B7-H3 suppresses CD8+ T cell immunologic function through reprogramming glycolytic metabolism.

Malignant neoplasms pose a formidable threat to human well-being. Prior studies have documented the extensive expression of B7 homolog 3 (B7-H3 or CD276) across various tumors, affecting glucose metabolism. Yet, the link between metabolic modulation and immune responses remains largely unexplored. Our study reveals a significant association between B7-H3 expression and advanced tumor stages, lymph node metastasis, and tumor location in oral squamous cell carcinoma (OSCC). We further elucidate B7-H3's role in mediating glucose competition between cancer cells and CD8+ T cells. Through co-culturing tumor cells with flow cytometry-sorted CD8+ T cells, we measured glucose uptake and lactate secretion in both cell types. Additionally, we assessed interferon-gamma (IFN-γ) release and the immune and exhaustion status of CD8+ T cells. Our findings indicate that B7-H3 enhances glycolysis in OSCC and malignant melanoma, while simultaneously inhibiting CD8+ T cell glycolysis. Silencing B7-H3 led to increased IFN-γ secretion in co-cultures, highlighting its significant role in modulating CD8+ T cell functions within the tumor microenvironment and its impact on tumorigenicity. We also demonstrate that glycolysis inhibition can be mitigated by exogenous glucose supplementation. Mechanistically, our study suggests B7-H3's influence on metabolism might be mediated through the phosphoinositide3-kinase (PI3K)/ protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling pathway. This research unveils how B7-H3 affects immune functions via metabolic reprogramming.

Research progress of biomineralization for the diagnosis and treatment of malignant tumors.

Malignant tumors have long been a prominent subject of research in order to foster innovation and advancement in diagnostic and therapeutic modalities. However, the current clinical treatment of malignant tumors faces significant limitations. In light of recent advancements, the World Health Organization (WHO) officially designated malignant tumors as a chronic disease in 2006. Accordingly, maintaining the tumor in a stable state and minimizing its detrimental impact on the body emerges as a potentially advantageous approach to oncological treatment. One emerging strategy that has garnered substantial attention from the academic community is the construction of a biomineralized layer surrounding solid tumors for tumor blockade therapy. This innovative approach is regarded as safe, effective, and long-lasting. This review aims to provide a comprehensive summary of the advancements made in the utilization of biomineralization for the diagnosis and treatment of malignant tumors.

Primary maxillary sinus carcinosarcoma with multidisciplinary management: a case report with 4 years follow-up and literature review.

BACKGROUND: Primary maxillary sinus carcinosarcoma (CS) is an extremely rare malignant tumor characterized by biphasic histologic components, lack of standardized treatment, high recurrence rate, and poor prognosis. This paper presents a case of primary maxillary sinus CS and its treatment. CASE PRESENTATION: A 39-year-old female patient complained of right facial pain and maxillary teeth numbness on March 21, 2018. Computed tomography examination revealed a malignant mass with osteolytic destruction. Preoperative biopsy suggested sarcomatoid carcinoma or CS. A total right maxillectomy under general anesthesia was performed on April 12, 2018. The final staging was T3N0M0 (ACJJ 2019). Postoperative radiotherapy and chemotherapy were performed. On May 26, 2018, the patient received the first cycle of doxorubicin plus ifosfamide. Two days before radiotherapy, the patient received an intra-oral prosthesis. From June 20, 2018, to August 22, 2018, the patient received concurrent chemoradiotherapy: radiotherapy (60 Gy in 30 fractions) and the second cycle of doxorubicin. Then, the patient received four cycles of doxorubicin plus ifosfamide. The patient was followed for 39 months with no evidence of disease. CONCLUSION: Using multidisciplinary therapy, clinical-stage T3N0M0 (ACJJ 2019) maxillary sinus CS may achieve a good prognosis.

Effect of piceatannol against malignant melanoma in vivo and in vitro.

OBJECTIVES: To study the antitumor effect of piceatannol (PIC) on malignant melanoma in vitro and in vivo. METHODS: B16F10 cells were cultured in vitro and treated with gradient concentrations of PIC. Cell viability was detected with methyl thiazolyl tetrazolium (MTT) assay; matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), spleen tyrosine kinase (Syk), and p-Syk were detected with Western blot; migration ability was detected with wound healing assay; invasion ability was detected with Transwell assay. Syk expression was suppressed through RNA interference for the detection of the possible mechanism of PIC in melanoma. An in vivo study was established by creating B16F10-bearing mice with intraperitoneal injection of PIC. RESULTS: The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. In vivo study revealed that different concentrations of PIC cangreatly inhibit melanoma progression. CONCLUSIONS: PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.

Increased expression of PFKFB3 in oral squamous cell carcinoma and its association with lymphangiogenesis.

OBJECTIVE: This study aimed to investigate the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and its association with lymphangiogenesis in oral squamous cell carcinoma (OSCC). STUDY DESIGN: The expression of PFKFB3 in OSCC and adjacent normal tissues was detected by immunohistochemistry, Western blot, and quantitative reverse transcription polymerase chain reaction in 78 patients with OSCC. Immunohistochemical analysis was performed to quantify lymphatic vessel density (LVD), which was labeled using podoplanin (PDPN) proteins of lymphatic endothelial cells, and PDPN mRNA was evaluated by quantitative reverse transcription polymerase chain reaction. RESULTS: Compared with adjacent normal tissues, the expression of PFKFB3 and PDPN protein was significantly higher in OSCC tissues (P < .0001). Moreover, PFKFB3 protein was associated with LVD and lymph node metastasis (P < .05). Compared with the normal tissues, increased mRNA expression of PFKFB3 and PDPN in the OSCC group (P < .05). In addition, the mRNA expression of PDPN was positively correlated with that of PFKFB3 (P < .0001) in the OSCC group. CONCLUSIONS: PFKFB3 and PDPN expression was increased in OSCC. Further, PFKFB3 expression was associated with PDPN expression and LVD, suggesting that PFKFB3 may be considered to mediate lymphangiogenesis and predict lymph node metastasis in OSCC.

Smad7 attenuates TGF-ß-mediated aging-related hypofunction of submandibular glands.

Submandibular glands have essential functions in taste, mastication, swallowing, and digestion. Submandibular gland hypofunction is prevalent in the elderly, impairing the patients' quality of life. Current clinical treatment strategies have not decelerated or reversed the pathological process of submandibular gland hypofunction. Therefore, novel restoration strategies should be explored. However, studies on the mechanism of aging-related submandibular gland hypofunction remain very limited. The role of the TGF-ß/Smad pathway in fibrosis has been studied in other organs. Therefore, this study aimed to elucidate the role of TGF-ß/Smad signaling in the aging-related submandibular gland hypofunction. The results showed that Smad7 knockout in mice decreased the salivary flow rate. H&E, Masson trichrome, and immunohistochemistry staining of MCP-1 and α-SMA showed that Smad7 knockout in mice resulted in lymphocytic infiltration, acinar cell atrophy, and interstitial fibrosis. The Western blotting of collagen I and III also confirmed extensive fibrosis. We then found that Smad7 depletion resulted in the TGF-ß-mediated fibrosis via mir-21, mir-29, and np_5318, and NFκB-driven inflammation activation. This study confirmed the inhibitory role of Smad7 in the aging-related submandibular gland hypofunction. Therefore, it provided a promising treatment target for aging-related dysfunction and sialadenitis of submandibular gland.

[Application of mixed reality in oromaxillofacial head and neck oncology surgery: a preliminary study].

Mixed reality (MR), characterized by the ability to integrate digital data into human real feeling, is a new technique in medical imaging and surgical navigation. MR has tremendous value in surgery, but its application in oromaxillofacial head and neck oncology surgery is not yet reported. This paper reports the application of MR in oromaxillofacial head and neck oncology surgery. The merits, demerits, and present research situations and prospects of MR are further discussed.

Performance of Different Imaging Techniques for Detection of Para-Aortic Lymph Node Metastasis from Gynecological Malignancies: A Systematic Review and Meta-Analysis.

OBJECT: The purpose of this review is to assess the diagnostic performance of different imaging techniques for the detection of para-aortic lymph node (PALN) metastasis from gynecological malignancies. METHODS: Six databases, from the earliest available date of indexing through July 22, 2018, were systematically searched. In addition, the reference lists of relevant articles were searched by hand. Study allocation, data extraction, and quality assessment were independently performed by 2 reviewers. The size effect, sensitivity (SEN), specificity (SPE), positive likelihood ratio, negative likelihood ratio, diagnostic OR, and 95% CIs were used in the meta-analysis. The area under the curve (AUC) and Q* were calculated to reflect the synthesized diagnostic accuracy. Statistical calculations of this meta-analysis were conducted using STATA version 14.0 software. RESULTS: Across 41 eligible studies (1,615 participants), pooled SEN, SPE, and AUC of magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), PET-CT, and lymphangiography analyses were 25%, 93%, 0.7675; 60%, 94%, 0.9050; 83%, 96%, 0.9422; 66%, 97%, 0.9501; 77%, 75%, 0.8332, respectively. Analysis of combined summary receiver operating characteristic curves indicated that PET and PET-CT were superior to other imaging modalities. CONCLUSION: The present meta-analysis demonstrated that PET and PET-CT should be the first choice for detecting PALN metastasis in gynecological malignancies. CT was also suitable for confirmation. MRI was not recommended. Further studies are needed for PALN assessment.

The immunoregulatory protein B7-H3 promotes aerobic glycolysis in oral squamous carcinoma via PI3K/Akt/mTOR pathway.

OSCC (oral squamous carcinoma) is one of most common malignant cancer. Although previous studies have found abnormal expression of B7-H3 in human OSCC, the exact role and molecular mechanism of B7-H3 in OSCC remain unknown. In this study, we investigated the role of B7-H3 in glucose metabolic reprogramming of OSCC cells in vitro and in vivo. We first detected the expression of B7-H3 in OSCC samples. Next, siRNAs and overexpression short-hairpin RNA of B7-H3 were transfected into SCC25 and Cal27 cells, and cell proliferation, migration and invasion were analyzed via CCK8, colony formation and transwell assays. Then glycolysis flux was determined through measuring glucose uptake and lactate production, and mRNA and protein expression levels were determined by real-time quantitative PCR and western blot respectively. The results presented here showed B7-H3 was upregulated in OSCC samples compared with normal tissues, and the expression level was associated with tumor size and nodal metastasis. B7-H3 affects OSCC cell proliferation, migration and invasion. We also found that B7-H3 promoted the Warburg effect, evidenced by increase glucose uptake and lactate production. We further demonstrated that B7-H3 enhanced OSCC glycolysis through the upregulation of HIF-1α and its downstream targets, Glut1 and PFKFB3, which are key factors in glycolysis. Mechanically, we demonstrated that B7-H3 regulates HIF-1α expression through PI3K/Akt/mTOR pathway. Metabolic imaging of human OSCC cancer xenograft in mice confirmed that B7-H3 enhanced tumor glucose uptake, glycolysis promoted genes expression and tumor growth. Taken together, our results have unveiled a mechanism that B7-H3 drives OSCC progression through enhancing of glycolytic metabolic program in OSCC.

Piezosurgery vs conventional rotary instrument in the third molar surgery: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/PURPOSE: The surgical removal of mandibular third molars is frequently accompanied by significant postsurgical sequelae. Different instruments such as piezosurgery and conventional rotary handpiece have been used to decrease such adverse events. There are controversial results from randomized controlled trials evaluating the effects of Piezosurgery in the mandibular third molar extraction, compared with conventional rotary instrument. This study was performed to determine the impact of piezosurgery versus conventional rotary instrument on postoperative reactions after extraction. MATERIALS AND METHODS: A systematic review and meta-analysis was performed to combine relevant RCTs results. RESULTS: Five RCTs were eligible for this study, enrolling a total of 402 patients. Compared with conventional rotary instrument, pain score at 6 or 7 days and mouth opening at 1 day after surgery was significantly lower in Piezosurgery group (SMD -0.33, 95% CI: -0.56 to -0.10, P = 0.005), as well as swelling score at 7 days after surgery (SMD -1.95, 95% CI: -3.22 to -0.67, P = 0.003). Furthermore, mouth opening at 1 day after surgery was significantly better in patients treated with Piezosurgery (SMD 0.84, 95% CI: 0.19 to 1.49, P = 0.01). However, more operation time will be required for Piezosurgery (MD 6.23, 95% CI: 3.32 to 9.14, P < 0.0001). With regard to analgesic dosage, pooled results from two RCTs suggested there were no significant differences between Piezosurgery and conventional rotary instrument (SMD -1.45, 95% CI: -4.39 to 1.49, P = 0.33). CONCLUSION: There might be some advantages on third mandibular molar extraction with piezosurgery compared to conventional rotary instrument. More multi-centre trials are required to get more conclusive results.

Association between integrin-linked kinase and hyperthermia in oral squamous cell carcinoma.

The present study aimed to observe the effect of the biological functions of integrin-linked kinase (ILK) silencing combined with hyperthermia on Tca8113 cells. Lentivirus-mediated short hairpin RNA (shRNA)-targeting ILK was transfected into oral squamous cell carcinoma (OSCC) Tca8113 cells and, combined with hyperthermia, several experimental methods were used to detect their biological behavior in vitro. On the basis of in vitro experiments, Tca8113 cells were transplanted into nude mice models, and ILK-shRNA-lentivirus was injected into the nude mice transplanted tumor and combined with hyperthermia. Tumor morphology and the associated protein expression changes were determined. Subsequent to ILK silencing combined with hyperthermia, the growth, migration and proliferation of Tca8113 cells were significantly inhibited. Flow cytometry revealed that the cells were blocked in the S phase, and western blot analysis demonstrated that ILK, phosphorylated (p)-RAC-alpha serine/threonine-protein kinase (Akt), p-glycogen synthase kinase-3ß and p-heat shock factor 1 protein expression levels were significantly decreased, while apoptosis-associated protein B-cell lymphoma-2-associated X protein expression and the efficacy of hypothermia were significantly increased. By ILK silencing combined with hyperthermia, a significant therapeutic effect on transplanted tumors was observed in nude mice. Immunohistochemistry revealed the same results as the in vitro experiments. ILK silencing combined with hyperthermia can inhibit the growth, proliferation and migration of Tca8113 cells, promote Tca8113 cell apoptosis, inhibit the phosphatidylinositol-3-kinase/Akt signaling pathway and increase hyperthermia sensitivity; the combination therapy exhibits a synergistic sensitizing effect. Therefore, ILK silencing combined with hypothermia may serve as a novel combination therapy strategy against OSCC.

A Hypothesis and Pilot Study of Age-Related Sensory Innervation of the Hard Palate: Sensory Disorder After Nasopalatine Nerve Division.

BACKGROUND The nasopalatine nerve may be injured during extraction of teeth embedded in the anterior hard palate. The neural recovery process and its impact on sensation in the anterior hard palatal region are controversial. In our clinical practice, we noticed a distinct recovery process in children compared with adolescents or adults after surgery. We hypothesized that the sensory innervations of the anterior palate might shift during later childhood and pre-adolescence, which is due to the development of the nasopalatine nerve along with the maxillary growth and permanent teeth eruption. MATERIAL AND METHODS Forty patients (20 females and 20 males, mean age 11.8±2.2) with impacted supernumerary teeth in anterior palatine area were included into our study, and were divided into 3 groups according to their age. A 24-week follow-up was conducted and the sensation in the anterior hard palate region was examined at every check point. All the data were collected and analyzed by Kaplan-Meier analysis. RESULTS Fourteen children did not complain of any numbness immediately after anesthetization, and other children with sensory disorders had shorter healing periods compared to adolescent/adult patients. CONCLUSIONS The results indicated that the dominant nerve of the anterior hard palate region was dramatically changed from the greater palatine nerve to the nasopalatine nerve, which is important in deciding when to operate and in selection of anesthesia method.

Effects of lentivirus-mediated shRNA targeting integrin-linked kinase on oral squamous cell carcinoma in vitro and in vivo.

Integrin-linked kinase (ILK), a highly conserved intracellular protein of serine/threonine protein kinase activities, which is associated with the integrin and growth factor receptor signaling pathway, is involved in the regulation of cell proliferation, apoptosis, differentiation, migration and epithelial-mesenchymal transition (EMT). Findings of a previous study showed that ILK overexpression was strongly correlated with a more aggressive tumor phenotype, recurrence and poor survival for oral squamous cell carcinoma (OSCC) patients, as well as some EMT markers. In order to investigate the underlying mechanisms involved, a lentivirus-mediated short hairpin RNA (shRNA) was employed to downregulate ILK. The results showed that the knockdown of ILK inhibited cell growth, adhesion and invasion ability in vitro, and OSCC cells deficient of ILK were blocked in the S phase and underwent apoptosis. Additionally, ILK shRNA inhibited EMT by impairing the expression of Snail, Slug and Twist2 and enhacning E-cadherin expression. ILK shRNA suppressed the phosphorylation of downstream signaling targets Akt and GSk-3ß. In addition, the knockdown of ILK inhibited tumor growth, invasion and metastasis of xenograft tumors in vivo. These results suggested that ILK is a promising therapeutic target for the treatment of OSCC.

Angiogenic gene-modified myoblasts promote vascularization during repair of skeletal muscle defects.

Vascularization is thought to be a principle obstacle in the reconstruction of skeletal muscle defects. Long-term survival of reconstructed skeletal muscle is dependent on good vascularization. In this study, we upregulated angiogenic gene expression in myoblasts in an attempt to promote vascularization during repair of skeletal muscle defects. Skeletal myoblasts were isolated and expanded from newborn male Sprague-Dawley (SD) rats. The cells were transfected with human vascular endothelial growth factor 165 (VEGF-165) or human stromal cell-derived factor 1 (SDF-1), using Lipofectamine™ 2000 transfection reagent, prior to seeding onto calf collagen scaffolds. Gene and protein overexpression was verified by ELISA, RT-PCR and western blot analysis. Cell-seeded scaffolds were transplanted into back muscle defects in female SD rats. At weeks 2, 4 and 8 after transplantation, Y chromosome detection was used to observe the survival of growth factor-producing cells within the scaffolds in vivo. Capillary density was investigated using microvessel density detection, haematoxylin and eosin (H&E) staining and immunohistochemical staining. We found that vascularization was enhanced by transfected myoblasts compared with non-transfected myoblasts. In addition, VEGF-165 and SDF-1 had a synergistic effect on vascularization during repair of skeletal muscle defects in vivo. In conclusion, we have combined myoblast-seeded collagen sponge with gene therapy, resulting in a promising approach for the construction of well-vascularized skeletal muscle.

[Expression and clinical significance of serine-threonine kinase/mammalian target of rapamycin/p70 S6K signal path- way in oral squamous cell carcinoma].

OBJECTIVE: To investigate the expressions of serine-threonine kinase (Akt)/mammalian target of rapamycin (mTOR)/p70 S6K in oral squamous cell carcinoma (OSCC) and provide references for early diagnosis and prognosis evalua- tion of OSCC. METHODS: A total of 51 cases of OSCC, 10 cases of paracancerous mucosa, and 10 cases of normal oral mucosa were collected. The expressions of Akt/mTOR/p70 S6K in these cases were detected using the SP method of immunohisto- chemistry. The correlation between their expressions in OSCC was also analyzed. RESULTS: The positive expressions ofp-Akt, p-mTOR, and p70 S6K in OSCC were significantly higher than those in normal oral mucosa and paracancerous mucosa. The expressions of p-Akt, p-mTOR, and p70 S6K in OSCC were not correlated with age, gender, and clinical stage; by comparison, these expressions were correlated with lymph node metastasis and pathological grade. Strong positive correlations were also observed between the expressions ofp-Akt, p-mTOR, and p70 S6K in OSCC. CONCLUSION: Akt/mTOR/p70 S6K signaling molecules exhibit active expressions in OSCC and may be implicated in the occurrence and development of OSCC.

Case report: postradiation chondrosarcoma with a short latency period of 6 months.

We describe a case of postradiation chondrosarcoma after basal cell carcinoma treatment. At the time he presented, the patient was a 35-year-old man who had received radiotherapy at a dose of 70 Gy for 8 weeks. Six months after radiation treatment, a rapidly growing mass at the upper right alveolar ridge of the gums, where radiation had been given, was diagnosed as chondrosarcoma. Generally, chondrosarcoma occurs after a latency period of several years following radiation. However, there are a few relevant reports indicating that maxillofacial chondrosarcoma can develop after radiotherapy for basal cell carcinoma, with a short latency of 6 months. We hypothesize that the dosage and treatment time of radiation may have played a role in the opening/closing of the Hh-signaling pathway in the case of this patient.

New advances in the mesenchymal stem cells therapy against skin flaps necrosis.

Mesenchymal stem cells (MSCs), multipotential cells that reside within the bone marrow, can be induced to differentiate into various cells, such as osteoblasts, adipocytes, chondrocytes, vascular endothelial progenitor cells, and other cell types. MSCs are being widely studied as potential cell therapy agents due to their angiogenic properties, which have been well established by in vitro and in vivo researches. Within this context, MSCs therapy appears to hold substantial promise, particularly in the treatment of conditions involving skin grafts, pedicle flaps, as well as free flaps described in literatures. The purpose of this review is to report the new advances and mechanisms underlying MSCs therapy against skin flaps necrosis.

Expression and clinical significance of serine-threonine kinase/mammalian target of rapamycin/p70 S6K signal path- way in oral squamous cell carcinoma / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the expressions of serine-threonine kinase (Akt)/mammalian target of rapamycin (mTOR)/p70 S6K in oral squamous cell carcinoma (OSCC) and provide references for early diagnosis and prognosis evalua- tion of OSCC.</p><p><b>METHODS</b>A total of 51 cases of OSCC, 10 cases of paracancerous mucosa, and 10 cases of normal oral mucosa were collected. The expressions of Akt/mTOR/p70 S6K in these cases were detected using the SP method of immunohisto- chemistry. The correlation between their expressions in OSCC was also analyzed.</p><p><b>RESULTS</b>The positive expressions ofp-Akt, p-mTOR, and p70 S6K in OSCC were significantly higher than those in normal oral mucosa and paracancerous mucosa. The expressions of p-Akt, p-mTOR, and p70 S6K in OSCC were not correlated with age, gender, and clinical stage; by comparison, these expressions were correlated with lymph node metastasis and pathological grade. Strong positive correlations were also observed between the expressions ofp-Akt, p-mTOR, and p70 S6K in OSCC.</p><p><b>CONCLUSION</b>Akt/mTOR/p70 S6K signaling molecules exhibit active expressions in OSCC and may be implicated in the occurrence and development of OSCC.</p>

Expression of integrin-linked kinase in adenoid cystic carcinoma of salivary glands correlates with epithelial-mesenchymal transition markers and tumor progression.

Integrin-linked kinase (ILK) plays a key role in cell-excellular matrix interactions mediated by integrins and several growth factors, regulating cell proliferation, apoptosis, differentiation, and migration. It has also been implicated in the development and progression in several malignancies involving epithelial to mesenchymal transition (EMT). However, the correlations between ILK and EMT markers and the progression of salivary adenoid cystic carcinoma (SACC) have not been well elucidated. Here, by immunohistochemistry, we studied the expression of ILK, Snail, E-cadherin, and N-cadherin in 94 SACC specimens and analyzed their correlations with clinicopathologic characteristics. Positive expression of ILK protein was detected in 76.6 % of the tumors. Increased expression of ILK and Snail and decreased E-cadherin expression correlated strongly with tumor solid type (P = 0.017, P = 0.008, and P = 0.038, respectively), advanced TNM stage (P = 0.021, P = 0.034, and P = 0.009, respectively), and increased risk of recurrence (P = 0.023, P = 0.011, and P = 0.039, respectively) and distant metastasis (P < 0.001, P < 0.001, and P = 0.001, respectively). Moreover, up-regulation of Snail and N-cadherin and down-regulation of E-cadherin correlated significantly with ILK over-expression (P < 0.001, P = 0.001, and P < 0.001, respectively) and a neural-invasive phenotype (P = 0.017, P = 0.002, and P < 0.001, respectively). Taken together, our results suggest that ILK may have an important role in progression and metastasis of SACC, possibly through EMT involving up-regulation of Snail and consequent aberrant expression of E-cadherin and N-cadherin. ILK should be considered as a potential therapeutic molecular target for patients with SACC.

Correlation between the expression of Id-1 and hyperthermia-associated molecules in oral squamous cell carcinoma.

OBJECTIVE: To investigate the expression of inhibitor of differentiation/DNA binding (Id-1), phosphatidylinositol-3-kinase/protein kinase B pathway proteins and hyperthermia-associated protein and their association with various clinicopathological factors in oral squamous cell cancer (OSCC), and explore the relationship among them in OSCC. METHODS: Id-1, phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase 3ß (p-GSK3ß) and phosphorylated heat shock factor 1 (p-HSF1) expression were assessed immunohistochemically in 76 OSCC. RESULTS: Id-1 (73.8%), p-Akt (65.8%), p-GSK3ß (60.5%) and p-HSF1 (75%) were found to be overexpressed in most of the oral cancer samples tested, and the expressions of them are correlated with advanced clinical stage, metastasis and recurrence (p<0.01), but there is no apparent relationship with gender, age, differentiation and habits (p>0.05). Survival curves show that the survival of patients with high Id-1, p-Akt, p-GSK3ß and p-HSF1 expression was significantly worse than those with low Id-1, p-Akt, p-GSK3ß and p-HSF1 expression (p=0.000). Id-1 expression was significantly higher in cases with high expression of p-Akt, p-GSK3ß and p-HSF1 than in those with low expression (p=0.002, p=0.003, p=0.001). CONCLUSIONS: This study revealed that there was a positive correlation between Id-1 expression and the expression of p-Akt, p-GSK3ß and p-HSF1. The inhibition of Id-1 expression can improve the efficacy of hyperthermia in OSCC.