Restoration of the immunogenicity of cisplatin-induced cancer cell death by endoplasmic reticulum stress.

In contrast to other cytotoxic agents including anthracyclins and oxaliplatin (OXP), cisplatin (CDDP) fails to induce immunogenic tumor cell death that would allow to stimulate an anticancer immune response and hence to amplify its therapeutic efficacy. This failure to induce immunogenic cell death can be attributed to CDDP's incapacity to elicit the translocation of calreticulin (CRT) from the lumen of the endoplasmic reticulum (ER) to the cell surface. Here, we show that, in contrast to OXP, CDDP is unable to activate the protein kinase-like ER kinase (PERK)-dependent phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α). Accordingly, CDDP also failed to stimulate the formation of stress granules and macroautophagy, two processes that only occur after eIF2α phosphorylation. Using a screening method that monitors the voyage of CRT from the ER lumen to the cell surface, we identified thapsigargin (THAPS), an inhibitor of the sarco/ER Ca(2+)-ATPase as a molecule that on its own does not stimulate CRT exposure, yet endows CDDP with the capacity to do so. The combination of ER stress inducers (such as THAPS or tunicamycin) and CDDP effectively induced the translocation of CRT to the plasma membrane, as well as immunogenic cell death, although ER stress or CDDP alone was insufficient to induce CRT exposure and immunogenic cell death. Altogether, our results underscore the contribution of the ER stress response to the immunogenicity of cell death.

[Primary teratoma of the orbit. Apropos of a case]. / Tératome primitif de l'orbite. A propos d'une observation.

Primary teratomas rarely occur in the orbit leading to major exophthalmia in the neonate. We report a case in a female infant who presented globular right exophthalmia extending beyond the orbit caused by a teratoma of the orbit. There was right ophthalmoplegia. Computed tomography showed enlargement of the orbit without modification of the bony structure despite the tumor volume. Tumoral enucleation was performed via the transconjunctive route. Histology reported benign mature multi-tissue teratoma. The postoperative course was uneventful. The CT-scan at 6 months evidence the absence of recurrence, outcome which has been confirmed after a 5-years follow-up.

[Secondary reconstruction of the mouth floor using a complete and prepared skin graft after non-interrupted pelvi-mandibulectomy]. / Reconstruction secondaire du plancher buccal par greffe de peau totale et appareillage après pelvimandibulectomie non interruptrice.

A technique of secondary reconstruction of the buccal floor after non interruptive pelvimandibulectomy by thin-split graft enables insertion of a dental prosthesis to assist functional recovery. Results of 46 grafts of this type performed at the Institut Gustave Roussy, Villejuif, France, including 21 cases previously analysed in the Annales d'oto-laryngologie, Paris 1985.

[Vagal paraganglioma. Apropos of 2 cases. Review of the literature]. / Paragangliome vagal. A propos de deux cas. Revue de la littérature.

The authors relate the case of two patients of 61 and 64 years old, each one having a high latero-cervical tumor, arching the soft palate, developed from the right vagus nerve and which was a chromaffin paraganglioma. After a recall about the APUD system tumors and the "paraganglioma" concept, they relate their observations at state of the vagal paraganglioma histology, pathology and treatment.