[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

[Clinical efficacy and safety of combined induction therapy with rituximab and ATG in highly sensitized kidney transplant recipients].

Objective: To summarize the efficacy and safety of the combination of rituximab and ATG as induction therapy in highly sensitized kidney transplant recipients. Methods: Clinical data of patients who received kidney transplantation from donation after cardiac death(DCD) in Organ Transplant Center of Second Affiliated Hospital of Guangzhou Medical University from January 1st 2015 to December 31th 2016 was retrospectively analyzed. Highly sensitized patients with over 30% active panel reactive antibody (PRA>30%) received rituximab, while non-sensitized recipients as controlled group. All selected patients were observed in the renal function, urine protein, hemogram and the variation of PRA at each time point. Acute rejection, infection required hospitalization, delayed graft function(DGF), primary nonfunction (PNF), graft dysfunction, the mortality rate of patients with good allograft function and the graft survival rate were also observed. Results: 46 groups of patients were selected into highly-sensitized group and non-sensitized group. In both groups, there was no statistical difference in the renal function, urine protein and WBC (all P>0.05). Highly sensitized recipients at day 7 and day 14 following the surgery, had a significantly lower percentage of lymphocyte counts and lymphocyte proportion compared to other groups, with statistical differences(all P<0.05). Both groups had a similar incidence of DGF(2.2%) and no occurrence of PNF. 19.5% of highly sensitized recipients experienced acute rejection and 13% in control group. More specifically, no statistical difference was noted in the rate of infection required hospitalization(30.4% vs 22.2%), graft loss(2.2% vs 0) and the mortality rate of patients with good allograft function(4.3% vs 2.2%)(all P>0.05). The graft survival rate was 97.8% in the highly-sensitized group, while 100% in the control group. And the rate of patient survival in these two groups was 95.7% and 97.8%, with no statistical differences(all P>0.05). Conclusions: Immune-induction therapy that combines Rituximab with ATG can significantly inhibit lymphocyte proliferation. It is effective and safe in treating hypersensitive patients. The survival rate of human/kidney of hypersensitive patients in the short and medium term is comparable to those with low immune risk.

Arthroscopic fixation of an avulsion fracture of the tibia involving the posterior cruciate ligament: a modified technique in a series of 22 cases.

A total of 22 patients with a tibial avulsion fracture involving the insertion of the posterior cruciate ligament (PCL) with grade II or III posterior laxity were reduced and fixed arthroscopically using routine anterior and double posteromedial portals. A double-strand Ethibond suture was inserted into the joint and wrapped around the PCL from anterior to posterior to secure the ligament above the avulsed bony fragment. Two tibial bone tunnels were created using the PCL reconstruction guide, aiming at the medial and lateral borders of the tibial bed. The ends of the suture were pulled out through the bone tunnels and tied over the tibial cortex between the openings of the tunnels to reduce and secure the bony fragment. Satisfactory reduction of the fracture was checked arthroscopically and radiographically. The patients were followed-up for a mean of 24.5 months (19 to 28). Bone union occurred six weeks post-operatively. At final follow-up, all patients had a negative posterior drawer test and a full range of movement. KT-1000 arthrometer examination showed that the mean post-operative side-to-side difference improved from 10.9 mm (standard deviation (sd) 0.7) pre-operatively to 1.5 mm (sd 0.6) (p = 0.001). The mean Tegner and the International Knee Documentation Committee scores improved significantly (p = 0.001). The mean Lysholm score at final follow-up was 92.0 (85 to 96). We conclude that this technique is convenient, reliable and minimally invasive and successfully restores the stability and function of the knee.

Characteristics of immune cell changes before and after immunotherapy and their clinical significance in patients with unexplained recurrent spontaneous abortion.

To investigate the characteristics of immune cells before and after immunotherapy and their clinical significance in patients with unexplained recurrent spontaneous abortion (URSA), an analysis of 67 URSA patients, 67 sporadic spontaneous abortion (SA) patients, and 22 normal nonpregnant women (as controls) was conducted. URSA patients underwent immunotherapy using paternal lymphocytes. Peripheral blood from patients and controls was examined for lymphocytes and other markers of immune status. Before the immunotherapy, lymphocyte counts, CD4:CD8 cell ratios, and the relative proportion of natural killer (NK) cells were significantly higher in the URSA patient group than in the SA patient and control groups (P < 0.05). After the therapy, all of these three measures were decreased, whereas the percentage of T cells was increased, and statistically significant differences before and after the immunotherapy were detected (P < 0.05). Therefore, the immune system appears to be activated in the URSA patients, and the abnormal immunologic state in the URSA patients is more severe than in the SA patients. The alterations in T and NK cells may be involved in the etiopathogenesis of URSA. Lymphocyte immunotherapy appears to be an effective treatment for URSA patients.

Fetal fibronectin detection for preterm birth prediction.

To study preterm birth prediction based on fetal fibronectin (fFN) in pregnant women, we randomly selected 124 patients. Vaginal posterior fornix secretions were analyzed using fFN quick test strips. Leucorrhea routine samples were collected to detect bacterial vaginosis, mycoplasma, and chlamydia. Delivery data at 7 days, 14 days, 34 weeks, and 37 weeks were documented and the sensitivity, specificity, positive predictive value, and negative predictive value were analyzed. Of the 124 cases, we found 2, 4, 10, and 18 cases of maternity within 7 days, 14 days, 34 weeks, and 37 weeks, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were as follows: 100, 77.8, 6.9, and 100% for 7 days; 75, 78.3, 10.3, and 98.9% for 14 days; 50.0, 78.9, 17.2, and 94.7% for 34 weeks; 33.3, 78.3, 20.7, and 87.4% for 37 weeks, respectively. Except for 18 preterm births, 23 cases were fFN-positive, 17 cases had lower genital tract infection. Eighty-three cases were fFN-negative, of which 18 cases had the lower genital tract infections. This difference was statistically significant (P < 0.05). Eighteen cases (14.5% of the pregnant women) had preterm birth. Ten cases delivered within 34 weeks. The negative predictive value and recent predictive value of fFN testing were higher; the positive predictive value was limited due to the impact of lower genital tract infection. The fFN-positive patients need timely clinical processing. During the pregnancy, monitoring of fFN changes and early detection of abnormalities help to reduce perinatal morbidity and mortality.

Chloroplast DNA polymorphism and evolutional relationships between Asian cultivated rice (Oryza sativa) and its wild relatives (O. rufipogon).

We analyzed chloroplast DNA (cpDNA) polymorphism and phylogenic relationships between 6 typical indica rice, 4 japonica rice, 8 javanica rice, and 12 Asian common wild rice (Oryza rufipogon) strains collected from different latitudes in China by comparing polymorphism at 9 highly variable regions. One hundred and forty-four polymorphic bases were detected. The O. rufipogon samples had 117 polymorphic bases, showing rich genetic diversity. One hundred and thirty-one bases at 13 sites were identified with indica/japonica characteristics; they showed differences between the indica and japonica subspecies at these sites. The javanica strains and japonica shared similar bases at these 131 polymorphic sites, suggesting that javanica is closely related to japonica. On the basis of length analyses of the open reading frame (ORF)100 and (ORF)29-tRNA-Cys(GCA) (TrnC(GCA)) fragments, the O. rufipogon strains were classified into indica/japonica subgroups, which was consistent with the results of the phylogenic tree assay based on concatenated datasets. These results indicated that differences in indica and japonica also exist in the cpDNA genome of the O. rufipogon strains. However, these differences demonstrated a certain degree of primitiveness and incompleteness, as an O. rufipogon line may show different indica/ japonica attributes at different sites. Consequently, O. rufipogon cannot be simply classified into the indica/japonica types as O. sativa. Our data support the hypothesis that Asian cultivated rice, O. indica and O. japonica, separately evolved from Asian common wild rice (O. rufipogon) strains, which have different indica-japonica differentiation trends.

A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic-pituitary-adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11ß-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases.

Prenatal nicotine exposure induced a hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in intrauterine growth retardation offspring rats.

Prenatal nicotine exposure inhibits the functional development of the hypothalamic-pituitary-adrenal (HPA) axis and alters glucose and lipid metabolism in intrauterine growth retardation (IUGR) fetal rats, but the postnatal consequence is unknown. We aimed to verify a neuroendocrine metabolic programmed alteration in IUGR offspring whose mothers were subcutaneously treated with 2mg/kgd of nicotine from gestational day 11 to 20. In the nicotine group, blood adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were higher before postnatal day 35 and then returned to lower than the respective control. The adult offspring showed unchanged blood glucose but increased blood total cholesterol (TCH) and triglyceride (TG) levels. However, after chronic stress, the mRNA expression levels of hippocampal glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) were lower, but gain rates of ACTH and CORT levels were greater compared to the control. Additionally, the level of blood glucose was increased, while the elevated levels of blood TCH and TG before stress were close to the control levels. These results suggested that prenatal nicotine exposure induced an HPA axis-associated neuroendocrine metabolic programmed alteration in adult offspring, which might be attributed to hippocampal functional injury in utero.

Nicotine-induced over-exposure to maternal glucocorticoid and activated glucocorticoid metabolism causes hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic alterations in fetal rats.

Fetuses with intrauterine growth retardation (IUGR) induced by prenatal nicotine exposure are susceptible to adult metabolic syndrome. Our goals for this study were to investigate the effects of prenatal nicotine exposure on the fetal hypothalamic-pituitary-adrenal (HPA) axis and glucose and lipid metabolism and to explain the susceptibility to adult metabolic syndrome for fetuses with nicotine induced-IUGR. Pregnant Wistar rats were administered 0.25, 0.5, and 1.0 mg/kg nicotine subcutaneously twice a day from gestational day 11 to 20. Nicotine exposure significantly increased the levels of fetal blood corticosterone and decreased the expression of placental 11ß-hydroxysteroid dehydrogenase-2 (11ß-HSD-2). Moreover, nicotine exposure significantly increased the expressions of fetal hippocampal 11ß-HSD-1 and glucocorticoid receptor (GR) and decreased the expressions of fetal hypothalamus corticotropin-releasing hormone, adrenal steroid acute regulatory protein, and cholesterol side-chain cleavage enzyme. Additionally, increased expressions of 11ß-HSD-1 and GR were observed in fetal liver and gastrocnemius muscle, and these tissues also expressed lower levels of insulin-like growth factor-1 (IGF-1), IGF-1 receptor, and insulin receptor, while expressing increased levels of adiponectin receptor, leptin receptors, and AMP-activated protein kinase α2. Prenatal nicotine exposure causes HPA axis-associated neuroendocrine metabolic alterations in fetal rats. The underlying mechanism may involve activated glucocorticoid metabolism in various fetal tissues.

Mesoporous SnO2@carbon core-shell nanostructures with superior electrochemical performance for lithium ion batteries.

SnO2@carbon nanostructure composites are prepared by a simple hydrothermal method. The composite exhibits unique structure, which consists of a mesoporous SnO2 core assembled of very small nanoparticles and a carbon shell with 10 nm thickness. The mesoporous SnO2@carbon core-shell nanostructures manifest superior electrochemical performance as an anode material for lithium ion batteries. The reversible specific capacity of the composite is about 908 mAh g(-1) for the first cycle and it can retain about 680 mAh g(-1) after 40 charge/discharge cycles at a current density of 0.3 C. Moreover, it shows excellent rate capability even at the high rate of 4.5 C. The enhanced performance was attributed to the mesoporous structure and a suitable carbon coating.

MicroRNA-451 functions as a tumor suppressor in human non-small cell lung cancer by targeting ras-related protein 14 (RAB14).

Accumulating evidence suggests that microRNAs (miRNAs) are important gene regulators, which can have critical roles in diverse biological processes including tumorigenesis. In this study, we analyzed the miRNA expression profiles in non-small cell lung carcinoma (NSCLC) by use of a miRNA microarray platform and identified 40 differentially expressed miRNAs. We showed that miRNA (miR)-451 was the most downregulated in NSCLC tissues. The expression level of miR-451 was found to be significantly correlated with tumor differentiation, pathological stage and lymph-node metastasis. Moreover, low miR-451 expression level was also correlated with shorter overall survival of NSCLC patients (P<0.001). Ectopic miR-451 expression significantly suppressed the in vitro proliferation and colony formation of NSCLC cells and the development of tumors in nude mice by enhancing apoptosis, which might be associated with inactivation of Akt signaling pathway. Interestingly, ectopic miR-451 expression could significantly inhibit RAB14 protein expression and decrease a luciferase-reporter activity containing the RAB14 3'-untranslated region (UTR). In addition,, RNA interference silencing of RAB14 gene could recapitulate the tumor suppressor function of miR-451, whereas restoration of RAB14 expression could partially attenuate the tumor suppressor function of miR-451 in NSCLC cells. Furthermore, we also showed that strong positive immunoreactivity of RAB14 protein was significantly associated with downregulation of miR-451 (P=0.01). These findings suggest that miR-451 regulates survival of NSCLC cells partially through the downregulation of RAB14. Therefore, targeting with the miR-451/RAB14 interaction might serve as a novel therapeutic application to treat NSCLC patients.

Transcriptional inactivation of secreted frizzled-related protein 1 by promoter hypermethylation as a potential biomarker for non-small cell lung cancer.

Epigenetic silencing of secreted frizzled-related protein (SFRP) genes, antagonists of the WNT pathway, contributes to the pathogenesis of several cancers including non-small cell lung cancer (NSCLC). We hypothesize that methylation analysis of SFRPs family could improve their use as a panel of biomarkers for diagnosing and staging of NSCLC in China. The expression of four SFRP members (SFRP1, 2, 4, and 5) in NSCLC samples was screened by RT-PCR and quantitative real-time PCR. Only SFRP1 was significantly downregulated in NSCLC, as compared to adjacent normal tissues and benign pulmonary disease tissues (P=0.006). Promoter hypermethylation of SFRP1 was found in 32.1% (25/78) NSCLC specimens and was closely correlated with loss of expression, besides SFRP1 hypermethylation was associated with lymph metastasis (P=0.039) and disease progression within one year (P=0.027). Furthermore, methylated SFRP1 was detected in 28.2% (22/78) of plasma samples from NSCLC patients while only 4% (2/50) in cancer-free controls, and the concordance of SFRP1 methylation status in tumor tissues and corresponding plasmas was satisfactory (P <0.001). In conclusion, epigenetic inactivation of SFRP1 is a common event contributing to lung carcinogenesis and maybe used as a potential biomarker for NSCLC in Chinese population.

2-Methoxyestardiol and bortezomib/proteasome-inhibitor overcome dexamethasone-resistance in multiple myeloma cells by modulating Heat Shock Protein-27.

Multiple myeloma (MM) remains fatal despite all available therapies. Initial treatment with conventional drugs such as, Dexamethasone (Dex) effectively induces MM cell death; however, prolonged drug exposures results in the development of chemoresistance. Our prior study demonstrated that 2-Methoxyestradiol (2ME2) induces apoptosis in multiple myeloma (MM) cells resistant to Dexamethasone (Dex). Here, we show the mechanism whereby 2ME2 overcomes Dex-resistance. The oligonucleotide array analysis demonstrates that Heat Shock Protein-27 (Hsp27) is upregulated in Dex-resistant, but not in Dex-sensitive MM cells. Proteomics analysis of Hsp27-immunocomplexes revealed the presence of actin in Dex-resistant, but not in Dex-sensitive cells. Biochemical interaction between Hsp27 and actin was examined by co-immunoprecipitation with anti-Hsp27 or actin Abs. Far western blot analysis using GST-Hsp27 fusion protein showed a direct association with actin both in vitro and in vivo. Importantly, 2ME2- or Bortezomib/Proteasome inhibitor (PS-341)-induced apoptosis in Dex-resistant MM cell lines and MM patient cells is associated with disruption of the Hsp27-actin complexes. Finally, blockade of Hsp27 by anti-sense strategy enhanced anti-MM activity of both 2ME2 and PS-341. These findings provide the clinical application of novel therapeutics targeting Hsp27 to improve patient outcome in MM.

High-speed detection of occult tumor cells in peripheral blood.

Although detection of tumor cells in peripheral blood using imitiunocytochemistry and optical scanning is a promising method for screening and monitoring cancer, it poses a major technical challenge due to the extremely low tumor cell concentration in blood. The preferred detection method - digital microscopy - is far too slow for analysis of the large numbers of cells required for statistical validity. We describe here a novel prescan instrument that rapidly identifies a small number of candidates for subsequent examination by digital microscopy to determine if they are genuine tumor cells. The prescan is 500 times faster than digital microscopy and yet has a similar sensitivity. The high prescan speed is accomplished by trading resolution for field of view. The resolution of the prescan is determined by the laser spot size of about 10 microns. While this resolution is much coarser than the submicron resolution of microscopes, it is still sufficient for detecting fluorescent cells because it matches the size of a typical cell. The wide field of view and high scan rate are enabled by a novel application of fiber optics.

Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle regulated and is required for G(1)/S checkpoint activation in response to DNA damage.

ATR [ataxia-telangiectasia-mutated (ATM)- and Rad3-related] is a protein kinase required for both DNA damage-induced cell cycle checkpoint responses and the DNA replication checkpoint that prevents mitosis before the completion of DNA synthesis. Although ATM and ATR kinases share many substrates, the different phenotypes of ATM- and ATR-deficient mice indicate that these kinases are not functionally redundant. Here we demonstrate that ATR but not ATM phosphorylates the human Rad17 (hRad17) checkpoint protein on Ser(635) and Ser(645) in vitro. In undamaged synchronized human cells, these two sites were phosphorylated in late G(1), S, and G(2)/M, but not in early-mid G(1). Treatment of cells with genotoxic stress induced phosphorylation of hRad17 in cells in early-mid G(1). Expression of kinase-inactive ATR resulted in reduced phosphorylation of these residues, but these same serine residues were phosphorylated in ionizing radiation (IR)-treated ATM-deficient human cell lines. IR-induced phosphorylation of hRad17 was also observed in ATM-deficient tissues, but induction of Ser(645) was not optimal. Expression of a hRad17 mutant, with both serine residues changed to alanine, abolished IR-induced activation of the G(1)/S checkpoint in MCF-7 cells. These results suggest ATR and hRad17 are essential components of a DNA damage response pathway in mammalian cells.

Serum level of the periostin, a homologue of an insect cell adhesion molecule, in thymoma patients.

Periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule. Periostin has a typical signal peptide at the N-terminal end suggesting it is a secreted protein. Recently, we developed a novel sandwich chemiluminescence assay to determine serum concentrations of periostin. We investigated the serum periostin level in thymoma patients, and attempted to determine the correlation between serum periostin level and clinicopathological factors of thymoma patients who had undergone surgery between January 1994 and July 1996. Serum periostin levels were not significantly different between the thymoma patients (1264.4+/-122.9 ng/ml) and the normal control (962.0+/-118.6 ng/ml) (P=0.0877). There was no relationship between serum periostin level and age, gender or pathological subtype. However the serum periostin level of stage IV patients (1497.0+/-285.8 ng/ml) was significantly higher than normal control (P=0.0460). These data suggest that serum periostin level may indicate tumor invasion and progression of thymoma.

Overexpression of HRad17 mRNA in human breast cancer: correlation with lymph node metastasis.

PURPOSE: A novel human gene, designated HRad17, was identified as the human homologue of the Rad17 of Schizosaccharomyces pombe and Rad24 of Saccharomyces cerevisiae. In yeast, these genes play a critical role in maintaining genomic stability. The aim of this study was to evaluate the expression of HRad17 in human breast cancer. EXPERIMENTAL DESIGN: We investigated HRad17 mRNA expression in 64 cases of human breast cancer by means of reverse-transcription-PCR, in situ hybridization, and immunohistochemistry. RESULTS: The HRad17 mRNA was overexpressed in 35 cases (54.7%). Twenty-four (68.6%) of 35 cases with HRad17 overexpression in cancer tissues were node-positive, whereas only 8 (27.6%) of 29 cases without HRad17 overexpressions were node-positive. The expression of HRad17 mRNA correlated with both lymph node metastasis (P = 0.001) and high Ki67 labeling index (P = 0.006). Although not significantly different, expression of HRad17 mRNA tended to correlate with tumor size (P = 0.06) and expression of mutant p53 protein (P = 0.10). Furthermore, expression of HRad17 mRNA was an independent predictor of axillary lymph node metastasis as well as of lymphatic permeation by multivariate analysis (P < 0.0001). CONCLUSIONS: Our study demonstrates that HRad17 might be related to the development of lymph node metastasis in human breast cancers. Although its function still remains unclear, the expression of HRad17 mRNA could open up a new window for the diagnostic staging and treatment of human breast cancers.

Serum level of the periostin, a homologue of an insect cell adhesion molecule, as a prognostic marker in nonsmall cell lung carcinomas.

BACKGROUND: Periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule. Periostin has a typical signal peptide at the N-terminal end, which suggests that it is a secreted protein. Recently, the authors developed a novel sandwich chemiluminescence assay to determine serum concentrations of periostin. METHODS: The authors investigated the serum periostin level in lung carcinoma patients and attempted to determine the influence of serum periostin level on clinical outcome for patients with nonsmall cell lung carcinoma (NSCLC) who had undergone surgery between January 1994 and July 1996. Expression of periostin messenger RNA was also examined by in situ RNA hybridization for lung carcinomas. RESULTS: The periostin gene was shown to be highly expressed at the tumor periphery of lung carcinoma tissue but not within the tumor by in situ RNA hybridization. Serum periostin levels were not significantly different between the NSCLC patients (1142.1 +/- 89.2 ng/mL) and the normal control (962.0 +/- 118.6 ng/mL) (P = 0.2985). There was no relation between serum periostin level and gender, stage, bone metastasis, N status, or T status. However, the serum periostin levels of NSCLC patients had decreased significantly by 4 weeks after the resection of the tumor. The NSCLC patients with high periostin level (> 962 ng/mL) had significantly poorer survival than the patients with normal periostin level (P = 0.0406). Using the Cox proportional hazards regression model, the authors found that stage (P < 0.0001) and serum periostin level (P = 0.0226) were independent prognostic factors. CONCLUSIONS: The in situ RNA hybridization data from the current study suggested that expression of periostin may be involved in tumor invasionand that the serum periostin level may serve as a prognostic marker for NSCLC.

Overexpression of Hrad17 gene in non-small cell lung cancers correlated with lymph node metastasis.

We used palindromic PCR-driven cDNA differential display technique to identify and isolate a gene, human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, from colon cancer tissues. The loss of checkpoint control in mammalian cells results in genomic instability, leading to the amplification, rearrangement, or loss of chromosomes, events associated with tumor progression. We hypothesized that the Hrad17 may be expressed in non-small cell lung cancer (NSCLC). We attempted to determine the influence of Hrad17 expression on clinicopathological features for patients with NSCLC who had undergone surgery. Expression of Hrad17 messenger RNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in 102 non-small cell lung carcinomas and adjacent histologically normal lung samples from patients for whom follow up data were available. Hrad17 transcripts were detected in 26 (25.5%) of the tumor samples, although some of the paired normal lung samples showed weak expression. There was no relationship between Hrad17 gene expression and age, gender or T-status. About 13 of 31 (41.9%) NSCLC patients with Hrad17 overexpressions were node positive, on the other hand, 13 of 76 (18.3%) cases without Hrad17 overexpressions were node positive. Thus the expression of Hrad17 mRNA correlated with lymph node metastasis (P=0.0231) from NSCLC. Hrad17 protein was highly expressed at the advancing margin of the tumor of lung cancer tissue but not within the normal lung tissue by immunohistochemistry. Thus the expression of Hrad17 might correlate with more advanced NSCLC.

Expression of Periostin, homologous with an insect cell adhesion molecule, as a prognostic marker in non-small cell lung cancers.

We used our palindromic polymerase chain reaction (PCR)-driven cDNA differential display technique to identify and isolate a gene, designated periostin, from cancer tissues and found it to be overexpressed in several human tumors. We attempted to determine the influence of periostin expression on clinical outcome in patients with non-small cell lung cancer (NSCLC) by reverse transcriptase (RT)-PCR analysis. Periostin gene was highly expressed at the tumor periphery of lung cancer tissue but not within the tumor by in situ RNA hybridization, suggesting that expression of periostin may be involved in the process of tumor invasion. Periostin transcripts were detected in 50 (49.0%) of the tumor samples, although some paired normal lung samples showed weak expression. There was no relationship between periostin gene expression and gender, N- or T-status. The NSCLC patients with periostin expression had significantly poorer survival than the patients without periostin expression (P = 0.0338).