Enhanced killing of androgen-independent prostate cancer cells using inositol hexakisphosphate in combination with proteasome inhibitors

Effective treatments for androgen-independent prostate cancer (AIPCa) are lacking. To address this, emerging therapeutics such as proteasome inhibitors are currently undergoing clinical trials. Inositol hexakisphosphate (IP6) is an orally non-toxic phytochemical that exhibits antitumour activity against several types of cancer including PCa. We have previously shown that treatment of PC3 cells with IP6 induces the transcription of a subset of nuclear factor-κB (NF-κB)-responsive and pro-apoptotic BCL-2 family genes. In this study, we report that although NF-κB subunits p50/p65 translocate to the nucleus of PC3 cells in response to IP6, inhibition of NF-κB-mediated transcription using non-degradable inhibitor of κB (IκB)-α does not modulate IP6 sensitivity. Treatment with IP6 also leads to increased protein levels of PUMA, BIK/NBK and NOXA between 4 and 8 h of treatment and decreased levels of MCL-1 and BCL-2 after 24 h. Although blocking transcription using actinomycin D does not modulate PC3 cell sensitivity to IP6, inhibition of protein translation using cycloheximide has a significant protective effect. In contrast, blocking proteasome-mediated protein degradation using MG-132 significantly enhances the ability of IP6 to reduce cellular metabolic activity in both PC3 and DU145 AIPCa cell lines. This effect of combined treatment on mitochondrial depolarisation is particularly striking and is also reproduced by another proteasome inhibitor (ALLN). The enhanced effect of combined MG132/IP6 treatment is almost completely inhibited by cycloheximide and correlates with changes in BCL-2 family protein levels. Altogether these results suggest a role for BCL-2 family proteins in mediating the combined effect of IP6 and proteasome inhibitors and warrant further pre-clinical studies for the treatment of AIPCa

Fístulas oroantrais: diagnóstico e propostas de tratamento Oroantral fistulas: diagnosis and management purposes

A comunicação buco-sinusal ou oro-antral é um dos acidentes mais comuns após extrações dentárias na região maxilar posterior, envolvendo principalmente o primeiro molar. O diagnostico é realizado através de métodos clínicos, radiográficos e endoscópico. O tratamento deve ser efetuado o mais precocemente possível, evitando-se a infecção do seio e instalação de uma sinusite maxilar. Nos casos da instalação prévia de uma sinusite, deve-se proceder ao tratamento da mesma antes do fechamento cirúrgico da fístula buco-sinusal. O propósito deste trabalho é relatar três casos clínicos de comunicação oro-antral bem como orientar os profissionais quanto ao diagnóstico e tratamento cirúrgico.<br>The oroantral communication is one of the accidents most common after dental extractions in posterior maxillary region, involving mainly the first molar. The diagnosis must be realized through radiographic and clinical methods (Valsalva's Maneuver) and the treatment must be effect early, avoiding infection of the sinus and installing itself maxillary sinusitis. The treatment of the previous maxillary sinusitis must be instituted before the oroantral fistula plastic closure. The purpose of the study was to report three clinical cases of oroantral communication, furthermore to direct the professionals to the diagnosis and surgical treatmen