Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antitumoral macrophages (MAK) were obtained by the culture of human mononuclear cells in hydrophobic bags. From one cytapheresis, up to 10(9) mature macrophages could be purified by elutriation after one week of culture in IMDM medium in the presence of 2% human AB serum. These MAK cells were used for adoptive treatment in metastatic cancer patient with no dose-limiting toxicity. The present study aimed to improve the average MAK yield by addition of GM-CSF and of dihydroxy-cholecalciferol. The differentiated macrophages obtained presented higher antitumoral functionality in response to rh-IFN gamma than in their absence. These MAK presented all the differentiation antigens of cytotoxic macrophages compared to MAK cells differentiated in standard medium. They killed human tumor targets effectively in vitro at a low (1/1) effector/tumor ratio; furthermore, the antitumoral activity reached by MAK cells after IFN gamma activation appeared to be stabilized for several days.
 ...
PMID:Production of human macrophages with potent antitumor properties (MAK) by culture of monocytes in the presence of GM-CSF and 1,25-dihydroxy vitamin D3. 129 73

The action of IFN-alpha has been studied in patients with carcinoid tumours. More than 300 patients have been treated with IFN-alpha for long periods of time (median 2.5 years). IFN-alpha exerts many pleiotrophic effects in carcinoid tumours. Antiproliferative effects are manifest mainly by a cell cycle block in GO-G1 phase and prolongation of the S-phase. Hormone synthesis is impaired with reduced circulating hormone levels after IFN-alpha therapy and the mechanism includes reduction of mRNA expression for various hormones. Induction in vitro of the nuclear enzyme 2'-5-A synthetase in tumour cells correlates with biochemical response and might account for reduced mRNA expression. IFN-alpha induces significantly increased intratumoral fibrosis in carcinoid metastases without significant changes in tumour size. Finally IFN-alpha causes alteration of the major histocompatibility complex (MHC) with increased expression of class I antigens on the tumour cells. The net result of all these effects of IFN-alpha is an antitumour effect in 70-80% of carcinoid tumour patients with biochemical control and abrogated tumour growth for extended periods of time. However, when IFN-alpha therapy is withdrawn tumour progression occurs within 3-9 months, indicating a controlling but not curing effect.
 ...
PMID:The action of interferon alpha on human carcinoid tumours. 135 93

The effect of interferon-gamma (IFN-gamma) on the interaction between tumor cells and mesothelial cell layers was studied from the aspect of changes in mesothelial permeability. Mesothelial permeability was assessed as the percentage diffusion of radiolabeled albumin across the mesothelial cell sheets on Matrigel-coated filter cup assemblies. When lined gastric carcinoma cells (KATO-III) were seeded on the confluent mesothelial cell layers, the fine cobblestone appearance of the cell sheet was disrupted and mesothelial permeability significantly increased. The increase in permeability was suppressed by the addition of as little as 1 U/ml of IFN-gamma. The effect of IFN-gamma was observed when either the conditioned medium of tumor cells alone or the IFN-gamma-resistant tumor cells, K-562, was placed onto the mesothelium. The cobblestone appearance of the cell sheet was relatively well preserved in the presence of IFN-gamma. In contrast, IFN-alpha did not suppress tumor-induced mesothelial permeability. These results suggest that IFN-gamma has the potential to protect the human mesothelial cell layers against tumor cells.
Clin Exp Metastasis 1992 Nov
PMID:Suppression by interferon-gamma of tumor cell-induced increase in mesothelial permeability. 145 47

A retrospective analysis of 59 patients with renal pelvic and ureter cancer (56 transitional cell carcinomas, 2 squamous cell carcinomas, and 1 adenocarcinoma), which were treated surgically, was performed in relation to postoperative recurrence, particularly distant metastasis. Of the 59 cases, postoperative recurrences developed as distant metastasis in 9 cases (15.3%), as bladder cancer in 19 cases (32.2%) and as contralateral renal pelvic and ureter cancer (bilateral metachronous cancer) in 3 cases (5.1%). Three of the 9 cases with the development of distant metastasis were squamous cell carcinoma or adenocarcinoma, and the others transitional cell carcinoma. All the metastases occurred within 2 years. In cases with transitional cell carcinoma, nonpapillary tumor, grade 3, high stage (pT3 and pT4), positive vascular invasion and IFN beta or gamma had a significant influence on the rate of distant metastasis. On the other hand, location, diversity and previous or coexistent bladder cancer did not seem to be related to the frequency of the development of distant metastasis. Thus, tumor aggressiveness was the only predictive valuable of the development of distant metastasis after surgery for renal pelvic and ureter cancer.
 ...
PMID:[Recurrence following surgery for primary renal pelvic and ureter cancer--clinicopathologic analysis of distant metastasis]. 149 3

Ninety-three collections of leucocytes by cytapheresis followed by separation of monocytes by centrifugal elutriation were undertaken in twelve metastatic cancer patients (four melanomas, six colon carcinomas, one ovarian carcinoma, and one lung cancer). The leucaphereses were performed aiming to collect a product, ready for introduction into the elutriation chamber, i.e., with low contamination by erythrocytes and granulocytes. The median collection of leucocytes was 7.3 x 10(9). After elutriation, purified monocytes (mean: 0.91 x 10(9)) were cultured with 3-5% autologous serum for 7 days in the presence of 250 IU/ml of recombinant human gamma-interferon (Rh-IFN gamma) for the last 18 h of culture. The median number of activated macrophages (MAK) available for reinfusion was 2.4 x 10(8) for each culture. The phenotypes and the antitumoral potentiality of MAK cells were documented. Reinfusions performed i.v. or i.p. were well tolerated with no major side effects. No complete tumor response was obtained. One partial response and two stabilizations of the disease were observed in one melanoma and two colon carcinomas.
 ...
PMID:Adoptive immunotherapy with activated macrophages grown in vitro from blood monocytes in cancer patients: a pilot study. 151 25

The pharmacokinetics of interferon alfa-2b (IFN-alpha-2b) were determined following intraperitoneal (IP) infusion of escalating doses, ie, 5, 10, and 15 million units (MU) and intrahepatal-intraarterial (IA) (IA, bolus v 24 hours continuous infusion of 3 and 5 MU) administration in patients with metastatic cancer. Pharmacokinetic parameters show that bioavailability of IFN-alpha-2b after IP administration is 30 times higher for the peritoneal fluid (PF) than for peripheral blood (PB) explaining also the low incidence of side effects. The high affinity of IFN-alpha-2b to the peritoneal cavity is furthermore substantiated by the total compartment clearance, which is only about 1 1/minute for the PF in comparison to about 30 1/minute as determined for PB. IFN-alpha-2b is eliminated from the PF with a half life (t1/2) of elimination 10 to 32 hours and from the blood with t1/2 of 5 to 13 hours. After IA bolus, IFN is distributed from the blood with a t1/2 below, 2 hours, with dose-dependent serum peak concentrations (c = 47 IU for 3 MU and 145 IU for 5 MU). Twenty-four-hour infusion leads to a steady state within 4 to 6 hours and maximum concentration of 8.5 or 12.5 IU/mL, respectively. During infusion IFN alpha-2b is slowly eliminated with a t1/2 of 16 hours. The lower area under the curve levels after bolus injection may suggest a better tissue uptake of IFN-alpha-2b by the liver. Further studies on pharmacokinetics are warranted to establish exact dose recommendations for an optimal schedule using this route and mode of IFN-alpha-2b administration in mono- and combination therapies.
 ...
PMID:Pharmacokinetic aspects of interferon alfa-2b after intrahepatic or intraperitoneal administration. 155 62

A 59-year-old man with metastatic renal cell carcinoma developed symptomatic thyroid dysfunction following interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) therapy. Thyroid evaluation prior to this therapy revealed evidence of subclinical Hashimoto's thyroiditis. Symptomatic thyrotoxicosis, including atrial fibrillation, developed after the initial two courses of intermittent intravenous bolus therapy with human recombinant IL-2 and IFN-alpha. At 4 weeks after initiation of immunotherapy, the thyroid antimicrosomal antibody (AMA) titer rose from 1:6,400 to 1:25,600; thyroid-stimulating immunoglobulin was negative. A technetium 99m-pertechnetate thyroid scan obtained while the patient was thyrotoxic showed diminished uptake in a symmetrically enlarged gland. The patient was temporarily treated with propranolol, digoxin, and quinidine. The atrial fibrillation quickly resolved, and thyrotoxicosis abated over the following 5 weeks, while the AMA titer rose further to 1:102,400. By 11 weeks after initiation of immunotherapy, hypothyroidism developed and persisted through two subsequent courses of cytokine therapy at Weeks 16 and 18. The tumor metastases partially responded to the immunotherapy. The patient has remained hypothyroid up to 27 weeks of follow-up. This case history suggests that IL-2 and IFN-alpha therapy may precipitate a fulminant autoimmune thyroiditis syndrome in a vulnerable patient with preexisting autoimmune thyroid disease.
 ...
PMID:Transient thyrotoxicosis and persistent hypothyroidism due to acute autoimmune thyroiditis after interleukin-2 and interferon-alpha therapy for metastatic carcinoma: a case report. 155 92

Owing to improved systemic control of widespread malignancy, neurological complications have become a major outcome factor and determinant of life quality in oncological patients. While solitary cerebrospinal metastases are often amenable to surgical and radiological treatment, the management of diffuse leptomeningeal neoplasia, mostly using combined radiochemotherapy, is still very difficult. Immunomodulative approaches represent a therapeutic alternative with increasing potential. We have analysed the natural immune response to leptomeningeal tumor invasion in 43 Patients by assessing cerebrospinal fluid (CSF) levels of albumin, IgG, IgM, interleukins (IL) 1, 2, 4 and 6, soluble IL-2 receptor (sIL-2R), interferon gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), and the tumor markers, carcinoembryonic antigen (CEA) and alphafetoprotein (AFP). In most patients, either elevated IgG index, IgM index, CSF IL-6, or detection of CSF oligoclonal immunoglobulin bands indicated a host reaction against tumor cells. IL-1, IL-2, and IL-4 were never detected in CSF or serum. sIL-2R and IFN gamma were rarely detected and were not associated with specific malignancies. CSF TNF alpha was only detected in melanoma patients and may be a specific indicator of that neoplasm. No correlation was found between levels of the tumor markers, CEA and AFP, and parameters of the immune response such as IgG, IgM or IL-6. The demonstration of intrathecal immune activation in a majority of patients with leptomeningeal neoplasia may offer a new option for immunomodulative oncological therapy.
 ...
PMID:[Intrathecal immune response in meningeosis neoplastica: IgG, IgM, oligoclonal bands and cytokines]. 159 86

We reported recently that a novel immunomodulator, 7-thia-8-oxoguanosine (7T8OG)2 inhibited formation of pulmonary melanoma metastases (1), prevented against viral infection in mice (2) and potentiated the efficacy of a weakly immunogenic leukemia vaccine (3). Since certain tumor metastases and virus infected cells are targets to natural killer cells (NK cells), we now investigated whether 7T8OG is capable of activating NK cells in mice using NK cell sensitive YAC-1 and B16 and NK cell insensitive P815 targets. CBA/CaJ spleen cells incubated in vitro with 7T8OG at concentrations ranging from 0.005 to 0.5 mM responded with increased NK cell activity (32-62%) compared to controls (4-8%) to YAC-1 targets. Similar levels of augmentation in NK cell activity were observed when 40-168 mg/kg of 7T8OG was administered in vivo. In addition to the spleen, 7T8OG activated NK cells in the bone marrow (BM), the lungs, the liver, and in peritoneal exudate cells (PE). Although 7T8OG elicited activation of NK cells was observed as early as three hours after treatment, the maximal activity was observed after 24 h in the spleen; 12 h in the BM; 48 h in the lungs, and 72 h in PE. Administration of the drug by s.c., i.v., and i.p. routes all induced activation of NK cells in spleen, BM and PE. 7T8OG was found to activate NK cells in seven inbred and an outbred mouse strain, suggesting that the induced cytotoxicity against allogeneic and syngeneic tumor cells is not strain specific as well as independent of MHC restriction. C3H/He, CBA/CaJ and BDF/1 displayed higher levels of increased NK cell activity, whereas AKR mice were low responders. Low concentrations of IL-2 (0.25-5 U/ml) that induce little or no NK cell activity, when used in combination with 7T8OG, elicited significant enhancement of NK cell cytotoxicity. In contrast, IFN and 7T8OG showed no such synergism.
 ...
PMID:Immunomodulatory activity of a novel nucleoside, 7-thia-8-oxoguanosine: I. Activation of natural killer cells in mice. 159 50

The aim of the present study has been to assess the therapeutic efficacy of various cytokines, singly or in combination, with and without chemotherapy (cyclophosphamide, Cy), in mice carrying advanced, weakly immunogenic tumors (MCA-105 sarcoma, M109 carcinoma). Treatment of animals with i.p. growths or experimental pulmonary metastases began 8-18 days after i.p. or i.v. tumor cell inoculation respectively. None of the cytokines tested [interleukin-2 (IL-2), interferon alpha (IFN alpha), tumor necrosis factor alpha (TNF alpha) and macrophage-colony-stimulating factor (M-CSF)] nor Cy had by itself a significant curative effect. A synergistic therapeutic effect was obtained with IL-2 or IFN alpha (but not with TNF alpha or M-CSF) in combination with Cy. The most efficacious regimen (65%-90% cure of mice carrying i.p. tumors) was the combination of Cy+IL-2+IFN alpha. Preliminary experiments suggested that sequential administration of these cytokines might be more beneficial than concurrent administration. Following successful immunotherapy, long-term (3-6 months) survivors showed a tumor-specific resistance to a second tumor challenge and their spleen contained an increased number of specific antitumor cytotoxic T lymphocyte precursors (5- to 20-fold, compared to control mice). In vitro and in vivo cell-depletion experiments using monoclonal antibodies revealed that T cells (primarily CD8), but not NK cells, are crucial for the therapeutic effects. This study indicates that a potent specific antitumor T cell immunity can be elicited against advanced weakly immunogenic tumors by combining chemotherapy (Cy) with IL-2 and IFN alpha.
 ...
PMID:Chemo-immunotherapy of murine solid tumors: enhanced therapeutic effects by interleukin-2 combined with interferon alpha and the role of specific T cells. 161 25


1 2 3 4 5 6 7 8 9 10 Next >>