Utilizzo:
Fa parte del modulo variabile. È particolarmente indicata in somministrazioni orali di 200-400 mg/die nelle situazioni di diffusioni metastatiche osteoarticolari in cui, con gli altri componenti del MDB interattivi sull’ECM, concorre alla riparazione di lesioni osteolitiche e degenerative.


Caratteristiche Farmacologiche:
È uno degli elementi basilari della matrice extracellulare, in cui gioca un ruolo importante non solo per il basso peso molecolare e la relativa capacità di diffondersi rapidamente nei tessuti e concentrarsi anche a livello intracellulare, ma anche in qualità di regolatore e inibitore della crescita. La sua formula N,N-bis(fosfometil)glicina chiarisce l’importanza funzionale che può esercitare nel complesso metabolismo della matrice extracellulare, in cui esercita la sue proprietà citostatiche. Il razionale antitumorale di questi componenti del modulo variabile MDB deriva dalla loro proprietà di essere alla base della sintesi di costituenti vitali della ECM, come i proteoglicani, le glicoproteine e i glicosamminoglicani, macromolecole saccaridiche di decine di migliaia di unità, ad elevato peso molecolare. Il loro meccanismo plurifunzionale di sostegno e sepimentazione di tessuti e parenchimi, di barriera di contenimento, di struttura elastica e mobile, in grado di influenzare la differenziazione e condizionare il fenotipo cellulare è legata alla loro idrofilia e ai radicali carbossilici e sulfidrilici a carica elettrica negativa, che possono veicolare molecole cationiche, fattori di crescita, citochine, ormoni, ioni e un’ampia varietà di molecole. A livello del citosol sono stati individuati, nelle piastrine, macrofagi, mastociti, megacariociti. I Glicosamminoglicani(GAG) vengono classificati e distinti in quattro tipi in relazione ai carboidrati residui, ai legami che li collegano, alla disposizione ed entità dei legami sulfidrilici. Essi, chimicamente coniugati a strutture proteiche, originano i proteoglicani. L’Ac Ialuronico (HA), prodotto in alta percentuale dalle cellule connettivali, si distingue dagli altri GAG per l’assenza di legami solforici e rappresenta la struttura portante dei proteoglicani, regolando attraverso molteplici meccanismi, tra cui l’idrofilia, l’alto peso molecolare, la carica negativa, la funzionalità della ECM con un’influenza bifasica sull’angiogenesi inversamente proporzionale al peso molecolare. Infatti, grandi polimeri da HA inibiscono l’angiogensi, stimolata al contrario da polimeri di basso peso molecolare. Pertanto la ialuronidasi può giocare un ruolo negativo scindendo i grandi polimeri in oligosaccaridi ad attività angiogenetica, come evidenziato in molteplici neoplasie degli epiteli aerodigestivi quali il carcinoma laringeo metastatico, negli adenocarcinomi vescicali, prostatici e del colon retto. Anche nei melanomi è stato documentato un incremento dei valori di jaluronidasi proporzionale alla progressione. La loro funzione determinante deriva dal legame con uno scheletro proteico che ne fa un componente essenziale sia macromolecolare (Versicano, Aggrecano), che micromolecolare (Fibromodulina, Biglicano, Decorina ecc) della ECM, oltre che della membrana cellulare (Sindecani). Questi proteoglicani attraversano la membrana cellulare e mediante un dominio intracellulare interagiscono con l’Actina, regolando la proliferazione e differenziazione cellulare. Aminoglucidi come glicosammina e galattosammina, unitamente a oligosaccaridi in percentuale ridotta rispetto alla componente proteica, che supera generalmente il 90%, costituiscono le glicoproteine strutturali (Collageno Elastina) e reticolari o di adesione (Fibronectina, Laminina), oltre a recettori cellulari di adesione (Integrine) della ECM, che oltre che a livello dei tessuti mesenchimali, svolgono un ruolo determinante nell’economia e nell’omeostasi neuroendocrina e metabolica, in qualità di enzimi ed ormoni. La superfamiglia CAM (Molecole di Adesione Cellulare) comprende molecole per l’adesione, il riconoscimento e il contatto intercellulare, come le H-CAMs, le Immunoglobuline, le Caderine , le Selectine, le Integrine, cui appartengono una ventina di recettori cellulari glicoproteici, che esercitano un ruolo primario non solo nei rapporti intercellulari, ma anche in quelle tra cellule ed ECM. Alcuni momenti critici della carcinogenesi, differenziazione, apoptosi, crescita, proliferazione, adesione, migrazione cellulare sono controllate dalle Integrine.

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