miR-320c regulates gemcitabine-resistance in pancreatic cancer via SMARCC1.

BACKGROUND: Gemcitabine-based chemotherapy is the standard treatment for pancreatic cancer. However, the issue of resistance remains unresolved. The aim of this study was to identify microRNAs (miRNAs) that govern the resistance to gemcitabine in pancreatic cancer. METHODS: miRNA microarray analysis using gemcitabine-resistant clones of MiaPaCa2 (MiaPaCa2-RGs), PSN1 (PSN1-RGs), and their parental cells (MiaPaCa2-P, PSN1-P) was conducted. Changes in the anti-cancer effects of gemcitabine were studied after gain/loss-of-function analysis of the candidate miRNA. Further assessment of the putative target gene was performed in vitro and in 66 pancreatic cancer clinical samples. RESULTS: miR-320c expression was significantly higher in MiaPaCa2-RGs and PSN1-RGs than in their parental cells. miR-320c induced resistance to gemcitabine in MiaPaCa2. Further experiments showed that miR-320c-related resistance to gemcitabine was mediated through SMARCC1, a core subunit of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex. In addition, clinical examination revealed that only SMARCC1-positive patients benefited from gemcitabine therapy with regard to survival after recurrence (P=0.0463). CONCLUSION: The results indicate that miR-320c regulates the resistance of pancreatic cancer cells to gemcitabine through SMARCC1, suggesting that miR-320c/SMARCC1 could be suitable for prediction of the clinical response and potential therapeutic target in pancreatic cancer patients on gemcitabine-based therapy.

Myofascial flap without skin for intra-oral reconstruction. 1: Animal studies.

BACKGROUND: Although myofascial flaps are already used clinically in intra-oral reconstruction, the source and process of epithelialization remain unclear. METHODS: The process of epithelialization of grafted myofascia in the oral cavity was investigated using the latissimus dorsi muscle of Wistar strain rats. RESULTS: The use of myofascial tissue to fill in defects may maintain the space by preventing shrinkage and contracture of the wound, and this myofascial tissue may induce regeneration of the mucosal epithelium. Myofascia itself did not have the potential to epithelialize. Epithelialization progressed gradually along the surface of the granulated myofascia from the surrounding incised mucosal margin of the recipient site to the central portion. Immunohistochemical staining showed that keratinocyte growth factor-expressing cells were found mainly in the granulated myofascia. Within the study period, regenerated epithelium with orthokeratosis consisting of stratified squamous cells was thin and had scanty rete pegs, but it was similar to normal epithelium. CONCLUSION: Grafted myofascia in the oral cavity may play a space-making role, and induce regeneration of the mucosal epithelium, associated with the production of keratinocyte growth factor.

Myofascial flap without skin for intra-oral reconstruction. 2: Clinical studies.

BACKGROUND: Based on the results of our animal experiment, we evaluated the clinical usefulness of myofascial graft materials in the reconstruction of intra-oral soft-tissue defects. METHODS: An axial-pattern or random-pattern myofascial flap was grafted to reconstruct oral soft-tissue defects caused by tumor resection in ten patients. A pectoralis major myofascial flap was employed in four patients, and a platysma myofascial flap was employed in six patients. RESULTS: All flaps survived, and epithelialization progressed gradually from the surrounding incised mucosal margin. Cicatricial contracture of the wound seemed to be mild and the regenerated mucosa was more flexible than skin. Because the myofascial tissue had only raw surfaces, the handling of the flaps in the oral cavity was very flexible. Moreover, cosmetically unsatisfactory scar formation and dysfunction at the donor site were mild. CONCLUSION: We feel that the myofascial graft procedure is a very useful option for the reconstruction of intra-oral soft-tissue defects, and will soon become a common procedure. We refer to this procedure as the "biological-guided mucosa regeneration (BGMR)" technique.

Changes in the ultrastructure of human cells related to certain biological responses under hyperthermic culture conditions.

It has been reported that human cancer cells are more sensitive to high temperatures than normal human cells, and that cell proliferation and viability are affected by the temperature environment. In this study, we proceeded further, and turning our attention to the close relationship between cell morphology and temperature, used two human cancer cell lines and two normal cell strains to investigate how intracellular fine structure changes in a high temperature environment. The results showed that 1) both of the human cancer cell lines were more sensitive to high temperature than the normal human cell strains, and a difference between the temperature sensitivity of the human cancer cell lines was also confirmed. 2) There is no clear difference between the manner in which normal human cells and malignant human cells are affected by hyperthermia. 3) Among other cell structures, effects on the membrane system were observed as early changes in cell structure. The mitochondria were particularly affected, followed by the rER. 4) Changes in the nucleoplasm, as well as the nuclear membrane (inner membrane), and then the intranuclear chromatin, etc., were observed as late changes. 5) Changes in mitochondria were observed in the early stage, but temporarily tended to recover, and were then fatally affected again in the late stage. We discuss the relationship between cell proliferation, cell viability, and cell ultrastructure based on the above results.