Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer was investigated in rats using magnetic resonance imaging. Experimental liver metastatic tumors were established in syngeneic BDIX rats after intrasplenic injection of DHD/K12 colon adenocarcinoma cells. Each rat with implanted liver tumors received s.c. injections of somatostatin analogue RC-160 (50 micrograms/kg) or the vehicle (control) twice a day for 4 weeks, starting 3 weeks after tumor inoculation. During the treatment with RC-160, the growth of liver tumors was studied quantitatively by measuring liver tumor volumes in vivo with magnetic resonance imaging at intervals of 7 days. Chronic administration of RC-160 inhibited the growth of hepatic metastases of colon cancer in rats. Significant inhibition of liver tumor growth in RC-160-treated rats was observed throughout the treatment. The final liver tumor volume in the treated rats was decreased by 56.1% as compared to the controls. The treatment with RC-160 reduced the percentage increase in liver tumor volume from 1575 +/- 674% (mean +/- SEM) for the control to 1034 +/- 727% in the treated group. The tumor volume doubling time in treated rats was 3.7 days longer than the controls. The liver tumor growth delay time was 15.1 days. At the end of the treatment, the incidence of ascites and the weights of tumorous livers were also decreased by RC-160 treatment. Administration of RC-160 prolonged the median survival time by 13 days in treated rats. In cell cultures, significant inhibitory effects of somatostatin-14 and RC-160 on the growth of DHD/K12 colon cancer cells were determined by MTT assay and [3H]-thymidine incorporation assay, indicating direct effects of these peptides on the growth of colon cancer cells in vitro. These data suggest that administration of RC-160 could inhibit the growth of colon cancer and their hepatic metastases in rats. Somatostatin analogue RC-160 might be considered as a potential new agent for the treatment of patients with hepatic metastases of colorectal cancers.
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PMID:Inhibitory effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer in rats: a study with magnetic resonance imaging. 135 23

In view of cellular adoptive immunotherapy we have studied monocyte-mediated cytostasis and cytotoxicity against U 937 cells, a human histiocytic lymphoma cell line. Highly purified human monocytes and monocyte-derived macrophages were activated with interferon gamma (IFN) or tumour necrosis factor alpha (TNF) to antileukemic immune effector cells. Antileukemic activity of human monocytes was dependent on monocyte differentiation into macrophages and on a dose- and time-dependent activation with IFN or TNF. Maximum cytostasis of 97.0 +/- 0.7% (mean +/- SEM) (conventional [3H]dT uptake assay) and 81.9 +/- 5.3% cytotoxicity (modified MTT assay) of U 937 cells was obtained by monocytes activated with 100 U/ml IFN for at least 24 h at an effector-to-target-cell ratio of 10. U 937 cells premodified with IFN showed an increase in susceptibility to monocyte-mediated cytotoxicity. U 937 cells premodified with TNF were almost resistant to monocyte-mediated cytotoxicity while activated monocytes maintained their cytotoxic potential. These data show that IFN and TNF are potent activators of monocyte-mediated cytotoxicity. Furthermore, IFN and TNF might be involved in the regulation of the susceptibility of leukemic cells to lysis by interactions with monocytes or macrophages.
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PMID:Role of interferon gamma and tumour necrosis factor alpha in monocyte-mediated cytostasis and cytotoxicity against a human histiocytic lymphoma cell line. 156 17

We describe a modification of the leukocyte adherence inhibition assay (LAI) in which we propose the use of 3-(4,5-dimethylthiazole-2-yl)-2-5-diphenyltetrazolium bromide (MTT) dye which is taken up and reduced by mitochondria. The method was tested by screening peripheral blood leukocytes from Schistosoma mansoni-infected patients. Peripheral blood leukocytes from patients (N = 21) but not from the blood of normal subjects (N = 10) failed to adhere to glass in the presence of soluble adult worm antigenic preparation (SWAP). The non-adherence index (NAI) values for schistosomiasis patients were in the range of 11.0 to 72.3 (mean +/- SEM = 29.3 +/- 4.3), whereas the values for normal subjects were -56.0 to +2.0 (-25.9 +/- 7.6) and those for treated patients -59.6 to +4.0 (-19.3 +/- 5.8). Our results show that the colorimetric LAI assay can be used as an auxiliary test for the diagnosis of schistosomiasis.
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PMID:Colorimetric leukocyte adherence inhibition assay: a new auxiliary technique for the diagnosis of schistosomiasis. 179 86

Exogenous peptide YY (PYY) decreases pancreatic exocrine secretion, pancreatic endocrine function, and pancreatic blood flow. We hypothesized that pancreatic cancer cell growth may be inhibited by PYY and a new synthetic analog, BIM-43004-1. Two human pancreatic ductal adenocarcinomas, PANC-1 and Mia PaCa-2, were examined in tissue cultures. Viable pancreatic cancer cells were counted with trypan blue on a hemocytometer slide. Cells (10K, 20K, 40K, and 80K) were cultured and allowed to grow for 36 hr (n = 14/cell concentration). Pancreatic cancer cells received either PYY or BIM-43004-1 at various concentrations. Control tissue cultures received an equivalent volume of saline inoculation. After incubation with the above peptides for 24 hr, MTT tetrazolium bromide was added to assay mitochondrial activity of pancreatic cancer cells in response to PYY and its analog. MTT assay reveals a significant decrease in pancreatic cancer cell growth when PYY and BIM-43004-1 are added to the cell culture. Results in Mia PaCa-2 reveal a 24% cell growth reduction after exposure to PYY and a 23% reduction in cell growth when treated with BIM-43004-1. In PANC-1 cells, a 25% reduction in growth of cells is noted after PYY treatment and a 24% reduction in growth after BIM-43004-1 treatment. (means +/- SEM, P < 0.05 by Student's t test). Our results reveal a significant reduction in human ductal pancreatic cancer growth when treated with either PYY or its analog, BIM-43004-1. These agents may be useful hormonal adjuncts in the chemotherapy of pancreatic adenocarcinoma.
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PMID:Human pancreatic cancer growth is inhibited by peptide YY and BIM-43004-1. 779 50

We investigated the production of leukemia inhibitory factor (LIF) by human carcinoma cell lines. LIF mRNA was detected by Northern blot analysis in all 24 carcinoma cell lines of the lung, breast, stomach, colon, liver, gallbladder, pancreas and melanocytes. Seventeen of them (70.8%) secreted LIF in the culture supernatant (range: 40.4-3990.3 pg/ml, mean +/- SEM: 611.8 +/- 262.9 pg/ml). Biologic activity of LIF was confirmed in the culture supernatant of carcinoma cell lines by the MTT assay using M1 cells. The present results showed that human carcinoma cell lines are constitutively producing biologically active LIF. The possible biological significance of LIF produced by cancer cells is discussed.
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PMID:Human carcinoma cell lines produce biologically active leukemia inhibitory factor (LIF). 799 57

Activated human monocytes and macrophages are involved in host defense against neoplastic cells. In view of cellular adoptive immunotherapy, we have studied the role of tumor necrosis factor-alpha (TNF-alpha) and gamma-interferon (IFN-gamma) in monocyte-mediated cytotoxicity on the level of both effector and leukemic target cells. Highly purified and IFN-gamma-activated monocytes were cytolytic to U937 cells up to 81.9 +/- 5.3% (mean +/- SEM) in a 24-hour MTT cytotoxicity assay at an effector-to-target-cell ratio of 10. Upon IFN-gamma activation these monocytes showed a 20-fold increase in TNF-alpha secretion of 663 +/- 122 pg/mL. Comparable concentrations of recombinant human TNF-alpha showed only cytostatic effects on U937 cells of approximately 20% after 24 hours, similar to the cytostatic effects of IFN-gamma-activated monocyte culture supernatants. These effects could be fully reversed by anti-TNF-alpha antibodies. U937 cells pretreated with TNF-alpha were almost completely resistant to monocyte-mediated cytotoxicity, supernatant-mediated cytostasis and to TNF-alpha up to 10(4) U/mL. IFN-gamma-activated monocytes were able to lyse TNF-alpha-modified U937 cells whereas IFN-gamma-activated monocyte supernatants showed only cytostatic activity after prolonged incubation. Additionally, target cell modulation by IFN-gamma potentiated the TNF-alpha-dependent cytolytic and cytostatic effects of monocytes, monocyte culture supernatants and TNF-alpha. We conclude that monocytes as a cellular component in monocyte-mediated cytotoxicity are far more potent in lysis of leukemic target cells than are secreted monokines. Furthermore, IFN-gamma and TNF-alpha are involved in the regulation of the susceptibility of leukemic cells for lysis by interactions with monocytes.
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PMID:Cellular and cytokine dependent monocyte-mediated leukemic cell death: modulation by interferon-gamma and tumor necrosis factor-alpha. 844 Mar 44

A MTT/formazan assay was used to evaluate the antitumor activity of vitamin C (Vit C), vitamin K3 (Vit K3), or vitamin C:vitamin K3 combinations against a human prostatic carcinoma cell line (DU145). Both Vit C and Vit K3 alone exhibited antitumor activity, but only at elevated doses. When Vit C and Vit K3 were combined at a C:K3 ratio of 100:1 and administered to the carcinoma cells, the 50% cytotoxic concentrations (CD50) of the vitamins decreased 10- to 60-fold. Subsequently, the DU145 cells were examined with transmission and scanning electron microscopy (TEM and SEM) following a 1 hour treatment with Vit C, Vit K3, or Vit C/K3 combined at their 50% cytotoxic dose. Our morphological data suggest that vitamin treatment with individual vitamins affects the cytoskeleton, the mitochondria, and other membranous components of the cell. Treatment with the vitamin combination appears to potentiate the effects of the individual vitamin treatment. Specifically, there are abundant necrotic cells. The surviving cells display morphological defects characteristic of cell injury.
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PMID:Scanning electron microscopy and transmission electron microscopy aspects of synergistic antitumor activity of vitamin C - vitamin K3 combinations against human prostatic carcinoma cells. 855 14

We investigated the possible value of an in vitro drug-induced cytotoxicity assay in predicting clinical response to fludarabine (FAMP) in chronic lymphocytic leukaemia (CLL). The median FAMP-LD50 values for cases designated as complete response (CR), partial response (PR), no response (NR) and progressive disease (PD) were 1.43, 2.05, 24.8 and 77.9 microg/ml, respectively (P=0.013). A significant lower mean FAMP-LD50 value was observed in the in vivo responding cases as compared to non-responding ones (3.0 +/- 0.82 SEM v 42.3 +/- 12.6 SEM, P=0.001). Only FAMP-LD50 < or = 2.5 microg/ml and more than four FAMP courses significantly influenced the response rate in univariate and multivariate analyses. The MTT assay may be of value in predicting clinical response to FAMP in CLL patients.
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PMID:In vitro drug-induced cytotoxicity predicts clinical response to fludarabine in B-cell chronic lymphocytic leukaemia. 969 69

The purpose of this study was to investigate the effects of 316L stainless steel (SS) corrosion products on the in vitro biomineralization process, because tissue necrosis, bone loss, impaired bone mineralization, and loosening of orthopedic implants are associated with ions and debris resulting from biodegradation. Rat bone marrow cells were cultured in experimental conditions that favored the proliferation and differentiation of osteoblastic cells and were exposed to SS corrosion products obtained by electrochemical means for periods ranging from 1 to 21 days. Quantification of total and ionized Ca and P, as well as Fe, Cr, and Ni, ions in the culture media of control and metal added cultures during the incubation period was performed to study the influence of corrosion products on the Ca and P consumption that occurs during the mineralization process. Control cultures and metal effects on cultures were evaluated concerning DNA content, enzymatic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and alkaline phosphatase (ALP) activity. Histochemical detection of ALP, Ca, and phosphate deposition, and examination of the cultures by scanning and transmission electron microscopy (SEM and TEM) were also performed. The presence of SS corrosion products resulted in impairment of the normal behavior of rat bone marrow cultures. Levels of Cr and Ni in the medium of cultures exposed to 316L SS corrosion products decreased throughout the incubation period, suggesting a regular deposition of these species; these results were supported by TEM observation of the cultures. Cultures exposed to the corrosion products presented lower DNA content, MTT reduction, and ALP activity and failed to form mineralized areas. These cultures showed negative staining on histochemical reactions for the identification of calcium and phosphate deposition and SEM and TEM examination did not show mineral globular structures or mineralization foci, respectively, which is characteristic of cultures grown in control conditions. These results suggest that metal ions associated with 316L SS are toxic to osteogenic cells, affecting their proliferation and differentiation.
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PMID:Decreased consumption of Ca and P during in vitro biomineralization and biologically induced deposition of Ni and Cr in presence of stainless steel corrosion products. 977 16

The phenomenon of dielectrophoretic particle manipulation holds promise for many biotechnology applications, including cell sorting. In our system cell manipulation normally involves transient exposure (15 minutes) to radio-frequency AC electric fields generated using planar microelectrodes. The present study was designed to investigate the range of acute effects of dielectrophoretic manipulation on the normal physiology of isolated cells. Cells were suspended in isoosmotic Mannitol and exposed to a 5 MHz, 21 V (peak to peak) electric field with 100 micrometer gap electrodes. Cells were assigned to three experimental groups; non-exposed controls, exposed cells processed immediately after cessation of the field, and exposed cells processed after a time delay. SEM observations of spread cells cultured on the devices showed no apparent acute effects of field exposure on cell morphology. Cell-doubling rates in exposed cells subsequent to field-exposure or transient incubation in mannitol were no different from control cells. An MTT 'mitochondrial stress' assay indicated no alteration in the rate of oxidative respiration in exposed cells 0.5 hour after exposure to the field. Western blot analysis indicated upregulation of fos protein in cells 0.5 hour after field-exposure, which was confirmed using densitometry. Reverse transcription of cellular mRNA followed by PCR amplification, polyacrylamide gel electrophoresis and autoradiography of cDNA banding revealed differential gene expression between controls and exposed cells processed immediately after cessation of the field. Differential gene expression persisted in exposed cells at least 0.5 hours after removal from the field. Observations indicated that temperature fluctuation in the mannitol solution was minimal, suggesting that upregulated mRNA may not have been related to thermally-induced heat shock protein. The present study has indicated that exposure to AC fields during dielectrophoretic cell manipulation is associated with upregulation of the intermediate-early gene cfos and also transcription of other as yet unidentified genes. These transcriptional events were not manifest as gross changes in cell morphology or cell-cycle dynamics.
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PMID:Cell reactions to dielectrophoretic manipulation. 1020 45


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