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)

Thirty-four patients with advanced malignant melanoma were treated with recombinant alpha-interferon (IFN) and chemotherapy consisting of carboplatin, vinblastine, and bleomycin (CVB). CVB was given for four cycles and IFN for 1 year or until progression. Of the 34 analyzed patients, 17 (50%) achieved an objective response, including two complete (6%) and 15 partial responses (44%). Responses were noted in cutaneous, lymph node, and pulmonary sites, with a median time to disease progression of 5 months (range, 3-20 months). The median survival from onset of therapy was 8 months (range, 1-22 months) for the 34 patients. Ninety-four percent of the patients experienced flu-like symptoms and 82% fatigue or weakness. Leukopenia grade 3-4 was observed in four patients (12%). There were two toxicity-related deaths (6%); one from bleomycin-induced pneumonitis and one from neutropenic sepsis. It is concluded that the addition of IFN to CVB regimen, in this study, showed no apparent advantage on response rates, disease-free interval, or survival. The observed treatment-related mortality was unacceptably high. IFN administered as maintenance therapy following CVB conferred no survival benefit.
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PMID:Recombinant interferon ALFA-2A in combination with carboplatin, vinblastine, and bleomycin in the treatment of advanced malignant melanoma. 863 45

We performed a phase Ia/Ib trial of chimeric anti-GD2 monoclonal antibody 14.18 (ch14.18) in combination with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to determine the maximum tolerated dose as well as immunologic and biologic responses to the regimen. Sixteen patients with metastatic malignant melanoma received escalating doses of ch14.18 (15-60 mg/m2) administered intravenously for 4 h on day 1. Twenty-four hours later, subcutaneous injections of rhGM-CSF were administered daily for a total of 14 days. Significant side effects were related to ch14.18 infusion and consisted of moderate to severe abdominal and/or extremity pain, blood pressure changes, headache, nausea, diarrhea, peripheral nerve dysesthesias, myalgias, and weakness. Dose-limiting toxicity was observed at 60 mg/m2 and consisted of severe hypertension, hypotension, and atrial fibrillation in one patient each, respectively. Significant increases in white blood cell count, granulocyte count, eosinophil count, and monocyte count occurred after rhGM-CSF treatment. Significant enhancement of in vitro and in vivo monocyte and neutrophil tumoricidal activity and antibody-dependent cellular cytotoxicity along with significant elevations in C-reactive protein and neopterin were observed. Despite these immunological and biological changes, no antitumor activity was seen. In short, the combination of ch14.18 and rhGM-CSF resulted in toxicity similar to that observed with ch14.18 alone without improvement in tumor response.
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PMID:Phase Ia/Ib trial of anti-GD2 chimeric monoclonal antibody 14.18 (ch14.18) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in metastatic melanoma. 881 95

Twenty-three patients with advanced melanoma were treated with a combination of subcutaneous recombinant human interleukin-2 (IL-2), and recombinant interferon alpha-2a (IFN-alpha) with chemotherapy consisting of four cycles of carboplatin (300 mg/m2, day 1) and vinblastine (6 mg/m2, day 1), every 28 days (CV-IL-IF). IL-2 was given at a dose of 4.5 x 10(6) U twice daily on days 3-6 and days 21-24 of each cycle; IFN-alpha dose was 4.5 x 10(6) U, starting on day 2, thrice weekly. Immunotherapy was intended to continue for 6 months. Of the 23 analyzed patients, 4 (17%) achieved an objective response, including 1 complete and 3 partial responses, in nonvisceral metastatic disease. The median time to progression was 5 months and the median survival from onset of the treatment 6 months (range 1-14 months). Four patients discontinued the treatment, due to nonhaematologic toxicity; 3 for severe weakness and the 4th patient for long-lasting CNS side-effects. Other grade 3-4 toxicities included weight loss (22%), nausea and vomiting (17%) and alopecia (13%). The haematologic toxicity was acceptable. No toxic death was noted. It is concluded that the CV-IL-IF regimen has limited activity and moderate toxicity.
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PMID:Subcutaneous low doses of interleukin-2 and recombinant interferon alpha with carboplatin and vinblastine in patients with advanced melanoma. 942 75

A 76-year old female patient with 9 year history of right mastectomy for an infiltrating ductal breast cancer and no evidence of recurrent nor metastatic disease, was admitted due to pain in the lower thoracic area radiating bilaterally to the posterior aspect of the chest wall at the same level, difficulties in micturition, urinary hesitancy, and progressive weakness of the lower limbs. Primary intramedullary spinal tumor was demonstrated by a MRI study of the spine, partially resected, and found to be a malignant melanoma on pathological study. Postoperative irradiation and administration of dexamethasone did not improve the neurologic status.
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PMID:Primary intramedullary spinal melanoma: diagnostic and treatment problems. 952 29

Amyloid deposition in skeletal muscle is a well-recognized but rare occurrence. Sixteen such cases seen in a 17-year period (1979 to 1996) out of a total of 3,937 muscle biopsy specimens (0.004%) form this study group. Either Congo red or sulfated alcian blue stains were routinely performed in each biopsy to screen for amyloid. Patients in this study (eight men, eight women) ranged in age from 42 to 90 years (mean, 61 years) at initial presentation. The most common symptoms at presentation included weakness/fatigue (n = 10), autonomic symptoms (n = 8), and weight loss/decreased appetite (n = 7). Five patients had a concomitant malignancy (myeloma, n = 3; malignant carcinoid tumor, n = 1; melanoma, n = 1). Two patients had known hereditary forms of amyloidosis. Five patients had amyloid diagnosed on another organ biopsy (excluding peripheral nerve). Histologically, amyloid was deposited in the interstitium or perivascular region in 14 muscles and endomysial region in seven muscles. All cases were confirmed with Congo red staining (apple green birefringence) or by electron microscopic identification of fibrillary amyloid material. Scattered angular atrophic esterase-positive muscle myofibers indicative of acute denervation atrophy were seen in 14 muscles. Eight muscles showed small group atrophy, and seven showed myofiber type grouping. Scattered regenerating muscle fibers were seen in nine cases, degenerating myofibers in six, and foci of chronic endomysial and perivascular inflammation in two. Four muscles showed type II muscle fiber atrophy. A concomitant sural nerve biopsy specimen was evaluated in seven patients; all seven contained amyloid, confirmed either by Congo red staining or electron microscopic examination. In two nerves, there was a mild loss of myelinated axons; four had a moderate loss, and one, severe loss. Six of seven nerves showed predominantly axonopathic changes. In conclusion, (1) the prevalence rate of amyloid myopathy in muscle biopsy specimens was low (in this series, 0.004%); (2) only a minority of patients had multiple myeloma, and most presented with muscle weakness/fatigue or autonomic symptoms; (3) most of the muscles showed neurogenic features histologically; (4) all concomitant sural nerve biopsy specimens contained amyloid, and most showed a predominance of axonopathic changes.
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PMID:Amyloid myopathy: clinicopathologic study of 16 cases. 959 69

Hereditary primary adrenal insufficiency syndromes due to ACTH resistance include hereditary glucocorticoid deficiency (HGD) and Allgrove's syndrome (AS). Patients with both conditions present in childhood with failure to thrive, weakness, and fatigue or adrenal crisis; patients with AS in addition have alacrima and achalasia (triple A syndrome). We studied four kindreds with HGD and four kindreds with AS for abnormalities of the ACTH receptor (ACTHR) gene. The ACTHR coding sequence in all AS kindreds and two HGD kindreds was normal. Analysis of the ACTHR gene of the proband in one of the HGD kindreds showed him to be homozygous for the previously described G221T transition causing a Ser74Ile substitution of the protein, which has been shown to inactivate the ACTHR in signal transduction. The proband in another HGD kindred was found to be a compound heterozygote with the G221T transition in one allele and a novel C818A transition in the other allele of ACTHR. The C818A transition caused the substitution of the highly conserved Pro273 by His in the receptor protein. In vitro expression of the mutated ACTHR in mouse melanoma M3 cells showed that at a medium ACTH concentration of 3 nM, cells transfected with the wild-type ACTHR produced twofold and threefold, respectively, of the amount of intracellular cAMP when compared to cells transfected with the ACTHR carrying the Pro273His and the Ser74Ile mutation, respectively, confirming that HGD in this kindred is caused by loss-of-function mutations of the ACTHR. These results showed that the genetic cause of the ACTH-resistant syndromes is heterogeneous.
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PMID:Genetic heterogeneity of adrenocorticotropin (ACTH) resistance syndromes: identification of a novel mutation of the ACTH receptor gene in hereditary glucocorticoid deficiency. 975 16

Interleukin 6 (IL-6) has antitumor activity comparable to IL-2 in murine models with less toxicity. Because the biological effects of intermittent and continuous infusions may differ, we conducted two concurrent Phase I trials of daily x5, 1-h, and continuous 120-h i.v. infusions to determine the toxicity, biological effects, and maximum tolerated dose of i.v. IL-6. Cohorts of six patients with advanced cancer received escalating doses (1, 3, 10, 30, 100, and 150 microgram/kg/day) of recombinant human IL-6 on days 1-5 and 8-12 of each 28-day course (1-h trial) or on days 1-5 of each 21-day course (120-h trial). Treatment was administered in regular inpatient wards and in outpatient clinics and was withheld in the event of grade 3 toxicity. Sixty-nine patients (1-h trial, n = 40; 120-h trial, n = 29) were enrolled, including 27 with renal cancer and 16 with melanoma. All were ambulatory, and 40 were asymptomatic. Fever (97%), anemia (78%), fatigue (56%), nausea or vomiting (49%), and elevated serum transaminase levels (42%) were the most frequent toxicities. Transient hypotension developed in 23 patients (33%). There were three deaths during the study due to progressive disease and/or infection. There were no objective responses. Dose-related increases in platelet counts and C-reactive protein levels were detected in most patients. Principal dose-limiting toxicities included atrial fibrillation (1 episode in the 1-h trial and 4 episodes in the 120-h trial) and neurological toxicities (3 episodes in the 1-h trial and 4 episodes in the 120-h trial). The neurological toxicities included confusion, slurred speech, blurred vision, proximal leg weakness, paraparesis, and ataxia. These effects were transient and reversed when IL-6 was discontinued. IL-6 can be given by i.v. infusion at biologically active doses with acceptable toxicity. Dose-limiting toxicities consisted mainly of a spectrum of severe but transient neurological toxicities and occasional episodes of atrial fibrillation. The maximum tolerated doses recommended for use with these i.v. schedules in Phase II trials are 100 microgram/kg/day by daily x5 1-h infusion and 30 microgram/kg/day by 120-h infusion. Phase II trials will be performed to determine the antitumor activity of IL-6 and better define its toxicity. Patients in these and other IL-6 studies should be monitored closely for neurological and cardiac effects.
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PMID:Concurrent phase I trials of intravenous interleukin 6 in solid tumor patients: reversible dose-limiting neurological toxicity. 981 35

We conducted a Phase IB trial of antidisialoganglioside chimeric 14. 18 (ch14.18) antibody and interleukin 2 (IL-2) to determine the maximal tolerated dose (MTD), immunological effects, antitumor effects, and toxicity of this treatment combination. Twenty-four melanoma patients received immunotherapy with ch14.18 antibody and a continuous infusion of Roche IL-2 (1.5 x 10(6) units/m2/day) given 4 days/week for 3 weeks. The ch14.18 antibody (dose level, 2-10 mg/m2/day) was scheduled to be given for 5 days, before, during, or following initial systemic IL-2 treatment. The ch14.18 MTD was 7.5 mg/m2/day, and 15 patients were treated with the ch14.18 MTD. Immunological effects included the induction of lymphokine-activated killer activity and antibody-dependent cellular cytotoxicity by peripheral blood mononuclear cells. In addition, serum samples obtained following ch14.18 infusions were able to facilitate in vitro antibody-dependent cellular cytotoxicity. Antitumor activity included one complete response, one partial response, eight patients with stable disease, and one patient with >50% decrease of hepatic metastases in the face of recurrence of a s.c. lesion. Dose-limiting toxicities were a severe allergic reaction and weakness, pericardial effusion, and decreased performance status. Most patients treated at the MTD had abdominal, chest, or extremity pain requiring i.v. morphine. One patient had an objective peripheral neuropathy. This IL-2 and ch14.18 treatment combination induces immune activation in all patients and antitumor activity in some melanoma patients. We are attempting to enhance this treatment approach by addition of the anti-GD3 R24 antibody to this IL-2 and ch14.18 regimen.
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PMID:Phase IB trial of chimeric antidisialoganglioside antibody plus interleukin 2 for melanoma patients. 981 10

A pleomorphic (giant cell) carcinoma of the esophagus is reported in a 52-year-old man who had dysphagia and weakness. The 8-cm-high vegetating tumor consisted of solid sheets of poorly cohesive epithelioid cells broken into clusters by strands of stroma. Numerous giant cells showing phagocytic phenomenon were present. Immunochemical analyses demonstrated the epithelial origin of the neoplasm, although most of the tumor cells strongly expressed vimentin. Numerous tumor cells expressed synaptophysin. Neurosecretory granules were detected in some tumor cells on electron microscopic examination. The patient died 4 months after he became symptomatic. As far as we can ascertain, this is the first case report describing a pleomorphic carcinoma arising in the esophagus. This poorly differentiated carcinoma might be of neuroendocrine differentiation. In the esophagus, pleomorphic carcinoma must be distinguished from polypoid tumors such as carcinosarcoma and malignant melanoma.
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PMID:Pleomorphic giant cell carcinoma of the esophagus with coexpression of cytokeratin and vimentin and neuroendocrine differentiation. 1062 46

Polymyositis is a systemic autoimmune disorder characterised by proximal muscle weakness which most frequently involves the limbs, neck and trunk. Alpha interferon is an antiviral molecule with well-known immunomodulatory and antiproliferative effects, but its use is often associated with a variety of side effects, in particular autoimmune phenomena. We report the occurrence of polymyositis during treatment with alpha-interferon in a patient affected by malignant melanoma. Indirect evidence suggests that in this case the patient's myositis was not linked to her neoplasia, since the melanoma was confirmed to be in remission both at the time of the diagnosis of the muscle disease and again after more than one year of follow-up.
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PMID:Polymyositis occurring during alpha-interferon treatment for malignant melanoma: a case report and review of the literature. 1065 Oct 86


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