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)

Isolated limb perfusion with melphalan is the treatment of choice for multiple (small) melanoma-in-transit metastases. The use of tumour necrosis factor alpha (TNFalpha) in isolated limb perfusion is successful for treatment of locally advanced limb soft-tissue sarcomas and other large tumours; this approach can avoid the need for amputation. TNFalpha was approved in Europe after a multicentre trial in patients with locally advanced soft-tissue sarcomas, deemed unresectable by an independent review committee; the response rate to isolated limb perfusion with TNFalpha plus melphalan was 76% and the limb was saved in 71% of patients. Moreover, the trial showed the efficacy of isolated limb perfusion of TNFalpha and melphalan against various other limb-threatening tumours such as skin cancers and drug-resistant bony sarcomas. Laboratory models of isolated limb perfusion have helped to elucidate mechanisms of action and to develop new treatment modalities. They have identified TNFalpha-mediated vasculotoxic effects on the tumour vasculature and have shown that addition of TNFalpha to the perfusate results in an increase of three to six times in uptake of melphalan or doxorubicin by tumours. New vasoactive drugs and new mechanisms of action are being discovered. Moreover, isolated limb perfusion is an effective modality for gene therapy mediated by an adenoviral vector. Various clinical phase I-II studies can be expected in the next few years.
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PMID:Current uses of isolated limb perfusion in the clinic and a model system for new strategies. 1285 Jan 94

We report two patients with leptomeningeal metastases from squamous cell cancer of the skin. In one patient cauda equina metastases appeared 6 years after initial presentation; the tumor from radical neck dissection demonstrated perineural invasion suggesting a possible route for subarachnoid dissemination. The other patient presented 2 years after initial diagnosis with confusion and cranial nerve seven and twelve palsies. Both patients died from complications of leptomeningeal metastases.
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PMID:Leptomeningeal metastases from recurrent squamous cell cancer of the skin. 1289 36

Dermatofibrosarcoma protuberans is a rare soft tissue cancer of the skin with the potential for intermediate malignity, characterized by local invasion and recurrence. Presenting with local atrophic and sometimes erythematous plaques, these lesions are best treated with surgery in which large excisions are necessary to reduce the risk of recurrence and to prevent rarely seen metastases. We report on a 26-year-old female patient with dermatofibrosarcoma protuberans on her breast, an very unusual site. As a novel surgical approach to treat the patient's tumor, a keyhole pattern was used, allowing wide safety margins during resection, while preserving the cosmetic appearance of the breast.
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PMID:Dermatofibrosarcoma protuberans of the breast. 1462 60

Cutaneous malignant melanoma remains the leading cause of skin cancer death in industrialized countries. Clinical and histological variables that predict survival, such as Breslow's index, tumor size, ulceration, or vascular invasion have been identified in malignant melanoma. Nevertheless, the potential relevance of biological variables still awaits an in-depth exploration. Using tissue microarrays (TMAs), we retrospectively analyzed 165 malignant melanoma samples from 88 patients corresponding to distinct histological progression phases, radial, vertical, and metastases. A panel of 39 different antibodies for cell cycle, apoptosis, melanoma antigens, transcription factors, DNA mismatch repair, and other proteins was used. Integrating the information, the study has identified expression profiles distinguishing specific melanoma progression stages. Most of the detected alterations were linked to the control of cell cycle G1/S transition; cyclin D1 was expressed in radial cases 48% (12 of 25) with significant lost of expression in vertical cases 14% (9 of 65), P = 0.002; whereas p16(INK4a) (89% in vertical versus 71% in metastatic cases, P = 0.009) and p27(KIP1) (76% in radial versus 45% in vertical cases, P = 0.010) were diminished in advanced stages. The study also defines a combination of biological markers associated with shorter overall survival in patients with vertical growth phase melanoma, that provided a predictor model with four antibodies (Ki67, p16(INK4a), p21(CIP1), and Bcl-6). This predictor model was validated using an independent series of 72 vertical growth phase melanoma patients.
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PMID:Progression in cutaneous malignant melanoma is associated with distinct expression profiles: a tissue microarray-based study. 1469 33

Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma. It has a propensity for both locoregional and distant recurrence despite treatment. We describe the case of a 51-year-old man diagnosed with MCC of the left forehead. At 14 months post surgery and adjuvant radiotherapy he developed an isolated deposit of metastatic MCC in the paraspinal soft tissues of his lower back. This atypical site of metastatic disease was treated with radiotherapy and combination chemotherapy. Atypical and isolated sites of metastatic MCC, although infrequently reported, highlight the often bizarre nature of this aggressive skin cancer. Treatment in such cases needs to be individualized.
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PMID:Metastatic Merkel cell carcinoma to the soft tissues of the lower back. 1496 7

Cutaneous metastases from internal malignancies or primary skin cancers are uncommon, particularly in a grouped pattern. We report a 58-year-old man with a known case of laryngeal squamous cell carcinoma who underwent radiotherapy after surgical excision of the tumor. Unilateral, grouped, red-brown, vesicle-like nodules appeared on his shoulder 9 months after the laryngeal surgery. The pathologic diagnosis of an excised nodule was metastatic squamous cell carcinoma.
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PMID:Grouped skin metastases from laryngeal squamous cell carcinoma and overview of similar cases. 1499

Metastasis is the process by which a primary malignancy establishes distant and discontiguous disease. It is a dreaded and ominous event that usually portends a worse prognosis, with greater tissue destruction, organ dysfunction, and potential mortality. Fortunately, metastasis is a rare event for nonmelanoma skin cancers (NMSC). Basal cell carcinomas (BCC) comprise the vast majority of NMSC (60-80%) and have a metastasis rate of only 0.0028%. For squamous cell carcinomas (SCC), the rate of metastasis is 2-6% and rises with certain high-risk features. Malignant melanoma (MM) is perhaps the most feared among common skin malignancies. It has a marked propensity for metastasis, and deaths from MM far outnumber the combined mortalities of both BCC and SCC. The 5-year survival of localized stage IA melanoma is 95%. This decreases to 67% for nodal disease and less than 20% for distant metastasis. Even more aggressive than MM are rare cutaneous tumors, such as Merkel cell carcinoma and malignant fibrous histiocytoma. This chapter will discuss the mechanisms of metastasis as they apply to cutaneous malignancies, particularly melanoma.
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PMID:Mechanisms of metastasis. 1526 6

Melanoma is the most fatal skin cancer, often highly resistant to chemotherapy. Here we show that treatment with an 11-base DNA oligonucleotide homologous to the telomere 3' overhang sequence (T-oligo) induces apoptosis of several established human melanoma cell lines, including the aggressive MM-AN line, whereas normal human melanocytes exposed to the same or higher T-oligo concentrations show only transient cell cycle arrest, implying that malignant cells are more sensitive to T-oligo effects. When MM-AN cells were briefly exposed to T-oligo in culture and injected into the flank or tail vein of SCID mice, eventual tumor volume and number of metastases were reduced 85-95% compared with control mice. Similarly, T-oligos administered intralesionally or systemically selectively inhibited the growth of previously established MM-AN tumor nodules in the flank and peritoneal cavity by 85 to 90% without detectable toxicity. We previously showed that T-oligos act through ATM, p95/Nbs1, E2F1, p16INK4A, p53, and the p53 homologue p73 to modulate downstream effectors and now additionally demonstrate striking down-regulation of the inhibitor of apoptosis protein livin/ML-IAP. We suggest that T-oligo mimics a physiologic DNA damage signal that is frequently masked in malignant cells and thereby activates innate cancer prevention responses. T-oligos may provide a novel therapeutic approach to melanoma.
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PMID:Telomere-based DNA damage responses: a new approach to melanoma. 1533 80

Melanoma is the most lethal skin cancer. Most deaths from melanoma result from metastases. Semaphorins have been shown to inhibit neuronal and endothelial cell migration, but the effects of semaphorins on tumor metastasis have not been documented. We found that semaphorin 3F (SEMA3F) was markedly downregulated in highly metastatic human cell lines in vitro and in vivo, which suggested that it may be a metastasis inhibitor. Metastatic human melanoma cells were transfected with SEMA3F and implanted into mice; the resultant tumors did not metastasize. Rather, the primary tumors resembled benign nevi characterized by large areas of apoptosis, diminished vascularity, inhibition of hyperplasia in overlying epidermal cells, and encapsulated tumor borders delineated by thick layers of fibroblasts and collagen matrix. This phenotype is in stark contrast to highly invasive, vascular mock-transfected tumors. In vitro, tumor cells expressing SEMA3F had a diminished capacity to adhere and migrate on fibronectin. Consistent with semaphorin-mediated chemorepulsion of neurons, tumor cells expressing SEMA3F were chemorepulsive for vascular and lymphatic endothelial cells expressing neuropilin-2 (NRP2), a novel mechanism for a tumor angiogenesis inhibitor. The repulsive activity was abrogated by NRP2 RNA interference. Together these results indicate that SEMA3F is a potent metastasis inhibitor that targets both tumor and stromal cells and raise the possibility of SEMA3F having therapeutic potential.
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PMID:Semaphorin 3F, a chemorepulsant for endothelial cells, induces a poorly vascularized, encapsulated, nonmetastatic tumor phenotype. 1552 Aug 58

Merkel cell carcinoma (MCC) is a skin cancer arising from neurosecretory cells which take part in APUD system. In most cases it is locally growing tumor with significant tendency to local recurrences after surgery. The authors have described four cases MCC localised on the skin of the middle angle of the eye, lower eyelid, auricle and cheek, without nodal metastases. All patients have been surgery treated, in two cases reconstructive surgery was performed. Radiotherapy followed surgery was used for two patients. The authors have reported 5-year survival rate in 2 cases, 2-year disease-free rate and 18 month in other cases.
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PMID:[Merkel cell carcinoma of the head and neck]. 1573 53


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