Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The thiocarbamate alcoholism drug disulfiram blocks the P-glycoprotein extrusion pump, inhibits the transcription factor nuclear factor-kappaB, sensitizes tumors to chemotherapy, reduces angiogenesis, and inhibits tumor growth in mice. Thiocarbamates react with critical thiols and also complex metal ions. Using melanoma as the paradigm, we tested whether disulfiram might inhibit growth by forming mixed disulfides with critical thiols in a mechanism facilitated by metal ions. Disulfiram given to melanoma cells in combination with Cu2+ or Zn2+ decreased expression of cyclin A and reduced proliferation in vitro at lower concentrations than disulfiram alone. In electrophoretic mobility shift assays, disulfiram decreased transcription factor binding to the cyclic AMP-responsive element in a manner potentiated by Cu2+ ions and by the presence of glutathione, suggesting that thiocarbamates might disrupt transcription factor binding by inducing S-glutathionylation of the transcription factor DNA binding region. Disulfiram inhibited growth and angiogenesis in melanomas transplanted in severe combined immunodeficient mice, and these effects were potentiated by Zn2+ supplementation. The combination of oral zinc gluconate and disulfiram at currently approved doses for alcoholism also induced >50% reduction in hepatic metastases and produced clinical remission in a patient with stage IV metastatic ocular melanoma, who has continued on oral zinc gluconate and disulfiram therapy for 53 continuous months with negligible side effects. These findings present a novel strategy for treating metastatic melanoma by employing an old drug toward a new therapeutic use.
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PMID:Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease. 1536 99

Malignant melanoma is one of the most common malignancies to metastasize to the gastrointestinal (GI) tract. Metastases to the GI tract can present at the time of primary diagnosis or decades later as the first sign of recurrence. Symptoms may include abdominal pain, dysphagia, small bowel obstruction, hematemesis, and melena. We report 2 cases of malignant melanoma metastatic to the GI tract, followed by a review of the literature. The first case is a 72-year-old man who underwent resection of superficial spreading melanoma on his back 13 years previously who presented with dysphagia. A biopsy specimen of a mucosal fold in a gastric fundus noted during endoscopy was taken and revealed metastatic malignant melanoma, which was resected 1 month later. Three weeks later, the patient was found to have an ulcerated jejunal metastatic melanoma mass, which was also resected. The second case is a 63-year-old man with an ocular melanoma involving the chorold of the left eye that had been diagnosed 4 years previously, which had been excised several times, who presented with anorexia, dizziness, and fatigue. He was found to have cerebellar and stomach metastases. He underwent adjuvant radiation therapy, chemotherapy, and surgical resection of the gastric melanoma metastasis. In patients with a history of melanoma, a high index of suspicion for metastasis must be maintained if they present with seemingly unrelated symptoms. Diagnosis requires careful inspection of the mucosa for metastatic lesions and biopsy with special immunohistochemical stains. Management may include surgical resection, chemotherapy, immunotherapy, observation, or enrollment in clinical trials. Prognosis is poor, with a median survival of 4 to 6 months.
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PMID:Metastatic malignant melanoma of the gastrointestinal tract. 1661 May 71

The liver is the most common site of metastatic disease from both gastrointestinal and extra-intestinal malignancies. Historically, only a minority of patients with colorectal liver metastases were candidates for resection. However, over the past several decades, liver resection has evolved as a safe and potentially curative treatment for hepatic colorectal metastases. The development of active chemotherapy and molecular targeted therapies, together with newer modalities like radiofrequency ablation, have expanded the indications for hepatic resection and improved survival. Selected patients with isolated liver metastases from neuroendocrine tumors, germ cell cancers, ocular melanoma, gastrointestinal stromal tumors (GIST), and breast cancer also may be considered for hepatic surgery.
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PMID:Surgical therapy of liver metastases. 1756 Sep 79

The major approach to the development of anticancer drugs involves searching for new compounds, efficient against malignancies, which are not, as yet, used clinically. This strategy is time-consuming and expensive. Recent studies have disclosed a surprising, but mechanistically consistent, anticancer activity of disulfiram (antabuse), a drug used for about 50 years in the treatment of alcoholism. Disulfiram has been successfully used to suppress hepatic metastases originating from ocular melanoma. The pharmacokinetics of disulfiram and its pharmacological profile in cancer cell lines and in cancer cells obtained from patients is well known. Disulfiram is a readily available and inexpensive substance whose adverse effects are negligible, compared to classical cancerostatics. In addition, the inhibitory potency of disulfiram against the proteasome conforms to current anticancer strategies and represents a new, promising approach to proteasome inhibition.
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PMID:The value of proteasome inhibition in cancer. Can the old drug, disulfiram, have a bright new future as a novel proteasome inhibitor? 1857 31

Ocular melanoma has a strong tendency to metastasize often several years after its initial diagnosis was made. We report on the case of a 50-year-old woman who was treated 20 years earlier for an ocular melanoma and currently seen regularly in our institute for liver metastases that were treated by chemotherapy. After three treatments, a check-up with computed tomography demonstrated the presence of a right ovarian mass. An ovariectomy was performed, and the pathological examination confirmed the diagnosis of an ovarian metastasis from an ocular melanoma. This is the fourth case of metastasis to the ovary from an ocular melanoma reported in the medical literature.
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PMID:Ovarian metastasis from choroidal melanoma. 1860 89

Unresectable primary and metastatic cancers confined to the liver often determine the prognosis for patients with primary hepatic cancers, colorectal cancer, ocular melanoma, and neuroendocrine tumors. Although many locoregional therapies have emerged as options for patients with unresectable liver malignancies, these treatments frequently have limited clinical benefit. Isolated hepatic perfusion (IHP) has emerged as a regional therapy effective in inducing tumor regression in isolated liver metastases from multiple histologies. Tumor necrosis factor alpha (TNF) is a biologic agent well suited to isolated therapy because of its single-dose efficacy, synergistic effect with hyperthermia, and effects on tumor neovasculature. When combined with chemotherapeutic agents in IHP, TNF may improve response rates in patients with hepatic metastases of some histologies. However, there are additional toxicities associated with the administration of TNF and further studies are needed to determine whether TNF confers a clinical advantage in IHP.
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PMID:TNF-based isolated hepatic perfusion. 1927 61

Patients with malignant melanoma are at an increased risk of developing subsequent primary melanomas and also nonmelanoma cutaneous cancers. Several studies have reported an association between malignant melanoma and breast cancer, bladder cancer, colorectal cancer, neuroectodermal tumours, non-Hodgkin's lymphoma, leukaemia and renal cell carcinoma. We report a case series of patients with a diagnosis of malignant melanoma who also developed a renal mass. In two of these cases, the renal mass became apparent on diagnostic imaging as part of the staging investigations at the time of initial diagnosis of the malignant melanoma. In both of these cases, biopsy of the renal mass confirmed the presence of a separate primary renal cell carcinoma which had presented concurrently with the malignant melanoma. A third case presented with bone metastases ten years after excision of a thin melanoma. Further imaging revealed pulmonary metastases and a renal mass, biopsy of which confirmed renal cell carcinoma. In contrast, a fourth patient underwent a right nephrectomy for a renal mass having presented with abdominal discomfort. The histology of this lesion was in keeping with metastatic melanoma, and the patient's past history included a diagnosis of ocular melanoma eight years prior to the development of metastatic disease in the right kidney. Survival rates for patients with many types of malignant disease are improving, and there have been significant advances in clinical imaging techniques. Consequently the development and detection of a second primary cancer, either presenting concurrently or on subsequent follow-up, is likely to be increasingly observed. The series of patients reported here highlights the importance of a diagnostic biopsy in patients with malignant melanoma who develop a renal mass in order to establish a diagnosis and to plan optimal treatment.
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PMID:Coexistent malignant melanoma and renal cell carcinoma. 1985 67

The development of effective treatment strategies to provide durable control of isolated diffuse metastases to the liver is a major challenge in clinical oncology. The number of patients afflicted annually with isolated liver metastases is considerable; of the 156,000 patients diagnosed with colorectal cancer in 2009, it is estimated that up to 40,000 will develop liver metastases as the sole or dominant site of disease progression and of whom only 10% to 20% will have tumors amenable to resection. Patients with neuroendocrine cancers and ocular melanoma will frequently develop isolated and diffuse liver metastases as the dominant mode of tumor metastasis and, although less frequent, patients with other types of cancers such as cutaneous melanoma or breast cancer can occasionally develop isolated diffuse metastases to the liver.Isolated hepatic perfusion and percutaneous hepatic perfusion are under clinical evaluation for patients with diffuse isolated liver metastases from various solid organ cancers. Both share the advantages of intensifying treatment to the cancer-burdened organ of the body to improve efficacy and limit unnecessary systemic toxicity by selectively delivering high-dose therapeutic agents into the hepatic arterial system from which established metastases derive their predominant blood supply. In this article, we will review the history and early clinical development of isolated perfusion, the techniques of isolated hepatic perfusion and percutaneous hepatic perfusion, the current clinical results with isolation perfusion, and discuss the potential future clinical use of these approaches.
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PMID:Development of isolated hepatic perfusion via the operative and percutaneous techniques for patients with isolated and unresectable liver metastases. 2040 10

Selective Internal Radiation Therapy is a relatively new technique that irradiates malignant liver lesions using microscopic beads. It provides micro-embolization coupled with high-dose interstitial radiotherapy. Besides colorectal cancers, this therapy has shown benefit in patients with a variety of other tumors including carcinoid tumors, lung, breast, sarcoma, colon, hepatocellular and ocular melanoma. Its clinical benefit can be as much as 85%, survival can be doubled and patients with extensive colorectal metastases not amenable to resection or ablation can be offered a 32% chance of surviving for 18 months. Ongoing and future studies will refine our understanding of optimizing patient eligibility, dosage, frequency as well as novel applications.
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PMID:Selective internal radiation therapy: 90Y (yttrium) labeled microspheres for liver malignancies (primary and metastatic). 2133 Jul 50

Selective internal radiation therapy is a relatively new technique that irradiates primary and metastatic liver cancer using yttrium 90 microspheres. Increasing reports have shown this to be a useful treatment for unresectable primary hepatocellular carcinoma and others metastases from colon, lung, breast, sarcoma, and ocular melanoma. On the other hand, more and more therapy-related complications have been described. Since the morphologic description of injured organs are relatively uncommon, we report 2 cases of selective internal radiation therapy-related gastric injury, which represent basophilic round bodies in gastric biopsies little known by pathologists. The appearances in esophagogastroduodenoscopy include gastrointestinal ulcer, edema, and bleeding. Histological findings are mucosal atrophy, mild to moderate cytologic atypia, edema of the stroma, and inflammatory infiltration. The most characteristic feature is the presence of round blue and dark microspheres in the stromal blood vessels.
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PMID:Basophilic round bodies in gastric biopsies little known by pathologists: iatrogenic yttrium 90 microspheres deriving from selective internal radiation therapy. 2356 5


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