PES1 is a critical component of telomerase assembly and regulates cellular senescence.

Telomerase defers the onset of telomere shortening and cellular senescence by adding telomeric repeat DNA to chromosome ends, and its activation contributes to carcinogenesis. Telomerase minimally consists of the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR). However, how telomerase assembles is largely unknown. Here, we demonstrate that PES1 (Pescadillo), a protein overexpressed in many cancers, forms a complex with TERT and TR through direct interaction with TERT, regulating telomerase activity, telomere length maintenance, and senescence. PES1 does not interact with the previously reported telomerase components Reptin, Pontin, p23, and Hsp90. PES1 facilitates telomerase assembly by promoting direct interaction between TERT and TR without affecting TERT and TR levels. PES1 expression correlates positively with telomerase activity and negatively with senescence in patients with breast cancer. Thus, we identify a previously unknown telomerase complex, and targeting PES1 may open a new avenue for cancer therapy.

FHL1 inhibits the growth of tongue squamous cell carcinoma cells via G1/S cell cycle arrest.

Four and a half LIM protein 1 (FHL1) has been characterized as a tumor suppressor in various types of tumor. However, the biological function and underlying mechanism of FHL1 in tongue squamous cell carcinoma (TSCC) remain to be elucidated. The present study demonstrated that FHL1 inhibits anchorage­dependent and ­independent growth of TSCC cells in vitro and tumor growth in nude mice, as determined by cell proliferation and soft agar assays. Knockdown of FHL1 with FHL1 small interfering RNA (siRNA) promoted tumor growth in nude mice. Mechanistically, flow cytometric analysis showed that knockdown of FHL1 promoted G1/S cell cycle progression. Furthermore, expression of cell cycle­associated regulators, cyclin D and cyclin E, were detected by western blotting and reverse transcription­quantitative polymerase chain reaction. Cyclin D and cyclin E were markedly elevated at both the protein and mRNA level in the FHL1 siRNA­transfected cells. These results suggested that FHL1 has a tumor suppressive role in TSCC and that FHL1 may be a useful target for TSCC gene therapy.

A comparative histologic study of rapid three-dimensional zygomatic suture expansion osteogenesis.

OBJECTIVE: To explore the histologic changes in zygomatic suture with 3-dimensional (3D) zygomatic suture expansion osteogenesis (SEO). STUDY DESIGN: The zygomatic bones were drawn by 3D external expansion appliance, and sutures of the zygomatic were extended. Biopsy specimens of the zygomatic bone were collected after 1, 3, 5, and 8 weeks. Each specimen was stained with Triplex staining as well as hematoxylin and eosin (HE), and the histologic changes were evaluated compared with the control section. RESULTS: With the 1-week study group, there were visible fibroblasts, osteoblasts, and capillary vessels in the expanded suture tissues. The fibers were connected to the sides of suture in an orderly way. In the 3-week group, active bone formation can be seen in expanded sides. The bone trabeculae were matured and oriented in the direction of distraction in the expanded sides of suture and most of them were collagen fibers; but the tissues of both sides of expanded suture were not in order. New woven bones were found in the histologic sections of the 5-week group. In the 8-week group, reticular and elastic fibers could not be observed, and bones were formed completely. Compared with the histologic examination of the same tissue section and its change in different periods of the biopsy specimen with Triplex staining and HE staining, the method of Triplex staining showed more clearly in collagen, reticular, and elastic fiber examination. The superiority of HE staining was in showing fibrous tissue, shape of cells, and bone formation in various degrees of maturation in rapid SEO. It is suggested that the 2 staining methods might be combined in distinguishing the collagen as well as reticular fibers from fibrin in the same section simultaneously. CONCLUSIONS: Collagen fibers and new bones were observed to form rapidly in expanded sides with direct SEO. Continual affluent blood supply, integral structure of periosteum and synostoses in the suture, and rapid uniform calcification of the whole new tissues are the histologic characteristics of SEO.

[A histological study of three-dimensional external zygomatic suture distraction osteogenesis].

OBJECTIVE: To explore the histological change in suture of zygomatic bone for the zygomatic suture direct distraction osteogenesis. METHODS: The zygomatic bone was distracted by 3-D external distraction appliance without osteotomy. The specimens were taken 1, 3, 5 and 8 weeks after, and then examined histologically and compared with the blank contralateral side. RESULTS: There were lots of fibroblasts, osteoblasts and capillary vessels in the distracted suture tissues one week after distraction, and the fibers were observed to connect the sides of suture and arranged orderly. The surfaces of the expanded suture were irregular. Bone formation was active in the expanded side. The bone trabeculae were mature and oriented in the direction of distraction in the distracted sides at 3 weeks. A great amount of new woven bones were found in 5-week specimen. New bones were formed completely 8 weeks after the distraction. CONCLUSIONS: New bone formed rapidly in the distracted side of zygomatic bone under suture distraction osteogenesis without osteotomy.

Three-dimensional sutural expansion osteogenesis to expand zygomatic bone: an experimental study.

Sutural expansion osteogenesis was used to extend zygomatic bone three-dimensionally by the formation of new bone in eight goats. A 3 cm incision without osteomy was made in the infraorbital part of the zygomatic bone. The external expansion appliance was then placed on the zygomatic bone. The expansion appliance was activated 10 days after the operation at a rate of 0.9 mm/day for 10 days. The direction could be changed through turning the nuts and moving the brace boards. All the zygomatic bones were expanded anterosuperolaterally and inferolaterally by a mean of 9 mm (range 7.8-11.5mm). The regenerating bone tissues in the distracted sutures were recorded radiographically, clinically, and histologically. The experiment succeeded in expanding the zygoma quickly. The three-dimensional external expansion appliance was simple to operate. The result of sutural expansion osteogenesis is stable and credible, and the method is feasible.

[An experimental study of 3-dimension zygomatic suture extension for suture osteogenesis].

OBJECTIVE: To explore a methods of 3-Dimension expansion of zygomatic suture in a goat model. METHODS: Seven goats were used in this study. The 3-D extensive applicator was designed and used to extend the zygomatic suture of the goats by placing it in the zygomatic bone through an infraorbital incision. Ten days after the first operation, it was gradually extended on a speed of 0.09 cm/d for 7 days. The zygomatic movement and the osteogenesis of the suture was evaluated in two weeks. RESULTS: The zygomatic bone was extended for 0.6 cm long in average, and the osteogenesis was also shown significantly in the suture. CONCLUSION: The above mentioned technique could be a safe and effect method to be applied for the zygomatic extension.