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)

A total of 139 patients with disseminated malignant melanoma were enrolled in an uncontrolled Phase II trial evaluating the activity of Melacine, allogeneic vaccine incorporating Detox, immunologic adjuvant. Nineteen patients, including 18 with progressive disease, dropped out of the study prior to receiving one full vaccination course of five injections over 6 weeks. Disease presentation among study participants included skin or lymph nodes (34%), pulmonary (24%), visceral (34%), and no evidence of disease (NED) (7%). One documented metastatic site was seen in 41%, two sites in 24%, and three or more sites in 27% of the patients studied. Objective clinical response rates for evaluable patients were CR 3%, PR 5%, minor response 4%, stable 23%, and progressive disease 65%. Median survival from time of diagnosis for patients treated with Melacine is presently estimated at 23 months (45/139 patients censored). Median date from diagnosis of metastatic disease to study entry was 3 months. Side effects were generally mild to moderate with pain at injection site (37%), granulomas (13%), erythema (6%), and flu-like symptoms (14-29%) predominating. Precursor antimelanoma cytotoxic T cell (pre-CTL) titers, in comparison with prestudy evaluations, clearly increased in 42% of the patients evaluated. Significantly extended survival characteristics were observed among patients who displayed an expansion of a population of CD57, CD8 co-positive lymphocytes during therapy in comparison with those patients not displaying this peripheral blood lymphocyte (PBL) population expansion (34 mo vs. 12 mo, respectively, p = 0.04) and among those patients displaying disease stabilization or better as a clinical response (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interim results of a phase II multicenter clinical trial evaluating the activity of a therapeutic allogeneic melanoma vaccine (theraccine) in the treatment of disseminated malignant melanoma. 851 15

The glucagonoma syndrome is a rare disorder characterized by weight loss, necrolytic migratory erythema (NME), diabetes, stomatitis, and diarrhea. We identified 21 patients with the glucagonoma syndrome evaluated at the Mayo Clinic from 1975 to 1991. Although NME and diabetes help identify patients with glucagonomas, other manifestations of malignant disease often lead to the diagnosis. If the diagnosis is made after the tumor is metastatic, the potential for cure is limited. The most common presenting symptoms of the glucagonoma syndrome were weight loss (71%), NME (67%), diabetes mellitus (38%), cheilosis or stomatitis (29%), and diarrhea (29%). Although only 8 of the 21 patients had diabetes at presentation, diabetes eventually developed in 16 patients, 75% of whom required insulin therapy. Symptoms other than NME or diabetes mellitus led to the diagnosis of an islet cell tumor in 7 patients. The combination of NME and diabetes mellitus led to a more rapid diagnosis (7 months) than either symptom alone (4 years). Ten patients had diabetes mellitus before the onset of NME. No patients had NME clearly preceding diabetes mellitus. Increased levels of secondary hormones, such as gastrin (4 patients), vasoactive intestinal peptide (1 patient), serotonin (5 patients), insulin (6 patients, clinically significant in 1 only), human pancreatic polypeptide (2 patients), calcitonin (2 patients) and adrenocorticotropic hormone (2 patients), contributed to clinical symptoms leading to the diagnosis of an islet cell tumor before the onset of the full glucagonoma syndrome in 2 patients. All patients had metastatic disease at presentation. Surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization offered palliation of NME, diabetes, weight loss, and diarrhea. Despite the malignant potential of the glucagonomas, only 9 of 21 patients had tumor-related deaths, occurring an average of 4.91 years after diagnosis. Twelve patients were still alive, with an average age follow-up of 3.67 years.
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PMID:The glucagonoma syndrome. Clinical and pathologic features in 21 patients. 860 27

Of the rare pancreatic endocrinomas, glu-cagonomas, either with or without diabetico-dermatogenic syndrome (DDS), are probably third in frequency after insulinomas and gastrinomas. This study was carried out to evaluate the present status of glucagonoma/DDS in a statistically reliable number of cases and to provide precise information to investigators actively working in this particular field of research. A total of 407 cases of glucagonoma were collected from the international literature and evaluated according to characteristic clinicopathologic features. Findings were: (1) The incidence of DDS was 57.2% (233/407). (2) The tail of the pancreas was predominantly involved, in 53.7% (213/397). (3) One-third of the tumors (80 of 276 for whom size was recorded; 29.0%) measured 20 mm or less. (4) Metastases occurred in 51.4% (209/407) and malignant tumors in 60.7% (247/407). (5) Multiplicity occurred in 11.8% (48/407), and associated multiple endocrine neoplasia type 1 in 13. 0% (53/407). (6) In the patients with DDS, the rates of hyperglucagonemia, necrolytic migratory erythema, diabetes mellitus, loss of weight, hypo-aminoacidemia, or anemia, as representative constituents of DDS, were all higher than rates in the overall series (P < 0.01). (7) The 10-year survival rate in the 233 patients with DDS was 51.6% in those with metastases and 64.3% in those without metastases (P < 0.001).
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PMID:Glucagonomas/diabetico-dermatogenic syndrome (DDS): a statistical evaluation of 407 reported cases. 988 Jul 81

A 47-year-old Bedouin man presented with an ulcerated nodule of several months' duration on the nape of the neck. The nodule developed on an asymptomatic, slowly growing plaque which appeared during childhood. Physical examination revealed two erythematous plaques covering the posterior and right lateral aspects of the neck. The border of the plaques was soft, circinate, with a reddish-brown color, while the center was slightly erythematous and atrophic. An ulcerated nodule measuring 2 cm was seen on one of the plaques. Physical examination was unremarkable with no lymphadenopathy. Laboratory tests, including complete blood cell count, erythrocyte sedimentation rate (ESR), and routine chemistry tests, were all within normal limits. Chest X-ray showed a small calcified perihilar lymph node. The Mantoux test was positive with erythema and induration of 15 mm after 48 h. Biopsy from a plaque showed extensive diffuse granulomatous infiltration throughout the dermis with epithelioid and Langhans giant cells surrounded by mononuclear inflammatory cells. No caseation necrosis was present. Ziehl-Neelsen, periodic acid-Schiff (PAS), and Giemsa stains were negative. Polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis and atypical mycobacteria from a skin sample was also negative. Fresh tissue cultures yielded M. tuberculosis after 6 weeks. A biopsy specimen from the ulcerated nodule demonstrated islands of atypical malignant squamous cells invading the dermis, which were compatible with moderately differentiated squamous cell carcinoma (SCC). The ulcerated nodule was completely excised, and treatment for tuberculosis was initiated with a combination of isoniazid, rifampicin, and pyrazinamide. Within 3 months of therapy, the patient's lesions resolved, leaving only slightly atrophic hypopigmented scars. A month after the treatment's initiation, an enlarged cervical lymph node was noted showing metastatic SCC on histologic examination. The patient underwent neck dissection and radiation therapy without evidence of any further metastases.
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PMID:Lupus vulgaris complicated by metastatic squamous cell carcinoma. 988 36

On the basis of compelling preclinical data in cats and dogs we initiated a clinical gene therapy study in nine patients with advanced solid tumors using xenogeneic fibroblasts secreting human IL-2 (Vero-IL-2 cells). Cohorts of three successive patients with tumors accessible to CT- or ultrasound-guided injection were treated repeatedly with 5 x 10(5), 5 x 10(6), or 5 x 10(7) Vero-IL-2 cells. Endpoints of the study were feasibility, toxicity, and clinical and biological effects of this novel approach to immunotherapy of cancer. Histopathological, immunological and molecular analyses were performed on biopsy specimens of tumors and blood samples from before, during and after treatment. Low levels of serum antibodies to Vero cells developed in 2/9 patients. Analysis of tumor biopsies showed increased expression of CD3 mRNA and enhanced tumor infiltration with varying lymphocyte subpopulations after treatment. In addition, monoclonal alterations of the TCR repertoire of blood and tumor lymphocytes were observed. Treatment was well tolerated and toxicity consisted of transient fever in one patient and short-lived, mild itching and erythema in two others. One patient with soft tissue sarcoma showed a more than 90% and more than 50% reduction of the volume of two distant, non-injected metastases, respectively, lasting for 22+ months. Four other patients showed stabilization of their disease for three to nine months, among whom was a patient with melanoma who developed marked vitiligo. We conclude that repeated injection of up to 5 x 10(7) Vero-IL-2 cells was safe and showed biological and clinical activity in heavily pretreated patients with advanced solid tumors. Further evaluation of intratumoral application of Vero-IL-2 seems warranted.
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PMID:Gene therapy with cytokine-transfected xenogeneic cells in metastatic tumors. 1002 23

Twenty patients with malignant uveal melanoma were treated at the The Svedbergh cyclotron in Uppsala from 1989 to 1991. Each tumour received a total dose of 54.6 Gy in four equal fractions on four following days. After treatment the melanoma in all eyes showed decrease in size combined with irradiation retinopathy. In eight patients the treatment was successful after five years. Nine eyes had to be enucleated, two due to recurrence and seven due to neovascular glaucoma. Three patients died, two from metastases and one from heart disease. In all patients the visual acuity was dependent on the distance between the irradiation field and the macula or optic nerve. Each patient suffered from transient post irradiation skin erythema and permanent loss of eyelashes and eyebrows when these were included in the irradiation field. The development of secondary glaucoma was positively correlated with tumour volume, but not to the age or sex of the patients. Histological examination of all the enucleated eyes revealed residual viable tumour without obvious radiation damage: mitotic figures were not identified. MRI examination, performed before and after treatment, demonstrated a marked shift in water binding properties after irradiation. The final visual acuity was dependent on the location of the tumour.
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PMID:Proton irradiation of malignant uveal melanoma. A five year follow-up of patients treated in Uppsala, Sweden. 1005 9

An 87-year-old woman developed erythema, induration and tenderness of the skin overlying each breast. One year before, she had undergone an axillary lymph node dissection because of metastases from melanoma. The primary site was unknown. A skin biopsy showed pigmented tumor nests within the dermal lymphatic vessels, and immunohistochemistry confirmed the melanocytic origin. The diagnosis of inflammatory metastatic melanoma was made.
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PMID:Inflammatory metastatic melanoma. 1008 2

We performed a phase I trial to evaluate the safety and tolerability of repeated skin injections of IL-2-transfected autologous melanoma cells into patients with advanced disease. Cell suspensions, propagated from excised metastases, were IL-2 gene transfected by adenovirus-enhanced transferrinfection and X-irradiated prior to injection. Vaccine production was successful in 54% of the patients. Fifteen patients (37%) received two to eight skin vaccinations of either 3 x 10(6) (intradermal) or 1 x 10(7) (half intradermal, half subcutaneous) transfected melanoma cells per vaccination (secreting 140-17,060 biological response modifier program units of IL-2/10(6) cells/24 hr). Analyses of safety and efficacy were carried out in 15 and 14 patients, respectively. Overall, the vaccine was well tolerated. All patients displayed modest local reactions (erythema, induration, and pruritus) and some experienced flu-like symptoms. Apart from newly appearing (4 of 14) and increasing (5 of 14) anti-adenovirus and newly detectable anti-nuclear antibody titers (1 of 15), recipients developed de novo or exhibited increased melanoma cell-specific delayed-type hypersensitivity (DTH) reactions (8 of 15) and vitiligo (3 of 15) and showed signs of tumor regression (3 of 15). This supports the idea of a vaccine-induced or -amplified anti-cancer immune response. None of the patients exhibited complete or partial regressions, but five of them experienced periods of disease stabilization. Three of these individuals received more than the four planned vaccinations and their mean survival time was 15.7 +/- 3.5 months as compared to 7.8 +/- 4.6 months for the entire patient cohort. These data indicate that IL-2-producing, autologous cancer cells can be safely administered to stage IV melanoma patients and could conceivably be of benefit to patients with less advanced disease.
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PMID:Immunotherapy of metastatic malignant melanoma by a vaccine consisting of autologous interleukin 2-transfected cancer cells: outcome of a phase I study. 1022 32

On the basis of compelling preclinical data in cats and dogs, we initiated a clinical gene therapy study in nine patients with advanced solid tumors using xenogeneic fibroblasts secreting human interleukin (IL)-2 (Vero-IL-2 cells). Cohorts of three successive patients with tumors accessible to computed tomography- or ultrasound-guided injection were treated repeatedly with 5 x 10(5), 5 x 10(6), or 5 x 10(7) Vero-IL-2 cells. The endpoints of the study were feasibility, toxicity, and the clinical and biological effects of this novel approach to immunotherapy of cancer. Histopathological, immunological, and molecular analyses were performed on biopsy specimens of tumors and blood samples before, during, and after treatment. Treatment was well tolerated, and toxicity consisted of transient fever in one patient and short-lived, mild itching and erythema in two others. One patient with soft-tissue sarcoma showed a reduction of >90% and >50% of the volume of two distant, noninjected metastases, lasting for 29+ and 26 months, respectively. Four other patients showed stabilization of their disease for 3-9 months; of these patients, one with melanoma developed marked vitiligo. We conclude that repeated injections of < or =5 x 10(7) Vero-IL-2 cells are feasible and safe in heavily pretreated patients with advanced solid tumors. An additional evaluation of an intratumoral application of Vero-IL-2 seems warranted.
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PMID:Gene therapy study of cytokine-transfected xenogeneic cells (Vero-interleukin-2) in patients with metastatic solid tumors. 1035 13

Glucagon-producing neuroendocrine tumors typically present with a characteristic constellation of symptoms including necrolytic migratory erythema, non-insulin-dependent diabetes, weight loss, anemia, glossitis, and an increased thrombotic tendency. Most glucagonomas are solid and arise in the body or tail of the pancreas. We report two cases of cystic glucagonoma, one found incidentally in an asymptomatic patient and one in a patient with weight loss and diabetes but no rash. In the first patient, distal pancreatectomy and splenectomy were curative, whereas the second patient continued to exhibit elevated serum glucagon levels and symptoms of glucose intolerance in the absence of demonstrable metastases. Cystic glucagonoma is a unique variant of classic glucagonoma and should be considered in the differential diagnosis of cystic pancreatic neoplasms.
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PMID:Cystic glucagonoma: A rare variant of an uncommon neuroendocrine pancreas tumor. 1045 11


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