Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The melanocortin 1 receptor, a seven pass transmembrane G protein coupled receptor, is a key control point in melanogenesis. Loss-of-function mutations at the MC1R are associated with a switch from eumelanin to phaeomelanin production, resulting in a red or yellow coat colour. Activating mutations, in animals at least, lead to enhanced eumelanin synthesis. In man, a number of loss-of-function mutations in the MC1R have been described. The majority of red-heads (red-haired persons) are compound heterozygotes or homozygotes for up to five frequent loss-of-function mutations. A minority of redheads are, however, only heterozygote. The MC1R is, therefore, a major determinant of sun sensitivity and a genetic risk factor for melanoma and non-melanoma skin cancer. Recent work suggests that the MC1R also shows a clear heterozygote effect on skin type, with up to 30% of the population harbouring loss-of-function mutations. Activating mutations of the MC1R in man have not been described. The MC1R is particularly informative and a tractable gene for studies of human evolution and migration. In particular, study of the MC1R may provide insights into the lightening of skin colour observed in most European populations. The world wide pattern of MC1R diversity is compatible with functional constraint operating in Africa, whereas the greater allelic diversity seen in non-African populations is consistent with neutral predictions rather than selection. Whether this conclusion is as a result of weakness in the statistical testing procedures applied, or whether it will be seen in other pigment genes will be of great interest for studies of human skin colour evolution.
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PMID:The melanocortin 1 receptor (MC1R): more than just red hair. 1088 70

We report a case of primary melanoma of the thoracic spinal cord revealed by progressive bilateral lower extremity weakness associated with sensory loss and urinary dysfunction. The preoperative MRI revealed an intramedullary tumour from T7 to T9. Treatment was by complete surgical excision without radiotherapy. Histopathology and immuno-histochemical studies confirmed the diagnosis. The postoperative course was satisfactory with no sign of recurrence after 28 months of postsurgical follow-up. Primary spinal melanomas are rare intramedullary tumours that can be cured by appropriate surgical treatment.
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PMID:Primary spinal melanoma: case report. 1101 77

Toyocamycin and some analogues have shown potent antitumor activities; however, none of them could be used clinically primarily owing to their cytotoxicity to normal human cells. In order to overcome the weakness of these nucleoside analogues, substitution of a variety of modified sugars for the ribofuranose was explored in our laboratories with expectation that certain sugar-modified toyocamycin analogues may be selectively cytotoxic to cancer cells. In this article, we report synthesis and cytotoxicity of 4'-C- and 5'-C-substituted toyocamycins, which were prepared via the condensations of 4-C- and 5-C-substituted ribofuranose derivatives 11, 12, 13, 20, 21, and 26 with the silylated form of 4-amino-6-bromo-5-cyanopyrrolo[2,3-]pyrimidine (27) and subsequent debromination and debenzoylation. When compared to the parent toyocamycin, all these analogues showed much lower cytotoxicity to human prostate cancer cells (HTB-81), mouse melanoma cancer cells (B16) as well as normal human fibroblasts. Compound 1e showed a significant cytotoxicity to the prostate cancer cells and a moderate selectivity. The results suggested that sugar modifications, especially those that may affect phosphorylation of nucleosides, could alter cytotoxicity profile significantly.
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PMID:Synthesis and cytotoxicity of 4'-C- and 5'-C-substituted toyocamycins. 1119 36

Malignant melanoma is increasing in frequency at a rapid rate in the United States. Metastatic disease is chemoresistant with DTIC considered the most active single agent. CI-980 is a synthetic mitotic inhibitor that blocks the assembly of tubulin and microtubules. It has shown cytotoxic activity against a broad spectrum of murine and human tumor cell tines. CI-980 can cross the blood brain barrier, is effective when given orally or parenterally, and is active against multidrug resistant cell lines overexpressing P-glycoprotein. In this trial, patients with disseminated melanoma with measurable disease, SWOG performance status of 0-1, no prior chemotherapy or immunotherapy for metastatic disease, and adequate hepatic and renal function, were enrolled. Treatment with CI-980 was given by 72 h continuous i.v. infusion at a dose of 4.5 mg/m2/day, days 1-3 every 21 days. Twenty-four patients were registered on this study with no patients ineligible. They ranged in age from 33-78 with performance status of 0 in 15 patients and 1 in 9 patients. Nineteen patients had visceral disease with 12 having liver involvement. There were no confirmed responses. The overall response rate was 0% (95% CI 0%-14%). The median overall survival is eleven months (95% CI 4-14 months). The most common toxicities were hematologic and consisted of leukopenia/granulocytopenia and anemia, with nausea/vomiting and malaise/fatigue/weakness also frequent. CI-980 administered at this dose and schedule has insufficient activity in the treatment of disseminated malignant melanoma to warrant further investigation.
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PMID:Phase II trial of CI-980 in patients with disseminated malignant melanoma and no prior chemotherapy. A Southwest Oncology Group study. 1156 81

Mucosal melanoma of the sinonasal tract is an uncommon clinical entity, which frequently presents in advanced stages and follows an unpredictable course. We describe a case of a 97-year-old white female who presented with a 5-month history of painless, intermittent epistaxis and who was found to have melanoma involving the right inferior turbinate. She required operative intervention because of chronic epistaxis that had resulted in anemia and weakness. The case is presented along with a review of the pertinent literature. The dilemmas involved in the clinical decision-making process and treatment of malignancy in the elderly patient are discussed. In general, treatment outcomes in cases of mucosal melanoma are poor despite combination therapy, and quality-of-life issues become as important as attempts at complete extirpation.
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PMID:Mucosal melanoma of the sinonasal tract. 1223 3

Malignant melanoma metastases in the gastrointestinal tract (GIT) are found in more than 60% of autopsies on patients who have died with disseminated melanoma; however, the rate of GIT metastases detected clinically averages only 2%. This discrepancy seems to be attributed to the nonspecific symptoms and signs of GIT involvement, which include weakness, fatigue, bleeding, anemia, and abdominal pain. Sometimes a diagnosis is only made when bowel obstruction occurs. We report a case of long-term survival after surgery for multiple melanoma metastases in the gastrointestinal tract and review the relevant literature. Both our case report and the literature review demonstrate the benefits of surgery for patients with melanoma metastases in the GIT. We also stress the need for meticulous follow-up, detailed history-taking, and rapid evaluation of any vague and unclear abdominal signs and symptoms for patients with melanoma.
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PMID:Gastrointestinal metastases from malignant melanoma: report of a case. 1517 May 54

Our case-review studies an unusual case of occult bleeding from the cephalad portion of the digestive tube, caused by a metastasis of the malignant melanoma in the gastric corpus. The worldwide rates of patients with confirmed metastatic affections of the abdominal cavity, reaches only 2%. On the contrary, in 60% patients who died in consequence with malignant melanoma generalization, sections revealed metastases to the gastrointestinal tract. Unspecific symptoms, most frequently general weakness, tiredness, unspecific pains, anaemia and sometimes difficult decision-making, are among the suspected causes of poor diagnostic outcomes. Our case-review and collected literature data have confirmed positive effects of surgery on condition of patients with metastatic affections of the gastrointestinal tract.
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PMID:[The malignant melanoma metastasis into the stomach corpus]. 1593 80

We report a 54-year-old patient with a complaint of weakness, abdominal pain and weight loss. During the clinical examination a palpable tumor resistance in the abdomen was found as well as iron deficiency anemia. Gastroscopy showed an exulcerated, dark brown, fungiform tumor about 4 cm in diameter at the great curve of stomach. Endoscopic biopsy revealed the diagnosis of malignant melanoma by demonstrating the presence of melanin containing tumor cells in gastric mucosa. The patient underwent subtotal gastrectomy, appendectomy and splenectomy. The diagnosis of gastric melanoma with regional lymph node metastases, as well as metastases in appendix adjacent tissue was confirmed by histology and immunohistochemistry. In three years follow up period patient developed cerebral and retroauricular subcutaneous metastases that were treated by surgery, adjuvant chemotherapy and radiotherapy. Finally, an explorative laparatomy was revealed advanced intraabdominal tumor dissemination with dark pigmented ascites. Concerning that all available diagnostic procedures failed to prove other site of melanoma, presented case was considered as primary gastric melanoma as a possible rare site of tumor.
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PMID:Primary malignant melanoma of the stomach. 1594 53

Tumor-induced skeletal muscle wasting (SMW) contributes to the fatigue and weakness experienced by persons with cancer cachexia. Tumor necrosis factor-alpha (TNFa) and cyclooxygenase (COX) activity have been implicated in SMW in some animal models of cancer cachexia. We report that indomethacin, a nonspecific inhibitor of COX, and NS398, a specific inhibitor of COX2, preserved muscle mass and reduced type 1 TNF receptors in muscles of mice bearing the Lewis lung carcinoma, but not in mice bearing the B16 melanoma. These data suggest that tumor-induced SMW can occur via a COX2-independent pathway. The COX2-dependent pathway may involve reducing the catabolic effects of TNFa in muscle. Further study is needed to understand the relationship between COX and SMW, and whether patients with cancer cachexia might benefit from COX inhibitors.
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PMID:Inhibitors of COX activity preserve muscle mass in mice bearing the Lewis lung carcinoma, but not the B16 melanoma. 1653 83

A 35-year-old woman presented with one month's history of progressive bilateral leg weakness and altered sensation. There had been no pain. She had noted urinary frequency and constipation in the previous two weeks. On examination, the patient had diffuse lower extremity weakness (2-3/5), with a T6 sensory level to pain and temperature sensation. MRI demonstrated a T4-5 intradural mass ventral to the spinal cord, with an enhancing dural tail, consistent with meningioma. At surgery an intradural, extramedullary, firm, black neoplasm was encountered, which invaded the ventral dura and elevated and distorted the spinal cord. The mass was removed, leaving only microscopic invasion of the ventral dura. There was no bone invasion. Serial sections revealed a homogeneous black tumor without necrosis. H&E stained sections showed an occasionally fascicular tumor of melanocytes and small round blue tumor spindle cells with melanin pigmentation and 1-2 mitotic figures per 10 high-powered fields. The nuclei are generally oval-shaped and elongated, with prominent nucleoli. Necrosis, hemorrhage, and nuclear and cellular pleomorphism are not present and mitotic figures are rare. Immunohistochemical staining was positive for S-100 and HMB-45. MIB-1 labeling averaged 1-2%. A diagnosis of primary meningeal melanocytic tumor was made. Primary meningeal melanocytic tumors (PMMTs) are rare; fewer than 100 cases have been described. PMMTs of the CNS consist of a spectrum of tumors ranging from well-differentiated melanocytoma to its overtly malignant counterpart, melanoma. Intermediate grade melanocytomas (IMGs) are the least common variant, comprising about 10% of PMMTs reported. IGMS occur in the spinal leptomeninges and intracranially in approximately equal proportions. IGMs are more cellular than the well-differentiated variant, with 1-3 mitotic figures per 10 HPFs and MIB-1 labeling of <6%. By contrast, melanomas contain more mitotic figures (3-15 per 10 HPF) and MIB-1 labeling rates up to 15%. Once metastasis, including drop metastasis from pigmented medulloblastomas, have been excluded, the differential includes pigmented meningiomas and schwannomas (solitary or as part of Carney complex), as well as other pigmented CNS tumors such as ependymoma and pineoblastoma and systemic diseases such as lymphoma . . . For primary CNS melanocytic neoplasms, complete tumor resection is preferred, as it leads to cure of well-differentiated and intermediate-grade melanocytomas and most melanomas. Radiotherapy is recommended for incomplete resection of IMGs and melanomas; the recurrence potential of low-grade melanocytomas is less clear and watchful waiting may be employed, since recurrent tumors may be treated surgically prior to radiation. Two months after surgery, the patient had normal sensation and strength. She was given focused radiotherapy to the region of the ventral thecal sac to 40 cGy. At one year following surgery, the patient's neurological examination is normal and she remains free of residual disease by MR examination.
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PMID:35-year-old woman with progressive bilateral leg weakness. 1676 59


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