ABSTRACT
BACKGROUND: In India, carcinoma breast is the most common cancer among urban women population and second most common cancer after carcinoma cervix in rural areas. One in 22 women in India develops carcinoma of the breast in their lifetime. Fluorine-18-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in breast cancer usually indicates the degree of tumor metabolism and hence can predict its behavior and prognosis. On the other hand, the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) or neu state of breast cancer is a biomarker that provides important prognostic information in addition to predicting response to therapy. AIMS: The main objective of this study is to assess whether a correlation exists between 18F-FDG uptake in untreated cases of breast cancer, their receptor status (ER, PR, and HER-2 or neu), tumor histology, and tumor size. SUBJECTS AND METHODS: Sixty consecutive female patients, with biopsy-proven primary breast cancer, were enrolled in this prospective study for whom 18F-FDG positron emission tomography-computed tomography scan was done in the Department of Nuclear Medicine. Results obtained were analyzed using appropriate statistical tests (t-test and Pearson Chi-square tests), and interpretation was made with 95% confidence level. RESULTS: In our series, a positive correlation between tumor size, high tumor grade, and standardized uptake value (SUV) was found. Tumors with positive receptor status for estrogen, progesterone, and HER-2/neu receptors had statistically insignificant lower maximum SUV (SUVmax) values than their negative counterparts. Triple-negative breast tumors (ER-, PR-, and no overexpression of HER-2/neu) are currently a subject of major interest because of their aggressiveness, poor prognosis, and lack of targeted therapy. Based on receptor status when the SUVmaxof the group with triple-negative receptor status (ER-/PR-/HER-2/neu-) was compared to rest of the patient group, it was seen that patients with negative receptor status had significantly higher mean SUVmaxvalues. CONCLUSIONS: We have inferred that in patients with breast cancer, various biological parameters such as tumor size, grade, histology, and hormonal receptor status have different impact on tumor metabolic activity.
Subject(s)
Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Fluorodeoxyglucose F18/administration & dosage , Adult , Aged , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Estrogen Receptor alpha/genetics , Female , Fluorodeoxyglucose F18/metabolism , Humans , India/epidemiology , Ki-67 Antigen/genetics , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Receptor, ErbB-2/genetics , Receptors, Progesterone/geneticsABSTRACT
A copper-promoted reductive homocoupling reaction, for the first time used for a metal complex, allowed obtaining a new kind of complexes with the encapsulated metal ions, C-C conjugated bis-clathrochelates. These compounds demonstrate extremely high transcription inhibition activity in the T7 RNA polymerase system with values of IC50 reaching as low as the submicromolar range, which places them among the most potent metal-based transcription inhibitors.
Subject(s)
Chelating Agents/pharmacology , Copper/chemistry , DNA-Directed RNA Polymerases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Ferrous Compounds/pharmacology , Transcription, Genetic/drug effects , Viral Proteins/antagonists & inhibitors , Chelating Agents/chemical synthesis , Chelating Agents/chemistry , DNA-Directed RNA Polymerases/genetics , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Ferrous Compounds/chemical synthesis , Ferrous Compounds/chemistry , Molecular Structure , Organometallic Compounds/chemistry , Oxidation-Reduction , Structure-Activity Relationship , Transcription, Genetic/genetics , Viral Proteins/geneticsABSTRACT
Drug delivery across the buccal mucosa is convenient and safe transport method. The efficiency of the buccal system of peptide delivery is, however, not yet satisfactory. To improve the buccal transport new absorption promoters should be developed to be sufficiently active and at the same time causing no side effects like irritation or unpleasant taste. We have found that lysalbinic acid, a product of the alkaline hydrolysis of egg albumin and a mild detergent, meets those requirements. The preparation and some physicochemical properties of lysalbinic acid are described. Hamster cheek pouch was used as a model for the penetration process studies lysalbinic acid was shown to increase significantly an oral mucosa permeability for alpha-interferon and insulin. So this substance of the natural origin can be applied as an absorption enhancer for the buccal delivery of peptide drugs.
Subject(s)
Absorption/drug effects , Albumins/chemistry , Drug Delivery Systems , Mouth Mucosa/drug effects , Peptides/metabolism , Surface-Active Agents/isolation & purification , Administration, Buccal , Animals , Cricetinae , Drug Combinations , Hydrolysis , In Vitro Techniques , Insulin/administration & dosage , Insulin/metabolism , Interferon-alpha/administration & dosage , Interferon-alpha/metabolism , Models, Animal , Peptides/administration & dosage , Surface-Active Agents/pharmacology , Time FactorsABSTRACT
UV absorption and fluorescence techniques with a thermal denaturation procedure were used in studies of the anchorage of an oligonucleotide hybridization by a covalently tethered nucleoside analogue of an intercalating imidazophenazine derivative (Pzn). The formation by the (dT)(10)Pzn conjugate of the duplex complex with (dA)(15) and the triplex complex with (dA)(15) or poly(dA).poly(dT) was studied in buffered solutions with 0.11 and/or 1M sodium ions at the oligomer strand concentration of 10 microM. Because of the Pzn emission sensitivity to the interaction with adenine bases, a fluorescence technique was found to be effective in the detection of melting transitions. The attached Pzn substantially enhanced the thermal stability of complexes formed by (dT)(10) because of the intercalation mechanism, which increased the temperature of half-dissociation of the duplex by 10-12 degrees C and of the triplexes by approximately 13 degrees C. With the assumption of a two-state model of transition, the thermodynamic parameters for duplex formations were derived. The investigated variant of conjugation has a certain advantage over the widely used attachment via a flexible linker, consisting of a predetermined location of the Pzn chromophore in target sequences that makes it useful as a fluorescent reporter of the hybridization correctness. Molecular modeling was used to construct the geometries of the intercalation sites that turned out to be in conformity with the behavior of the Pzn fluorescence.
Subject(s)
Nucleic Acid Hybridization/methods , Nucleosides/metabolism , Oligonucleotides/metabolism , Phenazines/metabolism , Fluorescence , Models, Molecular , Nucleic Acid Conformation , Nucleic Acid Denaturation , Nucleosides/chemistry , Oligonucleotides/chemistry , Temperature , ThermodynamicsABSTRACT
The 5'-aldehyde terminus is a DNA oxidative damage resulting from attack at C5' of 2-deoxyriboses by some potent natural or chemical DNA cleavers. To offer a fast and specific method for characterization of this type of damage, we used on-line electrospray ionization mass spectrometry (ESI-MS) detection during liquid chromatography analyses. The intrinsic reactivity of 5'-aldehyde terminus with nucleophiles (formation of hydrate with water, of a Tris adduct with Tris buffer) or through beta-elimination reaction resulted in complex LC profiles and MS data. We showed that derivatization of the aldehyde function as an oxime ether gives a stable derivative easy to characterize during on-line ESI-MS analyses. Complete structural characterization of the Tris adduct and the oxime ether derivative were obtained from MS and detailed NMR studies performed on derivatized 5'-aldehyde thymidine models.
Subject(s)
Aldehydes/chemistry , DNA Adducts/chemistry , DNA Damage , Deoxyribose/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Chromatography, High Pressure Liquid , DNA Adducts/analysis , Oxidation-Reduction , Oximes/chemistryABSTRACT
The synthesis of 2'-deoxyribosylurea by thymidine oxidation with potassium permanganate followed by alkaline hydrolysis of intermediates is described. The anomeric configuration of the resulting products was studied by NMR spectroscopy.
Subject(s)
Deoxyribose/analogs & derivatives , Deoxyribose/chemical synthesis , Thymidine/chemistry , Urea/analogs & derivatives , Urea/chemical synthesis , Deoxyribose/chemistry , Isomerism , Magnetic Resonance Spectroscopy , Oxidation-Reduction , Urea/chemistryABSTRACT
The Mn-TMPyP/KHSO(5) system was used to oxidize guanine contained within a dinucleoside monophosphate d(GpT). To identify the guanine oxidation product having a mass with 4 amu above the mass of guanine itself, this relatively unstable compound was reduced to a more stable one. The ESI/MS and NMR data allowed us to propose a dehydro-guanidinohydantoin structure for the (G+4) guanine oxidation product.
Subject(s)
Dinucleoside Phosphates/chemistry , Guanine/chemistry , DNA/chemistry , Magnetic Resonance Spectroscopy/methods , Molecular Structure , Oxidation-Reduction , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, UltravioletABSTRACT
New chemistry for the fluorescent labeling of oligonucleotides with cyanine dyes is proposed. It is based on the use of pyrylium salts as amine-specific reagents. Monomethyne pyrylium cyanine dye 1 was covalently linked to 5'-aminoalkyl modified oligonucleotide, with simultaneous conversion of the non-fluorescent dye 1 into fluorescent pyridinium cyanine structure 2.
Subject(s)
Fluorescent Dyes/chemistry , Oligonucleotides/chemistry , Staining and Labeling/methods , Thiazoles/chemistry , Amines/chemistry , Chromatography, High Pressure Liquid , Fluorescent Dyes/metabolism , Molecular Structure , Oligonucleotides/metabolism , Thiazoles/metabolismABSTRACT
During the preparation of a fluorescent conjugate based on a manganese cationic porphyrin carboxylate derivative linked to a 5'-amino-3'-fluorescein-labeled oligonucleotide, we observed the chemical transformation of the thiourea linkage to a guanidinium function during the deprotection in ammonia of the 3'-fluorescein-oligonucleotide from CPG support. We also noted a secondary reactivity of the activated carboxylate group of the metalloporphyrin precursor with the fluorescein entity of the conjugated oligonucleotide.
Subject(s)
Fluoresceins/chemistry , Guanidines/chemical synthesis , Oligonucleotides/chemistry , Thiourea/analogs & derivatives , Ammonia/metabolism , Fluorescein-5-isothiocyanate/metabolism , Manganese/chemistry , Mass Spectrometry , Metalloporphyrins/chemistry , Molecular Structure , SpectrophotometryABSTRACT
The feasibility of storing forensic urine drug specimens as dry stains on Whatman #3 paper was studied by evaluating the stability of the drugs and recovery from the stains. Drug stains prepared from urine (3 mL) were stores at -20 degrees C, 4 degrees C, and at room temperature for a period of 12 weeks. The study included: amphetamine, benzoylecgonine, 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), morphine, and phencyclidine (PCP) as examples of the HHS regulated drug classes. Drugs were eluted from the stains as follows: methanol:saline (1:1) for PCP and THC-COOH, saline for benzoylecgonine and carbonate/bicarbonate buffer pH 9.2 for amphetamine and morphine. Stains were eluted from the support matrix (Whatman #3 filter paper), extracted and analyzed by gas chromatography/mass spectrometry. All drugs were stable under all of the storage conditions except the THC-COOH urine stain stored at room temperature that degraded to zero after 12 weeks. Therefore, drug stains when kept frozen or refrigerated appear to provide a viable means for storing positive urine specimens.
Subject(s)
Illicit Drugs/isolation & purification , Illicit Drugs/urine , Specimen Handling/methods , Drug Stability , Feasibility Studies , Forensic Medicine , Gas Chromatography-Mass Spectrometry , HumansABSTRACT
Rapid procedure for the synthesis of oligonucleotides by the phosphotriester method has been developed. It is based on the use of O-nucleophilic intramolecular catalysis. The application of this method to automated solid-phase oligonucleotide synthesis allows to perform one elongation cycle for 6-7 min.
Subject(s)
Oligonucleotides/chemical synthesis , Catalysis , Indicators and Reagents , MethodsABSTRACT
An effective procedure for the synthesis of oligonucleotides by the phosphotriester method has been developed. The procedure is based on the use of phosphate protecting groups enabling O-nucleophilic intramolecular catalysis in the reaction of internucleotide bond formation under the action of arylsulfonyl chlorides and their derivatives. Using this new procedure, the time needed to perform one elongation step on polymer support is 7-8 min. The effectiveness of the methodology has been demonstrated in the synthesis of many oligodeoxyribonucleotides of different length with high yields.
