Biomarkers of malignant transformation in oral leukoplakia: from bench to bedside / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma, which indicates a high potential of malignancy. The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life; however, it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management. As a major problem in the field of head and neck pathologies, it is imperative to identify biomarkers of malignant transformation in oral leukoplakia. In this review, we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside. Although no single biomarker has yet been applied in the clinical setting, profiling for genomic instability might be a promising adjunct.

Effect of the sonic hedgehog inhibitor GDC-0449 on an in vitro isogenic cellular model simulating odontogenic keratocysts / 国际口腔科学杂志·英文版

Odontogenic keratocysts (OKCs) are common cystic lesions of odontogenic epithelial origin that can occur sporadically or in association with naevoid basal cell carcinoma syndrome (NBCCS). OKCs are locally aggressive, cause marked destruction of the jaw bones and have a propensity to recur. PTCH1 mutations (at ∼80%) are frequently detected in the epithelia of both NBCCS-related and sporadic OKCs, suggesting that PTCH1 inactivation might constitutively activate sonic hedgehog (SHH) signalling and play a major role in disease pathogenesis. Thus, small molecule inhibitors of SHH signalling might represent a new treatment strategy for OKCs. However, studies on the molecular mechanisms associated with OKCs have been hampered by limited epithelial cell yields during OKC explant culture. Here, we constructed an isogenic PTCH1 cellular model of PTCH1 inactivation by introducing a heterozygous mutation, namely, c.403C>T (p.R135X), which has been identified in OKC patients, into a human embryonic stem cell line using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. This was followed by the induction of epithelial differentiation. Using this in vitro isogenic cellular model, we verified that the PTCH1 heterozygous mutation causes ligand-independent activation of SHH signalling due to PTCH1 haploinsufficiency. This activation was found to be downregulated in a dose-dependent manner by the SHH pathway inhibitor GDC-0449. In addition, through inhibition of activated SHH signalling, the enhanced proliferation observed in these induced cells was suppressed, suggesting that GDC-0449 might represent an effective inhibitor of the SHH pathway for use during OKC treatment.

Long-term results of condylar reconstruction using pedicled-patella in the treatment of giant cell tumor of bone of lower femur / 中华骨科杂志

Objective To study the long term results of condylar reconstruction using pedicled patella in the treatment of giant cell tumor of lower femur. Methods From August 1964 to December 1996, 6 patients with giant cell tumor in the lateral condyle of femur were treated with unicondylar resection curettage and reconstruction with pedicled patella autograft. There were 3 males and 3 females. The average age of the pateints was 30.5 years. The operative indications were as the following: tumor was located in one condyle, complicated with pathological fracture or the tumor had invaded underneath cartilage which was difficult for curettage. Surgical procedure included: Lateral condyle resection according to X ray or CT image, curettage of the possible remaining tumor tissues in the medial condyle. A muscle pedicle of 2.5 cm wide from the quadriceps was raised with the patella, then the articular surface of patella was used to reconstruct the articular surface of femoral condyle, ilium graft(sometimes allograft) was used to fill the defect proximal to the patella. The grafts was fixed by screws and(or) plates. Anterior cross ligament was fixed to the patella. Results 6 patients were followed up for a mean period of 136 months. There were no infection, recurrence, metastasis and instability. All patients could walk for a long distance. The range of motion of the involved knees was between 80? and 120?. There was no varus deformity under stress test, but about 5 degrees valgus deformity under stress test could be found in some, muscle strenth was 5 grade. Conclusion Pedicled patella autograft is a good method for the treatment of giant cell tumor that invades unilateral condyle of lower femur, it is specially suitable to the patients with pathological fracture or severe destruction underneath the cartilage. Thorough resection and curretage of the tumor, preserving the blood supply of patella, refixing the cross ligament, and lower placement of patella are the key points to obtain the satisfactory results.