Cyclooxygenase-2 and tumor biology Kanaoka, Shigeru; Takai, Tetsunari; Yoshida, Ken-ichi
Advances in clinical chemistry,
2007, Volume:
43
Journal Article
Peer reviewed
There is now substantial evidence for the role of cyclooxygenase (COX)-2 in causation and prevention of cancer. Selective COX-2 inhibitors (coxibs) were considered attractive candidate ...chemoprevention agents; however, concerns over the toxicity of systemic selective inhibition have cast some doubt on COX-2 inhibition as a safe chemoprevention strategy. COX-2 can serve as a potential biomarker of tumor evaluation including prognosis. This chapter describes proposed mechanisms for the role of COX-2 in carcinogenesis, proliferation, inhibition of apoptosis, promotion of angiogenesis, enhanced invasiveness, immune modulation, and increased mutagenesis. Critical discussions focus on the use of COX-2 as a biomarker in the evaluation of neoplasm. Our chapter demonstrates that "Fecal COX-2 Assay," a novel method to detect COX-2 messenger RNA (mRNA) in feces from subjects with colorectal neoplasms, is potentially useful for colorectal cancer screening.
Abstract An 87-year-old male, prescribed digoxin and furosemide for congestive heart failure and Alzheimer disease, had dehydration and anemia due to poor food intake and hemorrhagic cystitis. ...Repeated vomiting due to an upper respiratory infection caused disturbance of consciousness and hypotension. The patient was admitted to hospital and diagnosed with digoxin intoxication and hypernatremia. The serum sodium (Na+ ) level was corrected, but the patient died 4 days after admission following uncontrollable seizure. A histologic examination after an autopsy revealed characteristic findings of central pontine myelinolysis (CPM). This is the first autopsy report on CPM triggered by vomiting in association with digoxin administration.
The addition of substituents to the pyridopyrimidine scaffold of MexAB-OprM specific efflux pump inhibitors was explored. As predicted by a pharmacophore model, the incorporation substituents at the ...2-position improved potency. Piperidines were found to be optimal, and further introduction of polar groups without compromising the activity was shown to be feasible. Careful positioning of the essential acidic moiety of the pharmacophore relative to the scaffold led to the discovery of vinyl tetrazoles with still greater potency.
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Purpose:
Early mobile tongue cancer can be controlled with interstitial radiotherapy (ISRT). We carried out a Phase III trial to compare the treatment results of low-dose-rate (LDR) ISRT and ...high-dose-rate (HDR) ISRT for early mobile tongue cancer.
Methods and Materials:
From April 1992 through October 1996, 59 patients with cancer of the early mobile tongue were registered in this Phase III study. Eight patients were excluded from the evaluation because of violations of the requirements for this study. Of 51 eligible patients, 26 patients were treated with LDR-ISRT (70 Gy/4–9 days) and 25 patients with HDR-ISRT (60 Gy/10 fractions/1 week). For the hyperfractionated HDR-ISRT, the time interval between 2 fractions was more than 6 h.
Results:
Five-year local control rates of the LDR and HDR groups were 84% and 87% respectively. Nodal metastasis occurred in 6 patients in each group. Five-year nodal control rates of the LDR and HDR groups were 77% and 76%, respectively.
Conclusion:
Hyperfractionated HDR-ISRT for early mobile tongue cancer has the same local control compared with continuous LDR-ISRT. Hyperfractionated HDR-ISRT is an alternative treatment for continuous LDR-ISRT.
Recent advancements in 16-slice multidetector-row computed tomography (16-slice MDCT) provide for non-invasive assessment of not only coronary artery disease (CAD), but also myocardial properties and ...the anatomy of the whole heart. The purpose of the present study was to investigate whether the aortic valve area (AVA) in patients with aortic stenosis (AS) assessed by 16-slice MDCT corresponds to echocardiographic assessment and to evaluate simultaneously the clinical accuracy in detecting CAD with 16-slice MDCT.
The AVA of 29 consecutive AS patients with transthoracic echocardiography (TTE) and 16-slice MDCT were analyzed. The AVA was estimated by means of the continuity equation method in 2-dimensional echocardiography (DE) and the quantitative planimetric method after multi-planar reformation in 16-slice MDCT. Concomitantly, the severity of the coronary artery stenosis was assessed by 16-slice MDCT. In the present study, the AVA assessed by TTE and 16-slice MDCT was 1.34+/-0.32 cm(2) and 1.38+/-0.32 cm(2), respectively. Regression analysis showed that the AVA in patients with AS determined by 16-slice MDCT correlated well with those determined by 2-DE (r=0.96, p<0.001). Significant coronary artery stenosis of more than 50% diameter reduction was present in 48% of the study population.
In patients with AS, the analysis of the severity of the AVA by 16-slice MDCT provides a feasible and accurate estimation with the concomitant evaluation of CAD.
With the completion of the determination of its entire genome sequence, one of the next major targets of Bacillus subtilis genomics is to clarify the whole gene regulatory network. To this end, the ...results of systematic experiments should be compared with the rich source of individual experimental results accumulated so far. Thus, we constructed a database of the upstream regulatory information of B.subtilis (DBTBS). The current version was constructed by surveying 291 references and contains information on 90 binding factors and 403 promoters. For each promoter, all of its known cis-elements are listed according to their positions, while these cis-elements are aligned to illustrate their consensus sequence for each transcription factor. All probable transcription factors coded in the genome were classified with the Pfam motifs. Using this database, we compared the character of B.subtilis promoters with that of Escherichia coli promoters. Our database is accessible at http://elmo.ims.u-tokyo.ac.jp/dbtbs/.
To perform the largest in vivo dosimetry study for interstitial brachytherapy yet to be undertaken using a new radiophotoluminescence glass dosimeter (RPLGD) in patients with pelvic malignancy and to ...study the limits of contemporary planning software based on the results.
Sixty-six patients with pelvic malignancy were treated with high-dose-rate interstitial brachytherapy, including prostate (n = 26), gynecological (n = 35), and miscellaneous (n = 5). Doses for a total of 1004 points were measured by RPLGDs and calculated with planning software in the following locations: rectum (n = 549), urethra (n = 415), vagina (n = 25), and perineum (n = 15). Compatibility (measured dose/calculated dose) was analyzed according to dosimeter location.
The compatibility for all dosimeters was 0.98 +/- 0.23, stratified by location: rectum, 0.99 +/- 0.20; urethra, 0.96 +/- 0.26; vagina, 0.91 +/- 0.08; and perineum, 1.25 +/- 0.32.
Deviations between measured and calculated doses for the rectum and urethra were greater than 20%, which is attributable to the independent movements of these organs and the applicators. Missing corrections for inhomogeneity are responsible for the 9% negative shift near the vaginal cylinder (specific gravity = 1.24), whereas neglect of transit dose contributes to the 25% positive shift in the perineal dose. Dose deviation of >20% for nontarget organs should be taken into account in the planning process. Further development of planning software and a real-time dosimetry system are necessary to use the current findings and to achieve adaptive dose delivery.