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81.
Lennart Olofsson Xiangkui Mu Simeon Nill Uwe Oelfke Bj?rn Zackrisson Mikael Karlsson 《Radiotherapy and oncology》2004,73(2):223-231
BACKGROUND AND PURPOSE: In recent years photon intensity modulated radiation therapy (IMRT) has gained attention due to its ability to improve conformity of dose distributions. A potential advantage of electron-IMRT is that the dose fall off in the depth dose curve makes it possible to modulate the dose distribution in the direction of the beam by selecting different electron energies. This paper examines the use of a computer based energy selection in combination with the IMRT technique to optimise the electron dose distribution. MATERIALS AND METHODS: One centimetre square electron beamlets ranging from 2.5 to 50 MeV were pre-calculated in water using Monte Carlo methods. A modified IMRT optimisation tool was then used to find an optimum mix of electron energies and intensities. The main principles used are illustrated in some simple geometries and tested on two clinical cases of post-operated ca. mam. RESULTS: It is clearly illustrated that the energy optimisation procedure lowers the dose to lung and heart and makes the dose in the target more homogeneous. Increasing the energy at steep gradients compensates for lack of target coverage at beam edges and steep gradients. Comparison with a clinically acceptable four segment plan indicates the advantage of the used electron IMRT technique. CONCLUSIONS: Using an intensity optimised mix of computer selected electron energies has the potential to improve electron treatments for mastectomy patients with good target coverage and reduced dose to normal tissue such as lung and heart. 相似文献
82.
JE McMICHAEL 《Journal of paediatrics and child health》1997,33(1):1-3
An understanding of the neurodevelopmental outcome of long-term survivors of neonatal intensive care is essential for the informed management of preterm or high risk infants. This annotation looks at the current status of neonatal follow-up services in Australasia and highlights problems in the collection and interpretation of data. It suggests that we should work towards achieving a consensus on standard definitions and test regimes and on national data collection. 相似文献
83.
L Patel PE Clayton ME Jenney JE Ferguson TJ David 《Archives of disease in childhood》1997,76(6):505-508
Cross sectional studies have reported impaired growth in children with atopic dermatitis. If this growth impairment is irreversible, it would be expected to adversely influence final height attainment. The standing heights and other anthropometric parameters were assessed in 35 adults with onset of atopic dermatitis before 5 years of age and a control group of 35 adults with adult onset contact dermatitis or psoriasis. There was no significant difference in the standing height SD score, mid-parental height SD score, sitting height SD score, subischial leg length SD score, nor body mass index between the atopic dermatitis and control groups. The standing height SD score was not significantly different among: (a) patients with atopic dermatitis affecting less than 50% of their body surface area and those with greater than 50% affected; (b) patients using the four different potency topical corticosteroids; and (c) patients with atopic dermatitis without asthma and those with coexisting asthma. It is concluded that short stature is not a feature of our group of adult patients with onset of atopic dermatitis before 5 years of age, continuing into adulthood, and severe enough to require specialist care. This suggests that if growth impairment occurs in childhood, it is likely to be temporary and reversible. 相似文献
84.
An association has previously been reported between exposure to medical diagnostic ionizing radiation and papillary thyroid cancer in women. To further evaluate potential mechanisms in carcinogenesis, the expression of p53, c-erbB-2, as well as Ki-67, estrogen and progesterone receptors were analyzed by immunohistochemistry in 19 women exposed to X-rays and for comparison in nine women without such reported exposure. They all had papillary thyroid cancer. No difference was found between these groups. The results of this study showed that p53, c-erbB-2, Ki-67, estrogen and progesterone receptors are not involved in papillary thyroid cancer associated with exposure to medical diagnostic ionizing radiation. 相似文献
85.
Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells 总被引:7,自引:5,他引:7
Cell to cell communication via gap junctions is essential in the
maintenance of the homeostatic balance of multicellular organisms. Aberrant
intercellular gap junctional communication (GJIC) has been implicated in
tumor promotion, neuropathy and teratogenesis. Oxidative stress has also
been implicated in similar pathologies such as cancer. We report a
potential link between oxidative stress and GJIC. Hydrogen peroxide, a
known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells
with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible
as indicated by the complete recovery of GJIC with the removal of H2O2 via
a change of fresh media. Free radical scavengers, such as t-butyl alcohol,
propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2,
which indicated that the effects of H2O2 on GJIC was probably not a
consequence of aqueous free radical damage. The depletion of intracellular
GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of
glutathione- sufficient cells with H2O2 resulted in the
hyperphosphorylation of connexin43, which is the basic subunit of the
hexameric gap junction protein, as determined by Western blot analysis.
TPA, a well-known tumor promoter, also inhibits GJIC via
hyperphosphorylation of GJIC, which is a result of protein kinase-C
activation. However, H2O2 also induced hyperphosphorylation in
GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism
of GJIC inhibition must be different from the TPA-pathway and involves GSH.
相似文献
86.
Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon 总被引:1,自引:1,他引:1
We have examined whether dietary polyamines influence the formation and
initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in
rat colon. Effects of a combination of dietary polyamines at three dose
levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g;
spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied
in animals in two different experimental situations: animals treated with
AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a
specific inhibitor of endogenous polyamine synthesis. In both experimental
situations, dietary polyamines enhanced the growth of ACF, expressed as the
number of large ACF (foci with three or more aberrant crypts, ACF > or =
3), whereas the formation of ACF, expressed as the number of ACF, was
apparently not altered. In animals treated with AOM alone, maximal growth
enhancing effect on ACF was nearly obtained with the median level of
dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO
reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of
DFMO was counteracted by dietary polyamines in a dose- dependent manner,
and it was abolished at the highest level of polyamines. In conclusion, it
was demonstrated that dietary polyamines are able to enhance the growth of
AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused
inhibition of ACF growth, probably by compensating for the DFMO-reduced
endogenous polyamine synthesis.
相似文献
87.
Hansen LA; Malarkey DE; Wilkinson JE; Rosenberg M; Woychik RE; Tennant RW 《Carcinogenesis》1998,19(10):1837-1845
We previously reported that papillomas can arise from the follicular
epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow
mutation (A(vy)) of the mouse agouti gene which regulates coat color
pigmentation by acting within the micro-environment of the hair follicle
has been shown to function as a tumor promoter in the liver, we
hypothesized that it may also play a role in TGxAC skin tumorigenesis.
Endogenous agouti protein product was detected in the outer root sheath of
anagen hair follicles following plucking of the hair shaft, but not in the
interfollicular epithelium, in TGxAC mice on an FVB/N genetic background.
It was also detected in papillomas from these mice produced by
12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking.
Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line
results in an approximately 2-fold increase in papilloma development
compared with controls which did not carry the A(vy) allele following
twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition,
TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but
not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of
humoral hypercalcemia mediated by parathyroid hormone-related protein
(PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus,
we conclude that the A(vy) allele can influence the development of skin
tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic
TGxAC mice.
相似文献
88.
Karlsson FA Berne C Björk E Kullin M Li Z Ma JY Schölin A Zhao L 《Upsala journal of medical sciences》2000,105(2):85-95
Type 1 diabetes is the result of a chronic inflammatory process that causes elimination of insulin-producing beta-cells, resulting in insulin deficiency and hyperglycemia. The destruction is thought to be mediated by an autoimmune process involving cytotoxic T cells recognizing beta-cell autoantigens in the context of MHC class I-peptide complexes. Autoantibodies against insulin, glutamic acid decarboxylase (GAD) and and ICA 512 protein tyrosine phosphatase are frequently found. At the clinical onset of diabetes, some beta-cells remain and after initiation of insulin treatment, most patients enter a period of remission, a phenomenon that may reflect diminished autoimmune activity in the islets. There is evidence to suggest that a further loss of beta-cells can be curtailed, and that patients, who maintain endogenous insulin production, have better glycemic control and less risk of complications. This is the basis for our current research. We are characterizing the remission phenomenon in epidemiological studies in order to identify determinants of beta-cell survival. In randomized, prospective multicenter trials, we are evaluating the benefit of beta-cell secretory rest for rescue of insulin production in patients at onset of clinical disease. In experimental studies, we are investigating expression and regulation of the key molecules of an autoimmune process in the islets. Further, selective beta-cell damage is induced in rat islets and measures to enhance beta-cell resistance and repair are being examined. We have recently identified a remarkable, beta-cell protective effect of K(ATP)-channel opening. 相似文献
89.
Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel. 总被引:4,自引:0,他引:4
Anja Henningsson Sharon Marsh Walter J Loos Mats O Karlsson Adam Garsa Klaus Mross Stephan Mielke Lucia Viganò Alberta Locatelli Jaap Verweij Alex Sparreboom Howard L McLeod 《Clinical cancer research》2005,11(22):8097-8104
PURPOSE: To retrospectively evaluate the effects of six known allelic variants in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes on the pharmacokinetics of the anticancer agent paclitaxel (Taxol). EXPERIMENTAL DESIGN: A cohort of 97 Caucasian patients with cancer (median age, 57 years) received paclitaxel as an i.v. infusion (dose range, 80-225 mg/m(2)). Genomic DNA was analyzed using PCR RFLP or using Pyrosequencing. Pharmacokinetic variables for unbound paclitaxel were estimated using nonlinear mixed effect modeling. The effects of genotypes on typical value of clearance were evaluated with the likelihood ratio test within NONMEM. In addition, relations between genotype and individual pharmacokinetic variable estimates were evaluated with one-way ANOVA. RESULTS: The allele frequencies for the CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP3A4*3, CYP3A5*3C, and ABCB1 3435C>T variants were 0.7%, 9.2%, 2.1%, 0.5%, 93.2%, and 47.1%, respectively, and all were in Hardy-Weinberg equilibrium. The population typical value of clearance of unbound paclitaxel was 301 L/h (individual clearance range, 83.7-1055 L/h). The CYP2C8 or CYP3A4/5 genotypes were not statistically significantly associated with unbound clearance of paclitaxel. Likewise, no statistically significant association was observed between the ABCB1 3435C>T variant and any of the studied pharmacokinetic variables. CONCLUSIONS: This study indicates that the presently evaluated variant alleles in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes do not explain the substantial interindividual variability in paclitaxel pharmacokinetics. 相似文献
90.
Viljoen M Karlsson MO Meyers TM Gous H Dandara C Rheeders M 《European journal of clinical pharmacology》2012,68(4):339-347