Nodular malignant melanoma and multiple cutaneous neoplasms under immunosuppression with azathioprine

Guenova, Emmanuella; Lichte, V.; Hoetzenecker, Wolfram; Woelbing, Florian; Moehrle, Matthias; Roecken, Martin; Schaller, Martin

doi:10.1097/cmr.0b013e32831bc44a

Cited by 14 publications

(9 citation statements)

References 17 publications

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“…As with our patient, donor transmission of melanoma generally presents in a metastatic fashion, sometimes with cutaneous manifestation or to other solid organs, but other times with miliary-like mucosal or peritoneal lesions [1, 2]. Recipients often die of complications related to uncontrolled metastatic disease [1, 3, 4]. …”

Section: Review Of the Literature And Discussionmentioning

confidence: 94%

Donor Transmission of Melanoma Following Renal Transplant

Chen

Olszanski

Farma

2012

Case Reports in Transplantation

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Donor transmission of melanoma is one of the more common and lethal of recipient malignancies, often presenting with systemic disease. Although some patients may receive durable remission of melanoma following explantation of the allograft and withdrawal of immunosuppression, donor transmission of melanoma is fatal in most patients. Here we present a case of a 44-year-old male who developed metastatic melanoma following renal transplant.

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Section: Review Of the Literature And Discussionmentioning

confidence: 94%

Donor Transmission of Melanoma Following Renal Transplant

Chen

Olszanski

Farma

2012

Case Reports in Transplantation

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“…For example, the nonsteroidal anti‐inflammatory drug diclofenac induces apoptosis in melanoma cell lines, 26 but induces clinical relapse in patients with IBD 27 . Conversely, the drug azathioprine used for treating IBD 21 increases the risk of melanoma in immunosuppressed patients 28 . Based on this anti‐correlation between melanoma and IBD, some drugs inducing one disease may be used to treat the other disease.…”

Section: Resultsmentioning

confidence: 99%

“…27 Conversely, the drug azathioprine used for treating IBD 21 increases the risk of melanoma in immunosuppressed patients. 28 Based on this anti-correlation between melanoma and IBD, some drugs inducing one disease may be used to treat the other disease. For example, drug hesperetin may be hypothesized to treat IBD which originally induces melanogenesis of murine melanoma cells.…”

Section: Case Studiesmentioning

confidence: 99%

Systematic Analysis of New Drug Indications by Drug‐Gene‐Disease Coherent Subnetworks

Wang

et al. 2014

CPT Pharmacom & Syst Pharma

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Drug targets and disease genes may work as driver factors at the transcriptional level, which propagate signals through gene regulatory network and cause the downstream genes' differential expression. How to analyze transcriptional response data to identify meaningful gene modules shared by both drugs and diseases is still a critical issue for drug-disease associations and molecular mechanism. In this article, we propose the drug-gene-disease coherent subnetwork concept to group the biological function related drugs, diseases, and genes. It was defined as the subnetwork with drug, gene, and disease as nodes and their interactions coherently crossing three data layers as edges. Integrating differential expression profiles of 418 drugs and 84 diseases, we develop a computational framework and identify 13 coherent subnetworks such as inflammatory bowel disease and melanoma relevant subnetwork. The results demonstrate that our coherent subnetwork approach is able to identify novel drug indications and highlight their molecular basis.

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“…thioguanine (TG), mercaptopurine, and azathioprine] have been commonly used in the treatment of cancer, autoimmune disorders, and in organ transplant. In each of these patient populations there have been a number of reports of cancer development after thiopurine therapy to include acute myeloid leukemias, lymphomas, and cancers of the skin and brain [8], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24]; although, the relevance of Tpmt status is not clear. However, in a study by Relling et al it was found that when patients were treated with antimetabolites (i.e.…”

Section: Introductionmentioning

confidence: 99%

Thiopurine Methyltransferase Predicts the Extent of Cytotoxicty and DNA Damage in Astroglial Cells after Thioguanine Exposure

et al. 2011

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Thiopurine methyltransferase (Tpmt) is the primary enzyme responsible for deactivating thiopurine drugs. Thiopurine drugs (i.e., thioguanine [TG], mercaptopurine, azathioprine) are commonly used for the treatment of cancer, organ transplant, and autoimmune disorders. Chronic thiopurine therapy has been linked to the development of brain cancer (most commonly astrocytomas), and Tpmt status has been associated with this risk. Therefore, we investigated whether the level of Tpmt protein activity could predict TG-associated cytotoxicity and DNA damage in astrocytic cells. We found that TG induced cytotoxicity in a dose-dependent manner in Tpmt+/+, Tpmt+/− and Tpmt−/− primary mouse astrocytes and that a low Tpmt phenotype predicted significantly higher sensitivity to TG than did a high Tpmt phenotype. We also found that TG exposure induced significantly more DNA damage in the form of single strand breaks (SSBs) and double strand breaks (DSBs) in primary astrocytes with low Tpmt versus high Tpmt. More interestingly, we found that Tpmt+/− astrocytes had the highest degree of cytotoxicity and genotoxicity (i.e., IC50, SSBs and DSBs) after TG exposure. We then used human glioma cell lines as model astroglial cells to represent high (T98) and low (A172) Tpmt expressers and found that A172 had the highest degree of cytoxicity and SSBs after TG exposure. When we over-expressed Tpmt in the A172 cell line, we found that TG IC50 was significantly higher and SSB's were significantly lower as compared to mock transfected cells. This study shows that low Tpmt can lead to greater sensitivity to thiopurine therapy in astroglial cells. When Tpmt deactivation at the germ-line is considered, this study also suggests that heterozygosity may be subject to the greatest genotoxic effects of thiopurine therapy.

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Nodular malignant melanoma and multiple cutaneous neoplasms under immunosuppression with azathioprine

Cited by 14 publications

References 17 publications

Donor Transmission of Melanoma Following Renal Transplant

Donor Transmission of Melanoma Following Renal Transplant

Systematic Analysis of New Drug Indications by Drug‐Gene‐Disease Coherent Subnetworks

Thiopurine Methyltransferase Predicts the Extent of Cytotoxicty and DNA Damage in Astroglial Cells after Thioguanine Exposure

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