Electrophoretic deposition of graphene oxide reinforced chitosan-hydroxyapatite nanocomposite coatings on Ti substrate.

Electrophoretic deposition (EPD) is a facile and feasible technique to prepare functional nanocomposite coatings for application in orthopedic-related implants. In this work, a ternary graphene oxide-chitosan-hydroxyapatite (GO-CS-HA) composite coating on Ti substrate was successfully fabricated by EPD. Coating microstructure and morphologies were investigated by scanning electron microscopy, contact angle test, Raman spectroscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis. It was found GO-CS surface were uniformly decorated by HA nanoparticles. The potentiodynamic polarization test in simulated body fluid indicated that the GO-CS-HA coatings could provide effective protection of Ti substrate from corrosion. This ternary composite coating also exhibited good biocompatibility during incubation with MG63 cells. In addition, the nanocomposite coatings could decrease the attachment of Staphylococcus aureus.

Reversal of cisplatin resistance in non-small cell lung cancer stem cells by Taxus chinensis var.

Drug resistance in cells is a major impedance to successful treatment of lung cancer. Taxus chinensis var. inhibits the growth of tumor cells and promotes the synthesis of interleukins 1 and 2 and tumor necrosis factor, enhancing immune function. In this study, T. chinensis var.-induced cell death was analyzed in lung cancer cells (H460) enriched for stem cell growth in a defined serum-free medium. Taxus-treated stem cells were also analyzed for Rhodamine 123 (Rh-123) expression by flow cytometry, and used as a standard functional indicator of MDR. The molecular basis of T. chinensis var.-mediated drug resistance was established by real-time PCR analysis of ABCC1, ABCB1, and lung resistance-related protein (LRP) mRNA, and western blot analysis of MRP1, MDR1, and LRP. Our results revealed that stem cells treated with higher doses of T. chinensis var. showed significantly lower growth inhibition rates than did H460 cells (P < 0.05). The growth of stem and H460 cells treated with a combination of T. chinensis var. and cisplatin was also significantly inhibited (P < 0.05). Rh-123 was significantly accumulated in the intracellular region and showed delayed efflux in stem cells treated with T. chinensis var. (P < 0.05), compared to those treated with verapamil. T. chinensis var.-treated stem cells showed significant downregulation of the ABCC1, ABCB1, and LRP mRNA and MRP1, MDR1, and LRP (P < 0.05) compared to H460 cells. Thus, T. chinensis var.-mediated downregulation of MRP1, MDR1, and LRP might contribute to the reversal of drug resistance in non-small cell lung cancer stem cells.

Differential expression of peroxisome proliferator-activated receptor γ, fatty acid synthase, and hormone-sensitive lipase in fat-tailed and thin-tailed sheep breeds.

Tail fat content affects meat quality, and it varies in different sheep breeds. Theoretically, lipid metabolism contributes to variation in tail fat content. Tail length, tail width, and tail girth were measured in live Tong sheep (with both short fat tail and long fat tail), Shaanbei fine wool sheep (long thin tail), Tan sheep (short fat tail), Kazakh sheep (hip fat tail), and Tibetan sheep (short thin tail). The expression levels of genes related to tail adipose tissue lipid metabolism were investigated, which included lipogenetic genes (PPARγ and FAS) and lipolytic gene (HSL). Differences were observed (P < 0.05) in PPARγ mRNA expression levels in the different breeds; FAS mRNA expression levels did not differ (P > 0.05) in Tong sheep with short fat tail, Tong sheep with long fat tail, Shaanbei fine wool sheep, and Tibetan sheep; HSL mRNA expression levels were not different (P > 0.05) in Tong sheep. PPARγ and HSL protein expression levels differed (P < 0.05) between the different breeds; FAS protein expression levels were different (P < 0.05) in Tong sheep with long fat tails, Tan sheep, Kazakh sheep, and Tibetan sheep, but did not differ (P > 0.05) in Tong sheep with short fat tails and Shaanbei fine wool sheep. These results provide useful information to further understand the function of PPARγ, FAS, and HSL in sheep tail lipid metabolism, which should be applicable to studies on the regulation of fat deposition and improvement of meat quality.

MicroRNA-133a functions as a tumor suppressor in gastric cancer.

MicroRNAs (miRNAs) are small and highly conserved non-coding RNAs that regulate gene expression of target mRNAs through posttranscriptional inhibition involved in the tumorigenesis and progression of multiple malignancies. Although miR-133a has been shown to function as a tumor suppressor in some cancers, the clinical significance and function of miR-133a in gastric cancer remain unclear. Hence, we were focused on the expression and mechanisms of miR-133a in the development of gastric cancer in this study. It was found that the expression of miR-133a was downregulated (P<0.001), while transgelin-2 (TAGLN2) was upregulated (P<0.05) in primary gastric cancer tissues, compared to the adjacent non-cancerous tissues (ANCT). Furthermore, decreased expression of miR-133a and increased expression of TAGLN2 were both associated with lymph node metastases in patients with gastric cancer (P<0.001; P=0.011). Functional analysis studies revealed that ectopic expression of miR-133a reduced cell proliferation and invasion, and induced cell apoptosis and cycle arrest via suppressing the level of TAGLN2 from transcriptional and translational levels and downregulated the expression of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2) in gastric cancer cells. In conclusion, these results demonstrate that decreased expression of miR-133a is associated with the lymph node metastases of patients with gastric cancer. Overexpression of miR-133a inhibits cell growth and invasion and induces cell apoptosis and cycle arrest through repressing TAGLN2 gene, suggesting that miR-133a might be used as a biomarker or therapeutic target for the treatment of gastric cancer.

5-Azacytidine suppresses the proliferation of pancreatic cancer cells by inhibiting the Wnt/ß-catenin signaling pathway.

5-Azacytidine has been shown to be an effective anti-pancreatic cancer drug, but the mechanism remains unknown. In the current study, we explored the effect of 5-azacytidine on abnormal activation of the Wnt-ß-catenin signaling pathway in pancreatic cancer cells. The human pancreatic cancer cell line Bxpc-3 was treated with different concentrations of 5-azacytidine for various times. The proliferation and early apoptosis of the cells were evaluated using the CCK8 method and flow cytometry, respectively. mRNA and protein expression of ß-catenin, c-myc, and cyclinD1 were detected using real-time fluorescent quantitative polymerase chain reaction and Western blot analysis, respectively. The proliferation of Bxpc-3 cells was suppressed by 5-azacytidine. The early apoptosis of the cells was significantly enhanced over time and with increasing drug concentrations. The expression of ß-catenin, c-myc, and cyclinD1 were down-regulated, showing significant differences between different concentrations and treatment times (P < 0.05). 5-Azacytidine suppressed the proliferation of pancreatic cancer cells by inhibiting the Wnt/ß-catenin signaling pathway, particularly the expression of ß-catenin, c-myc, and cyclinD1. This study may provide a new potential strategy for diagnosing and treating pancreatic cancer.

Clinical significance of immunogenic cell death biomarker rage and early growth response 1 in human primary gastric adenocarcinoma.

The receptor for advanced glycation end products (RAGE), a pattern recognition receptor that binds multiple ligands derived from a damaged cell environment, contributes to multiple pathologies including cancer. Early growth response 1 (EGR1) is a tumor suppressor gene or a tumor promoter involved in tumorigenesis and progression of some cancers. However, there is some lack of knowledge about the expression and clinical significance of RAGE and EGR1 in human primary gastric adenocarcinoma (GAC). The present study was aimed to investigate the expression and clinical significance of RAGE and EGR1 in human GAC. One hundred and twenty cases of GAC tissues, adjacent non-cancer tissues (ANCT) and metastatic lymph node (MLN) tissues were collected. The expression of RAGE and EGR1 was assessed using immunohistochemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were analyzed. As a result, the expression of RAGE in GAC and MLN tissues showed the positive staining mainly in the cytoplasm, with lower reactivity rate compared with the ANCT (P less than 0.001), while EGR1 expression had no significant difference between GAC, MLN tissues and ANCT (P=0.565). Moreover, the positive expression of RAGE was closely associated with the N stage of GAC patients, but did not correlate with their age, gender, tumor size, tumor sites, T stage, and metastatic lymph node (each P>0.05). In addition, Spearman Rank correlation analysis showed the positive correlation of RAGE expression with EGR1 in GAC tissues (r=0.658). Taken together, the expression of RAGE is decreased in GAC and MLN tissues, and is associated with the N stage of GAC patients, suggesting that RAGE may represent a potential therapeutic target for the treatment of GAC.

[Wu Shou and his work Shang Han Yun Yao Quan Shu published in the Ming Dynasty].

Wu Shou was a doctor in a medical family in Qiantang, Zhejiang in the Ming Dynasty. He was promoted as a medical officer in the local government and the Imperial Academy of Medicine. His work, considered a masterpiece Shang Han Yun Yao Quan Shu was published around 1505. The series consisted of four volumes. The main content of the book focused on the taxonomy study to the Treatise on Febrile Diseases (Shang Han Lun). Wu Shou was politically accused of being a person who pursued fame and fortune but lacked medical skills because of the conflicts and contradiction between medical officials and the political service system in the period of the Chenghua and Hongzhi in the Ming Dynasty. However, his medical and academic thinking and skills for typhoid treatment shown in the book demonstrated that they were not as awful as what was described at that time.

[Yi Wan She--Huzhou medical association in the late Ming Dynasty].

Yi Wan She, as a medical association in the Huzhou area, was organised by Lu Mingquan, Lu Shilong, Jin Desheng and other doctors in the late Ming Dynasty, developing daily medical theoretical discussions. It built up a hospital named Tian, paid deference to ancient medical doctors, and participated in activities to fight epidemics, organised by Hui Min Pharmacy, such as drug delivery, as an association of local affairs. This was recorded in Yi Wan She Cao and Lu Shi San Shi Yi Yan.

[The quotations of Yijing Dazhi from the Danxi Yi An].

The Yijing Dazhi (, Great Illustrated Directions on Medical Classics) was written by Haiyan He Yue in the Ming Dynasty. This book cited some sections from the Danxi Yi An ( , Danxi's Medical Cases), and some cases in this book were new discoveries. Using the method of philology, this paper compared the cited sections from the Danxi Yi An () in The Yijing Dazhi with the medical records in Danxi Yi An (), Gezhi Yu Lun (, Further Discourses on the Properties of Things), Danxi Zuanyao (, Collected Essentials of Master Danxi's Medical Book), and Danxi Zhifa Xinyao (, Heart and Essentials of Danxi's Treatment Methods). It found that Danxi Yi An() and Danxi Yi An () are actually two individual books. In addition, the contents of Yijing Dazhi cited from Danxi Yi An () are well preserved and have important reference value for collating the medical records of Zhu Danxi in other relevant medical archives.

Monitoring of CaSO(4) deposition behaviors on biofilm during nanofiltration via ultrasonic time-domain reflectometry (UTDR).

The ultrasonic time-domain reflectometry (UTDR) as a non-destructive real-time method was employed to monitor the CaSO(4) deposition behaviors on biofilm during nanofiltration (NF). Two parallel experiments were performed to compare the different behaviors of CaSO(4) deposition with and without biofilm on the membrane. Results showed that the flux decline during combined fouling was slower than that in case of CaSO(4) fouling alone. The Ca(2 + ) rejection obtained with biofilm was higher than that without. A larger acoustic differential signal obtained by UTDR in the combined fouling revealed a denser and thicker layer formed on the membrane surface. Furthermore, the amount of CaSO(4) deposition on the biofouled membrane was more than that on non-biofouled membrane as a result of microorganisms as crystal nucleus to induce CaSO(4) crystallization and deposition. SEM images indicate that the CaSO(4) crystals deposited in order on the non-biofouled membrane, whereas on the biofouled membrane they were embedded in the biofilm. The denser and thicker fouling layer formed with biofilm was impermeable, resulting in a high Ca(2 + ) rejection. The complexation of Ca with polysaccharide in biofilm would eliminate the cake-enhanced osmotic pressure effect leading to a slow flux decline. To sum up, the independent measurements corroborate the ultrasonic measurements.

Selective thromboxane inhibition after vascular protectant AGI-1067: results of assessment of lipoprotein profiles (ALPS) biomarkers in vitro and in vivo substudy.

BACKGROUND: Oxidative stress play an important role triggering platelet/endothelial activation. AGI-1067 is a novel, phenolic antioxidant, and vascular protectant which dose-dependently inhibits PEA biomarkers in vitro. Whether treatment with AGI-1067 alters platelets in vivo is not known. We serially assessed release of established PEA biomarkers in subjects treated with AGI-1067 versus placebo in the frame of Assessment of Lipoprotein Profiles Randomized Trial (ALPS). METHODS: Healthy subjects (18-65 years) with multiple risk factors for coronary artery disease were randomized 1:1 to receive 300 mg AGI-1067 (n = 112) or matching placebo (n = 117) daily for 12 weeks. Anticoagulants, aspirin, NSAIDS, and COX inhibitors were not permitted in this study. Plasma samples were collected at baseline, and at week 12 after randomization. Platelet factor 4 (PF4), beta-thromboglobulin (betaTG), P-selectin, thromboxane (TxB2), and prostacyclin (6-keto-PGF1a) were measured by ELISA. RESULTS: Treatment with AGI-1067 was associated with a highly significant reduction of TxB2 release (P < 0.0001) when compared to the placebo. There were no differences in PF4, betaTG, P-selectin, and 6-keto-PGF1a between and within groups. AGI-1067 also inhibits TxB2 release from calcium ionophore (A23187)-stimulated human platelets with the IC50 equals 1 microM; but does not interfere with 6-keto-PGF1alpha release in either A23187-, or TXA2-stimulated human aortic endothelial cells. CONCLUSION: AGI-1067 selectively reduces TxB(2 )production from stimulated platelets, and diminishes plasma TxB2 levels in ALPS participants. These data support earlier in vitro, and pilot ex vivo experiments suggesting antiplatelet properties of AGI-1067. Lack of 6-keto-PGF1a down regulation may represent an attractive advantage of AGI-1067 over currently available antiplatelet regimens.

Long noncoding RNA SNHG14 accelerates cell proliferation, migration, invasion and suppresses apoptosis in colorectal cancer cells by targeting miR-944/KRAS axis through PI3K/AKT pathway.

OBJECTIVE: Colorectal cancer (CRC) is a gastrointestinal tract cancer, which threatens the well-being of million of patients due to high metastasis. Recently, numerous studies have recognized nuclear RNA host gene 14 (SNHG14) as a remarkable oncogene in different cancers. However, the regulatory mechanism of SNHG14 in CRC development is mostly unclear. PATIENTS AND METHODS: The expression of SNHG14, miR-944 and Kirsten rat sarcoma (KRAS) in tissues and cells was measured by quantitative Real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were evaluated by cell counting kit-8 (CCK-8) and flow cytometry assay, respectively. Cell migration and invasion were assessed using transwell assay. Protein expression of KRAS, AKT, phosphorylated AKT (p-AKT), phosphatidylinositol-3-kinase (PI3K) and phosphorylated PI3K (p-PI3K) was detected by Western blot. Animal models were constructed by subcutaneously injecting SW620 cells stably transfected with sh-SNHG14 and sh-NC. The interaction among SNHG14, miR-944 and KRAS was determined by luciferase reporter assay and RIP assay. RESULTS: The expression of SNHG14 and KRAS was up-regulated whereas miR-944 was down-regulated in CRC tumors and cells compared with normal tissues and cells. In addition, SNHG14 silencing attenuated cell proliferation, migration and invasion, while accelerated apoptosis in CRC cells by suppressing PI3K/AKT pathway. Consistently, SNHG14 knockdown hindered tumor growth in vivo. MiR-944 was a target of SNHG14 and directly targeted KRAS. Moreover, miR-944 inhibitor abrogated silenced SNHG14-mediated inhibition on proliferation, migration and invasion, as well as promotion on apoptosis in CRC cells. Similarly, miR-944 regulated CRC cell progression by targeting KRAS through PI3K/AKT pathway. CONCLUSIONS: SNHG14 contributed to cell proliferation, migration and invasion, while suppressed apoptosis in CRC cells by targeting miR-944/KRAS axis through PI3K/AKT pathway, representing novel biomarkers for CRC therapy.

Amelioration of alkali soil using flue gas desulfurization byproducts: productivity and environmental quality.

In this study, flue gas desulfurization (FGD) byproducts are used to ameliorate alkali soil. The average application rates for soils with low exchangeable sodium percentage (ESP), mid ESP, and high ESP are 20.9, 30.6, and 59.3 Mg ha(-1), respectively. The experimental results obtained for 3 consecutive years reveal that the emergence ratios and yields of the crops were 1.1-7.6 times and 1.1-13.9 times those of the untreated control, respectively. The concentrations of Cr, Pb, Cd, As, and Hg in the treated soils are far below the background values stipulated by the Environmental Quality Standard for Soils (GB15618-1995). Their concentrations in the seeds of corn and alfalfa grown in the treated soils are far below the tolerance limits regulated by National Food Standards of China. The results of this research demonstrate that the amelioration of alkali soils using FGD byproducts is promising.

Morphological study of the changes after sagittal split ramus osteotomy in patients with facial asymmetry: measurements of 3-dimensional modelling.

The effects of bilateral sagittal split ramus osteotomy (BSSRO) on the temporomandibular joint (TMJ) are still not well understood. The aim of this study was to compare the morphological differences among unaffected subjects on the one hand, and patients with facial asymmetry before and after BSSRO on the other. Ten Chinese patients (preoperative and postoperative groups, mean (SD) age 25 (5) years) diagnosed with facial asymmetry and 10 unaffected subjects (control group, mean (SD) age 27 (5) years) were recruited prospectively. The 3-dimensional morphological measurements made on 3-dimensional models in each group were assessed by analysis-of-variance (ANOVA) and Student's t test, and probabilities of <0.05 were accepted as significant. The horizontal condylar angle (HCA), coronal condylar angle (CCA), sagittal ramus angle (SRA), medial joint space (MJS), lateral joint space (LJS), and superior joint space (SJS) differed significantly between the preoperative and control groups (HCA: p=0.000, CCA: p=0.000, SRA(left/undeviated side): p=0.002, MJS(left/undeviated side): p=0.000, MJS(right/deviated side): p=0.007, LJS(right/deviated side): p=0.000, SJS(left/undeviated side): p=0.000, SJS(right/deviated side): p=0.000). The SRA, MJS, LJS, and SJS differed significantly between the preoperative and postoperative groups (SRA(left/undeviated side): p=0.012, MJS(left/undeviated side): p=0.002, LJS(right/deviated side): p=0.021, SJS(left/undeviated side): p=0.000, SJS(right/deviated side): p=0.001), And the SRA, MJS, and LJS in the preoperative group differed significantly between the deviated and undeviated side (SRA: p=0.006; MJS: p=0.003; LJS: p=0.011). However, there were no significant differences in the postoperative and control groups between the deviated and undeviated sides. BSSRO improved the asymmetrical morphology of the TMJ and alleviated the symptoms.

Suppression of retinoic acid receptor beta in non-small-cell lung cancer in vivo: implications for lung cancer development.

BACKGROUND: Retinoids, analogues of vitamin A, are required for the normal growth and differentiation of human bronchial epithelium. They are also able to reverse premalignant lesions and prevent second primary tumors in some patients with non-small-cell lung cancer (NSCLC). These effects are thought to result from modulation of cell growth, differentiation, or apoptosis (programmed cell death). When certain retinoid receptors in the cell nucleus (i.e., retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which mediate most retinoid actions, are suppressed, abnormal activity may result that could enhance cancer development. PURPOSE: This study was designed to determine whether there are abnormalities in the expression of retinoid receptors in surgical specimens from patients with NSCLC. METHODS: Transcripts of nuclear retinoid receptors were detected in formalin-fixed, paraffin-embedded specimens by use of digoxigenin-labeled riboprobes specific for RAR alpha, RAR beta, RAR gamma, RXR alpha, RXR beta, and RXR gamma for in situ hybridization to histologic specimens from 79 patients with NSCLC and as control from 17 patients with non-lung cancer. The quality and specificity of the digoxigenin-labeled probes were determined by northern blotting, and the specificity of the binding of antisense riboprobes was verified by use of sense probes as controls. RESULTS: All receptors were expressed in at least 89% of control normal bronchial tissue specimens from 17 patients without a primary lung cancer and in distant normal bronchus specimens from patients with NSCLC. RAR alpha, RXR alpha, and RXR gamma were expressed in more than 95% of the NSCLC specimens. In contrast, RAR beta, RAR gamma, and RXR beta expression was detected in only 42%, 72%, and 76% of NSCLC, respectively. CONCLUSIONS: These data suggest that the expression of RAR alpha, RXR alpha, and RXR gamma is not altered in NSCLC; however, expression of RAR beta and possibly also of RAR gamma and RXR beta is suppressed in a large percentage of patients with lung cancer. IMPLICATIONS: The loss of expression of one or more of these nuclear retinoid receptors may be associated with lung carcinogenesis.

Nuclear retinoid acid receptor beta in bronchial epithelium of smokers before and during chemoprevention.

BACKGROUND: Retinoids can reverse neoplastic lesions and prevent second primary tumors in the aerodigestive tract. These effects are thought to be mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), each receptor group including three subtypes (alpha, beta, and gamma). Previously, we found that RARbeta expression was suppressed in lung cancer. In this study, we investigated whether expression of RARbeta is modulated by chemopreventive intervention. METHODS: Using in situ hybridization, we analyzed RARbeta messenger RNA (mRNA) expression in bronchial biopsy specimens from heavy smokers, at baseline and after 6 months of treatment with 13-cis-retinoic acid (13-cis-RA) or placebo. Since we had previously detected RARbeta expression in 90% of bronchial specimens from nonsmokers, we considered loss of RARbeta mRNA expression in at least one of six biopsy specimens at baseline in this study to be aberrant. RESULTS: RARbeta mRNA expression was aberrant in 30 (85.7%) of 35 subjects in the 13-cis-RA group and in 24 (72.7%) of 33 subjects in the placebo group. After 6 months of 13-cis-RA treatment, the number of subjects who were RARbeta positive in all six biopsy specimens increased from five of 35 to 13 of 35 (2.6-fold), so that the percentage of individuals with aberrant RARbeta expression decreased to 62.9% (22 of 35), which represents a statistically significant difference from baseline expression (two-sided P =.01). In the placebo group, no statistically significant difference in RARbeta expression was observed between baseline and 6 months. RARbeta expression was not related to current smoking status or reversal of squamous metaplasia. CONCLUSIONS: These results indicate that RARbeta is an independent marker of response to 13-cis-RA and may serve as an intermediate biomarker in chemoprevention trials of upper aerodigestive tract cancers.

Expression and up-regulation of retinoic acid receptor-beta is associated with retinoid sensitivity and colony formation in esophageal cancer cell lines.

Retinoids exhibit chemotherapeutic and chemopreventive activities, possibly due to their ability to modulate cell growth, differentiation, and apoptosis. These effects are thought to be mediated by nuclear retinoic acid (RA) receptors (RARs) and retinoid X receptors, each of which includes three subtypes (alpha, beta, and gamma) that act as transcription factors. To determine whether RARs play a role in mediating the effects of RA on human esophageal cancer (HEC) cells, we analyzed the effects of RA on: (a) the growth, differentiation, and apoptosis in seven HEC cell lines; (b) receptor expression; (c) receptor modulation by RA; and (d) expression of receptors in 20 surgical HEC specimens. RA inhibited the growth of five of seven cell lines and also the constitutive expression of the squamous differentiation markers cytokeratin 1 and transglutaminase I in all cell lines. The growth inhibition by RA was due to the induction of apoptosis in the five cell lines. All seven cell lines expressed RAR-alpha and RAR-gamma, and four cell lines showed some changes by RA, but not associated with apoptosis. In contrast, RAR-beta was expressed in five of seven cell lines and up-regulated by RA in these five cell lines, which were associated with apoptosis. Two cell lines that failed to express RAR-beta showed no growth inhibition or apoptosis and no RAR-beta inducibility. Interestingly, only these two cell lines were able to form colonies in soft agar. RAR-alpha, RAR-beta, and RAR-gamma mRNAs were expressed in all 20 adjacent normal esophageal tissues. The expression of RAR-alpha and RAR-gamma remains positive in HEC specimens, but RAR-beta expression was detected in only 6 of 20 HEC specimens. These data suggest that the expression of RAR-beta is associated with response of HEC cells to RA and that the loss of RAR-beta expression may be associated with HEC development.

Differential expression of nuclear retinoid receptors in normal, premalignant, and malignant head and neck tissues.

Retinoids reverse premalignant lesions and inhibit the development of second primary cancers in patients with upper aerodigestive tract cancers. It is thought that these effects result from the ability of retinoids to restore normal cell growth and differentiation. Since nuclear retinoid receptors (RARs and RXRs) are the ultimate mediators of retinoid actions, alterations in their expression could lead to cancer development. To determine whether the expression of the mRNAs of the receptors is related to the development of head and neck squamous cell carcinoma (HNSCC), we used digoxigenin-labeled antisense riboprobes of RAR-alpha, RAR-beta, RAR-gamma, RXR-alpha, and RXR-beta for in situ hybridization to histological sections of specimens from 7 normal volunteers and 31 HNSCC patients. All 31 tissue specimens contained carcinomas, 16 also contained dysplastic lesions, 22 also contained hyperplastic lesions, 17 also contained adjacent normal tissue, and 6 contained all 4 types of tissue. All specimens from normal volunteers expressed the 5 receptors. Similar levels of RAR-gamma and RXR-alpha and RXR-beta mRNAs were detected in most of the adjacent normal, hyperplastic, dysplastic, and malignant tissues. RAR-alpha mRNA was detected in 94% of adjacent normal tissues and hyperplastic tissues, in 87% of dysplasias, and in 77% of HNSCCs. In contrast, RAR-beta mRNA was detected in about 70% of adjacent normal and hyperplastic lesions, and its expression decreased further to 56% of dysplastic lesions and to 35% of HNSCCs. The difference in RAR-beta level in carcinoma and adjacent normal tissues was significant (P < 0.05). These results indicate that the decreased expression of RAR-beta may be associated with HNSCC development.