Expanding the concept of patient-derived xenografts cohorts in head and neck cancer: current and future perspectives / 华西口腔医学杂志

Head and neck cancer is the seventh common cancer in the world, and various existing treatment strategies provide modest benefit for most patients with head and neck cancer. Meanwhile, therapeutic strategies lacking molecular typing significantly hinder the development of individualized treatment for head and neck cancer. In recent years, connected by preclinical models, the novel ideal has gradually reached a consensus in terms of facilitating inter-transformation of clinical problems and basic achievements. As a bridge between basic research and clinical transformation, patient-derived xenografts (PDX) models precisely replicate genetic characteristics and tumor evolution, which are displaying great vitality in elucidating the mechanism of tumorigenesis and progression. Moreover, cohorts composed of several PDX models highlight the unique advantages of mice for drug screening and biomarker analysis for patients. This ideal preclinical model explores potential treatment strategies suited the ethical standards as much as possible for patients.

Metformin induced apoptosis of nasopharyngeal carcinoma cell CNE-1 by regulating miR-let-7a and IGF-1R / 医学研究生学报

Objective research the effects of metformin on proliferation and apoptosis in nasopharyngeal carcinoma cell CNE-1 and investigate the role of miR-let-7a、IGF-1R in it. Methods The nasopharyngeal carcinoma cell CNE-1 was treated with different concentrations of metformin for 24h, then the proliferation activity of cell was detected by CCK8 method; the apoptosis rate of cell was measured by flow cytometry; the expression levels of bcl-2、bax and IGF-1R mRNA and miR-let-7a were detected by real-time quantitative PCR; the expression level of IGF-1R protein was detected by Western blot. Results Compared with the control group, the cell proliferation activity of metformin group decreased(P<0.05), and it gradually decreased along with the increase of metformin concentration. The cell apoptosis rate of metformin group increased(P<0.05 except for the 5 mmol/L group), and it gradually increased along with the increase of metformin concentration. The expression levels of bax mRNA and miR-let-7a were up-regulated in the metformin group(P<0.05), while the expression levels of bcl-2 mRNA,IGF-1R mRNA and IGF-1R protein were decreased(P<0.05). Conclusion Metformin could inhibit the proliferation and induce apoptosis of CNE-1. The mechanism maybe related to the up-regulation of miR-let-7a and down-regulation of IGF-1R.

Mesenchymal stem cells from human umbilical cord ameliorate testicular dysfunction in a Male rat hypogonadism model / 亚洲男科学杂志(英文版)

Androgen deficiency is a physical disorder that not only affects adults but can also jeopardize children's health. Because there are many disadvantages to using traditional androgen replacement therapy, we have herein attempted to explore the use of human umbilical cord mesenchymal stem cells for the treatment of androgen deficiency. We transplanted CM-Dil-labeled human umbilical cord mesenchymal stem cells into the testes of an ethane dimethanesulfonate (EDS)-induced male rat hypogonadism model. Twenty-one days after transplantation, we found that blood testosterone levels in the therapy group were higher than that of the control group (P = 0.037), and using immunohistochemistry and flow cytometry, we observed that some of the CM-Dil-labeled cells expressed Leydig cell markers for cytochrome P450, family 11, subfamily A, polypeptide 1, and 3-β-hydroxysteroid dehydrogenase. We then recovered these cells and observed that they were still able to proliferate in vitro. The present study shows that mesenchymal stem cells from human umbilical cord may constitute a promising therapeutic modality for the treatment of male hypogonadism patients.

Differentiation of human umblical cord mesenchymal stem cells into Leydig cells in the rat testis interstitium: An experimental study / 中华男科学杂志

<p><b>Objective</b>To explore the feasibility of inducing human umbilical cord mesenchymal stem cells (HUMSCs) to differentiate into Leydig cells in the interstitial tissue of the rat testis.</p><p><b>METHODS</b>HUMSCs were obtained by tissue blocks culture attachment and their purity and multi-lineage differentiation ability were verified by flow cytometry and chondrogenic/adipogenic/osteogenic differentiation. Then the HUMSCs were marked by CM-Dil and transplanted into the interstitial tissue of the rat testis. At 4 and 8 weeks after transplantation, the survival and differentiation status of the HUMSCs were observed by immunofluorescence staining and flow cytometry. The suspension of the rat Leydig cells was obtained at 8 weeks for determining the expression of the Leydig cell marker 3β-HSD in the HUMSCs, the cells labeled with CM-Dil were sorted and cultured, and the medium collected after 3 days of culture for measurement of the testosterone level.</p><p><b>RESULTS</b>The expression of the Leydig cell marker CYPllal was not observed in the HUMSCs at 4 weeks but found at 8 weeks after transplantation and the differentiation rate of 3β-HSD was about 14.5% at 8 weeks. CM-Dil labeled cells survived after sorting and testosterone was detected in the medium.</p><p><b>CONCLUSIONS</b>HUMSCs are likely to differentiate into Leydig cells in the interstitium of the rat testis.</p>

Human umbilical cord mesenchymal stem cells may differentiate into Leydig cells through conditioned medium induction / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the feasibility of inducing human umbilical cord mesenchymal stem cells (HuMSCs) to differentiate into Leydig cells through conditioned medium derived from Leydig cells.</p><p><b>METHODS</b>HuMSCs and Leydig cells were obtained by tissue blocks culture attachment and enzymatic digestion respectively. HuMSCs were induced by conditioned medium of Leydig cells as an experiment group while those before induction were cultured as a control group. The expressions of LHR, 3β-HSD and StAR in the induced HuMSCs were determined by RT-PCR after 3, 7 and 10 days of culture; those of CYP11A1, CYP17A1 and 3β-HSD measured by immunofluorescence staining after 2 weeks; and that of 3β-HSD detected by Western blot after 4 weeks.</p><p><b>RESULTS</b>The experimental group showed positively expressed LHR, 3β-HSD and StAR at 3, 7 and 10 days, CYP11A1, CYP17A1 and 3β-HSD at 2 weeks, and 3β-HSD at 4 weeks, while the control group revealed negative expressions at all the time points.</p><p><b>CONCLUSION</b>Induced with conditioned culture medium derived from Leydig cells, HuMSCs are likely to differentiate into steroidogenic cells and eventually into Leydig cells.</p>

Induced differentiation of stem cells into androgen-secreting cells / 中华男科学杂志

Leydig cells are the major source of androgens in males. Stem cells can be induced to differentiate into androgen-secreting Leydig like cells, whose functions are regulated by the hypothalamus and pituitary, so that they precisely secret the necessary hormones to maintain physiological function. Therefore, the establishment of an effective protocol to induce the differentiation of stem cells into androgen-secreting cells is very helpful for the treatment of hypogonadism caused by abnormalities of Leydig cells. This review outlines the recent findings concerning the differentiation of stem cells into androgen-secreting cells.

Gamma knife radiosurgery for intracranial chondrosarcoma:a report of 4 cases and literature review / 中华神经医学杂志

Objective To discuss the clinical effect of gamma knife radiosurgery on patients with intracranial chondrosarcoma.Methods Four patients with residual chondrosarcoma (one male and three female),admitted to our hospital from November 2004 to January 2012 and verified by biopsy,were chosen in our study; their clinical data were retrospectively analyzed; the mean age of patients was 31.3 years (ranged from 26-36 years).The mean tumor volume of these patients by gamma knife radiosurgery was 13.8 cm3 (ranged from 0.6-25.4 cm3).The mean dose delivered to the tumor margin was 17.3 Gy (ranged from 15-20 Gy) and the mean tumor maximum dose was 35 Gy (ranged from 30-40 Gy).A mean often isocenters (range 4-19) were used for dose planning.All patients were followed up for 5 to 28 months (mean 14.5 months).Results Two patients had residual chondrosarcoma located in the left mastoid,and jugular foramen area and saddle area were followed up for 19 and 9 months,respectively;their tumors did not increase and the patients were alive and enjoyed good living.Recurrence happened inone patient had the right residual orbit-cranial communicating chondrosarcoma at 28 months of follow-up; she accepted twice operations because of the recurrent tumors,but the outcome was bad; and she was dead at 56 months after gamma knife treatment.One patient had residual chondrosarcoma in the left parasella appeared tumor recurrence with hydrocephalus at 5 months of follow-up,and then,follow up was lost.All the four patients had no complications associated with gamma knife radiosurgery.Conclusion Gamma knife radiosurgery can be an auxiliary therapy for residual chondrosarcoma after craniotomy,enjoying advantages as high accuracy,reliable clinical efficacy,being less damage to the surrounding tissues.

Structure-based identification of drug-like inhibitors of p300 histone acetyltransferase / 药学学报

A growing body of evidence suggests that p300 histone acetyltransferase plays important roles in cancer cell differentiation and proliferation. Here, we employed structure-based hierarchical virtual screening method to identify novel lead compounds of p300 histone acetyltransferase. From a screening library containing approximate 100 000 diverse druglike compounds, 33 compounds were chosen for experimental testing and one compound, 4-acetyl-2-methyl-N-morpholino-3,4-dihydro-2H-benzo[b][1, 4]thiazine-7-sulfonamide (17), showed as micromolar inhibitor. Based on its predicted binding pose, we investigated its binding characteristics by designing two series of structural modifications. The obtained structure-activity relationship results are consistent with the predicted binding model. We expect that the identified novel p300 histone acetyltransferase inhibitors will serve as starting points for further development of more potent and specific histone acetyltransferase inhibitors.

Expression of galectin-1 in carcinogenesis of oral mucosal epithelium / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the expression of galectin-1 in oral squamous cell carcinoma(OSCC) and its clinical significance.</p><p><b>METHODS</b>Detection of the mRNA and protein expression of galectin-1 in the in vitro cellular carcinogenesis model of OSCC, OSCC cell lines and tissue specimens from 30 primary OSCC patients were performed using real-time polymerase chain reaction (PCR), Western blotting and immunohistochemistry, respectively.</p><p><b>RESULTS</b>The value of galectin-1 mRNA and protein level in human immortalized oral epithelia cell (HIOEC) cell was 0.071 ± 0.023, 0.118 ± 0.046, Compared with the HIOEC, galectin-1 mRNA level and protein expression were increased significantly in all the cell lines (0.141 ± 0.049, 0.504 ± 0.33) (P < 0.01). The levels of mRNA and protein expression of galectin-1 were significantly higher in the cancerous tissue (0.059 ± 0.034, 1.5 ± 0.68) than in the normal adjacent tissues (0.029 ± 0.012, 0.4 ± 0.56) (P < 0.01).</p><p><b>CONCLUSIONS</b>The expression of galectin-1 gene up-regulated in carcinogenesis process of OSCC significantly may be related to the tumorigenesis and development of OSCC, which illustrates its potential clinical application as tumor marker for early diagnosis.</p>

Distribution changes of forefoot plantar pressure in hallux valgus / 医用生物力学

Objective To investigate the changes of distribution of plantar pressure in Hallux Valgus and provide laboratory proof for clinical therapy and rehabilitation of hallux valgus. Method 17 cases of hallux valgus with 34 involved feet were examined. 17 persons with normal feet were choosen as control group. Forefoot plantar pressure was measured during walking by Footscan system. The forefoot was divided into five regions according to the five metatarsals. The parameters, peak pressure (PP) and pressure time integral (PTI) of the five regions, were compared to evaluate the plantar pressure changes while walking. ResultsForefoot plantar pressure distribution of hallux valgus is quite different from that of normal feet. Among five regions PP and PTI under the third metatarsal are maximum, which was (24.01±12.33)Pa，(6.89±3.02) respectively. While the maximum of normal feet was under the second metatarsal, which was (16.79±7.65)Pa，(6.03±2.72) respectively. Conclusions There are biomechanical differences between hallux valgus and normal feet which can be embodied by the distribution of plantar pressure. The center of plantar pressure distribution obviously shifts from interior to exterior.

Inhibition effects of tumor necrosis factor-alpha gene transduced tumor drainage node of lymphocytes from tongue cancer on SCID mice transplanted tumor established with human tongue carcinoma cell lines / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To observe the in vivo inhibition effects of tumor necrosis factor-alpha (TNF-alpha) gene transduced tumor drainage node of lymphocytes (DNL) from tongue cancer on SCID mice transplanted tumor.</p><p><b>METHODS</b>15 human tongue carcinoma models were established in SCID mice by subcutaneously injection of squamous cell carcinoma line Tca8113. TNF-alpha gene introduced DNL, combined with low dose Pinyancin (PYC), were locally injected into tumor site. The inhibition rate was determined by the weights at the 8th week after tumor dissection and fresh specimens were prepared and subject to histopathologic examination under transmission electron microscope, and in situ TUNEL was used to detect apoptosis.</p><p><b>RESULTS</b>The TNF/DNL and rIL-2 group, and the TNF/DNL and rIL-2 and PYC group both exerted a strong inhibition effect on the implanted tumor. Treated tumors of the TNF/DNL and rIL-2 and PYC group were significantly reduced in comparison with those of the TNF/DNL and rIL-2 group (P < 0.05). The apoptosis of tumor in the TNF/DNL and rIL -2 group was evidenced based on transmission electron microscope and TUNEL analysis, and the apoptosis index was higher than that of control group (P < 0.05).</p><p><b>CONCLUSION</b>Local injection of DNL modified with TNF-alpha gene, combined with low dose PYC, exert a synergistic antitumor effect. Apoptosis may be an important mechanism of squamous cell carcinoma killed by TNF/DNL.</p>

Time trend analysis of incidence rate for nasopharyngeal carcinoma in urban Shanghai YANG / 中华流行病学杂志

Objective To explore the secular trend of incidence for nasopharyngeal carcinoma (NPC) in urban Shanghai during 1973-2005. Methods The incidence data from the population-based cancer registries in Shanghai was used in our analysis. We calculated the crude incidence rates, age-adjusted incidence rates, trucated rates and cumulative rates of NPC. The annual percentage change (APC) was used as an estimate of the secular trend. Results Over 33 years, a total of 7889 incident NPC cases in urban Shanghai were registered for 5555 males and 2334 females, respectively. The incidence of NPC had remained stable in males during the period (APC=-0.250%, P= 0.340), but a decreasing trend was observed in females with an average reduction of -1.577% (P=0.000) per year. During the period of 1973-1976 to 2001-2005, the crude incidence rates changed from 4.56 to 6.18 and from 3.96 to 2.41 per 100 000 in males and females, and the age-adjusted rates from 4.12 to 3.96 and from 2.18 to 3.42 per 100 000 in males and females, respectively. Conclusion From 1973 to 2005, the incidence of NPC was stable in males while having a decline in females, indicating that further epidemioiogical study and prevention for NPC should be addressed.

Sequential fluorescent labeling observation of maxillary sinus augmentation by a tissue-engineered bone complex in canine model / 国际口腔科学杂志·英文版

<p><b>AIM</b>To evaluate the effects of maxillary sinus floor elevation by a tissue-engineered bone complex of beta-tricalcium phosphate (beta-TCP) and autologous osteoblasts in dogs.</p><p><b>METHODOLOGY</b>Autologous osteoblasts from adult Beagle dogs were cultured in vitro. They were further combined with beta-TCP to construct the tissue-engineered bone complex. 12 cases of maxillary sinus floor elevation surgery were made bilaterally in 6 animals and randomly repaired with the following 3 groups of materials: Group A (osteoblasts/beta-TCP); Group B (beta-TCP); Group C (autogenous bone) (n=4 per group). A polychrome sequential fluorescent labeling was performed post-operatively and the animals were sacrificed 24 weeks after operation for histological observation.</p><p><b>RESULTS</b>Our results showed that autologous osteoblasts were successfully expanded and the osteoblastic phenol-types were confirmed by ALP and Alizarin red staining. The cells could attach and proliferate well on the surface of the beta-TCP scaffold. The fluorescent and histological observation showed that the tissue-engineered bone complex had an earlier mineralization and more bone formation inside the scaffold than beta-TCP along or even autologous bone. It had also maximally maintained the elevated sinus height than both control groups.</p><p><b>CONCLUSION</b>Porous beta-TCP has served as a good scaffold for autologous osteoblasts seeding. The tissue-engineered bone complex with beta-TCP and autologous osteoblasts might be a better alternative to autologous bone for the clinical edentulous maxillary sinus augmentation.</p>

An ectopic study of tissue-engineered bone with Nell-1 gene modified rat bone marrow stromal cells in nude mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tissue engineering techniques combined with gene therapy have been recently used to improve osteogenesis. NEL-like molecule-1 (Nell-1), a novel growth factor, has been reported to have specificity for osteochondral lineage. The study assessed the osteogenic differentiation of rat bone marrow stromal cells (bMSCs) after Nell-1 gene modification and examined its ectopic bone formation ability in a nude mice model with tissue engineering technique.</p><p><b>METHODS</b>bMSCs obtained from Fischer 344 rats were transduced with either AdNell-1 (Nell-1 group) or Ad-beta-galactosidase (AdLacZ, LacZ group) or left untransduced (untransduced group). The expression of Nell-1 protein was determined by Western blotting and transfer efficiency was assessed. mRNA expressions of osteopontin (OP), bone sialoprotein (BSP) and osteocalcin (OC) were assessed by real-time PCR 0, 3, 7, 14, and 21 days after gene transfer. Alkaline phosphatase (ALP) activity was measured and von Kossa test was also conducted. Finally, with a tissue engineering technique, gene transduced bMSCs, combining with beta-tricalcium phosphate (beta-TCP) at a concentration of 2 x 10(7) cells/ml, were implanted at subcutaneous sites on the back of nude mice. Four weeks after surgery, the implants were evaluated with histological staining and computerized analysis of new bone formation.</p><p><b>RESULTS</b>Under current transduction conditions, gene transfer efficiency reached (57.9 +/- 6.8)%. Nell-1 protein was detected in Nell-1 group but not in untransduced group and LacZ group. Induced by Nell-1, BSP and OP expression were increased at intermediate stage and OC expression was increased at later stage. ALP activity and the number of calcium nodules were highest in Nell-1 group. Four weeks after implanted into nude mice subcutaneously, the percentage of new bone area in Nell-1 group was (18.1 +/- 5.0)%, significantly higher than those of untransduced group (11.3 +/- 3.2)% and LacZ group (12.3 +/- 3.1)% (P < 0.05).</p><p><b>CONCLUSIONS</b>This study has demonstrated the ability of Nell-1 to induce osteogenic differentiation of rat bMSCs in vitro and to enhance bone formation with a tissue engineering technique. The results suggest that Nell-1 may be a potential osteogenic gene to be used in bone tissue engineering.</p>

Treatment outcome of repeat gamma knife radiosurgery for primary trigeminal neuralgia / 中华神经医学杂志

Objective To assess the feasibility, indications and therapeutic effect of repeatgamma knife radiosurgery for treatment of primary trigeminai neuralgia. Methods From January 1995to February 2006, 277 patients with primary trigeminal neuralgia underwent stereotactic radiosurgerytargeting the cistemal trigeminal nerve with a maximal central dose of 70-80 Gy. A second gamma kniferadiosurgery with a maximal central dose of 65-80 Gy was performed in 23 patients with refractory and15 with recurrent trigeminal neuralgia after the primary surgery. The 50% isodose line encompassed thetarget area for radiation. The trigeminal root entry zone was included in a single target area in 33 patients,and in 5 patients, two target areas were chosen. Results All patients were followed up for 12 to 108months (mean 55 months) by telephone. The pain relief lasted for 1 to 180 days (mean 120 days) after thesecond gamma knife radiosurgery. The primary stereotactic radiosurgery resulted in a complete or partialpain relief rate of 91.7%(254/277). In the 23 patients with refractory trigeminal neuralgia, the secondradiosurgery achieved a pain relief rate of 73.9% (17/23), significantly lower than the rate of 100%(15/15) in the 15 patients with recurrent trigeminal neuralgia (P=0.045). Facial numbness or paresthesiaoccurred in 30 patients (10.8%) after the primary radiosurgery, and in another 8 patients (21.1%) after thesecond surgery. Conclusion Gamma knife stereotactic radiosurgery is safe and effective and causesfew complications for relieving trigeminal neuralgia. A repeat gamma knife stereotactic radiosurgery isalso effective for management of recurrent or refractory trigeminal neuralgia, especially in recurrentcases.

Experience and thinking on establishing fine course of oral and maxillofacial surgery / 上海第二医科大学学报

Objective To explore the practical ways on establishing fine course of oral and maxillofacial surgery effectively. Methods Relying on the advantages of the discipline,great efforts had been made in step-by-step enhancement of the quality of teachers,teaching contents,teaching methods and administration. Results Through the establishing of fine course,we could improve the curriculum system,enhance the force of education team,and improve the quality of education. Conclusion Establishing fine course of oral and maxillofacial surgery depends on the environment of sharing educational resources,adjusting the curriculum system and establishing an excellent educational team.

Combined and sequential treatment of oral and maxillofacial malignancies: an evolving concept and clinical protocol / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To introduce the concept and rational regimens and present the latest development of combined treatment of oral and maxillofacial malignancies. Data sources The related published literature was searched through the CNKI database and MEDLINE using the terms of oral cancer, oral and maxillofacial malignancies, combined and sequential therapy, multidisciplinary approach. Study selection The available related literature was read and evaluated. Studies that met the inclusion criteria were selected.</p><p><b>RESULTS</b>The results show that oral and maxillofacial malignancies diagnosed at an early stages (stages I and II) can be well treated with surgery alone and/or radiotherapy with optimal outcome, but advanced or recurrent diseases should be treated with rational combined and sequential treatment modalities. The use of concomitant chemoradiotherapy, taxane-containing, three-drug induction regimens and Cetuximab in combination with chemotherapy or radiotherapy demonstrated favorable results in previously untreated patients with head and neck squamous cell carcinoma.</p><p><b>CONCLUSIONS</b>The concept of combined and sequential treatment of advanced oral and maxillofacial malignancies should be widely accepted, and the rational regimen for individual and each type of entity should be determined based on the anatomical site and the patient's performance status.</p>

Neoadjuvant chemotherapy of cisplatin and fluorouracil regimen in head and neck squamous cell carcinoma: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The benefit of neoadjuvant chemotherapy in the management of head and neck squamous cell carcinomas (HNSCC) still remains controversial. The aim of this meta-analysis is to evaluate the role of the neoadjuvant chemotherapy with the cisplatin and fluororacil (PF) regimen in enhancing the overall survival of and decreasing locoregional relapse and distant metastasis in HNSCC patients.</p><p><b>METHODS</b>Medline and manual searches were performed to identify all published randomized controlled trials (RCTs) investigating the efficacy of the neoadjuvant chemotherapy with the PF regimen. Outcomes assessed by meta-analysis included locoregional relapse, distant metastasis, and overall survival. The odds ratio was the principle measurement of effect, which was calculated as the treatment group (chemotherapy plus locoregional treatment) versus the control group (locoregional treatment alone) and was presented as a point estimate with 95% confidence intervals (CI).</p><p><b>RESULTS</b>Eight RCTs were adopted for analysis. The meta-analysis showed that the odds ratio for the locoregional relapse was 0.92 (0.70 - 1.22, 95% CI), which was not statistically significant. The odds ratios for distant metastasis and overall survival were 0.47 (0.33 - 0.68, 95% CI) and 1.28 (1.01 - 1.62, 95% CI) respectively, which were both statistically significant.</p><p><b>CONCLUSIONS</b>Neoadjuvant chemotherapy with the PF regimen in HNSCC patients has no effect on locoregional relapse. However, it shows a small but significant benefit in reducing distant metastasis and improving the overall survival.</p>

Benzo (a) pyrene induced tumorigenesity of human immortalized oral epithelial cells: transcription profiling / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The present study was designed to examine and analyze the global gene expression changes during the tumorigenesis of a human immortalized oral epithelial cell line, and search for the possible genes that may play a role in the carcinogenesis of oral cancer associated with benzo (a) pyrene.</p><p><b>METHODS</b>The human immortalized oral epithelial cells, which have been established through transfection of E6/E7 genes of human papillomavirus type 16 and proved to be non-tumorigenic in nude mice, were treated with benzo (a) pyrene. Tumorigenicity of the treated cells were examined through nude mice subcutaneous injection. The global gene expression profiles of immortalized cells and the tumorigenic cells were acquired through hybridization of a microarray of Affymetrix U133 plus 2.0. The data were analyzed using Spring 7.0 software and treated statistically using one-way analysis of variance (ANOVA). The differentially expressed genes were classified using a Venn diagram and annotated with gene ontology. Several highlighted genes were validated in cells using a real-time polymerase chain reaction.</p><p><b>RESULTS</b>There were 883 differentially expressed genes during the tumorigenesis and most of them changed expression in the early stage of tumorigenesis. These genes mainly involved in macromolecule metabolism and signal transduction, possessed the molecular function of transition metal ion binding, nucleotide binding and kinase activity; their protein products were mainly integral to membranes or localized in the nucleus and cytoskeleton. The expression patterns of IGFBP3, S100A8, MAP2K, KRT6B, GDF15, MET were validated in cells using a real-time polymerase chain reaction; the expression of IGFBP3 was further validated in clinical oral cancer specimens.</p><p><b>CONCLUSIONS</b>This study provides the global transcription profiling associated with the tumorigenesis of oral epithelial cells exposed to benzo (a) pyrene; IGFBP3 may play a potential role in the initiation of oral cancer related to benzo (a) pyrene exposure.</p>

Occult cervical lymph node metastases in 100 consecutive patients with cN0 tongue cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Squamous cell carcinoma (SCC) of the tongue is one of the most common cancers in the oral and maxillofacial region. To provide clinical evidence for selective neck dissection in management of cN0 patients by analyzing the characteristics and correlation of factors of occult cervical lymph node metastases (OCLNM) in patients with SCC of the tongue.</p><p><b>METHODS</b>From 2002 to 2006, 100 consecutive patients with SCC of the tongue were reviewed by analyzing the characteristics of OCLNM, diameter of the tumor, T classifications, depth of invasion, forms of growth, pathological grade and degree of differentiation.</p><p><b>RESULTS</b>The rate of OCLNM in 100 patients with SCC of the tongue was 22%. The most common region with OCLNM was level II in the ipsilateral neck, followed by levels I and III. There were 51.61% (16/31) of OCLNM in level II and 87.10% (27/31) of OCLNM in levels I - III. There was no significant correlation between the diameter of tumor and OCLNM (P > 0.05). OCLNM was statistically significantly correlated with the depth of invasion, forms of growth, pathological grade and degree of differentiation (P < 0.05). The rate of occult metastases increased with the increased pathological grade, the decreased degree of differentiation and the increased depth of invasion.</p><p><b>CONCLUSIONS</b>The most common regions with OCLNM in cN0 patients with SCC of the tongue were levels I - III in the ipsilateral neck. Supraomohyoid neck dissection should be the elective treatment to the neck in patients with cN0 SCC of the tongue by consideration of the clinical and pathological factors for the depth of invasion, forms of growth, pathological grade, and degree of differentiation.</p>