Immunotherapy of transitional cell carcinoma of urinary bladder

Karcinom prijelaznog epitela mokraćnog mjehura najčešći je karcinom mokraćnog sustava. Klinički razlikujemo dva oblika ove bolesti: mišićno-neinvazivni i mišićno-invazivni oblik. Temeljna klinička odrednica mišićno-neinvazivnih tumora su recidivne novotvorinske promjene; 60 – 90 % mišićno-neinvazivnih tumora recidivirat će ako se liječe samo transuretralnom resekcijom (TUR). Upravo stoga se nakon TUR-a u pacijenata u kojih postoji visoki rizik od ponovne pojave ili progresije bolesti provodi intravezikalna imunoterapija BCGom (bacillus Calmette-Guerin). BCG predstavlja živi atenuirani soj Mycobacterium bovis. U primjeni BCG-a intravezikalne terapije razlikujemo indukcijsku terapiju i terapiju održavanja. Intravezikalna aplikacija BCG-a uzrokuje masivan ulazak upalnih stanica u stijenku mokraćnog mjehura te produkciju citokina detektibilnih u sluznici mjehura i u urinu, što dovodi do imunog odgovora protiv tumora. Činjenica je kako BCG uzrokuje dugotrajan i dugodjelujući imuni odgovor. Do eradikacije tumorskih stanica dolazi zbog celularnih fokusa u stijenci mjehura, a kao direktan antitumorski efektorski mehanizam navodi se direktna antitumorska aktivnost IFN (interferon) i citotoksičnost NK (engl. natural killer) stanica.Bladder cancer is the most common cancer in urinary system. There are two clinical aspects of this disease: muscle non-invasive and muscle invasive disease. Basic characteristic of non-muscle invasive disease is tumor recurrence; 60-90 % of tumors will recurr if treated by transurethral resection (TUR) only. That is the reason why patients in whom exists the risk of recurrence or progression undergo intravesical bacillus Calmette-Guerin (BCG) immunotherapy. BCG represents live attenuated Mycobacterium bovis. There are two phases in BCG therapy: induction and maintenance therapy. Intravesical BCG application causes massive agregation of immune cells in bladder wall and producton of cytokins which causes cytotoxic tumor response. Direct effector mechanism is achieved by IFN (interferon) and NK (natural killer) cell cytotoxicity

Air-Induced <i>anti</i>-Markovnikov Addition of Secondary Phosphine Oxides and H-Phosphinates to Alkenes

Air (oxygen) induces the addition of secondary phosphine oxides and H-phosphinates to alkenes to selectively produce the corresponding anti-Markovnikov adducts in good to high yields. Mechanistic studies show that the addition probably proceeds via a radical chain mechanism

Air-Induced <i>anti</i>-Markovnikov Addition of Secondary Phosphine Oxides and H-Phosphinates to Alkenes

Air (oxygen) induces the addition of secondary phosphine oxides and H-phosphinates to alkenes to selectively produce the corresponding anti-Markovnikov adducts in good to high yields. Mechanistic studies show that the addition probably proceeds via a radical chain mechanism

Palladium-Catalyzed Insertion of Isocyanides into P(O)−H Bonds: Selective Formation of Phosphinoyl Imines and Bisphosphinoylaminomethanes

Palladium and rhodium catalyzed the addition of H-phosphine oxides to isocyanides to selectively generate α-iminophosphine oxides and bisphosphinoylaminomethanes, respectively

Cyclopropanation of Vinylidenecyclopropanes. Synthesis of 1-(Dihalomethylene)spiropentanes

Synthesis of 1-(dihalomethylene)spiropentanes via cyclopropylidenecyclopropanes generated by cyclopropanation of vinylidenecyclopropanes by dihalocarbenes is described. Reaction of diarylvinylidenecyclopropanes with dibromocarbene and dichlorocarbene exclusively gave 1-(dihalomethylene)spiropentanes in high yields. Reaction of monoarylvinylidenecyclopropanes with dihalocarbenes afforded cyclopropylidenecyclopropanes as the major product with the formation of a small amount of 1-(dihalomethylene)spiropentanes. The efficiency of the thermal rearrangement from the cyclopropylidenecyclopropanes to the 1-(dihalomethylene)spiropentane derivatives depended on the substituents and the reaction temperature. Reaction of diarylvinylidenecyclopropanes with diphenylcarbene and phenylthiocarbene gave the corresponding spiropentane derivatives. This type of thermal rearrangement was applicable to the cyclopropanation of 1,1-diarylallenes

Cyclopropanation of Vinylidenecyclopropanes. Synthesis of 1-(Dihalomethylene)spiropentanes

Synthesis of 1-(dihalomethylene)spiropentanes via cyclopropylidenecyclopropanes generated by cyclopropanation of vinylidenecyclopropanes by dihalocarbenes is described. Reaction of diarylvinylidenecyclopropanes with dibromocarbene and dichlorocarbene exclusively gave 1-(dihalomethylene)spiropentanes in high yields. Reaction of monoarylvinylidenecyclopropanes with dihalocarbenes afforded cyclopropylidenecyclopropanes as the major product with the formation of a small amount of 1-(dihalomethylene)spiropentanes. The efficiency of the thermal rearrangement from the cyclopropylidenecyclopropanes to the 1-(dihalomethylene)spiropentane derivatives depended on the substituents and the reaction temperature. Reaction of diarylvinylidenecyclopropanes with diphenylcarbene and phenylthiocarbene gave the corresponding spiropentane derivatives. This type of thermal rearrangement was applicable to the cyclopropanation of 1,1-diarylallenes

Cyclopropanation of Vinylidenecyclopropanes. Synthesis of 1-(Dihalomethylene)spiropentanes

Synthesis of 1-(dihalomethylene)spiropentanes via cyclopropylidenecyclopropanes generated by cyclopropanation of vinylidenecyclopropanes by dihalocarbenes is described. Reaction of diarylvinylidenecyclopropanes with dibromocarbene and dichlorocarbene exclusively gave 1-(dihalomethylene)spiropentanes in high yields. Reaction of monoarylvinylidenecyclopropanes with dihalocarbenes afforded cyclopropylidenecyclopropanes as the major product with the formation of a small amount of 1-(dihalomethylene)spiropentanes. The efficiency of the thermal rearrangement from the cyclopropylidenecyclopropanes to the 1-(dihalomethylene)spiropentane derivatives depended on the substituents and the reaction temperature. Reaction of diarylvinylidenecyclopropanes with diphenylcarbene and phenylthiocarbene gave the corresponding spiropentane derivatives. This type of thermal rearrangement was applicable to the cyclopropanation of 1,1-diarylallenes

Cyclopropanation of Vinylidenecyclopropanes. Synthesis of 1-(Dihalomethylene)spiropentanes

Synthesis of 1-(dihalomethylene)spiropentanes via cyclopropylidenecyclopropanes generated by cyclopropanation of vinylidenecyclopropanes by dihalocarbenes is described. Reaction of diarylvinylidenecyclopropanes with dibromocarbene and dichlorocarbene exclusively gave 1-(dihalomethylene)spiropentanes in high yields. Reaction of monoarylvinylidenecyclopropanes with dihalocarbenes afforded cyclopropylidenecyclopropanes as the major product with the formation of a small amount of 1-(dihalomethylene)spiropentanes. The efficiency of the thermal rearrangement from the cyclopropylidenecyclopropanes to the 1-(dihalomethylene)spiropentane derivatives depended on the substituents and the reaction temperature. Reaction of diarylvinylidenecyclopropanes with diphenylcarbene and phenylthiocarbene gave the corresponding spiropentane derivatives. This type of thermal rearrangement was applicable to the cyclopropanation of 1,1-diarylallenes

The Pt-Catalyzed Carboselenation of Alkynes by Selenoesters

The Pt-catalyzed carboselenation of terminal alkynes with selenoesters provided vinylselenides regio- and stereoselectively in moderate yields

Photorearrangement of Vinylidenecyclopropanes to 1,2,3-Butatriene Derivatives

Photoirradiation of benzene solutions containing 1-diarylvinylidene-2,2,3,3-tetramethylcyclopropanes (2a−d) afforded rearranged products 1,2,3-butatrienes (3a−d) in good to high yields. Photorearrangement from 2,2,3-trimethyl and 2,2- and 2,3-dimethyl derivatives 2e−g also proceeded, but the rates of the rearrangement were lower than those of 2a−d. A singlet mechanism is proposed for this photorearrangement, where alkyl migration occurs from 1,3-biradical intermediates generated via the homolysis of the C1−C2 bond. Generation of diarylvinylidene carbenes from 1,3-biradicals might be competitive with the formation of 3