The Chemokine CCL4 Stimulates Angiopoietin-2 Expression and Angiogenesis via the MEK/ERK/STAT3 Pathway in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with a poor prognosis and is a major public health burden in Taiwan. Angiogenesis, the formation of new blood vessels, promotes tumor proliferation, maintenance, and metastasis. Angiopoietin 2 (Angpt2), a mitogen with a strong angiogenic effect, is highly specific to endothelial cells and a key player in angiogenesis. The inflammatory chemokine (C-C motif) ligand 4 (CCL4) is also important in the pathogenesis and progression of cancer. In this study, an analysis of records from The Cancer Genome Atlas (TCGA) database found higher CCL4 expression in oral cancer tissue than in normal healthy tissue. CCL4 treatment of oral cancer cells upregulated Angpt2 expression and stimulated mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase 1/2 (ERK), and signal transducer and activator of transcription 3 (STAT3) phosphorylation. Transfection of oral cancer cells with MEK, ERK, and STAT3 inhibitors and their small interfering RNAs inhibited CCL4-induced promotion of Angpt2 expression and angiogenesis. In a mouse model of OSCC, CCL4-treated cells promoted neovascularization in implanted Matrigel plugs, whereas inhibiting CCL4 expression suppressed Angpt2 expression and angiogenesis. CCL4 shows promise as a new molecular therapeutic target for inhibiting angiogenesis and metastasis in OSCC.

Visfatin Polymorphisms, Lifestyle Risk Factors and Risk of Oral Squamous Cell Carcinoma in a Cohort of Taiwanese Males.

Oral cancer is the eighth greatest generally diagnosed cancer amongst males worldwide and the fourth most generally malignancy amongst Taiwanese males. The pro-inflammatory adipocytokine visfatin promotes tumor growth. Elevated plasma visfatin levels have been identified in patients with oral squamous cell carcinoma (OSCC), although the biological mechanisms underlying the involvement of visfatin in the pathogenesis of OSCC are not well understood. Moreover, no information is available regarding associations between visfatin polymorphisms and carcinogenic lifestyle factors with OSCC. This study, therefore, investigated the effects of four visfatin gene polymorphisms (rs11977021, rs61330082, rs2110385, and rs4730153) and carcinogenic lifestyle factors (betel nut chewing, alcohol consumption and cigarette smoking) on the risk of developing OSCC in 1,275 Taiwanese males with OSCC, and 1,195 healthy males (controls). We also examined the associations between these visfatin genotypes and OSCC histopathological prognostic factors (pathological stage, tumor status, lymph node status, and metastasis). We found that compared with subjects with the CC genotype of SNP rs11977021, those with the CT+TT genotype were less likely to progress OSCC. In addition, an association was found between the rs4730153 variant and lymph node metastasis in the OSCC cohort.

Reduced tissue and serum resistin expression as a clinical marker for esophageal squamous cell carcinoma.

Esophageal cancer is one of the most common malignancies and leading cause of cancer-associated mortality worldwide. However, the molecular mechanisms underlying esophageal cancer progression and the development of clinical tools for effective diagnosis remain unclear. Resistin, which was originally identified as an adipose tissue-secretory factor, has been associated with obesity-related diseases, including certain types of cancer. Thus, the present study aimed to investigate the expression levels of resistin in tissue and serum specimens from patients with esophageal squamous cell carcinoma (ESCC) to determine the potential biological effects of resistin on ESCC cells. The results demonstrated that both tissue and serum resistin levels were significantly lower in patients with ESCC compared with healthy controls. In addition, resistin expression was positively associated with the body mass index of patients with ESCC. In vitro studies revealed that resistin inhibited the migratory ability of ESCC cells, while having no effect on ESCC cell proliferation. Taken together, these results suggest that resistin may have the potential to be developed into a clinical marker for ESCC. However, further studies are required to investigate resistin receptor expression and determine the potential involvement of resistin-associated biological pathways, which may provide insight for future development of targeted therapies for resistin-mediated ESCC.

Postoperative Changes in Tongue Area and Pharyngeal Airway Space following Mandibular Setback Surgery through Intraoral Vertical Ramus Osteotomy.

PURPOSE: The aim of this study was to determine changes in the tongue area and pharyngeal airway space (PAS) after intraoral vertical ramus osteotomy (IVRO). MATERIALS AND METHODS: Serial lateral cephalograms of 40 patients with mandibular prognathism who underwent IVRO were evaluated before (T1), immediately after (T2), and more than 1 year after (T3) surgery. Paired t-tests and Pearson's correlation analysis were used to evaluate the postoperative changes in the mandible, nasopharyngeal airway (NOP), retropalatal pharyngeal airway (RPP), retroglossal pharyngeal airway (RGP), hypopharyngeal airway (HOP), PAS, and tongue area (TA). The null hypothesis states that there are no significant correlations among the extent of mandibular setback and the changes in the TA and PAS after IVRO. RESULTS: Immediately after the operation (T12), the mandible was set back by 12.6 mm. The NOP, HOP, and PAS were significantly reduced by 35.7 mm2, 116 mm2, and 185 mm2, respectively. The TA was increased by 69.6 mm2. The changes in PAS and TA revealed no significant difference between female and male patients at T12, T23, and T13. Moreover, no significant correlations were found among the extent of mandibular setback, TA changes, and PAS changes after IVRO. Thus, the null hypothesis was accepted. CONCLUSIONS: At the final follow-up (T13), no significant change was found in the PAS (including NOP, RPP, RGP, and HOP) and TA. The changes in PAS and TA revealed no significant difference between female and male patients at T12, T23, and T13.

Traumatic dislocation of the mandibular condyle into the middle cranial fossa treated by an intraoral approach.

Dislocation of the mandibular condyle is one of several consequences of facial trauma that can be anticipated. The condylar neck is inherently weak and likely to fracture at the time of impact before dislocating into the middle cranial fossa. A review of the literature revealed that most cases of dislocation of the mandibular condyle into the middle cranial fossa are treated by open reduction and internal fixation via an extraoral approach or are treated conservatively with closed reduction. An intraoral approach is rare. Here we present a patient with traumatic dislocation of the mandibular condyle into the middle cranial fossa who was treated successfully by condylectomy and coronoidectomy through an intraoral approach and intermaxillary fixation followed by mouth-opening exercises and rehabilitation. Stable occlusion and movement of the mandible was achieved and the long-term results have been good. The intraoral approach may be an option in patients with traumatic dislocation of the mandibular condyle into the middle cranial fossa.

The Changes of Cheek Line (Lateral) and Face Line (Frontal) after Correction of Mandibular Prognathism.

OBJECTIVE: The purpose of the present study was to investigate the improvements of facial profile and postoperative stability by single mandibular setback surgery. MATERIALS AND METHODS: The study included twenty-seven patients who underwent mandibular prognathism correction by sagittal split ramus osteotomy (SSRO). Cephalometric radiograms (lateral and frontal) were collected and analyzed at three intervals: preoperatively (T1), immediately postoperatively (T2), and final follow-up postoperatively (T3). The lateral and frontal cephalometric parameters were measured. The immediate postoperative change (T21), postoperative stability (T32), and final surgical change (T31) were calculated and analyzed. The null hypothesis is that postoperative stability (T32) was not significantly correlated to amount of mandibular setback (T21). RESULTS: The immediate postoperative change (T21) of menton (Me) was significantly backward 8.7 mm. In the final postoperative change (T31), average chin points anterior movements were approximately 0.32 mm. Investigating frontal appearance, inter ramus posterior (InterRp) and intergonion (InterGo) widths were significantly increased with 1.8 and 2.2 mm, respectively. Bilateral ramus angles were not significantly increased, about 1°. The horizontal Me (T32) had significant correlation (p = 0.028) with amount of setback (T21). Therefore, null hypothesis is rejected. CONCLUSION: Postoperative relapse was significantly correlated to the amount of setback. The frontal transverse changes (InterRp and InterGo) were significantly increased.

Facial profile and frontal changes after bimaxillary surgery in patients with mandibular prognathism.

BACKGROUND/PURPOSE: Patients are always concerned about their postoperative appearance before surgery for facial deformity correction. The present study investigated the facial profile and frontal changes following two-jaw surgery. METHODS: Forty patients who underwent two-jaw surgery were divided by the amount of mandibular setback (group I: ≤8 mm and group II: >8 mm). Cephalometric radiograms (lateral and frontal) were collected and analyzed at three intervals: preoperatively (T1), immediately postoperatively (T2), and final follow-up (T3). The following points were identified: cheek points (C1-C5), pronasale (Prn, tip of the nose), anterior nasal spine (ANS), subnasal (Sn), point A, labrale superius (Ls), incision superius (Is), labrale inferius (Li), incision inferius (Ii), point B, labiomental sulcus (Si), pogonion (Pog), soft tissue pogonion (PogS), ramus point (RP), and gonion (Go). The immediate postoperative changes (T21), final postoperative changes (T32), and final stability (T31) were calculated and analyzed. RESULTS: In T31, the cheek line showed significant advancements of 2.3 mm (group I) and 1.6 mm (group II). The soft:hard tissue ratios were significantly correlated: Prn:ANS (0.37:1), Prn:A (0.39:1), Sn:A (0.85:1), C3:A (0.82:1), Ls:Is (0.92:1), Li:Ii (0.91:1), Si:B (0.88:1), and PogS:Pog (group I, 0.78:1 and group II, 0.93:1). The intercondylion and intergonial widths of group II (T31) significantly increased 1.8 and 4 mm, respectively. Regarding the postoperative skeletal stability (T32), group I showed significant correlations between amounts of mandibular setback, but group II did not. CONCLUSION: In the facial profile, the cheek line showed significant advancement postoperatively. The frontal mandibular transverse dimensions were significantly increased.

Comparisons of Jaw Line and Face Line after Mandibular Setback: Intraoral Vertical Ramus versus Sagittal Split Ramus Osteotomies.

BACKGROUND: This study investigates the differences in the lateral profile and frontal appearance after sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO) procedures for the correction of mandibular prognathism. METHODS: Sixty patients (30 SSRO and 30 IVRO) underwent mandibular setback surgery. Serial cephalograms were obtained: (1) T1: approximately 1 month before surgery; (2) T2: at least 6 months after surgery for SSRO and at least 1 year after surgery for IVRO. The landmarks, linear distances, and related angles were measured. The t-test was applied to the intragroup and intergroup comparisons. The null hypothesis was that SSRO and IVRO made no difference in the facial appearance. RESULTS: In the IVRO group, the ramus and gonial widths significantly decreased by 3.9 mm and 5.8 mm, respectively. SSRO significantly reduced the gonial angle by 2.6°, and IVRO increased it significantly by 5.3°. The postoperative increases at frontal bone levels 0 and 1 after IVRO were significantly larger than those after SSRO, but, at level 3, the increases after SSRO were larger than those after IVRO. In the frontal muscular and facial planes, SSRO and IVRO presented no difference. The frontal jaw angle and face angle were significantly larger with IVRO than with SSRO. Therefore, the null hypothesis was rejected. CONCLUSIONS: The ramus width and gonial width were significantly decreased in IVRO compared to SSRO. IVRO increased angles in the lateral profile (gonial angle and mandibular plane angle) and frontal appearance (jaw angle and face angle) more than SSRO did.

Tibial cancellous bone grafting in jaw reconstruction: 10 years of experience in Taiwan.

BACKGROUND: Use of proximal tibia as a donor site has been applied in jawbone reconstruction since the 1990s. Catone and colleagues described a U-shaped incision made on the iliotibial tract during tibial cancellous bone procurement for maxillofacial reconstruction in 1992. We used a curvilinear incision on the iliotibial tract in lateral approach in our tibial cancellous bone harvesting procedure. OBJECTIVES: The objectives of this retrospective study are to describe our modified lateral approach for procuring cancellous graft from the proximal tibia and to assess the bone volume, donor site morbidity, and associated complications. MATERIAL AND METHODS: Eighty consecutive jawbone reconstructions utilizing autogenous tibial cancellous bone grafts in 78 patients from March 1998 through March 2008 were reviewed. The patient group consisted of 45 males and 33 females, ages 18 to 76 (average age 36.1 ± 12.3). Minimal postoperative follow-up period was 3 months. Unlike the traditional U-shaped trapdoor incision on the iliotibial tract, our curvilinear incision was made almost parallel to the fibers of that tract. RESULT: Only mild complications were observed at donor sites, including temporary paresthesia, gait disturbance, and an unpleasant scar. The average procured graft volume was 17.8 mL. We also present the first case of reconstruction of mandibular continuity defects of up to 6 to 7 cm lengthwise by tibial cancellous bone grafting, which has not previously been reported in the English literature. CONCLUSION: The modified incision on the iliotibial tract allowed access to obtain an equally good bone volume from the lateral aspect of the proximal tibia, and it rendered wound closure much easier than the procuring techniques described in the earlier literature.