Recent Advances in Digital Technology in Implant Dentistry.

Digital technology has emerged as a transformative tool in dental implantation, profoundly enhancing accuracy and effectiveness across multiple facets, such as diagnosis, preoperative treatment planning, surgical procedures, and restoration delivery. The multiple integration of radiographic data and intraoral data, sometimes with facial scan data or electronic facebow through virtual planning software, enables comprehensive 3-dimensional visualization of the hard and soft tissue and the position of future restoration, resulting in heightened diagnostic precision. In virtual surgery design, the incorporation of both prosthetic arrangement and individual anatomical details enables the virtual execution of critical procedures (e.g., implant placement, extended applications, etc.) through analysis of cross-sectional images and the reconstruction of 3-dimensional surface models. After verification, the utilization of digital technology including templates, navigation, combined techniques, and implant robots achieved seamless transfer of the virtual treatment plan to the actual surgical sites, ultimately leading to enhanced surgical outcomes with highly improved accuracy. In restoration delivery, digital techniques for impression, shade matching, and prosthesis fabrication have advanced, enabling seamless digital data conversion and efficient communication among clinicians and technicians. Compared with clinical medicine, artificial intelligence (AI) technology in dental implantology primarily focuses on diagnosis and prediction. AI-supported preoperative planning and surgery remain in developmental phases, impeded by the complexity of clinical cases and ethical considerations, thereby constraining widespread adoption.

[The clinicopathological features of adult thyroid tumors with DICER1 mutation].

A total of 37 cases of thyroid tumors with pathological features suggestive of DICER1 gene mutation were selected to detect the DICER1 gene and BRAF gene using Sanger sequencing. A total of 10 patients (27.0%) exhibited DICER1 gene mutation all of whom were female with an age of [M(Q1, Q3)] 38.0 (30.5, 47.5) years. All patients had wild-type BRAFV600E gene. The ultrasound examination showed high-low echogenic well-demarcated intra-thyroidal nodules with abundant peripheral and internal blood flow signals in the DICER1 mutated thyroid tumor. The tumor was confined within the thyroid gland, with a diameter of (3.68±1.31) cm. The pathological features are as follows: the majority of tumors are encapsulated, which mainly composed of large follicles rich in colloid and some are small and micro follicles. The nucleus is round and deeply stained or slightly light stained, small to medium-sized, with occasional nuclear grooves and a lack of nuclear pseudoinclusion bodies within the nucleus. Immunohistochemical staining shows that Ki67 proliferation index of approximately 2%-10%. All cases were followed up for 11 to 18 months, and there was no recurrences or distant metastase. This study confirmed that the DICER1 gene mutation is mutually exclusive with the BRAFV600E gene mutation. The thyroid tumor with DICER1 mutation are in big size and are more common in young females with a good prognosis. Cases with the wild-type DICER1 gene may exhibit similar morphological features, and molecular testing is recommended. If somatic DICER1 mutation is confirmed, patients should undergo germline mutation testing to rule out DICER1 syndrome in order to define whether genetic counseling is necessary.

[Fibrocartilaginous mesenchymoma: a clinicopathological analysis of four cases].

Objective: To investigate the clinical, radiological, histological and molecular features and the differential diagnosis of fibrocartilaginous mesenchymoma (FM). Methods: Four cases of FM diagnosed in the Department of Pathology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine from 2020 to 2022 were analyzed. Related literature was also reviewed. Results: Case 1 was a 10-year-old girl with bone destruction in the sacrum and L5 articular processes revealed by CT scan. Case 2 was a 7-year-old girl with an aggressive lesion in her right distal ulna. Case 3 was an 11-year-old boy with a lesion in the metaphysis of his left proximal tibia. Case 4 was an 11-year-old boy with bone destruction in the distal portion of a radius. Microscopically, the four tumors all consisted of numerous spindle cells, hyaline cartilage nodules, and bone trabeculae. The hypocellular to moderately cellular spindle cell component contained elongated cells with slightly hyperchromatic, mildly atypical nuclei arranged in bundles or intersecting fascicles. Benign-appearing cartilaginous nodules of various sizes and shapes were scattered throughout the tumors. There were areas mimicking epiphyseal growth-plate characterized by chondrocytes arranged in parallel columns and areas of enchondral ossification. The stroma was rich in mucus in case 1. Mutation of GNAS and IDH1/IDH2 and amplification of MDM2 gene were not found in any of the three tested cases. Conclusions: FM is very rare and tends to affect young patients. It most frequently occurs in the metaphysis of long tubular bones, followed by the iliac-pubic bones and vertebrae. FM is characterized by a mixed population of spindle cells, hyaline cartilage nodules and trabeculae of bone, without specific immunophenotypes and molecular alternations. As a borderline, locally aggressive neoplasm, surgical removal with a wide margin is generally the treatment of choice for FM.

[Establishment and application of animal models of pulmonary alveolar proteinosis].

Pulmonary alveolar proteinosis (PAP) is a rare respiratory disease, but this disease has slow research progress. Animal model is an effective tool for basic research. Current PAP animal models are based on the main pathogenesis of granulocyte-macrophage colony stimulation factor (GM-CSF) signal disorder and environmental homeostasis imbalance in the alveoli. Application researches focus on the treatment strategies of PAP. The existing PAP animal models cannot fully reflect to the development of human PAP, which should be further developed and improved to provide the basis for clinical practice.

Deep small RNA-Seq reveals microRNAs expression profiles in lactating mammary gland of 2 sheep breeds with different milk performance.

Micro ribonucleic acid (miRNA) is a type of noncoding RNA, and it has been revealed to play important roles in the activity of the mammary gland (MG) in some species. However, the function of miRNAs in MG of sheep is poorly understood. In the study, Gansu Alpine Merino (GAM; n = 9) and Small-tailed Han sheep (STH; n = 9) with different milk production traits were investigated. Microstructures and the expression profile of miRNAs of MG tissues at peak lactation were studied. Mature alveolar lumens of MG in appearance were larger in STH than GAM. The expression levels of CSN2 and the content of rough endoplasmic reticulum were also higher in STH ewes than GAM ewes. A total of 124 mature miRNAs were expressed, and 18 of these were differentially expressed between the 2 breeds. The KEGG analysis results showed that the targeted genes of differentially expressed miRNAs were mainly involved in some metabolic pathways and signaling pathways related to MG development, milk protein, and fat synthesis. The findings in the study can improve our understanding of the roles of miRNAs in the development and lactation of MG in sheep.

Value of sTNF-R1 and linc0597 as indicators for disease activity and diagnosis of lupus nephritis.

OBJECTIVE: To explore whether Soluble tumor necrosis factor-receptor 1 (sTNF-R1) and linc0597 can be used as indicators for disease activity and diagnosis of lupus nephritis (LN). PATIENTS AND METHODS: Eighty LN patients treated in our hospital were enrolled as the LN group, while 60 Systemic Lupus Erythematosus (SLE) patients without nephritis were included in the SLE group, and 50 healthy subjects who conducted physical examination during the same period as the control group. After admission, 5 mL of venous blood was taken from all the study subjects to measure sTNF-R1 level and linc0597 expression by enzyme-linked immunosorbent assay (ELISA) and RT-qPCR respectively. In addition, the receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic value of serum sTNF-R1 and linc0597 for LN, and Spearman correlation coefficient was adopted for the correlation between sTNF-R1, linc0597, and LN clinical disease Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Moreover, the logistic multiple regression analysis was applied to analyze the independent risk factors affecting the complication of LN in SLE patients. RESULTS: The LN group presented significantly higher serum sTNF-R1 and linc0597 levels than the control group and the SLE group. Besides, ROC curve analysis revealed that sTNF-R1 and linc0597 had good clinical diagnostic value in LN and SLE. Furthermore, Spearman correlation coefficient indicated that serum sTNF-R1 and linc0597 were positively correlated with disease activity index SLEDAI (r=0.551, p<0.001; R =0.604, p<0.001). Moreover, multivariate Logistic regression analysis demonstrated that age (p=0.001), fever (p=0.004), arthralgia (p=0.034), serum uric acid (p=0.019), decreased complement C3 (p=0.023), ANA peripheral type (p=0.007), anti-ds-DNA antibody (p=0.003), ANCA (p=0.002), sTNF-R1 (p=0.001), and linc0597 (p<0.001) were all independent risk factors affecting the complication of LN in SLE patients. CONCLUSIONS: STNF-R1 and linc0597 can be used as the indicators for disease activity and diagnosis of LN.

Clinical efficacy of lopinavir/ritonavir in the treatment of Coronavirus disease 2019.

OBJECTIVE: The Coronavirus disease 2019 (COVID-19) which outbroke in December 2019 is highly contagious with a low cure rate. In view of this, there is an urgent need to find a more appropriate therapeutic scheme against COVID-19. The study aimed to investigate whether lopinavir/ritonavir (LPV/r) in combination with other pneumonia-associated adjuvant drugs has a better therapeutic effect on COVID-19. PATIENTS AND METHODS: Totally 47 patients with COVID-19 infection who were admitted to Rui'an People's Hospital between January 22 and January 29, 2020 were collected. The patients were divided into the test group and the control group according to whether they had been treated with LPV/r or not during hospitalization. Patients in the test group were treated with LPV/r combined with adjuvant medicine, while those in the control group were just treated with adjuvant medicine. The changes of body temperature, blood routine and blood biochemistry between the two groups were observed and compared. RESULTS: Both groups achieved good therapeutic effect with the body temperature of patients decreased gradually from admission to the 10th day of treatment. But the body temperature of patients in the test group decreased faster than that of the control group. Blood routine indexes showed that compared with the control group, the abnormal proportion of white blood cells, lymphocytes and C-reactive protein of the test group could be reduced to some extent. Blood biochemical indexes exhibited that the proportion of patients with abnormal alanine aminotransferase and aspartate aminotransferase in the test group were lower than the control group. The number of days for nCoV-RNA turning negative after treatment was significantly decreased in the test group than that in the control group. CONCLUSIONS: Compared with the treatment of pneumonia-associated adjuvant drugs alone, the combination treatment with LPV/r and adjuvant drugs has a more evident therapeutic effect in lowering the body temperature and restoring normal physiological mechanisms with no evident toxic and side effects. In view of these conclusions, we suggested that the use of LPV/r combined with pneumonia-associated adjuvant drugs in the clinical treatment for patients with COVID-19 should be promoted.

[Surgical concept and techniques of recurrent cervical cancer patients accompanied with high risk of intestinal obstruction after radical radiotherapy].

Objective: To explore the method of relieving intestinal obstruction in patients with recurrent cervical cancer accompanied with intestinal obstruction after radical radiotherapy. Methods: The data of 10 recurrent cervical cancer patients accompanied with high risk weak constitution and intestinal obstruction after radical radiotherapy from May 2012 to May 2018 were retrospectively analyzed, including preoperative radiotherapy dose, physique and obstruction status, operation time, operation blood loss, postoperative digestive tract patency and diet. All of the 10 patients with cervical cancer recurrence accompanied with intestinal obstruction and disturbance of independent walking after radical radiotherapy. Results: The median fasting time of the 10 patients was 21 days, the median weight was 35.5 kg, the median body mass index (BMI) was 13.3 kg/m(2,) the median value of hemoglobin was 67 g/L, and the median value of platelet was 44×10(9) /L. All of the patients underwent enterostomy. the median operation time was 6.0 min and the median amount of bleeding was 5.0 ml. All of the patients defecated after operation, fed on the first day after operation, and were able to walk on their own 5 days after operation. Conclusions: Although the cervical cancer patients with recurrent intestinal obstruction after radical radiotherapy are extremely weak, some patients still have the opportunity to relieve intestinal obstruction if the treatment strategy and surgical method are appropriate.

[Follow-up of people living with HIV/AIDS by primary health care institutions in rural area of Jiangxi province].

Objective: To understand the current status of follow up of people living with HIV/AIDS by health service at grass root in rural area of Jiangxi province and related factors, and provide references for the promotion of the follow up by grass root health service. Methods: People living HIV/AIDS aged ≥18 years and diagnosed before 31 December 2017 in 6 townships of Xinjian, Yushan counties and Guixi city were included in the study in Jiangxi province. They had been followed up for more than one time after the first epidemiologic survey. The information about their demographic characteristics and HIV infection status were collected by using self-designed questionnaire. Univariate and multivariate logistic regression analyses were conducted to identify the factors that influencing the acceptance of follow up by grass root health service. Results: Of the 373 surveyed HIV infected subjects aged (53.06±16.15) years, 261 were males (70.0%, 261/373). Among the surveyed subjects, the illiteracy and people who received only primary school education accounted for 54.7% (204/373). The rate of follow up of the HIV infected subjects by grass root health service was 55.8% (208/373), and those through heterosexual contact were 58.5% (190/325). The multivariate regression analysis showed that the acceptance of follow up by grass root health service was higher in those who were farmers (OR=7.36, 95%CI: 2.52-21.45), had family support (OR=16.01, 95%CI: 2.25-49.73), didn't worry about discrimination (OR=12.97, 95%CI: 4.75-35.42), trusted health care provider (OR=5.07, 95%CI: 2.19-11.76) and showed AIDS symptoms (OR=10.58, 95%CI: 2.25- 49.73). Conclusions: The performance of follow up of people living with HIV/AIDS by grass root health service was well, suggesting it is a feasible management model. Being famer or not, family member supporting or not, worry about discrimination or not, trusting health care provider or not and showing AIDS symptoms or not were the main factors influencing the acceptance of follow up by grass root health service.

Molecular characterization and transcriptional analysis of the female-enriched chondroitin proteoglycan 2 of Toxocara canis.

Toxocara canis is an important but neglected zoonotic parasite, and is the causative agent of human toxocariasis. Chondroitin proteoglycans are biological macromolecules, widely distributed in extracellular matrices, with a great diversity of functions in mammals. However, there is limited information regarding chondroitin proteoglycans in nematode parasites. In the present study, a female-enriched chondroitin proteoglycan 2 gene of T. canis (Tc-cpg-2) was cloned and characterized. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure the transcription levels of Tc-cpg-2 among tissues of male and female adult worms. A 485-amino-acid (aa) polypeptide was predicted from a continuous 1458-nuleotide open reading frame and designated as TcCPG2, which contains a 21-aa signal peptide. Conserved domain searching indicated three chitin-binding peritrophin-A (CBM_14) domains in the amino acid sequence of TcCPG2. Multiple alignment with the inferred amino acid sequences of Caenorhabditis elegans and Ascaris suum showed that CBM_14 domains were well conserved among these species. Phylogenetic analysis suggested that TcCPG2 was closely related to the sequence of chondroitin proteoglycan 2 of A. suum. Interestingly, a high level of Tc-cpg-2 was detected in female germline tissues, particularly in the oviduct, suggesting potential roles of this gene in reproduction (e.g. oogenesis and embryogenesis) of adult T. canis. The functional roles of Tc-cpg-2 in reproduction and development in this parasite and related parasitic nematodes warrant further functional studies.

Involvement of LeMRP, an ATP-binding cassette transporter, in shikonin transport and biosynthesis in Lithospermum erythrorhizon.

Shikonin and its derivatives are important medicinal secondary metabolites accumulating in roots of Lithospermum erythrorhizon. Although some membrane proteins have been identified as transporters of secondary metabolites, the mechanisms underlying shikonin transport and accumulation in L. erythrorhizon cells still remain largely unknown. In this study, we isolated a cDNA encoding LeMRP, an ATP-binding cassette transporter from L. erythrorhizon, and further investigated its functions in the transport and biosynthesis of shikonin using the yeast transformation and transgenic hairy root methods, respectively. Real-time PCR was applied for expression analyses of LeMRP and shikonin biosynthetic enzyme genes. Functional analysis of LeMRP using the heterologous yeast cell expression system showed that LeMRP could be involved in shikonin transport. Transgenic hairy roots of L. erythrorhizon demonstrated that LeMRP overexpressing hairy roots produced more shikonin than the empty vector (EV) control. Real-time PCR results revealed that the enhanced shikonin biosynthesis in the overexpression lines was mainly caused by highly up-regulated expression of genes coding key enzymes (LePAL, HMGR, Le4CL and LePGT) involved in shikonin biosynthesis. Conversely, LeMRP RNAi decreased the accumulation of shikonin and effectively down-regulated expression level of the above genes. Typical inhibitors of ABC proteins, such as azide and buthionine sulphoximine, dramatically inhibited accumulation of shikonin in hairy roots. Our findings provide evidence for the important direct or indirect role of LeMRP in transmembrane transport and biosynthesis of shikonin.

The role of miR-146a in modulating TRAF6-induced inflammation during lupus nephritis.

OBJECTIVE: Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). A previous study showed decreased expression level of microRNA (miR)-146a in LN patients, indicating its possible role in LN pathogenesis. PATIENTS AND METHODS: A total of 98 LN patients were recruited, for the collection of renal tissue samples during biopsy or surgery. Another cohort of 15 patients who had renal tumor resection was recruited as the control group, for the further comparison of expression levels of miR-146a, TRAF6 and p-p65 in tissues. Human glomerular mesangial cells were treated with miR-146a mimics, si-TRAF6 or both, followed by the evaluation of p65, p-p65, IL-1ß, IL-6, IL-8 and TNF-α. Transwell assay was performed to detect the effect of mesangial cells on chemotaxis of macrophage. RESULTS: MiR-146a expression was significantly depressed in renal tissues of LN patients, while TRAF6 expression, macrophage infiltration and p-p65 expression were all elevated as the activity of LN was induced. The up-regulation of miR-146a and/or down-regulation of TRAF6 can significantly inhibit NF-κB transcriptional activity of glomerular mesangial cells, while the gene expressions of IL-1ß, IL-6, IL-8 and TNF-α were suppressed. CONCLUSIONS: The expression of miR-146a in renal tissues of LN patients was significantly depressed, while the transcriptional activity of TRAF6 and NF-κB was enhanced. MiR-146 thus inhibited NF-κB transcriptional activity and inflammatory factor synthesis, and alleviated chemotactic effect towards macrophage via the inhibition of TRAF6 activity.

TM4SF5-CTD-2354A18.1-miR-4697-3P may play a key role in the pathogenesis of gastric cancer.

AIMS: Our aim is to identify important lncRNAs and mRNAs which may play a key role in contributing to pathogenesis of gastric cancer. METHODS: Different LncRNAs and mRNAs are identified by microarray in gastric cancer tissue and corresponding normal tissues. The function and relationship of different LncRNAs and mRNAs is performed by GO analysis and Pathway analysis and made code-non-code network (CNC) by Pearson correlation coefficients (PCC). Then mRNA-miRNA relationship is predicted through mRNA-miRNA relationship software (http://www.targetscan.org). Lastly, mRNA-miRNA-LncRNA network is established for further research. RESULTS: The expression profiles of 3732 lncRNAs showed different expression (fold change (FC)≥2.0, p<0.05) in gastric cancer tissue and normal tissue and expression profiles of 3994 mRNAs also showed different expression (FC≥2.0, p<0.05) in gastric cancer and corresponding normal tissue. CONCLUSION: The expression of TM4SF5, CTD-2354A18.1 and miR-4697-3P is in balance at physiological conditions, however, the balance is disrupted by some situations, which may contribute to gastric cancer. GO analysis and Pathway analysis also showed TM4SF5 played an important role in proliferation, differentiation and apoptosis. Therefore, TM4SF5-miR-4697-3P- CTD-2354A18.1 may play a key role in the pathogenesis of gastric cancer (Tab. 2, Fig. 4, Ref. 30).

Health-related quality of life of patients with intermediate hepatocellular carcinoma after liver resection or transcatheter arterial chemoembolization.

BACKGROUND: The aim of our present study was to compare quality of life (QoL) between intermediate-stage (BCLC-B) HCC patients who had undergone either liver resection or transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: A total of 102 intermediate-stage HCC patients participated in our study, including 58 who had undergone liver resection and 44 who had undergone TACE. Baseline demographic characteristics, tumor characteristics, and long-term outcomes, such as tumor recurrence, were compared and analyzed. QoL was assessed using the Short Form (SF)-36 health survey questionnaire with the mental and physical component scales (SF-36 MCS and PCS). This questionnaire was filled out at HCC diagnosis and 1, 3, 6, 12, 24 months after surgery. RESULTS: For the preoperative QoL evaluation, the 8 domains related to QoL were comparable between the two groups. The PCS and MCS scores were significantly decreased in both the TACE and resection groups at1 month after surgery, and this decrease was greater in the resection group. These scores were significantly lower in the resection group compared with the TACE group (P<0.05). However, these differences disappeared at 3 and 6 months following surgery. One year after surgery, the resection group showed much higher PCS scores than the TACE patients (P=0.018), and at 2 years after surgery, the PCS and MCS scores for the resection group were significantly higher than those for the TACE group (P<0.05). Eleven patients (19.0%) in the resection group and 17 (38.6%) in the TACE group suffered HCC recurrence (P<0.05). Univariate and multivariate analyses indicated that tumor recurrence (HR=1.211, 95%CI: 1.086-1.415, P=0.012) was a significant risk factor for poorpostoperative QoL in the HCC patients. CONCLUSIONS: Due to its effects on reducing HCC recurrence and improving long-term QoL, liver resection should be the first choice for the treatment of patients with intermediate-stage HCC.

A PC-based laparoscopic surgery skills training and assessment system.

The purpose of this study is to build a cost-effective and easy-to-popularize laparoscopic training system based on improving traditional training box. The system has the capability of objective skills assessment and the function of automatic recording of training process and results, as well as 3-dimensional coordinate tracking of instruments. The results of pilot experiment in laparoscopic-assisted grip skill assessment had been shown the system can assess the different grip ability level between the senior surgeons and junior residents. Regarding to the evaluation of training effectiveness, five subjects without laparoscopic surgery experiences were asked to perform grip training for five days to observe their training curves. According to the experimental results, the total time taken for subject 1 to subject 5 are improved by 54.9%, 52.0%, 60.6%, 23.3%, and 63.5% separately.

Mixed-spin pairing condensates in heavy nuclei.

We show that the Bogoliubov-de Gennes equations for nuclear ground-state wave functions support solutions in which the condensate has a mixture of spin-singlet and spin-triplet pairing. We find that such mixed-spin condensates do not occur when there are equal numbers of neutrons and protons, but only when there is an isospin imbalance. Using a phenomenological Hamiltonian, we predict that such nuclei may occur in the physical region within the proton dripline. We also solve the Bogoliubov-de Gennes equations with variable constraints on the spin-singlet and spin-triplet pairing amplitudes. For nuclei that exhibit this new pairing behavior, the resulting energy surface can be rather soft, suggesting that there may be low-lying excitations associated with the spin mixing.

Some additional data to the occurrence, morphology and validity of Myxobolus turpisrotundus Zhang, 2009 (Myxozoa: Myxosporea).

Myxobolus turpisrotundus Zhang, 2009, infects allogynogenetic gibel carp Carassius auratus gibelio (Bloch) and is always regarded as synonymous with Myxobolus rotundus Nemeczek, 1911, since its first report in goldfish Carassius auratus auratus (L.) in China in 1955. In this study, it was comprehensively examined by morphological and molecular biological methods. The round spores of M. turpisrotundus are similar to those of M. rotundus from common bream Abramis brama (L.) in morphology; however, we detected slight differences in morphometry. The ratios of the length and width of the spore to the length and width of the polar capsule of M. turpisrotundus are usually below 2.0 and 1.9, respectively, however these ratios are always above 2.0 and 1.9 in M. rotundus. The plasmodium size of M. turpisrotundus is 600-6,200 microm in diameter and that of M. rotundus is 60-180 microm in diameter. Scanning observation showed the spore surface of M. turpisrotundus was generally pitted. Yet the surface of M. rotundus is smooth. Sequence comparison revealed the small subunit ribosomal RNA gene sequence of M. turpisrotundus did not match any published sequences of M. rotundus (EU710583, 85% over 742 bp; FJ851447, 85% over 742 bp, FJ851448, 85% over 742 bp; FJ851449, 85% over 742 bp). Moreover, phylogenetic analysis showed M. turpisrotundus clustered with the species from allogynogenetic gibel carp with high bootstrap values (100% neighbor-joining, NJ; 100% maximum parsimony, MP) and M. rotundus from common bream composed a new cluster with high bootstrap values (100% NJ, 100% MP). From the morphological and molecular biological data, we gain enough evidences to support the validity of M. turpisrotundus.

Altered expression of the RON receptor tyrosine kinase in various epithelial cancers and its contribution to tumourigenic phenotypes in thyroid cancer cells.

Aberrant expression of the RON receptor tyrosine kinase has been implicated in the pathogenesis of epithelial tumours. The aim of this study was to determine RON expression in various normal epithelial cells and their corresponding tumours by immunohistochemistry. The role of RON in regulating tumourigenic phenotypes was also studied using thyroid cancer cells as a model. RON was almost exclusively expressed at variable levels in normal epithelial cells from the digestive track, lung, kidney, pancreas, liver, breast, bladder, skin, and others. Among 15 types of cancer studied, RON was overexpressed in significant numbers in cancers derived from breast (56%), colon (51%), lung (48), thyroid (42%), skin (37%), bladder (36%), and pancreas (33%). In contrast, limited RON overexpression was observed in cancers from stomach, kidney, brain, liver, ovary, and prostate. Detailed analysis of thyroid tissues showed that RON was hardly detected in normal thyroid cells, moderately expressed in adenoma samples, but overexpressed in about half of papillary and follicular cancer specimens. Overexpression correlated with advanced clinical stage and was associated with lymph node metastasis. In cultured thyroid cancer cells, RON was highly expressed, with constitutive phosphorylation. Activation of RON increased cell growth and migration via the MAP kinase and AKT pathways. Silencing RON expression significantly prevented cell growth and increased cell apoptotic death. These findings show that RON overexpression occurs in a particular group of epithelial cancers. The requirement for RON in sustaining tumourigenic phenotypes suggests that it is a potential target for therapeutic intervention.