Biomedical subjects

C Yu

Publications and source records attributed to C Yu.

At least 19 recordsLinked to original sources

PubMed2026

Longitudinal ctDNA tracking in early and recurrent breast cancer using an ultrasensitive structural variant-based assay: an extended analysis from the TRACER study.

BACKGROUND: Detection of circulating tumor DNA (ctDNA) following curative-intent therapy is prognostic of disease recurrence in early-stage breast cancer (EBC). An ultrasensitive structural variant (SV)-based ctDNA assay was evaluated previously in a 100-patient EBC cohort treated with neoadjuvant therapy, demonstrating high sensitivity, specificity, and a long lead-time to relapse. The stability of primary tumor-specific SVs at and after metastatic recurrence and their utility for longer-term ctDNA monitoring had not been established. PATIENTS AND METHODS: An updated retrospective analysis of ctDNA dynamics was conducted in an expanded cohort of 121 patients with EBC treated with neoadjuvant therapy. Plasma samples were collected at key clinical timepoints and serially in several patients who experienced metastatic recurrence. Clinical variables were abstracted from medical records. Associations between ctDNA detection, dynamics, and clinical outcomes were evaluated in the early-stage and metastatic settings. RESULTS: Thirty of 121 patients experienced clinical recurrence (28 distant, 2 local) over a median follow-up of 4.2 years (range 0.5-8.8; 25 ctDNA evaluable with adjuvant timepoints). All patients with detectable ctDNA in the adjuvant setting developed metastatic recurrence (22/22). Median lead time from ctDNA detection to metastatic recurrence was 346 days (range 0-1937). Among recurrent cases, 79% of primary tumor-specific SVs (n = 17 patients, tumor fraction ≥0.1%) remained detectable in plasma [range 7% (1/14 SV)-100% (15/15); median: 92%]. ctDNA dynamics in the recurrent metastatic setting demonstrated a strong relationship with radiographic outcomes in evaluable patients (n = 9). CONCLUSION: This SV-based digital PCR assay provided ultrasensitive ctDNA detection in an expanded EBC cohort, maintaining 100% positive predictive value for metastatic recurrence. In patients with recurrence, ctDNA dynamics were concordant with radiographic outcomes. Prospective studies evaluating the clinical utility of longitudinal ctDNA monitoring are warranted.

MRD↗

PubMed2006

Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis.

Transcription factors with helix-loop-helix (HLH) motif play critical roles in controlling the expression of genes involved in lineage commitment, cell fate determination, proliferation, and tumorigenesis. To examine whether the newly identified HLH protein GCIP/CCNDBP1 modulates cell fate determination and plays a role in hepatocyte growth, proliferation, and hepatocarcinogenesis, we generated transgenic mice with human GCIP gene driven by a liver-specific albumin promoter. We demonstrated that in GCIP transgenic mice, the overall liver growth and regeneration occurred normally after liver injury induced by carbon tetrachloride (CCl4). In the diethylnitrosamine (DEN)-induced mouse hepatocarcinogenesis, we demonstrated that overexpression of GCIP in mouse liver suppressed DEN-induced hepatocarcinogenesis at an early stage of tumor development. The number of hepatic adenomas at 24 weeks was significantly lower or not detected in GCIP transgenic male mice compared to the control mice under the same treatment. Although GCIP has little inhibition on the number of hepatic tumors at later stages (40 weeks), hepatocellular tumors in GCIP transgenic mice are smaller and well-differentiated compared to the poorly differentiated tumors in wild-type mice. Furthermore, we demonstrate that GCIP functions as a transcriptional suppressor, regulates the expression of cyclin D1, and inhibits anchorage-independent cell growth and colony formation in HepG2 cells, suggesting a significant role of GCIP in tumor initiation and development.

Animals↗

PubMed2006

Schistosoma japonicum triose-phosphate isomerase plasmid DNA vaccine protects pigs against challenge infection.

The protective efficacy of a Schistosoma japonicum, Chinese strain, triose-phosphate isomerase (TPI) plasmid DNA vaccine was examined in naïve pigs. Pigs were vaccinated with the TPI DNA-plasmid alone, or in conjunction with IL-12 as pcDNA3.1-P35, pcDNA3.1-P40 plasmids via intramuscular injection. Control pigs were immunized with equivalent amounts of pcDNA3.1. Pigs were immunized 3 times at 21-day intervals and challenged 30 days after the final boost. Forty-five days post-challenge, pigs were sacrificed and perfused to compare adult worm burdens, female worm burdens, liver egg burdens and granuloma size. We found that pigs vaccinated with SjCTPI DNA alone had adult worm burdens reduced by 48.3% and that a further decrease in adult worm burdens was not seen in the group vaccinated with SjCTPI DNA in conjunction with IL-12 (46.2% reduction). The SjCTPI DNA vaccines had a more pronounced effect on reducing female worm burdens i.e. 53.6% SjCTPI alone and 59.6% for SjCTPI+IL-12. Vaccination with SjCTPI-DNA reduced liver eggs by 49.4% and this response was significantly enhanced by the addition of IL-12 (65.8% reduction in liver eggs). In addition to the dramatic protective effects seen in vaccinated pigs, we also noted that granuloma size was reduced by 42% in both groups. Thus, vaccination of pigs and other large animals in China with SjCTPI DNA vaccine will likely reduce transmission by reducing adult worm burdens and worm egg output and simultaneously reduce hepatic egg-associated pathology.

Animals↗

PubMed2006

Radioactive materials in biosolids: dose modeling.

The Interagency Steering Committee on Radiation Standards (ISCORS) has recently completed a study of the occurrence within the United States of radioactive materials in sewage sludge and sewage incineration ash. One component of that effort was an examination of the possible transport of radioactivity from sludge into the local environment and the subsequent exposure of humans. A stochastic environmental pathway model was applied separately to seven hypothetical, generic sludge-release scenarios, leading to the creation of seven tables of Dose-to-Source Ratios (DSR), which can be used in translating from specific activity in sludge into dose to an individual. These DSR values were then combined with the results of an ISCORS survey of sludge and ash at more than 300 publicly owned treatment works, to explore the potential for radiation exposure of sludge workers and members of the public. This paper provides a brief overview of the pathway modeling methodology employed in the exposure and dose assessments and discusses technical aspects of the results obtained.

Environmental Monitoring↗

PubMed2006

Altered placental syncytin and its receptor ASCT2 expression in placental development and pre-eclampsia.

OBJECTIVE: To investigate the alterations of syncytin, a fusogenic membrane protein involved in syncytiotrophoblastic layer formation, and its receptor ASCT2 expression in placental development and pre-eclampsia. DESIGN: Analyses of syncytin and ASCT2 expression in placentas from different stages of pregnancy and women with pre-eclampsia and in cytotrophoblasts cultured in normoxic and hypoxic conditions. SETTING: Placental samples were collected from a tertiary medical centre. POPULATION: Sixteen women with pre-eclampsia and 58 pregnant women presented as pregnancy (5-19 weeks of gestation) for elective termination, preterm birth, or normal term delivery. METHODS: The quantitative real-time polymerase chain reaction was used to study the syncytin and ASCT2 expression during placental development in 35 placentas from women without pre-eclampsia (ranged from 5 to 40 weeks of gestation) and the alterations of pre-eclamptic placentas (n=16) compared with gestational-age-matched controls (n=16). Western blot analysis was performed to study the protein level of syncytin in pre-eclamptic placentas and gestational-age-matched controls. The hypoxic effect on trophoblastic syncytin and ASCT2 expression was further studied in cytotrophoblasts cultured in 2% oxygen (n= 7). MAIN OUTCOME MEASURES: Syncytin and ASCT2 messenger RNA (mRNA) in placental tissue and cytotrophoblasts. RESULTS: The level of syncytin mRNA expression increased significantly since the first trimester of pregnancy until 37 weeks of gestation, when the level of syncytin expression was reduced. The ASCT2 mRNA expression was decreased significantly since the second trimester and was relatively stable since then to 40 weeks of gestation. Furthermore, a significant reduction in syncytin mRNA expression was observed in pre-eclamptic placentas and cytotrophoblasts cultured in hypoxia, but not a reduction in ASCT2 mRNA expression. Correlatively, the protein level of syncytin was decreased in pre-eclamptic placentas. CONCLUSIONS: A reduced placental expression of syncytin but not ASCT2 may contribute to altered cytotrophoblastic cell fusion processes and disturbed placental function in pre-eclampsia. Correspondingly, hypoxia decreases syncytin but not ASCT2 gene expression in cultured cytotrophoblasts.

Amino Acid Transport System ASC↗

PubMed2006

Relationship between patient complaints and surgical complications.

BACKGROUND: Patient complaints are associated with increased malpractice risk but it is unclear if complaints might be associated with medical complications. The purpose of this study was to determine whether an association exists between patient complaints and surgical complications. METHODS: A retrospective analysis of 16,713 surgical admissions was conducted over a 54 month period at a single academic medical center. Surgical complications were identified using administrative data. The primary outcome measure was unsolicited patient complaints. RESULTS: During the study period 0.9% of surgical admissions were associated with a patient complaint. 19% of admissions associated with a patient complaint included a postoperative complication compared with 12.5% of admissions without a patient complaint (p = 0.01). After adjusting for surgical specialty, co-morbid illnesses and length of stay, admissions with complications had an odds ratio of 1.74 (95% confidence interval 1.01 to 2.98) of being associated with a complaint compared with admissions without complications. CONCLUSIONS: Admissions with surgical complications are more likely to be associated with a complaint than surgical admissions without complications. Further research is necessary to determine if patient complaints might serve as markers for poor clinical outcomes.

Adult↗

PubMed2005

Comparative analyses of linac and Gamma Knife radiosurgery for trigeminal neuralgia treatments.

Dedicated linac-based radiosurgery has been reported for trigeminal neuralgia treatments. In this study, we investigated the dose fall-off characteristics and setup error tolerance of linac-based radiosurgery as compared with standard Gamma Knife radiosurgery. In order to minimize the errors from different treatment planning calculations, consistent imaging registration, dose calculation and dose volume analysis methods were developed and implemented for both Gamma Knife and linac-based treatments. Intra-arc setup errors were incorporated into the treatment planning process of linac-based deliveries. The effects of intra-arc setup errors with increasing number of arcs were studied and benchmarked against Gamma Knife deliveries with and without plugging patterns. Our studies found equivalent dose fall-off properties between Gamma Knife and linac-based radiosurgery given a sufficient number of arcs (>7) and small intra-arc errors (<0.5 mm) were satisfied for linac-based deliveries. Increasing the number of arcs significantly decreased the variations in the dose fall-off curve at the low isodose region (e.g. from 40% to 10%) and also improved dose uniformity at the high isodose region (e.g. from 70% to 90%). As the number of arcs increased, the effects of intra-arc setup errors on the dose fall-off curves decreased. Increasing the number of arcs also reduced the integral dose to the distal normal brain tissues. In conclusion, linac-based radiosurgery produces equivalent dose fall-off characteristics to Gamma Knife radiosurgery with a high number of arcs. However, one must note the increased treatment time for a large number of arcs and isocentre accuracies.

Dose-Response Relationship, Radiation↗

PubMed2005

Inhibition of the PI3K pathway sensitizes fludarabine-induced apoptosis in human leukemic cells through an inactivation of MAPK-dependent pathway.

In the present study, we have investigated the effects of PI3K/Akt pathway on the response of human leukemia cells to fludarabine. Inhibition of PI3K/Akt pathway with a selective inhibitor (e.g., LY294002, or wortmannin) in leukemic cells markedly potentiated fludarabine-induced apoptosis. Inhibition of the PI3K/Akt downstream target mTOR by rapamycin also significantly enhanced fludarabine-induced apoptosis. The co-treatment of fludarabine/LY294002 resulted in significant attenuation in the levels of both phospho-Erk1/2 and phospho-Akt, as well as a marked increase in the level of phospho-JNK. The broad spectrum caspase inhibitor BOC-D-fmk markedly blocked fludarabine/LY-induced apoptosis, had no effect on cytochrome c release to the cytosol, and did abrogate caspase and PARP cleavage. This indicates that mitochondrial dysfunction is upstream of the caspase cascade. Moreover, constitutive activation of the MEK/Erk pathway completely blocked apoptosis induced by the combination of fludarabine/LY294002. Additionally, either constitutive activation of Akt or blockage of the JNK pathway significantly diminished apoptosis induced by the combination. Collectively, these findings demonstrate that inactivation of MAPK, Akt, and activation of the JNK pathway contributes to the induction of apoptosis induced by fludarabine/LY. Comparatively, MAPK inactivation plays a crucial role in fludarabine/LY-induced apoptosis. These results also strongly suggest that combining fludarabine with an inhibitor of the PI3K/Akt/mTOR pathway may represent a novel therapeutic strategy for hematological malignancies.

Apoptosis↗

PubMed2005

siRNA targeting the leader sequence of SARS-CoV inhibits virus replication.

SARS-CoV (the SARS-Associated Coronavirus) was reported as a novel virus member in the coronavirus family, which was the cause of severe acute respiratory syndrome. Coronavirus replication occurs through a unique mechanism employing Leader sequence in the transcripts when initiating transcription from the genome. Therefore, we cloned the Leader sequence from SARS-CoV(BJ01), which is identical to that identified from SARS-CoV(HKU-39849), and constructed specific siRNA targeting the Leader sequence. Using EGFP and RFP reporter genes fused with the cloned SARS-CoV Leader sequence, we demonstrated that the siRNA targeting the Leader sequence decreased the mRNA abundance and protein expression levels of the reporter genes in 293T cells. By stably expressing the siRNA in Vero E6 cells, we provided data that the siRNA could effectively and specifically decrease the mRNA abundance of SARS-CoV genes as analyzed by RT-PCR and Northern blot. Our data indicated that the siRNA targeting the Leader sequence inhibited the replication of SARS-CoV in Vero E6 cells by silencing gene expression. We further demonstrated, via transient transfection experiments, that the siRNA targeting the Leader sequence had a much stronger inhibitory effect on SARS-CoV replication than the siRNAs targeting the Spike gene or the antisense oligodeoxynucleotides did. This report provides evidence that targeting Leader sequence using siRNA could be a powerful tool in inhibiting SARS-CoV replication.

5' Untranslated Regions↗

PubMed2005

Synergistic interactions between MEK1/2 and histone deacetylase inhibitors in BCR/ABL+ human leukemia cells.

Interactions between the histone deacetylase inhibitor SAHA and the pharmacologic MEK1/2 inhibitor PD184352 were examined in Bcr/Abl+ human leukemia cells. Coadministration of minimally toxic concentrations of SAHA (or sodium butyrate) and PD184352 (or U0126) resulted in a synergistic increase in mitochondrial damage, caspase activation, and apoptosis in K562 and LAMA 84 cells. Similar interactions were observed in CD34+ cells from two patients with CML and in imatinib mesylate-resistant K562 cells but not in normal human CD34+ bone marrow cells. These events were associated with a marked increase in ROS generation, inactivation of ERK and Akt, downregulation of p21CIP1, Bcr/Abl, and cyclin D1, and activation of JNK. Of these events, ROS generation, ERK inactivation, and cytochrome c/AIF release were largely caspase-independent, whereas the other phenomena displayed varying degrees of caspase-dependence. Using pharmacologic and genetic approaches, generation of ROS, p21CIP1 downregulation, and inactivation of Akt and MEK were found to play significant functional roles in SAHA/PD184352-mediated lethality, whereas JNK activation and Raf-1 downregulation were determined to represent secondary events. These findings indicate that interruption of the MEK/ERK pathway substantially lowers the threshold for HDAC inhibitor-mediated oxidative injury, mitochondrial dysfunction, and apoptosis, suggesting that this approach warrants further examination in Bcr/Abl+-related malignancies.

Antigens, CD34↗

PubMed2005

Resveratrol inhibits rhabdomyosarcoma cell proliferation.

Rhabdomysarcoma is the most common soft tissue tumour in children under the age of 15. Although the introduction of multimodal treatment programmes, including chemotherapy, radiation therapy and excision have increased the overall survival, the chemotherapeutic agents currently used for the treatment of rhabdomyosarcoma exhibit considerable toxicity. The aim of this study was to investigate the effects and possible mechanism(s) of action of resveratrol on human embryonal rhabdomyosarcoma (RD) cells. Resveratrol is a natural polyphenolic compound produced in a number of edible plants and has received considerable attention as a potential chemopreventive and/or chemotherapeutic agent against various types of cancers. In the present study, resveratrol was shown to inhibit cell proliferation of RD cells in a dose-dependent manner with an IC50 of 48.1 micromol/l and induce an arrest in the S/G2 phase of the cell cycle. As evident from immunocytochemical data, resveratrol treatment increased the size of the RD cells. Furthermore, resveratrol treatment resulted in a significant downregulation of cyclin B expression as demonstrated by western blot analyses. In conclusion, the present study shows that resveratrol exerts a strong inhibition of rhabdomyosarcoma cell proliferation in part by arresting cells in S/G2 phase of the cell cycle. These findings warrant further investigation to establish potential use of resveratrol as a relatively non-toxic chemotherapeutic agent for the treatment of rhabdomyosarcoma.

Anticarcinogenic Agents↗

PubMed2005

Achilles tendinopathy after treatment with fluoroquinolone.

Fluoroquinolone antibiotic therapy is a recognized but poorly understood cause for Achilles tendinopathy. We report here a patient who developed bilateral partial Achilles tendon tears as a result of fluoroquinolone therapy. Ultrasound and MRI were both useful in identifying and distinguishing between Achilles tendinosis and tendon rupture. The current published literature on this problem was also reviewed.

Achilles Tendon↗

PubMed2004

Survival of glass ionomer restorations placed in primary molars using atraumatic restorative treatment (ART) and conventional cavity preparations: 2-year results.

OBJECTIVE: To compare the survival of glass ionomer cement (GIC) restorations placed in a dental clinic setting using both the atraumatic restorative treatment (ART) approach with hand instruments, and conventional cavity preparation with rotary instruments. METHOD AND MATERIALS: Two encapsulated high-strength conventional GICs (Fuji IX GP, Ketac-Molar Aplicap) were placed in 82 Class I and 53 Class II preparations and one encapsulated non-gamma 2 amalgam alloy (GK-amalgam) was placed in 32 Class I preparations, in the primary molars of 60 Chinese children with a mean age of 7.40 +/- 1.24 (SD) years. Thus, 9 treatment groups were formed. RESULTS: After two years, there were no significant survival differences found among 7 of the 9 treatment groups (p = 0.99). However, two groups comprising Fuji IX GP and Ketac-Molar Aplicap placed in Class II cavities prepared using the ART approach showed significantly lower restoration survivals (p < 0.001). Only 3 of the 72 initially sealed fissures adjacent to the restorations appeared to retain any GIC material. CONCLUSIONS: In a clinic setting, both the ART hand instrument and conventional rotary instrument methods were equally suitable for high Class I restoration survival, but not for Class II restoration survival where the conventional cavity preparation method was preferable.

Child↗

PubMed2004

Use of gastroprotective agents and discontinuations due to dyspepsia with the selective cyclooxygenase-2 inhibitor etoricoxib compared with non-selective NSAIDs.

BACKGROUND: Most nonsteroidal anti-inflammatory drugs (NSAIDs) are non-selective cyclooxygenase-1 (COX-1) and COX-2 inhibitors and are associated with upper gastrointestinal (GI) dyspeptic symptoms often resulting in GI co-medication usage or treatment discontinuation. OBJECTIVE: To compare the rates of new use of gastroprotective agents and discontinuations due to dyspepsia with the COX-2 selective inhibitor etoricoxib compared with non-selective NSAIDs. RESEARCH DESIGN AND METHODS: This pre-specified combined analysis used data from nine randomized, double-blind, controlled, clinical trials with etoricoxib in patients with osteoarthritis, rheumatoid arthritis, chronic low back pain, or ankylosing spondylitis. The cumulative incidences of (1) new use (new prescription or increased dose) of gastroprotective agents (GPA) and (2) discontinuation due to dyspeptic symptoms were compared among patients treated with etoricoxib (60 mg, 90 mg, or 120 mg daily) vs. non-selective NSAIDs (diclofenac 50 mg. t.i.d. or naproxen 500 mg. b.i.d.). RESULTS: The overall rates/100 patient-years for new use of GPAs were 9.1 and 13.0 for etoricoxib and NSAIDs, respectively (RR = 0.75; 95% confidence interval [CI] 0.64, 0.89; p < 0.001). A benefit with etoricoxib was seen in the first 6 months when most new GPA usage occurred; after 6 months new use of GPAs was similar between etoricoxib and NSAIDs. The rates/100 patient-years of treatment discontinuation due to dyspeptic symptoms with etoricoxib and NSAIDs were 1.5 and 2.7, respectively (RR = 0.60; 95% CI 0.41, 0.87; p = 0.007). Analyses of placebo-controlled treatment periods showed significantly more new GPA use and more discontinuations due to dyspeptic symptoms with NSAIDs vs. placebo, but not with etoricoxib vs. placebo. CONCLUSION: In this combined analysis of clinical trials of patients with OA, RA, chronic low back pain, or AS, new use of gastroprotective agents was significantly lower with etoricoxib than with the comparator non-selective NSAIDs during the initial 6 months of treatment and similar thereafter. There were significantly fewer discontinuations for dyspeptic symptoms with etoricoxib than with NSAIDs over the entire follow-up period.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers.

Chronic infections with the hepatitis B virus (HBV) and high-risk human papillomaviruses (HPVs) are important risk factors for hepatocellular carcinoma (HCC) and cervical cancer (CC), respectively. HBV and HPV are DNA viruses that almost invariably integrate into the host genome in invasive tumors. The viral integration sites occur throughout the genome, leading to the presumption that there are no preferred sites of integration. A number of viral integrations have been shown to occur within the vicinity of important cancer-related genes. In studies of HBV-induced HCC and HPV-induced CC, we have identified two HBV and three HPV integrations into the human telomerase reverse transcriptase (hTERT) gene. Detailed characterization of the integrations revealed that four integrations occurred within the hTERT promoter and upstream region and the fifth integration occurred in intron 3 of the hTERT gene. None of the integrations altered the hTERT coding sequence and all resulted in juxtaposition of viral enhancers near hTERT, with potential activation of hTERT expression. Our work supports the hypothesis that the sites of oncogenic viral integration are nonrandom and that genes at the sites of viral integration may play important roles in carcinogenesis.

Base Sequence↗

PubMed2003

Ultrasound examination at 37 weeks' gestation in the prediction of pregnancy outcome: the value of cervical assessment.

OBJECTIVE: To examine the potential value of routine measurement of cervical length in singleton low-risk pregnancies at 37 weeks of gestation in the prediction of onset and outcome of labor. METHODS: Cervical length was measured by transvaginal sonography at 37 weeks in 1571 singleton low-risk pregnancies. Outcome measures were gestation at spontaneous onset of labor, post-term delivery, duration of labor and mode of delivery. RESULTS: The median cervical length at 37 weeks was 30 mm and there was a significant association between cervical length and gestation at delivery, which increased from a mean of 38 weeks for cervical length of 10 mm to 41 weeks for cervical length of 35 mm. The incidence of delivery after 40 weeks and 10 days was 296 (18.8%) and the incidence increased with cervical length at 37 weeks from 0% to 6%, 35% and 68% for respective cervical lengths of < 20, 21-30, 31-40 and 41-50 mm. In the pregnancies with spontaneous onset of labor the incidence of Cesarean section for failure to progress increased from 3.6% to 6.0%, 6.4% and 11.8% for cervical lengths of < 20, 21-30, 31-40 and 41-50 mm, respectively. In the pregnancies requiring induction for post-term the incidence of Cesarean section for failed induction or failure to progress increased from 7.5% to 20.1% to 25.0% for cervical lengths of 21-30, 31-40 and 41-50 mm, respectively. CONCLUSION: Measurement of cervical length at 37 weeks can define the likelihood of spontaneous delivery before 40 weeks and 10 days and the risk of Cesarean section in those requiring induction for prolonged pregnancy.

Adolescent↗

PubMed2003

Complementary studies of the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib.

BACKGROUND: Cyclo-oxygenase-2-selective non-steroidal anti-inflammatory drugs are intended to preserve cyclo-oxygenase-1-mediated gastroprotection and platelet function, whilst inhibiting cyclo-oxygenase-2-mediated inflammation. AIM: To assess the gastrointestinal safety of the cyclo-oxygenase-2-selective inhibitor etoricoxib vs. non-selective non-steroidal anti-inflammatory drugs. METHODS: Two randomized, double-blind, placebo- and active-controlled studies were performed: (i) daily faecal red blood cell loss was measured in 62 subjects receiving etoricoxib (120 mg once daily), ibuprofen (800 mg t.d.s.) or placebo for 28 days; (ii) the incidence of endoscopically detectable gastric/duodenal ulcers was determined in 742 osteoarthritis or rheumatoid arthritis patients receiving etoricoxib (120 mg once daily), naproxen (500 mg b.d.) or placebo over 12 weeks. RESULTS: In the first study, the between-treatment ratio of faecal blood loss for etoricoxib vs. placebo (1.06) was not significantly different from unity; however, the ratios for ibuprofen vs. placebo (3.26) and etoricoxib (3.08) were significantly greater than unity (P < 0.001). In the second study, the incidence of ulcers of > or = 3 mm with naproxen (25.3%) was significantly higher than that with etoricoxib (7.4%) or placebo (1.4%; P < 0.001); the results were similar for ulcers of > or = 5 mm. CONCLUSIONS: The reduced toxicity of etoricoxib (less faecal blood loss and fewer endoscopically detectable lesions) suggests that use of this drug will may be associated with a reduced incidence of gastrointestinal perforations, ulcers and bleeds.

Adolescent↗

PubMed2003

CT slice index and thickness: impact on organ contouring in radiation treatment planning for prostate cancer.

OBJECTIVE: To assess the impact of CT slice index and thickness (3 mm versus 5 mm) on (i) prostate volume, dimensions, and isocenter coordinates, (ii) bladder and rectal volumes, and (iii) DRR quality, in the treatment of prostate cancer. METHODS: 16 patients with prostate cancer underwent two planning CT-scans using 3 and 5 mm slice index/thickness. Prostate, bladder, and rectum were outlined on all scans. Prostate isocenter coordinates, maximum dimensions, and volumes were compared along with bladder and rectal volumes. Bladder volumes and maximum diameters were further investigated using a second observer. A comparative analysis of DRR quality was conducted as well as a dosimetric analysis using DVH. RESULTS: The differences in measurements of prostate volume, isocenter coordinates and maximum dimensions between the 3 and 5 mm scans, were small and not statistically significant. Similar finding was seen for rectal volume. However, bladder volume was always larger on the 3 mm scan (mean difference=27.9 cc; SE=4.8 cc; 95% CI: 17.7-38.2 cc; p<0.001) and the findings were reproduced with the second observer (mean difference=31.9 cc; SE=4.7 cc; 95% CI: 21.9-41.9 cc; p<0.001). The differences in volume are caused by a slight increase in (1) the measurement of the longitudinal dimensions on the 3 mm scans, and (2) the slice by slice measured bladder area on the 3 mm scans. The latter is due to partial volume effect. The 3 mm DRR were slightly better than the 5 mm DRR. The bladder DVH differed significantly in some patients. CONCLUSION: Bladder volume is significantly larger on the 3 mm scans. Differences in contoured areas may be accounted for, in part, by the partial volume effect.

Adenocarcinoma↗