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1.
ABSTRACT: BACKGROUND: A significant number of cancers are caused by defects in p21 causing functional defects in p21 or p53 tumour-suppressor proteins. This has led to many therapeutic approaches including restoration by gene therapy with wild-type p53 or p21 using viral or liposomal vectors, which have toxicity or side-effect limitations. We set out to develop a safer, novel fusion protein which has the ability to reconstitute cancer cell lines with active p21 by protein transduction. METHODS: The fusion protein was produced from the cell-translocating peptide Antennapedia (Antp) and wild-type, full-length p21 (Antp-p21). This was expressed and refolded from E. coli and tested on a variety of cell lines and tumours with differing p21 or p53 status. RESULTS: Antp-p21 penetrated and killed cancer cells that do not express wild type p53 or p21. This included cells that were matched to cogenic parental cell lines. Antp-p21 killed cancer cells selectively that were malignant as a result of mutations or nuclear exclusion of the p53 and p21 genes and over-expression of MDM2. Non-specific toxicity was excluded by showing that Antp-p21 penetrated but did not kill p53- or p21- wild-type cells. Antp-p21 was not immunogenic in rabbits. Recombinant Antp peptide alone was not cytotoxic, showing that killing was due to the transduction of the p21 component of Antp-p21. Antp-p21 was shown to penetrate cancer cells engrafted in vivo and resulted in tumour eradication when administered with conventionally-used chemotherapeutic agents, which alone were unable to produce such an effect. CONCLUSIONS: Antp-p21 may represent a new and promising targeted therapy for patients with p53-associated cancers supporting the concept that rational design of therapies directed against specific cancer mutations will play a part in the future of medical oncology. 相似文献
2.
Summary The risk of developing a chronic carriage state after acute hepatitis B infection in adults was evaluated. Two hundred and eighty-nine HBV-susceptible heterosexual partners of acute hepatitis B patients were used to investigate the effectiveness of post-exposure immunoprophylaxis; 75 of them received hepatitis B vaccine, 72 hepatitis B hyperimmune globulin (HBIG), 71 vaccine plus HBIG and 71 placebo. Participants were interviewed, clinically examined and serum specimens were taken at 1, 3, 6 and 9 months after their first intervention. Serum samples were tested for ALT and HBV markers (HBsAg, anti-HBc and anti-HBs) using radio immunoassays. Forty-six (15.9%) of the heterosexual partners examined were infected; the incidence of HBV infections was higher among placebo (18.3%, 13/71) and HBIG (18.1%, 13/72) recipients compared to vaccine (16.0%, 12/75) and HBIG plus vaccine (11.3%, 8/71) recipients, but the differences were not statistically significant. Infections were significantly more often subclinical after immunoprophylaxis (p=0.03). HBsAg was detected in all eight clinical and in 13 of the 38 subclinical cases. In the remaining 25 subclinical cases HBV infections were diagnosed by the development of anti-HBc and anti-HBs during the follow-up period. Finally, all 46 cases studied cleared the HBsAg.
Bei Erwachsenen ohne Abwehrstörung geht die B-Hepatitis nur selten in eine chronische Lebererkrankung über
Zusammenfassung Die Entwicklung eines chronischen Trägerstatus wurde bei 289 für eine HBV-Infektion empfänglichen heterosexuellen Partnern von Patienten mit akuter Hepatitis B verfolgt, bei denen die Wirksamkeit einer postexpositionellen Immunprophylaxe geprüft wurde. Bei 75 Personen wurde Hepatitis B-Vakzine eingesetzt, bei 72 Hyperimmunglobulin (HBIG), bei 71 Vakzine plus HBIG und bei 71 Placebo. Anamnestische Befragung und Nachuntersuchungen erfolgten jeweils 1, 3, 6 und 9 Monate nach der ersten Intervention. Serumspiegel von ALT und HBV-Markern (HBsAg, anti-HBc und anti-HBs) wurden mittels Radioimmunoassay bestimmt. Insgesamt hatten 46 der heterosexuellen Partner die HBV-Infektion erworben (15,9%). Nach Placebogabe waren 13/71 (18,3%) mit HBV infiziert, nach HBIG 13/72 (18,1%). Die Infektionraten waren nach Vakzine (12/75; 16%) sowie nach HBIG plus Vakzine (8/71; 11,3%) neidriger, jedoch war der Unterschied nicht statistisch signifikant. Nach Immunprophylaxe verliefen die Infektionen signifikant häufiger subklinisch als nach Placebogabe (p=0,03). HBsAg war in allen acht Fällen einer klinischen und in 13 von 38 Fällen einer subklinischen HBV-Infektion nachzuweisen. In den übrigen 25 subklinischen Fällen wurde die HBV- Infektion durch das Auftreten von anti-HBc und anti-HBs im Verlauf der Beobachtungszeit diagnostiziert. In allen 46 Fällen wurde HBsAg schließlich eliminiert.相似文献
3.
Koutroubakis IE Petinaki E Dimoulios P Vardas E Roussomoustakaki M Maniatis AN Kouroumalis EA 《International journal of colorectal disease》2003,18(3):254-259
BACKGROUND AND AIMS: Initiation of a fibrotic process has been suggested as part of the intestinal response to chronic inflammation in inflammatory bowel disease. YKL-40 has been proposed as a new serum marker of fibrosis. We studied compared the serum levels of YKL-40 in patients with ulcerative colitis or Crohn's disease with inflammatory and healthy controls. PATIENTS AND METHODS: YKL-40 serum levels were measured in 179 patients with inflammatory bowel disease (94 ulcerative colitis, 85 Crohn's disease), in 23 with intestinal inflammation of other causes, and 70 matched healthy controls using a commercially available enzyme-linked immunosorbent assay. YKL-40 levels were assessed in terms of disease activity, type and localization. RESULTS: Mean serum YKL-40 levels were 102.6+/-82.7 ng/ml in ulcerative colitis patients and 112.2+/-83.7 ng/ml in Crohn's disease patients, significantly higher than in healthy controls (64.1+/-21.4 ng/ml) but not significantly different from inflammatory controls (77.8+/-23.1 ng/ml). Disease activity and C-reactive protein levels were significantly correlated with YKL-40 levels in both ulcerative colitis and Crohn's disease. Crohn's disease patients with ileum localization had significantly higher YKL-40 levels than those with ileocolonic or colonic disease. Patients with stenotic disease had mean YKL-40 levels not significantly different than those with nonstenotic disease. CONCLUSION: Serum levels of YKL-40 are increased in patients with inflammatory bowel disease, and this is associated with the inflammatory process rather than with the degree of fibrosis. 相似文献
4.
Neuromuscular diseases and their cardiac manifestations under the spectrum of cardiovascular imaging
Alexandridis Georgios M. Pagourelias Efstathios D. Fragakis Nikolaos Kyriazi Maria Vargiami Efthymia Zafeiriou Dimitrios Vassilikos Vassilios P. 《Heart failure reviews》2022,27(6):2045-2058
Heart Failure Reviews - Neuromuscular diseases (NMDs) include a broad spectrum of disorders that affect motor unit in every possible site, extending from the cell body of peripheral nerves to the... 相似文献
5.
Salmonella bacteraemia in a tertiary children's hospital 总被引:2,自引:0,他引:2
Papaevangelou V Syriopoulou V Charissiadou A Pangalis A Mostrou G Theodoridou M 《Scandinavian journal of infectious diseases》2004,36(8):547-551
A retrospective study was conducted between July 1990 and July 2002 to investigate the epidemiology, clinical characteristics, and the outcome of Salmonella bacteraemia in children. A total of 148 episodes of bacteraemia were identified in 144 children. The annual incidence ranged from 1.6 to 8.3 cases per 100,000 children < or = 14 y of age, and higher numbers of cases occurred in summer than in winter months. In 22 children the bacteraemia was caused by S. typhi and in 122 by S. non-typhi. S. enteritidis was the most common serotype isolated. Resistance to ampicillin was exhibited by 28.5% of Salmonella isolates, whereas all S. typhi isolates were susceptible to commonly used antibiotics. The mean age was 40.3 months (range 50 d to 14 y). Children with S. typhi bacteraemia were significantly older than children with S. non-typhi bacteraemia (7.8 vs 2.4 y, p < 0.01). 11 children were immunosuppressed. The immunosuppressed children had longer duration of fever, longer hospitalization stay, and higher relapse rates compared to normal children (p < 0.05). Four children developed complications and 1 died. Although the incidence of S. typhi bacteraemia is decreasing, the non-typhi species continue to cause significant morbidity in our geographical region. 相似文献
6.
7.
Boulbou MS Koukoulis GN Makri ED Petinaki EA Gourgoulianis KI Germenis AE 《International journal of cardiology》2005,98(1):39-44
BACKGROUND: Risk factors for atherosclerosis such as hypertension, type 2 diabetes, obesity and dyslipidemia affect endothelial function and stimulate adhesion molecules expression. The aim of the study was to examine endothelial activation in type 2 diabetes and hypertension as indicated by adhesion molecule levels and further to investigate whether the coexistence of the above conditions has a different effect. METHODS: Serum levels of soluble E-selectin, ICAM-1 and VCAM-1 were measured in 17 hypertensive type 2 diabetic patients (DM-HY), 32 normotensive type 2 diabetic patients (DM), 11 hypertensive nondiabetic patients (HY) and 15 healthy subjects. RESULTS: In diabetic patients (either DM-HY or DM), soluble E-selectin levels were significantly increased compared to healthy subjects (p<0.001). In HY patients, both sE-selectin (66.44+/-71.59 vs. 29.42+/-15.56 ng/ml, p=0.033) and sVCAM-1 (1529+/-433.33 vs. 1027+/-243.56 ng/ml, p=0.03) levels were found significantly higher compared to healthy subjects (p<0.05). The coexistence of diabetes and hypertension (DM-HY) did not have an additive effect on circulating adhesion molecules levels compared with the levels observed in either diabetes or hypertension. Systolic and diastolic blood pressure (BP) were independent factors correlated respectively with sE-selectin and sVCAM-1 levels (R=0.454, p=0.034 and R=0.578, p=0.005) in nondiabetic subjects (hypertensive and normotensive). CONCLUSIONS: Type 2 diabetes mellitus and hypertension induce endothelial activation as indicated by elevated levels of soluble adhesion molecules. This effect is not different when comorbidity is present. 相似文献
8.
9.
A trial of low doses (1.25 and 0.625 micrograms) of recombinant hepatitis B vaccine in 110 males aged 17-19 years is reported. Follow-up was extended to one year and further data are reported for participants from earlier trials of 10, 5 and 2.5 microgram doses for comparison. Seroconversion rates after the booster dose were 94% at 1.25 micrograms and 89% at 0.625 micrograms, compared to 100% at higher doses. Geometric mean titres (GMT) of antibody to hepatitis B surface antigen (anti-HBs) were significantly lower with the 0.625 microgram dose than with 1.25 micrograms at all times, reaching a GMT of 42.6 IU l-1 and 152.9 l-1, respectively, after the booster dose. GMT values at 12 months were 513.9, 510.0, 320.7, 46.5 and 13.3 IU l-1 in the 10, 5, 2.5, 1.25 and 0.625 microgram dose groups, respectively. Increases in GMT after the booster dose were parallelled in all groups. GMT decreased by approximately equal to 65% between 7 and 12 months in the three lowest dose groups, significantly less than the fall of 80% at 5 and 10 micrograms. However, to secure variability among vaccinees, the minimum effective dose for young adults should be greater than 5 micrograms per dose. 相似文献
10.
Transjugular intrahepatic portosystemic shunt in cavernomatous portal vein occlusion 总被引:2,自引:0,他引:2
Brountzos EN Malagari K Alexopoulou E Nikolaou VE Panagiotou I Argyriou P Efstathopoulos E Kelekis DA 《Hepato-gastroenterology》2004,51(58):1168-1171
A 72-year-old patient with liver cirrhosis and cavernomatous portal vein occlusion presented with refractory ascites. We treated the patient with transjugular intrahepatic portosystemic shunt: transjugular transhepatic puncture of an intrahepatic hilar collateral vein was performed; transjugular intrahepatic portosystemic shunt was created between the right hepatic vein and the patent superior mesenteric vein using this hilar collateral vein as the connecting pathway. The ascites was resolved and the patient remains asymptomatic, while shunt patency is maintained 16 months after the intervention. 相似文献