ABSTRACT
Reconstruction of the anterior part of the anterior skull base with a nasoseptal flap (NSF) is technically demanding. This challenge is mainly related to the real possible length of the flap. Herein, we describe a new technique for extending the NSF such that it can sufficiently cover the far anterior part of the anterior skull base. Three cadaveric heads were used for mucosal graft extension of the NSF. The graft was harvested from the other side, sutured to the NSF, then repositioned over the skull base after opening all the paranasal sinuses. Each head was operated by a rhinologist and a skull base surgeon. The study variables were the initial length of the NSF, the length of the graft harvested, the new length of the graft-extended NSF, and the length of the new graft-extended NSF from the nasal spine. The average length of the NSFs was 6.4 cm (± 0.2); that of the harvested grafts was 2.93 cm (± 0.1); that of the graft-extended NSF was 9.33 cm (± 0.4); and that of the graft-extended NSF from the nasal spine was 3.93 cm. The graft-extended NSF is an easy and extremely useful technique for the reconstruction of the far anterior parts of the skull base. However, further prospective studies on the clinical usefulness of this technique and its long-term results are yet to be performed. Level of evidence: IV.
ABSTRACT
INTRODUCTION: Studying cancer tumors' microenvironment may reveal a novel role in driving cancer progression and metastasis. The biological interaction between stromal (mesenchymal) stem cells (MSCs) and cancer cells remains incompletely understood. Herein, we investigated the effects of tumor cells' secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs. METHODS: Morphological changes were assessed using fluorescence microscopy. Changes in gene expression were assessed using Agilent microarray and qRT-PCR. GeneSpring 12.1 and DAVID tools were used for bioinformatic and signaling pathway analyses. Cell migration was assessed using a transwell migration system. SB-431542, PF-573228 and PD98059 were used to inhibit transforming growth factor ß (TGFß), focal adhesion kinase (FAK), and mitogen activated protein kinase kinase (MAPKK) pathways, respectively. Interleukin-1ß (IL1ß) was measured using ELISA. RESULTS: MSCs exposed to secreted factors present in conditioned media (CM) from FaDu, MDA-MB-231, PC-3 and NCI-H522, but not from MCF7 and HT-29, developed an elongated, spindle-shaped morphology with bipolar processes. In association with phenotypic changes, genome-wide gene expression and bioinformatics analysis revealed an enhanced pro-inflammatory response of those MSCs. Pharmacological inhibitions of FAK and MAPKK severely impaired the pro-inflammatory response of MSCs to tumor CM (approximately 80% to 99%, and 55% to 88% inhibition, respectively), while inhibition of the TGFß pathway was found to promote the pro-inflammatory response (approximately 3-fold increase). In addition, bioinformatics and pathway analysis of gene expression data from tumor cell lines combined with experimental validation revealed tumor-derived IL1ß as one mediator of the pro-inflammatory phenotype observed in MSCs exposed to tumor CM. CONCLUSIONS: Our data revealed tumor-derived IL1ß as one mediator of the pro-inflammatory response in MSCs exposed to tumor CM, which was found to be positively regulated by FAK and MAPK signaling and negatively regulated by TGFß signaling. Thus, our data support a model where MSCs could promote cancer progression through becoming pro-inflammatory cells within the cancer stroma.
