types. KSHV interactions with the host cell surface molecules and its mode of entry in the various target cells are critical for the understanding of KSHV pathogenesis. KSHV is the first herpesvirus shown to interact with adherent target cell integrins and this interaction initiates the host cell pre-existing signal pathways that are utilized for successful infection. This chapter discusses the various aspects of the early stage of KSHV infection of target cells, receptors used and issues that need to be clarified, and future directions. The various signaling events triggered by KSHV infection and the potential role of signaling events in the different stages of infection are summarized providing the framework and starting point for further detailed studies essential to fully comprehend the pathogenesis of KSHV.

Frontiers