Combination therapy with PEG-IFN-alpha and 5-FU inhibits HepG2 tumour cell growth in nude mice by apoptosis of p53.

When the tumour suppressor p53 is activated by DNA damage, it stimulates the transcription of its target genes, which then induce cell cycle arrest or apoptosis. Here, we examined the role p53 plays in the antitumour effect of combination treatment with pegylated interferon (PEG-IFN)-alpha and 5-fluorouracil (5-FU), which has been shown to effectively treat advanced hepatocellular carcinoma (HCC). Nude mice were injected subcutaneously with cultured HepG2 cells, in which p53 is functional. They were treated a week later with PEG-IFN and/or 5-FU for 7 weeks, after which we measured and examined their tumours. Combination groups showed significantly lower tumour volumes and higher tumour cell apoptosis than the other groups. Combination treatment and PEG-IFN monotherapy also significantly elevated the p53 protein and mRNA levels in the tumour but only combination treatment increased the degree of p53 phosphorylation at serine46 and induced p53-regulated apoptosis-inducing protein 1 (p53AIP1) expression. The antitumour effects of combination treatment is due in part to the elevation by PEG-IFN of p53 protein and mRNA expression and in part to the DNA damage that is generated by 5-FU, which induces p53 serine46 phosphorylation, which in turn upregulates p53AIP1 expression.

Physical restriction of pods causes seed size reduction of a brassinosteroid-deficient faba bean (Vicia faba).

BACKGROUND AND AIMS: A brassinosteroid-deficient mutant faba bean (Vicia faba 'Rinrei') shows dwarfism in many organs including pods and seeds. 'Rinrei' has normal-sized seeds together with dwarf seeds, suggesting that dwarfism in the seed may be indirectly caused by brassinosteroid deficiency. The mechanism of seed size reduction in this mutant was investigated. METHODS: The associations between seed orientation in the pod, seed numbers per pod and pod lengths with seed sizes were analysed in 'Rinrei' and the wild-type plant. KEY RESULTS: 'Rinrei' seeds are tightly arranged in pods containing two or three seeds. Seed size decreased as the number of seeds per pod increased or as the length of the pod decreased. Where no physical restriction occurred between seeds in a pod, the wild-type faba bean seeds had a nearly constant size regardless of seed number per pod or pod length. 'Rinrei' seeds in pods containing single seeds were the same size as wild-type seeds. Brassinolide treatment increased the seed size and the length of pods containing three seeds in 'Rinrei'. CONCLUSION: Seed size of 'Rinrei' is mainly regulated through a reduction of pod length due to brassinosteroid deficiency; physical restriction within pods causes a reduction in seed size. These results suggest a possible mechanism for increasing faba bean yields to optimal levels.

Dynamic imaging of pancreatic diseases by contrast enhanced coded phase inversion harmonic ultrasonography.

BACKGROUND: Coded phase inversion harmonic ultrasonography, a newly available sonographic technique, enables visualisation of slow flow in minute vessels in a real time fashion with the use of a sonographic contrast agent containing monosaccharide. Our purpose was to employ this novel technique to observe microvessels in pancreatic tumours. SUBJECTS AND METHODS: Sixty five patients with suspicious pancreatic tumours received contrast enhanced coded phase inversion harmonic ultrasonography, contrast enhanced computed tomography, and endosonography. Final diagnoses based on histological findings were pancreatic ductal carcinomas in 49 patients, inflammatory pseudotumours with chronic pancreatitis in seven, and endocrine tumours in nine. For contrast enhanced coded harmonic ultrasonography, Levovist, a contrast agent, was injected intravenously as a bolus. When the first microbubble signal appeared in the pancreas, images of the ideal scanning plane were displayed in a real time continuous fashion (vessel images). Subsequently, interval delay scanning (perfusion images) was taken to demonstrate parenchymal flow. Tumour vascularity was evaluated by using the two types of imaging. Sensitivities for depicting pancreatic tumours were compared between three examinations. RESULTS: Contrast enhanced ultrasonography demonstrated tumour vessels in 67% of pancreatic ductal carcinomas, although most were relatively hypovascular compared with the surrounding pancreatic tissue. The vascular patterns of tumours obtained by contrast enhanced ultrasonography were closely correlated with those obtained by contrast enhanced computed tomography. Values for sensitivity in depicting pancreatic tumours of 2 cm or less in size were 68% for contrast enhanced computed tomography, 95% for endosonography, and 95% for contrast enhanced ultrasonography. CONCLUSION: Contrast enhanced coded phase inversion harmonic ultrasonography successfully visualised fine vessels in pancreatic tumours and may play a pivotal role in the depiction and differential diagnosis of pancreatic tumours.

Preparation and opioid activities of N-methylated analogs of [D-Ala2,Leu5]enkephalin.

Analogs of opioid pentapeptide [D-Ala2,Leu5]enkephalin were prepared using two kinds of N-methylation reactions, namely quaternization and amide-methylation. Quaternization reaction with CH3I-KHCO3 in methanol was applied to the deprotected N-terminal group of the pentapeptide derivatives affording trimethylammonium group-containing analogs. [Me3+Tyr1,D-Ala2,Leu5]enkephalin and its amide were found to show opioid activity on guinea pig ileium assay only slightly lower than the parent unmethylated peptides. Application of amide-methylation reaction using CH3I-Ag2O in DMF to the protected pentapeptide yielded a pentamethyl derivative in which all of the five N atoms were methylated. Deprotection of the derivative gave pentamethyl analogs of [D-Ala2,Leu5]enkephalin, which showed no significant activity on the guinea pig ileum assay and opiate-receptor binding assay.

[Clinical results of cefaclor treatment of infections of oral regions].

Cefaclor (CCL) is a cephem antibiotic for oral use. Thirty cases of infection of oral regions, in the First Department of Oral and Maxillofacial Surgery, School of Dentistry, the University of Tokushima, were treated with CCL at 750 mg/day. The results were as follows: The efficacy rate for all kinds of diseases was 80.0% in 3 days and 96.7% in 5 days and 86.7% as an overall assessment by the patients' doctors. With regard to the degree of symptoms, the efficacy rate for cases with moderate symptoms was less than that for mild cases in 3 days and according to the assessment by the patients' doctors. Some moderate cases required increased medication because no beneficial effect was observed. In sensitivity tests, CCL was shown to be effective on all 27 isolated clones of bacteria tested. CCL caused no detectable changes in laboratory data. No side effects were observed in any case. From these results, it is concluded that CCL is a highly effective antibiotic for use on infections of the oral regions.