[Short-term outcomes of all-inside endoscopic running locked stitch technique for acute achilles tendon ruptures].

Objective: To evaluate the short-term outcomes of all-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures. Methods: This is a retrospective case series study. Forty cases with acute Achilles tendon rupture were treated with the all-inside endoscopic running locked stitch technique from April 2020 to March 2022. There were 44 males and 4 females, aged (34.8±7.4) years (range: 24 to 50 years). Body mass index was (21.2±2.4)kg/m2 (range: 18 to 26 kg/m2); There were 29 cases (60.4%) on the left side and 19 cases (39.6%) on the right side. Under endoscopic control, the proximal tendon stumps were stitched with the running locked method using a semi-automatic flexible suture passer. The threads of the high-strength suture were grasped through the paratenon sub-space and then fixed into calcaneal insertion with a knotless anchor. MRI of Achilles tendon, surgical time and complications were assessed. Achilles tendon total rupture score (ATRS), Achilles tendon resting angle, and heel rise height scale were utilized to evaluate final clinical outcomes. The differences of bilateral limbs were compared using the paired t test. Results: The follow-up time was (24.1±3.5)months (range:18 to 32 months). Appropriate tendon regeneration was observed on MRI at post-operative 12 months. The median ATRS score (M(IQR)) was 95.0 (4.7) points. Furthermore, there was no significant difference between the injured and contralateral side in the Achilles tendon resting angle ((17.1±2.4)° vs. (17.4±2.6)°, t=1.92,P=0.062) and heel rise height ((14.2±1.7)cm vs. (14.4±1.5)cm, t=1.71,P=0.094). No nerve injuries, infection, deep vein thrombosis and re-ruptures were encountered. Sports activity resumed six months postoperative in 46 patients. One patient had a slight anchor cut-out, due to an addition injury, which was removed after 5 months. Conclusions: All-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures shows promising results. It provides stable connection of the tendon stumps with a low risk of complications.

Secondary ear reconstruction based on the Nagata method after unsatisfactory microtia surgery outcomes.

BACKGROUND: Follow-up studies on auricular reconstruction procedures have reported postoperative complications; some of which can only be reversed with revision surgery. This study aims to provide a feasible surgical strategy based on the Nagata method for patients requiring secondary revision and verify mid-term aesthetic outcomes. METHODS: Secondary auricular reconstructions based on the Nagata method were performed on seven patients seeking secondary revision between 2017 and 2021. Scores of a five-point Likert scale and artificial intelligence ratings based on convolutional nerve networks were used as outcome measures. RESULTS: Five patients underwent complete two-stage ear reconstruction, and the other two patients underwent the first-stage microtia procedure only. Few complications were observed, except in Case 4; this patient required an additional minor surgery after frame exposure 6 weeks after the first-stage procedure. All revised ears showed clear anatomical structures, and all patients were satisfied with the aesthetic results. Statistical analysis showed a significant increase in postoperative versus preoperative scores by convolutional neural network models (p < 0.05). Cases 5 and 6, which involved projection surgeries only, had decreased artificial intelligence appearance scores postoperatively. CONCLUSION: After adequate preoperative evaluation, secondary auricle reconstruction based on the Nagata method can achieve reliable aesthetic outcomes with few complications. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov ID: NCT05604456.

BAP18 induces growth of non-small-cell lung carcinoma through upregulating transcriptional level of CCND1/2.

OBJECTIVE: To elucidate the biological function of BAP18 (BPTF-associated protein of 18 kDa) in non-small-cell lung carcinoma (NSCLC) and the molecular mechanism. PATIENTS AND METHODS: Relative levels of BAP18 in NSCLC tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and its influence on pathological characteristics of NSCLC patients was analyzed. Correlation between BAP18 and Ki67 levels in NSCLC was assessed by Pearson correlation test. Furthermore, Kaplan-Meier curves were depicted for revealing survival difference in NSCLC patients expressing high or low level of BAP18. Relative levels of BAP18, CCND1, CCND2 and CCND3 in A549 and H1299 cells transfected with siBAP18 were determined, as well as colony number. In addition, after knockdown of protein level of BAP18 in A549 and H1299 cells by lentivirus transfection, cell cycle progression was examined. Co-regulation of BAP18 and CCND1/2 on cell growth of NSCLC was finally detected. RESULTS: BAP18 was upregulated in NSCLC tissues, especially cases with advanced stage (III-IV) or large tumor size (>5 cm). BAP18 was closely linked to tumor size, TNM staging and lymphatic metastasis in NSCLC. Knockdown of BAP18 reduced transcriptional levels of CCND1 and CCND2 in A549 and H1299 cells. Furthermore, knockdown of BAP18 delayed transition from G1 to S phase, and weakened growth of NSCLC cells. CONCLUSIONS: BAP18 triggers the progression of NSCLC by regulating transcriptional activities of CCND1/2, which may be a potential target for the treatment and diagnosis of NSCLC.

LINC00106 prevents against metastasis of thyroid cancer by inhibiting epithelial-mesenchymal transition.

OBJECTIVE: Thyroid cancer (TC) is a common malignant tumor of the endocrine system, and its morbidity and mortality are in the high places. Recent studies have focused on exploring biological markers and targeted therapy for TC. This research aims to elucidate the role of LINC00106 in the progression of TC and the regulatory mechanisms. PATIENTS AND METHODS: Differential level of LINC00106 in a downloaded profile containing TC and normal tissues from GEPIA database was analyzed. Subsequently, its level in TC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between LINC00106 level and clinical data of TC patients was assessed, including age, tumor staging, lymphatic metastasis, and overall survival. After transfection of si-LINC00106, TC cell metastasis was evaluated by wound healing and transwell assay. Relative levels of E-cadherin, N-cadherin, ß-catenin, and Vimentin regulated by LINC00106 were determined using qRT-PCR and Western blot. RESULTS: LINC00106 was downregulated in TC tissues than normal ones. Its level was correlated to tumor staging, lymphatic metastasis and overall survival in TC patients. The knockdown of LINC00106 in BCPCP and TPC-1 cells enhanced migratory and invasive abilities and triggered the process of epithelial-mesenchymal transition (EMT). CONCLUSIONS: LINC00106 is lowly expressed in TC specimens, which attenuates migratory and invasive abilities in TC by inhibiting EMT as a tumor suppressor.

Correlations of IL-6 and CRP gene polymorphisms with pulmonary heart disease.

OBJECTIVE: To explore the correlations of interleukin-6 (IL-6) and C-reactive protein (CRP) gene polymorphisms with pulmonary heart disease (PHD). PATIENTS AND METHODS: A total of 98 patients with PHD and 102 healthy persons receiving physical examinations were enrolled. Their general clinical information was collected, and the levels of IL-6 and CRP in the plasma were determined. The pulmonary functions and blood gas were detected, and the TaqMan-minor groove binder (MGB) probe was used to detect the polymorphisms of IL-6 rs1800796 and CRP rs1800796. RESULTS: Observation group had higher levels of IL-6 and CRP than control group (p<0.05). The forced expiratory volume in 1 second (FEV1) (%), FEV1/forced vital capacity (FVC) ratio (%), and arterial partial pressure of oxygen (PaO2) in observation group were lower than those in control group (p<0.05), but the arterial partial pressure of carbon dioxide (PaCO2) was higher than that in control group (p<0.05). There were differences in the distribution frequencies of the genotypes and alleles of IL-6 rs1800796 and CRP rs1800796 between the two groups (p<0.05). CONCLUSIONS: IL-6 and CRP are correlated with the onset of PHD, and there are also correlations between the polymorphisms of IL-6 rs1800796 and CRP rs2794521 and the disease.

Novel microsatellite markers for the oriental fruit moth Grapholita molesta (Lepidoptera: Tortricidae) and effects of null alleles on population genetics analyses.

The oriental fruit moth (OFM) Grapholita molesta (Lepidoptera: Tortricidae) is an important economic pest of stone and pome fruits worldwide. We sequenced the OFM genome using next-generation sequencing and characterized the microsatellite distribution. In total, 56,674 microsatellites were identified, with 11,584 loci suitable for primer design. Twenty-seven polymorphic microsatellites, including 24 loci with trinucleotide repeat and three with pentanucleotide repeat, were validated in 95 individuals from four natural populations. The allele numbers ranged from 4 to 40, with an average value of 13.7 per locus. A high frequency of null alleles was observed in most loci developed for the OFM. Three marker panels, all of the loci, nine loci with the lowest null allele frequencies, and nine loci with the highest null allele frequencies, were established for population genetics analyses. The null allele influenced estimations of genetic diversity parameters but not the OFM's genetic structure. Both a STRUCTURE analysis and a discriminant analysis of principal components, using the three marker panels, divided the four natural populations into three groups. However, more individuals were incorrectly assigned by the STRUCTURE analysis when the marker panel with the highest null allele frequency was used compared with the other two panels. Our study provides empirical research on the effects of null alleles on population genetics analyses. The microsatellites developed will be valuable markers for genetic studies of the OFM.

Novel polymorphisms of the PRKAG2 gene and their association with body measurement and meat quality traits in Qinchuan cattle.

Body measurement and meat quality traits play important roles in the evaluation of productivity and economy in cattle, which are influenced by genes and environmental factors. PRKAG2, which encodes the γ2 regulatory subunit of AMPK, is associated with key metabolic pathways in muscle. We detected bovine PRKAG2 gene polymorphisms and analyzed their associations with body measurement and meat quality traits of cattle. DNA samples were taken from 578 Qinchuan cattle aged 18-24 months. DNA sequencing, polymerase chain reaction-restriction fragment length polymorphism, and time-of-flight mass spectrometry were used to detect PRKAG2 single nucleotide polymorphisms (SNPs). Sequence analysis revealed three SNPs in exon 3 (g.95925G>A, g.95973G>C, and g.95992A>G) and one g.96058T>C mutation in intron 3. g.95973G>C, g.95992A>G, and g.96058T>C each showed 3 genotypes: GG, GC, and CC; AA, AG, and GG; and TT, TC, and CC, respectively. In contrast, g.95925G>A only showed 2 genotypes, GG and GA. Analysis showed that g.95925G>A had no effects on body measurement and meat quality traits, whereas the other 3 polymorphisms were significantly associated with some of the body measurement and meat quality traits in the Qinchuan cattle population. It is inferred that the PRKAG2 gene can be used for marker-assisted selection to improve the body measurement and meat quality traits in the Qinchuan cattle population.

Characterization of novel microsatellite markers for Hyphantria cunea and implications for other Lepidoptera.

This is the first report of microsatellite markers (simple sequence repeats, SSR) for fall webworm, Hyphantria cunea (Drury) (Lepidoptera: Arctiidae), an important quarantine pest in some European and Asian countries. Here, we developed 48 microsatellite markers for H. cunea from SSR enrichment libraries. Sequences isolated from libraries were sorted into four categories and analyzed. Our results suggest that sequences classified as Grouped should not be used for microsatellite primer design. The genetic diversity of microsatellite loci was assessed in 72 individuals from three populations. The number of alleles per locus ranged from 2 to 5 with an average of 3. The observed and expected heterozygosities of loci ranged from 0 to 0.958 and 0 to 0.773, respectively. A total of 18 out of 153 locus/population combinations deviated significantly from Hardy-Weinberg equilibrium. Moreover, significant linkage disequilibrium was detected in one pair of loci (1275 pairs in total). In the neutral test, two loci were grouped into the candidate category for positive selection and the remainder into the neutral category. In addition, a complex mutation pattern was observed for these loci, and F ST performed better than did R ST for the estimation of population differentiation in different mutation patterns. The results of the present study can be used for population genetic studies of H. cunea.

Genetic polymorphisms of the FATP1 gene and their associations with meat quality traits in Chinese Qinchuan cattle.

Fatty acid transport protein 1 (FATP1), an integral membrane protein that facilitates long-chain fatty acid influx, is involved in the genetic network for oleic acid synthesis. The aim of this study was to examine the association of FATP1 polymorphisms with live animal meat quality traits in Chinese Qinchuan cattle. Quantitative real-time PCR analysis demonstrated that FATP1 has a broad tissue distribution in Qinchuan cattle and is highly expressed in longissimus dorsi muscle and back fat. Using direct DNA sequencing of the FATP1 gene in 458 Qinchuan cattle, four single nucleotide polymorphisms (SNPs; g.28265 G>C, g.28381 G>A, g.28470 T>C, and g.28672 G>A) were identified for genotyping within a 671-bp region, including exon 3, intron 3, exon 4, intron 4, and part of exon 5 of the FATP1 gene. Positive effects of genotypes CC (g.28470 T>C locus) and AA (g.28672 G>A locus) on meat quality traits were obtained by association analysis. These results indicate the associations of g.28470 T>C and g.28672 G>A with meat quality traits in Qinchuan cattle. Thus, the FATP1 gene may be used in marker-assisted selection of beef cattle in breeding programs.

Association of SIRT2 gene polymorphisms with body measurement and growth traits of Qinchuan cattle.

Silent information regulator 2 (SIRT2), a member of the Sirtuin family of class III nicotinamide adenine dinucleotide-dependent protein deacetylases, plays an important role in senescence, metabolism, and apoptosis. This study was conducted to detect potential polymorphisms of the bovine SIRT2 gene and explore their relationships with meat quality and body measurement traits (BMTs) in Qinchuan cattle. Four single nucleotide polymorphisms (A7445G, C7711T, G17937A, and G20937A) in the fourth intron, fourth exon, ninth exon, and twelfth exon of the SIRT2 gene, respectively, were identified according to the sequencing results of 520 individuals of a Qinchuan cattle population. The genotypic distributions of both A7445G and G20937A were in agreement with the Hardy-Weinberg equilibrium (P < 0.05), whereas the other two mutations were not (0.05 < P < 0.01), based on the X(2) test. Association analysis indicated that the four loci were significantly correlated with several BMTs and meat quality traits. When in combination, the H1H1 (AA-CC-GG-CC) diplotypes showed better BMT and meat quality traits than those by other combinations. Collectively, the results show that SIRT2 is involved in the regulation of the growth and meat quality of cattle, suggesting that the SIRT2 gene may be a candidate gene for marker-assisted selection in the development of future breeding programs for Qinchuan cattle.

The working experiences of novice psychiatric nurses in Taiwanese culture: a phenomenological study.

Novice psychiatric nurses experience heavy workloads, insufficient training and support in Taiwan. The aim of this study was to understand the working experiences of novice psychiatric nurses during their first year in a clinical setting. A qualitative phenomenological approach, using semi-structured face-to-face interviews was used. Narratives were analyzed using Colaizzi's seven-step method. Data saturation was reached after interviews were conducted with 15 nurses based on the purposive sampling. Four themes and eight sub-themes were identified: struggling (lacking a sense of security and competency), emulating (learning the process of interaction with clients and families, learning an appropriate role from nursing staff), prevailing (developing core competency, creating a therapeutic environment) and belonging (coping with the job, becoming a part of the psychiatric nursing staff). The findings from this study demonstrate that nurses are often inadequately prepared for psychiatric nursing. They have little understanding of mental illness, are unable to communicate appropriately with clients and struggle to cope with the conditions. Our study supports the importance for helping nurses to improve their essential knowledge and skills for coping with the job and providing good quality care, particularly in the first year.

Recruitment of patients into an internet-based clinical trials database: the experience of OncoLink and the National Colorectal Cancer Research Alliance.

PURPOSE: In March 2001, the National Colorectal Cancer Research Alliance (NCCRA) and OncoLink (http://www.oncolink.org) established a database to facilitate patient enrollment onto clinical trials. This study describes the population registering with the database and identifies discrepancies between individuals registering through the Internet and those registering through a telephone call center. METHODS: Participants registered with the NCCRA/OncoLink database through the Internet or a telephone call center. All participants entering the database completed a questionnaire regarding basic demographics, colon cancer risk factors, and indicated how they became aware of the database. Comparisons were made between individuals registering through the Internet and those registering through the telephone call center. RESULTS: A total of 2,162 participants registered during the first 16 months of the database. Most patients registered through the Internet rather than the telephone call center (88% v 12%; P < .001). More females than males registered (73% v 27%; P < .001). The majority (89%) were white. Participants registering through the Internet were younger than those registering through the call center (mean, 48.8 v 55.0 years; P < .001). There was no difference between the two groups with regard to sex or ethnicity. CONCLUSION: The Internet has the potential to increase the likelihood that interested individuals find appropriate clinical trials. Some of the discrepancies that are known to exist for access to the Internet were also seen for those registering with the database through the Internet. Despite these differences, the potential to increase clinical trial enrollment with this type of Internet-based database is high.

Comparison of motor conduction techniques in the diagnosis of carpal tunnel syndrome.

OBJECTIVE: To compare the sensitivities of motor wrist-to-palm (W-P) conduction velocity and two median-ulnar motor latency differences with that of sensory W-P conduction velocity in the diagnosis of carpal tunnel syndrome (CTS). METHODS: This study included 116 consecutive patients with CTS (160 hands) referred for evaluation and 100 volunteers who served as controls. Median motor and sensory nerve responses with wrist and palm stimulation allowed for the determination of motor and sensory W-P CV (W-P MCV and SCV). Two motor distal latency (MDL) differences between the median-thenar and ulnar-hypothenar (M-U) muscles and between the median-second lumbrical and ulnar-interossei muscles (2L-INT) were measured and calculated. The mean values of controls plus or minus 2.5 SD served as the normal limits. RESULTS: Among the 160 hands with suspected CTS, 11 (6.88%) had normal electrodiagnostic studies and 149 (93.1%) had at least one abnormal electrodiagnostic study. Among the 149 hands with an abnormality, 139 (86.88%) had abnormal W-P MCV and 129 (80.63%) had abnormal W-P SCV. The sensitivity for 2L-INT was 77.5%, and it was 70% for M-U, 68.75% for median MDL, and 73.75% for sensory distal latency. Combining W-P MCV and W-P SCV allowed for the detection of abnormalities in 147 hands (91.88%) and yielded a markedly improved diagnostic rate compared with W-P SCV alone. CONCLUSION: Motor W-P conduction study is more valuable and no more difficult than sensory W-P conduction study for the diagnosis of CTS. In patients with suspected CTS in whom the results of conventional nerve conduction studies are normal, studying both motor and sensory W-P conduction increases the diagnostic yield.

Indomethacin lowers the threshold thermal exposure for hyperthermic radiosensitization and heat-shock inhibition of ionizing radiation-induced activation of NF-kappaB.

PURPOSE: It is well established that salicylate and several other non-steroidal anti-inflammatory agents (NSAID), including indomethacin, can activate the heat-shock response, albeit at high concentrations. This is significant since heat shock significantly alters the cellular cytotoxic response to ionizing radiation (IR). It was previously shown that heat shock, as well as NSAIDs, inhibits IR-induced activation of NF-kappaB and that NF-kappaB protects against IR-induced cytotoxicity. Hence, it is hypothesized that pretreatment with indomethacin before heating will lower the temperature and heating times required to inhibit the activation of NF-kappaB and induce significant hyperthermic radiosensitization. MATERIALS AND METHODS: Experiments were performed in HeLa cell lines and the DNA-binding activity was determined by EMSA. Cellular radiosensitivity was determined by clonogenic assay. RESULTS: HeLa cells pretreated with indomethacin showed a decrease in the temperature-time combination necessary to inhibit IR-induction of NF-kappaB DNA binding. In addition, clonogenic cell survival assays using identical conditions showed an indomethacin dose-dependent enhancement of hyperthermic radiosensitization. Thus, similar concentrations of indomethacin both lowered the threshold thermal exposure to inhibit activation of NF-kappaB DNA-binding and increased the sensitivity of tumour cells to hyperthermic radiosensitization-induced cytotoxicity. In HeLa cells treated with N-alpha-tosylphenylalanyl-chloromethyl ketone (TPCK), a serine protease inhibitor that blocks activation of NF-kappaB, an increase in radiosensitivity was observed. Interestingly, no additional cell killing was observed when heat shock was added to cells treated with TPCK before IR, suggesting a possible common cytotoxic pathway. CONCLUSIONS: The results demonstrate that indomethacin lowers the temperature-time conbination necessary to induce several physiological processes associated with the heat-shock response. Furthermore, NSAID may be potential adjuvants in improving the clinical effectiveness of hyperthermia in radiation therapy.

Indomethacin-induced radiosensitization and inhibition of ionizing radiation-induced NF-kappaB activation in HeLa cells occur via a mechanism involving p38 MAP kinase.

Although ionizing radiation (IR) activates multiple cellular factors that vary depending on dose and tissue specificity, the activation of NF-kappaB appears to be a well-conserved response in tumor cells exposed to IR. Recently, it also has been demonstrated that nonsteroidal anti-inflammatory agents inhibit tumor necrosis factor and interleukin-1-induced NF-kappaB activation and act as radiosensitizing agents. These observations reinforce the growing notion that NF-kappaB may be a protective cellular factor responding to the cytotoxicity of IR and other damaging stimuli. As such, we addressed the idea and mechanism that NF-kappaB is a downstream target of the nonsteroidal anti-inflammatory agent indomethacin and is involved in the process of radiosensitization. In this study, we report that indomethacin inhibited IR-induced activation of NF-kappaB and sensitized HeLa cells to IR-induced cytotoxicity at similar concentrations. Pretreatment of HeLa cells with SB 203580, a pyridinyl imidazole compound that specifically inhibits p38 mitogen-activated protein kinase (MAPK), abrogated the ability of indomethacin to inhibit IR-induced activation of NF-kappaB and diminished the indomethacin radiosensitizing effect. In addition, the transient genetic activation of p38(MAPK) inhibited IR induction of NF-kappaB gene expression in the absence of indomethacin. Finally, permanently transfected cell lines genetically unable to activate NF-kappaB, because of expression of a dominant negative I-kappaBalpha gene, demonstrated increased sensitivity to IR-induced cytotoxicity. Taken together, these results suggest that p38 MAPK is a target involved in indomethacin-induced radiosensitization and that NF-kappaB may be one downstream target in this process.

Increased activator protein 1 activity as well as resistance to heat-induced radiosensitization, hydrogen peroxide, and cisplatin are inhibited by indomethacin in oxidative stress-resistant cells.

It has been established that tumor cells develop resistance to a variety of therapeutic agents after multiple exposures to these agents/drugs. Many of these therapeutic agents also appear to increase the activity of transcription factors, such as activator protein 1 (AP-1), believed to be involved in cellular responses to oxidative stress. Therefore, we hypothesized that cellular resistance to cancer therapeutic agents may involve the increased activity of transcription factors that govern resistance to oxidative stress, such as AP-1. To investigate this hypothesis, a previously characterized cisplatin, hyperthermia, and oxidative stress-resistant Chinese hamster fibroblast cell line, OC-14, was compared to the parental HA-1 cell line. Electrophoretic mobility shift and Western blot assays performed on extracts isolated from OC-14 cells demonstrated a 10-fold increase in constitutive AP-1 DNA-binding activity as well as increased constitutive c-Fos and c-Jun immunoreactive protein relative to HA-1 cells. Treatment of OC-14 cells with indomethacin inhibited constitutive increases in AP-1 DNA-binding activity and c-Fos/c-Jun-immunoreactive protein levels. Clonogenic survival assays demonstrated that pretreatment with indomethacin, at concentrations that inhibited AP-1 activity, significantly reduced the resistance of OC-14 cells to heat-induced radiosensitization, hydrogen peroxide, and cisplatin. These results demonstrate a relationship between increases in AP-1 DNA-binding activity and increased cellular resistance to cancer therapeutic agents and oxidative stress that is inhibited by indomethacin. These results support the hypothesis that inhibition of AP-1 activity with nonsteroidal anti-inflammatory drugs, such as indomethacin, may represent a useful adjuvant to cancer therapy.

Tumor invasiveness and liver metastasis of colon cancer cells correlated with cyclooxygenase-2 (COX-2) expression and inhibited by a COX-2-selective inhibitor, etodolac.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to reduce the risk and mortality of colorectal cancer (CRC). Although the exact mechanisms remain unclear, the inhibition of cyclooxygenase (COX) by NSAIDs appears to abort, if not prevent, CRC carcinogenesis or metastatic tumor progression. The aim of our study was to investigate the association between COX-2 expression and CRC tumor cell invasiveness. The differences in immunoblot-detectable COX-2 protein contents in primary CRCs, metastatic hepatic lesions and corresponding normal mucosa from the same individual were evaluated in 17 patients. Three different colon cancer cell lines, SW620, Lovo, HT-29 and a metastatic variant of HT-29, HT-29/Inv3, were employed to evaluate COX-2 expression and prostaglandin E(2) (PGE2) production in relation to their invasive abilities in vitro. The effects of a COX-2-selective inhibitor, etodolac, on cell proliferation and invasive activity were also determined. The results showed that 15 of 17 (88%) metastatic CRC cells from the liver and 14 of 17 (82%) primary CRC tissue exhibited much higher levels of COX-2 than corresponding adjacent normal mucosa from the same patient. Among those patients with relatively high COX-2 expression in the primary tumors, almost all exhibited even higher levels of COX-2 in their hepatic metastases. Among the 4 colon cancer cell lines, HT-29/Inv3 manifested the highest COX-2 expression, PGE2 production and in vitro invasive activity. The selective COX-2 inhibitor, etodolac, could especially exert cytotoxicity and markedly suppress the invasive property and PGE(2) production, although not the COX-2 protein level, in HT-29/Inv3 cells. Our results imply that COX-2 expression may be associated with the invasive and metastatic properties of CRC tumor cells.

[Effect of nerve growth factor on the visual evoked potential of rats pretreated by CS2].

AIM: To study the therapeutic effect of NGF to rats with newly CS2 deranged. METHODS: The model of rats with deranged visual nerve was made by CS2 (i.p) for three weeks. Rats were then treated with different dosages of NGF for three weeks, and the changes of visual evoked potential were determined. RESULTS: The latency of PREP and FEP shortened significantly vs control after treatment for 10 and 20 days. CONCLUSION: NGF can improve the conductivity of visual with dose-effect relationship, suggesting that NGF has a significant therapeutic effect on the deranged visual nerve.

Dose-dependent differences in the profile of mutations induced by carcinogenic (R,S,S,R) bay- and fjord-region diol epoxides of polycyclic aromatic hydrocarbons.

Chinese hamster V79 cells were exposed to a high or low concentration of the highly carcinogenic (R,S,S,R) or the less active (S,R,R,S) bay- or fjord-region diol epoxides of benzo[a]pyrene, benzo[c]phenanthrene or dibenz[c,h]acridine. Independent 8-azaguanine-resistant clones were isolated, and base substitutions at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus were determined. For the three (R,S,S,R) diol epoxides studied, the proportion of mutations at AT base pairs increased as the concentration of diol epoxide decreased. Concentration-dependent differences in the mutational profile were not observed, however, for the three (S,R,R,S) diol epoxides. In studies, with V-H1 cells (a DNA repair deficient variant of V79 cells), a concentration-dependent difference in the profile of mutations for the (R,S,S,R) diol epoxide of benzo[a]pyrene was not observed. These results suggest that concentration-dependent differences in the mutational profile are dependent on an intact DNA repair system. In additional studies, we initiated mouse skin with a high or low dose of benzo[a]pyrene and promoted the mice for 26 weeks with 12-O-tetradecanoylphorbol-13-acetate. Papillomas were examined for mutations in the c-Ha-ras proto-oncogene. Dose-dependent differences in the profile of c-Ha-ras mutations in the tumors were observed. In summary, (i) dose-dependent differences in mutational profiles at the hprt locus were observed in Chinese hamster V79 cells treated with several highly mutagenic and carcinogenic (R,S,S,R) bay- or fjord-region diol epoxides but not with their less active (S,R,R,S) diol epoxide enantiomers, (ii) a dose-dependent difference in the mutational profile was not observed for the (R,S,S,R) diol epoxide of benzo[a]pyrene in a DNA-repair defective V79 cell line, and (iii) a dose-dependent difference in the mutational profile in the c-Ha-ras proto-oncogene was observed in tumors from mice treated with a high or low dose of benzo[a]pyrene.