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)

To evaluate the influence of [2-(3-carboxy-1-probylthio)-4-methyl-1,3-thiazole]acetic acid (tiprotimod, HBW 538) on the host defense mechanisms, a number of experimental studies in different animal models were performed. The prophylactic treatment of NMRI mice with tiprotimod significantly prolonged the mean survival time of the animals after intravenous infection with Candida albicans 200/175 and increased the resistance to the fungal infection to 180% in comparison to controls. In vitro the drug showed no direct fungistatic or fungicidal activity. In an experimental model of persistent systemic candidiasis Balb/c mice infected intravenously with Candida albicans were treated with the immunomodulator tiprotimod after the fungal colonization of kidney was manifested (3 days post infection). The treatment of the mice after the infection resulted in a reduction of the infectious load and the abscess formation in kidney as well as in a decrease of numbers of yeasts in the urine. In the syngeneic B16 melanoma tumor model tiprotimod significantly prolonged the medium survival time and reduced the number of visuable metastases in the lungs even when applied after resection of the primary tumor graft. Tiprotimod also beneficially influenced the course of the disease in two murine graft-vs-host models (hemolytic anemia and immune complex glomerulonephritis) which lead to a B cell mediated autoimmune disease with fatal outcome. The application of the drug in the induction phase mitigated the development of the diseases and prevented animals from dying.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunomodulation by the new synthetic thiazole derivative tiprotimod. 3rd communication: influence on host resistance to microorganisms, tumors and on experimental immune disorders. 269 70

A number of partial or complete remissions have been induced within the past 3 years in patients with metastatic melanoma treated with biomodulators, such as low-dose cyclophosphamide (CY) and interleukin-2 (IL-2), or active specific immunotherapy. Six of the most successfully treated patients, with prolonged remissions in skin, lymph nodes, liver and/or lung, all had relapses in the brain. At the time of relapse in the CNS, remissions were continuing in the other viscera. A large single intracerebral metastasis was found in four of the six patients; the other two patients had three metastases each, one of which also had meningeal seeding. Resection was performed in the four patients with single lesions, without postoperative radiotherapy. Intrathecal IL-2 successfully controlled meningeal disease. To date, the median survival of the group exceeds 7 months, in contrast to the usual reported median of 1 to 4 months, reflecting the predominance of resectable single lesions. Immunological therapy failed to prevent or treat metastases to the CNS, but may have influenced the patients' reactivity to the disease, producing single rather than diffuse metastases. If melanoma is to be cured now by any systemic therapy, particularly biomodulation, new regional strategies must be devised to overcome the blood-brain barrier. By analogy with autoimmune disease of the CNS such as multiple sclerosis, in which excessive cell-mediated immunity is found, several possible immunological maneuvers are suggested.
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PMID:Relapse in the central nervous system in melanoma patients successfully treated with biomodulators. 280 83

Two hundred thymomas, surgically treated between 1955 and 1982 at the Marie Lannelongue Surgical Center, were subjected to statistical analysis, comparing clinical stages and histologic types and relating them to survival. Clinical stages were defined as follows. Stage I: no invasiveness, total excision; Stage II: localized invasiveness (no more than two mediastinal structures); Stage III: largely invasive, with or without distant tumorous grafts, lymph node deposits, or metastases. Four histologic types were retained: (1) spindle or oval cell type thymoma, (2) lymphocyte-rich thymoma, (3) differentiated epithelial thymoma, and (4) undifferentiated epithelial thymoma. Invasiveness remained a major prognostic factor, but the degree of invasion did not affect the survival rate or always justify radical surgery. Thus, the survival rate dropped from 85% at 5 years and 80% at 10 years in noninvasive tumors to 50% and 35%, respectively, in invasive tumors, but without significant difference between moderately invasive Stage II and largely invasive Stage III tumors. Histologic typing indicated a good correlation between the degree of differentiation of the tumors and prognosis. The survival rates were 80% at 5 years and 75% at 10 years for spindle cell type 1 and lymphocyte-rich type 2 thymomas, 75% at 5 years and 50% at 10 years for differentiated epithelial type 3, and nil at 5 years for undifferentiated type 4 thymomas. Although invasiveness often paralleled histologic typing, they appeared as two distinct parameters with separate prognostic significance, particularly in differentiated and undifferentiated epithelial tumors. One hundred five patients had myasthenia gravis and 14 had another autoimmune disease. The associated syndromes were no longer an adverse factor in the prognosis of thymoma.
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PMID:Thymoma. A comparative study of clinical stages, histologic features, and survival in 200 cases. 396 92

Measurement of thyroglobulin (Tg) in serum with anti-Tg autoantibodies (TgAb) represents a difficult challenge. Immunoradiometric assays (IRMA) employing monoclonal anti-Tg antibodies not cross-reacting with endogenous TgAb have recently been developed and proposed for Tg assays in TgAb-positive sera. The aim of the present investigation was to assess the clinical reliability of this approach. Assays of serum Tg in patients with and without TgAb using one such monoclonal antibody IRMA (Thyroglobulin IRMA-Pasteur; IRMA-1) were compared with those obtained by a conventional IRMA employing polyclonal anti-Tg antibodies (HTGK-Sorin; IRMA-2). Preliminary studies for assessment of the interference of TgAb showed that the recovery of added Tg was significantly higher (P < 0.01) when determined by IRMA-1 (64.6 +/- 23%) than by IRMA-2 (49.5 +/- 20%). Study groups included 79 patients with differentiated thyroid carcinoma (DTC) treated by total thyroidectomy and radioiodine ablation; 24 had no metastases or residual thyroid tissue, 31 had a thyroid residue, and 24 had metastatic disease. Seventy-five patients with autoimmune thyroid disease (47 with Graves' and 28 with Hashimoto's disease) were also included. In TgAb-negative sera from DTC patients, similar Tg concentrations were found by both IRMA, i.e. undetectable in most patients with no residual thyroid or neoplastic tissue, low to moderately elevated in the majority of those with residual thyroid tissue, and markedly elevated in all patients with metastatic disease. Serum Tg was undetectable by both assays in several TgAb-positive sera from DTC patients with residual thyroid tissue or metastatic disease, respectively, in whom a detectable or even high serum Tg concentration was expected. Despite the lower in vitro interference of TgAb in IRMA-1, there was no difference between the two assays. In the group of patients with thyroid autoimmune disease, serum Tg concentrations were found to be high in TgAb-negative sera and much lower in TgAb-positive sera by both IRMAs. In conclusion, the present study demonstrates that the use of a monoclonal antibody IRMA for serum Tg, although less susceptible to in vitro TgAb interference, does not necessarily provide any substantial advantage with respect to a conventional polyclonal IRMA in detecting Tg in TgAb-positive sera. The finding of undetectable or lower than expected serum Tg by either method in TgAb-positive serum may well reflect a truly reduced serum Tg concentration. This might be due to an accelerated Tg metabolic clearance in the presence of TgAb.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Assay of thyroglobulin in serum with thyroglobulin autoantibodies: an unobtainable goal? 785 6

A substantial proportion of neoplastic and nonneoplastic parotid diseases have a prominent lymphoid component. The lymphoid element in lesions such as papillary cystadenoma lymphomatosum, sebaceous lymphadenoma, and lymphoepithelial carcinoma are readily recognized as a required diagnostic element. However, when other types of benign and malignant salivary gland neoplasms demonstrate tumor-associated lymphoid proliferation, the tumor may be either misclassified or misinterpreted as metastatic disease. Examples of primary benign and malignant parotid neoplasms exhibiting tumor-associated lymphoid proliferation are documented and illustrated. Other parotid lesions that may have a lymphoid element include sialadenitis, cysts with associated lymphoid tissue, parenchymal neoplasms with an expected lymphoid component or those that arise within an intraparotid lymph node, autoimmune disease, malignant lymphoma, and metastatic disease. An approach to recognition and separation of these entities is discussed.
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PMID:Tumor-associated lymphoid proliferation in the parotid gland. A potential diagnostic pitfall. 810 90

A simplified model for tumorigenesis, locoregional growth, and metastases is proposed for carcinoma of the cervix. With the use of this model, four potential areas for future directions for radiobiologic-clinical research are identified. The first area concerns the influence of human papillomavirus infection and p53 mutations on tumor biology, with particular reference to radiosensitivity and metastatic potential. Research in this area should be most fruitful. The second area focuses on the influence of hypoxia on clinical outcome in carcinoma of the cervix. The use of selective hypoxic cell toxins (e.g., tirapazamine) for phase II testing in hypoxic tumors is recommended. The third area concerns the development and clinical confirmation of assays for the prediction of intrinsic tumor radiosensitivity (e.g., surviving fraction after 2 Gy) and normal tissue radiosensitivity. The need exists for more rapid assays so that their results can be available prior to institution of therapy. The influence of the intrinsic radiosensitivity of normal tissues (especially in patients who are heterozygotes for ataxia-telangiectasia and patients with autoimmune disease) may permit identification of those at increased risk for complications so that alternative, less toxic treatment can be allocated. The fourth area for additional study concerns the influence of both intrinsic (c-myc amplification, matrix metalloproteinase levels) and extrinsic factors (fever, immunosuppression) on the development of distant metastases. Such investigations will permit identification of patients at high risk of developing distant metastases so that adjuvant treatments (e.g., chemotherapy or metalloproteinase inhibitors) can be explored. It is believed that future clarification of our proposed model will lead to other worthwhile areas for therapeutic intervention.
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PMID:New directions for radiation biology research in cancer of the uterine cervix. 902 43

CD44 is a transmembrane glycoprotein involved in cell-cell and cell-substrate interactions. As a cell surface molecule, CD44 may be shed or released into the circulation by proteolytic enzymatic mechanisms. Therefore, soluble CD44 can be found in cell culture supernatants as well as in plasma. In this study we evaluated the levels of soluble total CD44 (sCD44) in serum samples of patients with breast and colorectal carcinoma as well as non-Hodgkin's lymphoma in order to correlate prognosis with sCD44 expression. Besides, we evaluated other clinical tumour markers routinely used, Cancer Antigen (CA) 15.3 and CA 19.9. We investigated 132 serological samples from breast cancer patients, 48 sera from colorectal tumours, 48 samples from stage IV non-Hodgkin's lymphoma and sera from 80 individuals without evidence of cancer or autoimmune disease. Breast cancer patients were divided into three groups: a) patients with no clinical evidence of positive nodules and no metastatic disease; b) patients with positive nodules; and c) patients with metastasis. sCD44 mean serum levels in these groups were 198+/-54 ng/ml, 221+/-78 ng/ml and 242+/-119 ng/ml, respectively, while the marker CA 15.3 values were 15.6+/-6.6 U/ml, 14.0+/-5.8 U/ml and 211.5+/-358.9 U/ml, respectively. sCD44 levels for colorectal tumour were 243+/-72 ng/ml, while CA 19.9 serum levels were 230+/-270 U/ml. Stage IV non-Hodgkin's lymphoma sCD44 levels were 398+/-160 ng/ml. sCD44, CA 15.3 and CA 19.9 values for healthy individuals without evidence of any cancer pathology were 223+/-58 ng/ml, 16.4+/-6.2 U/ml and 33+/-14 U/ml, respectively. From these results we conclude that sCD44 might be used as a reliable marker for patients with non-Hodgkin's lymphoma. However, sCD44 levels failed to correlate with prognosis, tumour burden or metastasis in breast and colorectal cancer patients. Neither was any correlation found between high CA 15.3 or CA 19.9 levels and soluble CD44 serum level.
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PMID:Evaluation of soluble CD44 in patients with breast and colorectal carcinomas and non-Hodgkin's lymphoma. 1042 14

Among patients with advanced melanoma, the development of autoimmune phenomena or of hypothyroidism during therapy has been associated with a favourable outcome. The objective of this study was to determine the prevalence of autoimmunity and of hypothyroidism in the melanoma population as a whole and to determine if these disease states confer a survival advantage for patients with metastatic disease. We report our findings in the uveal melanoma population. The study population (n = 91) consisted of all patients registered at this institution with the diagnosis of uveal melanoma during a 2 year study period. Eight (8.8%) had a systemic autoimmune disease; 12 (13.2%) were hypothyroid, including 9/46 (19.6%) females. Survival of the stage 4 patients was determined from diagnosis of the primary tumour (SvDx) and from diagnosis of metastatic disease (SvMt), and was compared to that of age/sex matched stage 4 controls. For autoimmune patients versus controls, the median SvDx was 111 months vs 37 months (P = 0.2734) and the median SvMt was 17 months vs 4 months (P = 0.0887). For the hypothyroid patients versus controls, the median SvDx was 58 months vs 49 months (P = 0.5348) and the median SvMt was 4 months vs 8 months (P = 0.2437). We conclude that there is a trend toward longer survival from the date of metastasis in uveal melanoma patients with a systemic autoimmune disorder, suggesting that systemic autoimmunity may play a role in modifying the activity of established metastases. This trend is not seen among the uveal melanoma patients with hypothyroidism. The high prevalence of hypothyroidism suggests a possible molecular interaction between the two disease processes.
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PMID:Autoimmunity and hypothyroidism in patients with uveal melanoma. 1172 10

Autoimmune phenomena are frequently associated with differentiated thyroid carcinomas. However, the significance of thyroid gland autoimmune aggression on the outcome of these patients is still controversial. To address this issue, we studied 173 patients (123 with papillary and 50 with follicular carcinomas) who underwent surgery complemented by radioiodine ablation and followed up for 0.5-29 (6 +/- 5.76) years. Analysis of the prognostic factors revealed that higher age, male gender, larger nodule size, follicular tumors, presence of metastases at diagnosis, grade of differentiation, and stage correlated positively with the occurrence of death, metastasis and/or recurrence, while the presence of antibodies and the previous history of autoimmune disease correlated negatively with these events. Long distant metastases increased the odds for a lower disease-free rate for patients with papillary (8.366 times) and follicular (7.373 times) carcinoma. However, univariate and multivariate analysis failed to demonstrate that neck node involvement could influence the outcome for patients with well-differentiated thyroid carcinoma. The odds for patients with previous history of thyroid autoimmune disease (p < 0.02) or with thyroid autoantibodies (p < 0.001) to have a worse outcome were lower than for patients with no evidence of autoimmune activity, suggesting that autoimmune activity against the gland may exert a protective effect on the outcome of differentiated thyroid carcinoma patients.
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PMID:Impact of previous thyroid autoimmune diseases on prognosis of patients with well-differentiated thyroid cancer. 1285 17

Vogt-Kaganayi-Harada (VKH) syndrome is a rare autoimmune disease characterized by panuveitis, neuropathy and aseptic meningitis. Most patients require long-term treatment with steroids and immunosuppressants. Patients may develop concurrent autoimmune diseases, especially endocrinopathies. Secondary malignancies are rare associations. We report a Chinese man with VKH syndrome presenting with multiple cranial nerve palsy and bilateral pan-uveitis, who developed disseminated high-grade B cell lymphoma after 3-year treatment with azathioprine. This is the first report of systemic non-Hodgkin lymphoma in patients with VKH syndrome. The carcinogenic properties of azathioprine on an abnormally expanded but non-clonal lymphoid system may play a role in the pathogenesis.
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PMID:High-grade lymphoma after azathioprine treatment for Vogt-Kaganayi-Harada syndrome. 1562 16


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