Intensity-modulated radiotherapy for localized nasopharyngeal amyloidosis : Case report and literature review.

BACKGROUND: Primary localized amyloidosis is characterized by the deposition of amyloid proteins restricted to one organ, without systemic involvement. Primary nasopharyngeal amyloidosis is an exceedingly rare condition, for which the standard treatment remains unknown. Because of its challenging anatomical position, surgery alone hardly results in complete resection of the localized amyloidosis. Therefore, an interdisciplinary planning board to design optimal treatment is of particular importance. PATIENT AND METHODS: A 39-year-old man presented with a several-week history of nasal obstruction and epistaxis. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a retro-odontoid nonenhancing soft tissue mass. RESULTS: The endoscopic biopsy demonstrated that the mass was amyloid in nature. An extensive systemic workup revealed an absence of inflammatory process, systemic amyloidosis, or plasma cell dyscrasia. The patient was treated with a combination of surgery and radiotherapy, showing no evidence of recurrence or progression at his 1­year follow-up. CONCLUSION: Primary solitary amyloidosis is a rare form of amyloidosis. To the best of our knowledge, this is the first report of a nasopharyngeal amyloidosis case treated with excision and radiation leading to complete remission. Because of the difficulty for surgeons to achieve radical resection with such lesions, radiotherapy proved to be an excellent adjuvant treatment in this case.

Targeting mTOR to overcome epidermal growth factor receptor tyrosine kinase inhibitor resistance in non-small cell lung cancer cells.

AIMS: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have shown dramatic clinical benefits in advanced non-small cell lung cancer (NSCLC); however, resistance remains a serious problem in clinical practice. The present study analyzed mTOR-associated signaling-pathway differences between the EGFR TKI-sensitive and -resistant NSCLC cell lines and investigated the feasibility of targeting mTOR with specific mTOR inhibitor in EGFR TKI resistant NSCLC cells. METHODS: We selected four different types of EGFR TKI-sensitive and -resistant NSCLC cells: PC9, PC9GR, H1650 and H1975 cells as models to detect mTOR-associated signaling-pathway differences by western blot and Immunoprecipitation and evaluated the antiproliferative effect and cell cycle arrest of ku-0063794 by MTT method and flow cytometry. RESULTS: In the present study, we observed that mTORC2-associated Akt ser473-FOXO1 signaling pathway in a basal state was highly activated in resistant cells. In vitro mTORC1 and mTORC2 kinase activities assays showed that EGFR TKI-resistant NSCLC cell lines had higher mTORC2 kinase activity, whereas sensitive cells had higher mTORC1 kinase activity in the basal state. The ATP-competitive mTOR inhibitor ku-0063794 showed dramatic antiproliferative effects and G1-cell cycle arrest in both sensitive and resistant cells. Ku-0063794 at the IC50 concentration effectively inhibited both mTOR and p70S6K phosphorylation levels; the latter is an mTORC1 substrate and did not upregulate Akt ser473 phosphorylation which would be induced by rapamycin and resulted in partial inhibition of FOXO1 phosphorylation. We also observed that EGFR TKI-sensitive and -resistant clinical NSCLC tumor specimens had higher total and phosphorylated p70S6K expression levels. CONCLUSION: Our results indicate mTORC2-associated signaling-pathway was hyperactivated in EGFR TKI-resistant cells and targeting mTOR with specific mTOR inhibitors is likely a good strategy for patients with EGFR mutant NSCLC who develop EGFR TKI resistance; the potential specific roles of mTORC2 in EGFR TKI-resistant NSCLC cells were still unknown and should be further investigated.

[Improvement of refolding efficiency of HLA-A2-peptide complex in vitro by preformed disulfide bonds in heavy chain].

AIM: To improve the refolding efficiency of soluble HLA-A2-peptide complex in vitro. METHODS: The heavy chain (HC) of MHC class I was extracted from bacteria under denaturing and non-reducing conditions. Anion-exchange and (NH4)2SO4 precipitation were applied to purify the HC. Then the purified HC, beta2m and an antigenic peptide (N-YMDGTMSQV-COOH of Try(369-377)) were refolded to form an HLA-A2-peptide complex by dilution method in the buffer of pH 6.6. The refolded products were detected by Western blot and ELISA with W6/32 and anti-human beta2m antibody. RESULTS: The refolded products consisted of HLA-A2-peptide complex, beta2m, and a little amount of HC polymer. The refolding efficiency was 2.5 fold higher than that of the conventional method. CONCLUSION: This study confirmed that the refolding efficiency of the method reported in this paper is higher as compared with the conventional method, which is of importance to the preparation of HLA-peptide tetramers and artificial antigen presenting cells.