Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0267964 (PAA)
 2,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression, tissue distribution, and preliminary characterization of a cell surface molecule, apparently a glycolipid, recognized by a monoclonal antibody, anti-PAA, were described. This antibody (anti-PAA) was produced by the fusion of myeloma cells NS-1 with spleen cells from a BALB/c mouse, which were sensitized with activated human T-cells generated by allogeneic stimulation in mixed-lymphocyte culture (MLC). Resting human peripheral blood T-cells, B-cells, and monocytes demonstrated weak anti-PAA binding. Binding of proliferating T-cells (phytohemagglutinin- and MLC-activated T-cells) and thymocytes to anti-PAA was two to six times greater than that of resting T-cells. A fifteenfold-increased binding was observed with acute lymphocytic leukemia T-cell lines. Epstein-Barr virus-transformed B-cell lines bound anti-PAA up to sixteenfold greater than resting B-cells. Tumor cell lines of various nonlymphoid origins demonstrated marked reactivity with this antibody. Both benign and malignant cells in hyperplastic tissues, of various origins, bound anti-PAA, whereas their normal, nonproliferating counterparts did not. Normal proliferating cells in these tissues, including cells of the placental chorionic villi and trophoblasts, also bound anti-PAA. Of all lymphoid and nonlymphoid cell lines examined, only chronic lymphocytic leukemia (CLL) cells and some cell lines derived from Burkitt's lymphoma showed weak or no binding. This antibody also failed to react with a variety of nonprimate cell lines. Anti-PAA antibody did not immunoprecipitate any protein from lymphoid tumor cell lines to which it demonstrated a quantitatively high degree of binding, nor did protease treatment of these lines decrease antibody binding. Anti-PAA did, however, bind to glycolipids extracted from these cell lines. Binding of this monoclonal antibody to a minor neutral glycolipid, isolated from the erythroleukemia cell line K562, was about sixfold greater than that of any other K562 neutral glycolipid or ganglioside. Anti-PAA demonstrated weak or undetectable binding to purified, predominant, lymphoid cell membrane's neutral glycolipids and gangliosides. The monoclonal antibody anti-PAA appeared, therefore, to recognize a unique, proliferation-associated, neutral glycolipid present on normal as well as on benign and malignant proliferating cells. The antigen appeared to be universally expressed on proliferating cells from all human tissues with the exception of some Burkitt's cell lines and CLL cells. Nonhuman cell lines, except those for closely related primates, did not express PAA.
J Natl Cancer Inst 1987 Feb
PMID:Unique proliferation-associated marker expressed on activated and transformed human cells defined by monoclonal antibody. 354 53

The plasma and tissue distribution of doxorubicin-poly-L-aspartic acid (DX-PAA) and doxorubicin (DX) at equitoxic doses have been studied by a fluorescence assay in tumor bearing mice following administration of a single i.v. bolus injection. A relatively short distribution phase followed by a slow elimination phase characterized the DX-PAA plasma disappearence: at 48 hr after the treatment the conjugate was still detected in plasma. The plasma under the concentration vs. time curve (AUC) of drug equivalents following free DX administration resulted 2.6 times higher than the plasma AUC of free equivalents produced by DX-PAA treatment. In lung, liver and spleen the DX-PAA was accumulated in high concentrations. Low amount of DX equivalents were found in the heart following the conjugate administration: after 2 hr only traces of free anthracycline equivalents were detectable. On the contrary, drug equivalents following free DX treatment remained evaluable in the heart up to 24 hr from the drug administration. No significative differences were observed in the tumor AUC of free DX equivalents produced by free or polymer-linked DX. These data suggest that DX-PAA might act as a depot system slowly releasing the cytotoxic agent. Furthermore the observed accumulation of the conjugate and free DX equivalents in the lung and in the liver suggest a possible therapeutic advantages of DX-PAA in tumors with potential metastasis in these organs.
Cancer Drug Deliv 1986
PMID:Comparative distribution of free doxorubicin and poly-L-aspartic acid linked doxorubicin in MS-2 sarcoma bearing mice. 377 1

The synthetic polypeptide, poly-L-aspartic acid (PAA, mol. wt = 20,000) has been used as a macromolecular carrier for doxorubicin. The drug may be released in vivo through hydrolysis of the ester linkage formed between the carboxyl groups of the polymer and the drug side chain. PAA has been found to be a suitable carrier since it is a soluble, biodegradable, multivalent and nontoxic polymer. The toxicity and the therapeutic efficacy of free and polymer-linked doxorubicin have been evaluated in normal and tumour-bearing mice, using a variety of experimental tumour systems. In studies on single and multiple drug administration, the results indicated that the polymeric derivative of doxorubicin had approximately 3-fold lower toxicity than did free drug. In addition, the severity of specific toxic effects, including cardio- and vesicant toxicity, were appreciably reduced following conjugation to PAA. The doxorubicin-PAA conjugate gave similar or rather greater therapeutic effects than free drug at less toxic doses. This effect, more evident in the highly sensitive tumours, suggests an improvement of the therapeutic index of the polymer-linked drug.
Br J Cancer 1985 Dec
PMID:Poly-L-aspartic acid as a carrier for doxorubicin: a comparative in vivo study of free and polymer-bound drug. 407 38

Tetrasaccharide Fuc alpha 1-2Gal beta 1-4(Fuc alpha 1-3)GlcNAc is known as carbohydrate determinant of cancer- and AIDS-associated antigen Lewisy (Ley). Synthetic antigen to generate mouse monoclonal antibodies (MAbs) directed to Ley was prepared and constructed as a spacer-armed tetrasaccharide coupled with lipophilized polymer, Ley-PAA-PE, where PAA is a 30-kD polyacrylamide and PE is phosphatidylethanolamine. An efficient immune response was provided by using Ley-PAA-PE adsorbed on Salmonella minnesota. Positive hybridomas were screened by enzyme-linked immunosorbent assay (ELISA) using Ley-PAA as a coating agent. An inhibitory version of the same test system showed absolute specificity of two MAbs: only hapten Ley and Ley-PAA were strong inhibitors, in contrast to Leb, tri- and disaccharidic fragments of the mentioned tetrasaccharides, as well as their PAA-conjugates. MAbs obtained against synthetic antigen specifically stained the Ley (+) cell line A431.
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PMID:Monoclonal antibodies directed to the synthetic carbohydrate antigen Ley. 780 50

The in vitro cytotoxic activity profile of nine novel phenylarsonic acid (CAS 98-05-5, PAA) compounds against 17 human cancer cell lines including (a) ovarian cancer cell lines ES-2, PA-1, CAOV-3, OVCAR-3, (b) testicular cancer cell lines Ntera-2, Tera-2, N2NICP, 833K, and 64CP, (c) multiple myeloma cell lines ARH77, HS-Sultan, RPMI-8226, and U266, and (d) acute lymphoblastic leukemia (ALL) cell lines NALM-6, MOLT-3, ALL-1, and RS4; 11, was determined by the MTT assay. The lead compounds, 2-methylthio-4-[(4'-aminophenylazo)-phenylarsonic acid] pyrimidine (PHI-370) and 2-methylthio-4-(4'-phenylarsonic acid)-aminopyrimidine (PHI-380) caused apoptotic death in all 17 cancer cell lines at low micromolar concentrations, as documented by TUNEL assays and confocal laser scanning microscopy. PHI-380 was also tested and found to be very active against primary tumor cells isolated from surgical biopsy specimens of 14 patients with therapy-refractory non-small cell lung cancer, breast cancer, colon cancer, lymphoma, hepatoblastoma, or Wilm's tumor as well. Because of their broad-spectrum and potent anticancer activity and ability to induce apoptosis in primary tumor cells from therapy-refractory cancer patients, PAA compounds such as PHI-370 and PHI-380 may provide the basis for effective salvage regimens for patients with recurrent cancer.
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PMID:Phenylarsonic acid compounds with broad-spectrum and potent cytotoxic activity against human cancer cells. 1287 14

The use of chlorinated disinfectants during drinking-water production has been shown to generate halogenated compounds as a result of interactions of humic acids with chlorine. Such chlorinated by-products have been shown to induce genotoxic effects and consumption of chlorinated drinking-water has been correlated with increased risk for cancer induction in human populations. The aim of this work was to test the potential genotoxic effects on circulating erythrocytes of the fish Cyprinus carpio exposed in vivo to well-waters disinfected with sodium hypochlorite (NaClO), chlorine dioxide (ClO2) or peracetic acid (CH3COO2H, PAA), in the absence or presence of standard humic acids (HA). The effects were measured by use of the micronucleus (MN) and the single-cell gel electrophoresis (Comet) assays at different sampling times after a 3-day exposure period. The exposure to chlorine disinfectants without the addition of HA produced a clear toxic effect. Significant cytogenetic damage (i.e. MN induction) was detected in fish populations exposed to both NaClO and ClO2 with humic acids. In the Comet assay, a significant decrease of DNA migration was observed in erythrocytes of specimens after exposure to NaClO-disinfected water without HA. No effects were observed in any other experimental condition.
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PMID:Modulating effects of humic acids on genotoxicity induced by water disinfectants in Cyprinus carpio. 1620 43

The retinoblastoma (RB) tumour suppressor gene is implicated in the development of several malignancies including osteosarcoma. Recent studies postulated its loss of heterozygosity (LOH) to be a poor prognostic factor at diagnosis of osteosarcoma (OS). It remains unclear whether LOH of the RB gene is suitable as a prognostic factor at diagnosis in patients with osteosarcoma. In this study we aimed to determine the early prognostic value of RB-LOH as well as the ability of denaturating high performance liquid chromatography (DHPLC) to detect LOH at this gene locus in comparison to classical PAGE. We therefore analysed 41 samples of OS on restriction fragment length polymorphisms in introns 1, 17 and 25, and variable numbers of tandem repeats (VNTRs) in intron 20. PCR fragments were separated on 1.5% agarose gel electrophoresis. VNTRs with length differentiation of only a few base pairs were analysed by 8% PAA/Spreadex gels and additionally by DHPLC. One-hundred percent concordance was observed between the results obtained by classical PAGE and DHPLC. The latter improved intron 20 analysis as a sensitive and high throughput method for detecting LOH. Overall we found 16 RB-LOH in 41 OS (39%). Three tumours exhibited additional microsatellite instability. There was no significant correlation of the event-free- and overall-survival rate or response to chemotherapy with RB-LOH found in our study. LOH positivity was associated with a significantly younger age at diagnosis. In conclusion RB-LOH could not be verified as a poor prognostic factor for osteosarcoma in the present study.
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PMID:Determination of the prognostic value of loss of heterozygosity at the retinoblastoma gene in osteosarcoma. 1739 23

Thermo-responsive poly(N-isopropylacrylamide-co-acrylamide)-block-polyallylamine-conjugated albumin nanospheres (PAN), new thermal targeting anti-cancer drug carrier, was developed by conjugating poly(N-isopropylacrylamide-co-acrylamide)-block-polyallylamine (PNIPAM-AAm-b-PAA) on the surface of albumin nanospheres (AN). PAN may selectively accumulate onto solid tumors that are maintained above physiological temperature due to local hyperthermia. PNIPAM-AAm-b-PAA was synthesized by radical polymerization, and AN was prepared by ultrasonic emulsification. AN with diameter below 200 nm and narrow size distribution was obtained by optimizing the preparative conditions. Rose Bengal (RB) was used as model drug for entrapment into the AN and PAN during the particle preparation. The release rate of RB from PAN compared with AN in trypsin solution was slower, and decreased with the increase of PNIPAM-AAm-b-PAA molecular weight, which suggested that the existence of a steric hydrophilic barrier on AN made digestion of AN more difficult. Moreover, the release of RB from PAN above the cloud-point temperature (T(cp)) of PNIPAM-AAm-b-PAA became faster. This was because the density of temperature-responsive polymers on AN was not so high, so that the interspace between the polymer chains increased after they shrunk due to the high temperature. As a result, the biodegradable AN was attacked more easily by trypsin. The design of PAN overcame the disadvantages of temperature-responsive polymeric micelles.
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PMID:Preparation and characterization of thermo-responsive albumin nanospheres. 1765 29

A new ursane-based compound, astilbotriterpenic acid (1), was isolated from the rhizomes of Astilbe chinensis. Its structure was determined on the basis of chemical evidence and extensive spectroscopic methods, including 1D- and 2D-NMR. The pentacyclic triterpenoid 1 was assayed for its in vitro cytotoxicity against Bcap37, HeLa, HepG2, HO-8910, K562, PAA, SGC7901, and P388 cancer cells, as well as for its apoptosis-inducing activity in HeLa cells. Compound 1 was found to strongly inhibit tumor-cell growth through induction of apoptosis and may, thus, be further evaluated as a novel chemotherapeutic agent.
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PMID:A new cytotoxic, apoptosis-inducing triterpenoid from the rhizomes of Astilbe chinensis. 1820 22

Oral administration of anticancer agents is preferred by patients for its convenience and potential for use in outpatient and palliative setting. In addition, oral administration facilitates a prolonged exposure to the cytotoxic agents. Enhancement of bioavailability of emerging cytotoxic agents is a pre-requisite for successful development of oral modes of cancer treatment. Over the last decade, our studies have focused specifically on the utilization of large (MW>10(5)) and non-degradable polymers in oral chemotherapy. A family of block-graft copolymers of the poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) Pluronic(R) polyethers and poly(acrylic acid) (PAA) bound by carbon-carbon bonds emerged, wherein both polymeric components are generally recognized as safe. Animal studies with Pluronic-PAA copolymers demonstrated that these molecules are excreted when administered orally and do not absorb into the systemic circulation. The Pluronic-PAA copolymers are surface-active and self-assemble, at physiological pH, into intra- and intermolecular micelles with hydrophobic cores of dehydrated PPO and multilayered coronas of hydrophilic PEO and partially ionized PAA segments. These micelles efficiently solubilize hydrophobic drugs such as paclitaxel and steroids and protect molecules such as camptothecins from the hydrolytic reactions. High surface activity of the Pluronic-PAA copolymers in water results in interactions with cell membranes and suppression of the membrane pumps such as P-glycoprotein. The ionizable carboxyls in the micellar corona facilitate mucoadhesion that enhances the residence time of the micelles and solubilized drugs in the gastrointestinal tract. Large payloads of the Pluronic-PAA micelles with weakly basic and water-soluble drugs such as doxorubicin and its analogs, mitomycin C, mitoxantrone, fluorouracil, and cyclophosphamide are achieved through electrostatic interactions with the micellar corona. Mechanical and physical properties of the Pluronic-PAA powders, blends, and micelles allow for formulation procedures where an active is simply dispersed into an aqueous Pluronic-PAA micellar formulation followed by optional lyophilization and processing into a ready dosage form. We review a number of in vivo and in vitro experiments demonstrating that that the oral administration of the cytotoxics formulated with the Pluronic-PAA copolymer micelles results in enhanced drug bioavailability.
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PMID:Polymeric micelles in oral chemotherapy. 1832 19


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