Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that efflux of cytotoxic drugs from multidrug resistant (MDR) cell lines can be quantitated at the single cell level using a sensitive fluorescence microscopy technique. Based on the structure of compounds which inhibited the efflux of Rhodamine-123 (Rho-123) using this methodology, we hypothesized that the antiemetic, antihistaminic agent benzquinamide (BZQ) would interfere with P-glycoprotein (P-gp) mediated drug transport and potentiate the effects of anticancer agents in MDR cell lines. We show that BZQ interferes with P-gp mediated drug efflux and increases drug accumulation in MDR cells using Rho-123 as a fluorescent probe. BZQ increases the cytotoxicity of chemotherapeutic agents to both human and hamster MDR cell lines in vitro. A slight increase in cytotoxicity to chemotherapeutic agents is also observed in the parental cell lines with BZQ. BZQ increases [3H]daunorubicin accumulation and inhibits the binding of [125I]iodoaryl azidoprazosin to the P-gp in MDR cells. BZQ is a new agent to increase the cytotoxic effects of anticancer agents in MDR cells and may ultimately prove useful as an adjunct in cancer chemotherapy.
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PMID:Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates anticancer agent cytotoxicity in multidrug resistant cells. 136 4

Twenty-five patients with mass lesions involving the musculoskeletal system were studied with positron emission tomography (PET) in order to determine if a relationship exists between histologic grade and tumor uptake of [fluorine-18]2-deoxy-2-fluoro-D-glucose (FDG). There were 6 benign lesions and 19 malignant lesions of various grades. A high correlation (Rho = 0.83) was found between the normalized uptake of tracer and the NCl grade. The high-grade malignancies had significantly greater (p = 0.0091) uptake of FDG than the combination of benign lesions and low-grade malignancies. All lesions with a normalized uptake value of 1.6 or greater were high-grade, while all lesions less than 1.6 represented either benign tumors or low grade malignancies. This strong relationship between FDG uptake and grade among neoplasms from a wide variety of cell types within a single organ system suggests that the technique may be useful in predicting grade even when the cell type is unknown.
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PMID:Noninvasive grading of musculoskeletal tumors using PET. 186 70

Mutated ras genes can acquire a transforming potential and are frequently detected in human tumors. The mammalian ras gene family includes at least 35 distinct members that can be divided into three main groups on the basis of their sequence similarity to ras, rho, or rab genes. All these genes encode small GTP-binding proteins. Rho proteins are implicated in actin organization and control of cell shape, probably by interacting with the cytoskeleton and intracellular membranes. Rab proteins are involved in vesicular traffic, and appear to control the translocation of vesicles from donor to acceptor membranes. The precise function of ras proteins is unknown, although the prevailing view is that they act as transducers of mitogenic signals. We propose that ras proteins, by analogy with rho and rab, are involved in the lateral segregation of multi-protein complexes at the plasma membrane, and we suggest how this process may be important for mitogenic signal transduction.
Cancer Cells 1991 Apr
PMID:Small GTP-binding proteins of the ras family: a conserved functional mechanism? 190 53

Five patients with liposarcomas of the thigh were studied using positron emission tomography (PET) with [18F]2-deoxy-2-fluoroglucose (FDG). There were three low-grade tumors (all National Cancer Institute Grade 1 myxoid liposarcomas) and two high-grade tumors (both pleomorphic liposarcomas, Grades 2 and 3). The low-grade liposarcomas were easily identified with an average dose uptake ratio (DUR) of 1.38 +/- 0.045 (mean +/- SD). The high-grade lesions were more avid for FDG with a mean DUR of 2.45 +/- 0.24. There was a significant difference (p = 0.004) in the DUR for the two groups and the histological grade of malignancy was highly correlated with the DUR for FDG (Rho = 0.89). These findings suggest that FDG-PET may be useful for distinguishing between low-grade and high-grade liposarcomas.
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PMID:Grading liposarcomas with PET using [18F]FDG. 222 75

In a highly populated and industrialised zone of the province of Milan (Health Area 68, Rho) a study was made of mortality due to malignant neoplasms of the digestive organs in the years 1980-1987. The highest mortality percentage in both sexes is caused by stomach cancer, followed by neoplasms of the large bowel, particularly of the colon, malignant neoplasms of the pancreas, primary liver cancer and, in males, of the oesophagus. On the whole mortality from malignant neoplasms of the digestive organs is high in subjects over 75 years and in males a little earlier. Age standardised mortality rates of malignant neoplasms of the stomach and intestine are higher in the area being studied than in Italy. However in males mortality from cancer of the large bowel is lower than in Lombardy, especially in middle-aged subjects. The years 1980-87 have shown a statistically significant increasing trend in males of death from cancer of the colon, rectum and liver. There is an identical trend in females as regards cancer of the colon and liver with the addition of stomach cancer but mortality from cancer of the rectum is stationary. In both sexes mortality from malignant neoplasms of the digestive organs is on the increase but in females this coincides with a general increase in cancer mortality as a whole. Differences have emerged, however, between the sexes depending on age: in males the increasing trend refers mainly to the 35-64 year age group and in females to the over 65 age group. This is particularly true in the case of tumours of the large bowel. In the area being examined the middle-aged population was particularly affected by immigration caused by the rapid industrial development of the area in the 1960's and 70's. It is reasonable to assume that the increasing trend in tumours of the digestive organs, and in particular of the large bowel can also be explained by the fact that people coming on the whole from regions with a lower specific risk factor have had to adapt to different life styles and dietary habits that are typical of a highly industrialised metropolitan area. This assumption can be verified with case-control studies or with statistical techniques (e.g. the logistic regression model for the analysis of proportionate mortality data) that are more typical of occupational epidemiology. In this way it would be possible to understand better the effects of living in the area being studied, as well as of more specific risk factors.
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PMID:[Mortality from malignant tumors of the digestive system in an area of the province of Milan from 1980 to 1987]. 248 89

Since the acquired immunodeficiency syndrome (AIDS) is characterized by opportunistic infections and malignancies indicative of a profound suppression in cell-mediated immunity, we investigated the antibody-dependent cell-mediated cytotoxicity (ADCC) of peripheral blood mononuclear cells of patients with AIDS against chicken red blood cells (CRBC). A marked decrease in ADCC-CRBC activity was observed from patients with AIDS as compared to healthy controls. Furthermore, suppression in ADCC activity was seen when mononuclear cells from healthy subjects were assayed using media containing 25% or 40% sera from AIDS patients. Two of two patients with AIDS and impaired ADCC-CRBC activity were also found to have in vivo impaired reticuloendothelial system Fc-specific clearance of 51Cr-labelled, anti-Rho (D) IgG-sensitized autologous erythrocytes. These data provide further evidence of monocyte-macrophage dysfunction in AIDS and help explain the widespread occurrence of opportunistic pathogens in AIDS.
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PMID:Impaired antibody-dependent cell-mediated cytotoxic activity in patients with the acquired immunodeficiency syndrome. 294 21

Pleiotropic resistance to rhodamine 123 (Rho-123) in Adriamycin (ADM)-resistant Friend leukemia cells was circumvented by cotreatment with 10 microM verapamil. Increased cytotoxicity corresponded to higher intracellular Rho-123 levels. The verapamil-induced increase of drug accumulation in resistant cells is accounted for at least in part by the blockage or slowing of Rho-123 efflux from these cells. In contrast, accumulation and consequent cytotoxicity of Rho-123 in sensitive cells are not increased by verapamil. Similar results were obtained when ADM was used in this cell system. These results suggest that the efflux system for Rho-123 and ADM in sensitive cells is either reduced or absent. Although Rho-123 accumulates specifically in mitochondria and ADM mainly in the nucleus, the loss of these two different classes of compounds from resistant cells appears to occur via a similar or common mechanism. The similarities in drug transport between Rho-123 and ADM may have important implications when applied to an in vivo environment.
Cancer Res 1985 Jun
PMID:Reversal of resistance to rhodamine 123 in adriamycin-resistant Friend leukemia cells. 398

Cross-resistance to rhodamine 123 (Rho-123) has been found in Adriamycin (ADM)-resistant and daunorubicin (DNR)-resistant Friend leukemia cell variants. Cytotoxicity in sensitive cells correlates with the intracellular amount of Rho-123, as determined by high-pressure liquid chromatography. Differential resistance coincides with Rho-123 accumulation which in sensitive cells was 20-fold higher than in resistant cells after 180 min of treatment. Sodium azide, which has been shown to inhibit ADM efflux and consequently increase drug accumulation in ADM-resistant cells, did not inhibit Rho-123 efflux. The difference in Rho-123 accumulation between sensitive and resistant cells correlates with cytotoxicity, which is in contrast to what has been found in these cells when treated with either ADM or DNR. Moreover, in contrast to the known effects of ADM and DNR on macromolecular synthesis, Rho-123 in sensitive cells was found to inhibit protein synthesis but had no effect on DNA or RNA synthesis. At Rho-123 doses which inhibited protein synthesis, drug localization changed from mitochondrial specific to generalized cytoplasmic. This effect was never achieved in resistant cells, even with prolonged drug exposure. The relevance of these findings is that different mechanisms of resistance to different drug types can be identified in the same cells even though similar resistance occurs. The similarity in resistance need not share a common mechanism. Although the drugs are effluxed more efficiently in resistant cells, the mechanisms for resistance in each case seem to differ. In the case of ADM and DNR, it appears to be multifactorial, whereas with Rho-123, total intracellular accumulation seems to be most important.
Cancer Res 1984 Dec
PMID:Cross-resistance to rhodamine 123 in Adriamycin- and daunorubicin-resistant Friend leukemia cell variants. 649 16

Tuberous sclerosis (TSC) is a human genetic syndrome characterized by the development of benign tumors in a variety of tissues, as well as rare malignancies. Two different genetic loci have been implicated in TSC; one of these loci, the tuberous sclerosis-2 gene (TSC2), encodes an open reading frame with a putative protein product of 1784 amino acids. The putative TSC2 product (tuberin) contains a region of limited homology to the catalytic domain of Rap1GAP. We have generated antisera against the N-terminal and C-terminal portions of tuberin, and these antisera specifically recognize a 180-kDa protein in immunoprecipitation and immunoblotting analyses. A wide variety of human cell lines express the 180-kDa tuberin protein, and subcellular fractionation revealed that most tuberin is found in a membrane/particulate (100,000 x g) fraction. Immunoprecipitates of native tuberin contain an activity that specifically stimulates the intrinsic GTPase activity of Rap1a. These results were confirmed in assays with a C-terminal fragment of tuberin, expressed in bacteria or Sf9 cells. Tuberin did not stimulate the GTPase activity of Rap2, Ha-Ras, Rac, or Rho. These results suggest that the loss of tuberin leads to constitutive activation of Rap1 in tumors of patients with tuberous sclerosis.
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PMID:Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity. 760 12

Preferential retention and cytotoxicity of Rhodamine-123 (Rho-123) was originally reported in a number of carcinoma cell types isolated from a variety of tissues as compared to normal epithelial cells from a limited number of other tissues. In the present study, we have examined Rho-123 selectivity in normal and tumor cell lines isolated from the same tissue source, i.e., human breast. We found that: (a) in matched pairs of normal and carcinoma breast cells, Rho-123 displays no preferential retention in either cell type; (b) there is no preferential toxicity in carcinoma as compared to normal breast cells; in fact, one of the carcinoma cell lines (MDA-MB231) shows moderate resistance to this dye; (c) all of the human breast cell lines do not express P-glycoprotein-mediated multidrug resistance; (d) the normal monkey kidney epithelial cell line CV-1, which was originally used as a model to demonstrate the relative resistance of normal epithelial cells to this drug, is found to express high levels of the mdr-1 gene, is resistant to other multidrug-resistant drugs (taxol and vinblastine), and its resistance to Rho-123 as well as decreased Rho-123 retention can be reversed by verapamil; and (e) taxol and vinblastine are found to block increased Rho-123 efflux in CV-1 cells. Thus, overall the data suggest that preferential retention and cytotoxicity of Rho-123 in carcinoma versus normal epithelial cells is related to the differential expression of the mdr-1 gene.
Cancer Res 1995 Apr 15
PMID:Relationship of multidrug resistance to rhodamine-123 selectivity between carcinoma and normal epithelial cells: taxol and vinblastine modulate drug efflux. 771 66


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