ABSTRACT
El cáncer de cabeza y cuello comprende a todos aquellos tumores que se desarrollan en el tracto aerodigestivo superior, una de las características de éstos es su diversidad, que no es solo desde el punto de vista histológico y etiológico, sino que incluyen diversas formas de presentación, progresión y enfoques terapéuticos. Son de causa multifactorial, siendo el alcohol y el tabaco los principales factores de riesgo asociados; en los últimos años se ha relacionado a ciertos virus con potencial oncogénico con la génesis tumoral, entre ellos al Virus del Papiloma Humano, lo que ha permitido modificar el sistema de estadificación tumor primario-nodos linfáticos cancerosos-metástasis (TNM); presentándolo ahora en dos grandes grupos acorde a la Proteína supresora de tumores P16: P16+ y P16-,los cuales tienen características y manejo diferente. En vista de la heterogeneidad de la enfermedad, son diversos los tratamientos que se ha empleados para el manejo de la misma, entre ellos cirugía, radioterapia, quimioterapia e/o inmunoterapia; ésta última terapéutica, está dirigida hacia la estimulación del sistema inmune del paciente con la finalidad de generar la destrucción de las células tumorales, se realizan previo a una intervención quirúrgica para reducir el tamaño del tumor. Una forma destacable, es la del bloqueo de puntos de control inmunitarios, especialmente hacia proteínas de control inmune moduladoras de respuesta de células T, como los anti-PD-1 y los anti-CTLA-4. La inmunoterapia cada vez va tomando más protagonismo en oncología, en especial las formas de evasión de las reacciones inmunitarias por parte de las células cancerígenas(AU)
Head and neck cancer includes all those tumors that develop in the upper aerodigestive tract, one of the characteristics of these is their heterogeneity, which is not only from the histological and etiological, but also include various forms of presentation, progression and therapeutic approaches.They have a multifactorial cause, with alcohol and tobacco being the main associated risk factors, however, in recent year scertain viruses with oncogenic potential have been linked to tumor genesis, including HPV, which has made it possible tomodify the TNM staging system; now presenting it in two large groups, P16+ and P16-, which have different characteristics and management. In view of the heterogeneity of the disease, there are various treatments that have been used to manageit, including surgery, radiotherapy, chemotherapy and/ orimmunotherapy which will be determined taking into account the location and tumor extension. The latter treatment, is aimedat stimulating the patient's immune system in order to generate the destruction of tumor cells, are performed prior to a surgical intervention to reduce the size of the tumor. A remarkable therapy is that of blocking immune checkpoints, especially anti-PD-1 and anti-CTLA. Immunotherapy is becoming more and more prominent, however, there is still much to discover, so we believe that we should continue investigating the ways of evasion of immune reactions by cancer cells(AU)
Subject(s)
Humans , Male , Female , Tobacco Use Disorder , Alcohol Drinking , Risk Factors , Head and Neck Neoplasms/etiology , Immunotherapy , T-Lymphocytes , Papillomaviridae/pathogenicityABSTRACT
A bienzymatic supramolecular assembly of CAT and SOD is reported. CAT was chemically glycosilated with CD branched CMC and then associated with SOD modified with 1-adamantane carboxylic acid. SOD was remarkably resistant to inactivation by H(2)O(2) and its anti-inflammatory activity was 4.5-fold increased after supramolecular association with the modified CAT form. [structure: see text]
Subject(s)
Anti-Inflammatory Agents/chemistry , Catalase/chemistry , Superoxide Dismutase/chemistry , Animals , Carbohydrate Conformation , Carrageenan , Catalase/blood , Cattle , Edema/chemically induced , Edema/drug therapy , Erythrocytes/enzymology , Glycosylation , Hydrogen Peroxide/metabolism , Kinetics , Macromolecular Substances , Male , Models, Molecular , Rats , Rats, Wistar , Superoxide Dismutase/bloodABSTRACT
Superoxide dismutase was glycosidated with cyclodextrin-branched carboxymethylcellulose. The modified enzyme contained 1.4 mol polymer per mol protein and retained 87% of the initial activity. The anti-inflammatory activity of superoxide dismutase was 2.2-times increased after conjugation and its plasma half-life time was prolonged from 4.8 min to 7.2 h.
Subject(s)
Anti-Inflammatory Agents/pharmacokinetics , Carboxymethylcellulose Sodium/analogs & derivatives , Cyclodextrins/pharmacokinetics , Superoxide Dismutase/pharmacokinetics , Animals , Carboxymethylcellulose Sodium/chemical synthesis , Carboxymethylcellulose Sodium/chemistry , Carboxymethylcellulose Sodium/pharmacokinetics , Carrageenan , Cyclodextrins/chemical synthesis , Edema/chemically induced , Edema/drug therapy , Foot , Male , Rats , Rats, Wistar , beta-Cyclodextrins/chemistryABSTRACT
Bovine liver catalase (EC 1.11.1.6) was chemically modified with mannan, carboxymethylcellulose, and carboxymethylchitin. The enzyme retained about 48-97% of the initial specific activity after glycosidation with the polysaccharides. The prepared neoglycoenzyme was 1.9-5.7 fold more stable against the thermal inactivation processes at 55 degrees C, in comparison with the native counterpart. Also, the modified enzyme was more resistant to proteolytic degradation with trypsin. Pharmacokinetics studies revealed higher plasma half-life time for all the enzyme-polymer preparations, but better results were achieved for the enzyme modified with the anionic macromolecules.
Subject(s)
Catalase/pharmacokinetics , Polysaccharides/chemistry , Animals , Area Under Curve , Carbohydrate Sequence , Carboxymethylcellulose Sodium/chemistry , Carboxymethylcellulose Sodium/metabolism , Catalase/administration & dosage , Catalase/chemistry , Cattle , Enzyme Stability , Half-Life , Hot Temperature , Hydrogen-Ion Concentration , Injections, Intravenous , Liver/enzymology , Male , Molecular Sequence Data , Molecular Structure , Rats , Rats, Wistar , Solubility , Spectrophotometry , Substrate Specificity , Water/chemistryABSTRACT
Mannan from Sacharomyces cerevisiae was activated by oxidation with NaIO4 (sodium m-periodate) and further linked to SOD (superoxide dismutase) via reductive alkylation with NaBH4 (sodium borohydride). The gly-cosidated enzyme contained an average of 1,2 mol of polysaccharide per mol of protein and retained 52 per cent of its initial activity. The modified enzyme was 560-fold more resistant to inactivation with H2O2 and acquired a lectin-recognition capacity in respect of concanavalin A. The anti-inflammatory activity of SOD was increased 2-fold and its plasma half-life time was prolonged from 4.8 min to 1.7 h after glycosylation with the polymer(AU)
Subject(s)
Animals , Male , Mice , Mannans/pharmacology , Superoxide Dismutase/pharmacology , Superoxide Dismutase/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic useABSTRACT
Mannan from Sacharomyces cerevisiae was activated by oxidation with NaIO(4) (sodium m-periodate) and further linked to SOD (superoxide dismutase) via reductive alkylation with NaBH(4) (sodium borohydride). The glycosidated enzyme contained an average of 1.2 mol of polysaccharide per mol of protein and retained 52% of its initial activity. The modified enzyme was 560-fold more resistant to inactivation with H(2)O(2) and acquired a lectin-recognition capacity in respect of concanavalin A. The anti-inflammatory activity of SOD was increased 2-fold and its plasma half-life time was prolonged from 4.8 min to 1.7 h after glycosylation with the polymer.
Subject(s)
Inflammation/drug therapy , Mannans/chemistry , Superoxide Dismutase/chemistry , Superoxide Dismutase/therapeutic use , Alkylation , Animals , Borohydrides/chemistry , Carbohydrate Conformation , Carbohydrate Sequence , Carrageenan , Enzyme Activation/drug effects , Glycosylation , Hydrogen Peroxide/pharmacology , Inflammation/chemically induced , Male , Molecular Sequence Data , Oxidation-Reduction , Periodic Acid/chemistry , Rats , Rats, Wistar , Saccharomyces cerevisiae/chemistry , Structure-Activity Relationship , Superoxide Dismutase/blood , Time FactorsABSTRACT
An enzymatic approach, based on a transglutaminase-catalyzed coupling reaction, was investigated to modify bovine liver catalase with an end-group aminated dextran derivative. We demonstrated that catalase activity increased after enzymatic glycosidation and that the conjugate was 3.8-fold more stable to thermal inactivation at 55 degrees C and 2-fold more resistant to proteolytic degradation by trypsin. Moreover, the transglutaminase-mediated modification also improved the pharmacokinetics behavior of catalase, increasing 2.5-fold its plasma half-life time and reducing 3-fold the total clearance after its i.v. administration in rats.
Subject(s)
Catalase/chemistry , Dextrans/chemistry , Transglutaminases/chemistry , Animals , Cadaverine/analogs & derivatives , Cadaverine/chemistry , Catalase/blood , Catalase/pharmacokinetics , Catalysis , Cattle , Dextrans/pharmacokinetics , Diamines/chemistry , Female , Fluorescent Dyes/chemistry , Rats , Rats, Wistar , Streptomyces/enzymologyABSTRACT
Dextran, mannan and carboxymethylcellulose, previously activated by periodate oxidation, were grafted with beta-cyclodextrin moieties by reductive alkylation in the presence of sodium borohydride. These polymers were used as supramolecular carriers for naproxen, improving the "in vivo" anti-inflammatory properties of this drug.
