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31.
Perkins SN; Hursting SD; Haines DC; James SJ; Miller BJ; Phang JM 《Carcinogenesis》1997,18(5):989-994
Transgenic mice with both alleles of the p53 tumor suppressor gene product
'knocked out' by gene targeting are susceptible to early development of
tumors, chiefly lymphomas and sarcomas. Compared with the control group,
administration of dehydroepiandrosterone (DHEA) at 0.3% of the diet to male
p53-deficient mice extended their lifespan by delaying death due to
neoplasms (from 105 to 166 days on study, P = 0.002), primarily by
suppressing lymphoblastic lymphoma (from 45 to 6% of neoplastic deaths, P =
0.010). Treatment with a synthetic DHEA analog,
16alpha-fluoro-5-androsten-17-one (compound 8354), at 0.15% of the diet
also increased lifespan, to 140 days for mice that developed tumors (P =
0.037). The effects of these steroids on lifespan and tumor development did
not appear to be strongly related to inhibition of food consumption and
weight gain, in that a group pair-fed with control diet to the reduced food
consumption of the DHEA-treated group developed and died of the same types
of neoplasms at the same rate as the controls fed ad libitum. The
chemopreventive effect of these steroids has been proposed to be due to
suppression of DNA synthesis by inhibition of glucose 6-phosphate
dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway.
Although DHEA and its analog are strong non- competitive inhibitors of this
enzyme in vitro, treatment with DHEA did not deplete cellular nucleotide
pools in the liver, as would have been predicted. The chemopreventive
effect of DHEA in this model may be due to steroid-induced thymic atrophy
and suppression of T cell lymphoma, permitting these mice to survive long
enough to develop tumors with longer latency.
相似文献
32.
Wu DC; Liu JM; Chen YM; Yang S; Liu SM; Chen LT; Whang-Peng J 《Japanese journal of clinical oncology》1997,27(2):115-118
Hemolytic uremic syndrome spontaneously arises in a few patients with
advanced cancer, but it is more commonly related to the use of certain
chemotherapeutic agents. Mitomycin-C is, etiologically, the most common
causative agent inducing hemolytic uremic syndrome, in a dose dependent
manner. We report this syndrome, attributable to mitomycin-C at a
cumulative dose of 40 mg/m2, in a gastric cancer patient. A 42-year-old
female with stage III gastric cancer underwent radical gastrectomy and was
given mitomycin-C at 10 mg/m2 intravenously every four weeks as adjuvant
therapy. Hemolytic uremic syndrome was diagnosed three months after the
last dose of mitomycin-C administration. The most prominent symptoms
included pallor, hypertension and anasarca, with laboratory evidence of
microangiopathic hemolytic anemia, azotemia and hyperkalemia. Her disease
was progressive, but fortunately stabilized after staphylococcus column A
dialysis. Her disease remained in remission for 24 months from the time of
diagnosis, and then relapsed in the form of peritoneal carcinomatosis with
partial intestinal obstruction.
相似文献
33.
MM Harjai DC Agarwal P Dave SS Jog P Arora SM VSM 《Medical Journal Armed Forces India》2005,61(2):143-147
Background
The sudden increase in incidence and magnitude of mine blast injuries prompted us to highlight the problem and its management.Methods
The cases of mine blast injuries occurring during mining and demining in a particular geographical area were analysed. Total 27 cases of mine blast injuries occurred during mining or demining operations in a period of 13 months.Results
Various body regions were involved in the mine blast injuries but the main brunt was borne by feet and legs followed by multiple body regions due to splinters. 14 patients underwent below knee (BK) amputation while 4 patients required through knee (TK) amputations. The effect of blast was so severe that most of the cases required 2 to 5 times wound debridements. The initial aggressive debridement / open stump amputation saved the limb and life of all patients.Conclusion
A mine blast causes extensive injuries and psychological trauma. Management is needed urgently, surgery is difficult, and amputation is often inevitable. Maximum lives and limbs can be saved with aggressive debridement, repeated inspections and dressings under anaesthesia and definitive closure at optimum time.Key Words: Amputation, Antipersonnel mine, Crush syndrome, Debridements, Mine blast injury, Secondary missiles, Shrapenels 相似文献34.
35.
Transient induction of cytochromes P450 1A1 and 1B1 in MCF-7 human breast cancer cells by indirubin 总被引:6,自引:0,他引:6
The aryl hydrocarbon receptor (AhR), when activated by exogenous ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), regulates expression of several phase I and phase II enzymes and is also involved in the regulation of cell proliferation. Several studies suggest that endogenous AhR ligand(s) may exist. One putative endogenous ligand is indirubin, which was recently identified in human urine and bovine serum. We determined the effect of indirubin in MCF-7 breast cancer cells on induction of the activities of cytochromes P450 (CYP) 1A1 and 1B1, as measured by estradiol and ethoxyresorufin metabolism, and on induction of the CYP1A1 and CYP1B1 mRNAs. With 4-hr exposure, the effects of indirubin and TCDD at 10nM on CYP activity were comparable, but the effects of indirubin, unlike those of TCDD, were transitory. Indirubin-induced ethoxyresorufin-O-deethylase activity was maximal by 6-9 hr post-exposure and had disappeared by 24 hr, whereas TCDD-induced activities remained elevated for at least 72 hr. The effects of indirubin on CYP mRNA induction were maximal at 3 hr. Indirubin was metabolized by microsomes containing cDNA-expressed human CYP1A1 or CYP1B1. The potency of indirubin was comparable to that of TCDD in a CYP1B1-promoter-driven luciferase assay, when MCF-7 cells were co-exposed to the AhR ligands together with the CYP inhibitor, ellipticine. Thus, if indirubin is an endogenous AhR ligand, then AhR-mediated signaling by indirubin is likely to be transient and tightly controlled by the ability of indirubin to induce CYP1A1 and CYP1B1, and hence its own metabolism. 相似文献
36.
Spink DC Zhang F Hussain MM Katz BH Liu X Hilker DR Bolton JL 《Chemical research in toxicology》2001,14(5):572-581
Sulfate conjugates of the B-ring unsaturated estrogens, equilin, equilenin, and 8-dehydroestrone, and their 17alpha- and 17beta-dihydro analogues, constitute about 54% of Premarin (Wyeth-Ayerst), the most commonly prescribed estrogen formulation in estrogen replacement therapy. Despite the wide clinical use of Premarin, there have been very few studies on the metabolism of the B-ring unsaturated estrogens in humans and there is no information regarding the fate of these compounds in breast tissue or tumors. In this study, we investigated the metabolism of equilenin in two lines of human breast-cancer cells, MCF-7 and MDA-MB-231. MCF-7 cells respond to treatment with Ah-receptor agonists with induction of cytochromes P450 1A1 and 1B1, whereas in MDA-MB-231 cells P450 1B1 is predominantly induced. Metabolites of equilenin were identified and quantified by GC/MS utilizing a series of synthetic metabolite standards and deuterium-labeled analogues as internal standards. In the two cell lines, the same pathways of equilenin metabolism were observed. Equilenin was reduced at C-17 to the 17beta-dihydro form, with minimal production of the 17alpha-dihydro isomer. Both equilenin and 17beta-dihydroequilenin were hydroxylated at the C-4 position, and the resultant catechol metabolites were methylated to form 4-methoxyequilenin and 4-methoxy-17beta-dihydroequilenin. Rates of equilenin metabolism were markedly elevated in cultures exposed to the Ah-receptor agonists, 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3,4,4',5-tetrachlorobiphenyl, implicating the activities of P450s 1A1 and 1B1 in the metabolism. The 2-hydroxylation pathways of equilenin and 17beta-dihydroequilenin metabolism were not observed. In microsomal reactions with cDNA-expressed human enzymes, both P450s 1A1 and 1B1 catalyzed the 4-hydroxylation of 17beta-dihydroequilenin, whereas with 17beta-estradiol as substrate P450 1A1 catalyzes predominantly 2-hydroxylation and P450 1B1 predominantly 4-hydroxylation. Since P450 1B1 is constitutively expressed and both P450s 1A1 and 1B1 are inducible in many extrahepatic tissues including the mammary epithelium, these results indicate the potential for 4-hydroxylation of equilenin and 17beta-dihydroequilenin in extrahepatic, estrogen-responsive tissues. 相似文献
37.
The slow components of the potentials evoked acoustically by pure tones (1 kHz, 0 to 90 dB HL) were compared between two groups of subjects. All subjects of one group were 22 years old; the members of the other group had an average age of 63 years. The P2-latencies of the older subjects were significantly shorter for 60, 75 and 90 dB HL than those of the younger group. This finding was interpreted as a sign of a decreased efferent inhibition of several nuclei of the auditory pathway in the older subjects. No significant difference between the two groups could be found for the amplitudes (N1/P2), the exponent of the intensity function, or the latencies of P1 and N1. 相似文献
38.
The use of the Bene-Anthony Family Relations Test is described and illustrated by three examples of child abuse. This test should be considered in the investigation of definite or suspected cases of abuse and as part of the preparation of court evidence. 相似文献
39.
Complex and simple coronary artery stenoses: a new way to interpret coronary angiograms based on morphologic features of lesions 总被引:1,自引:0,他引:1
For many years, atherosclerotic coronary artery lesions have been described by angiographers only in terms of location and degree of narrowing. However, it has become apparent that coronary stenoses generally have distinct morphologic features that can be recognized at angiography and that allow them to be classified as either "simple" or "complex" plaques. Complex plaques are those characterized by ulcerated or ruptured surfaces, subintimal hemorrhage, superimposed partially occluding thrombi, recanalized thrombi, or some combination. Pathologic studies have shown a very high frequency of these lesions at sites of total thrombotic occlusion of coronary arteries. Clinical and angiographic studies have demonstrated a high frequency of such lesions in living patients with both unstable angina and acute myocardial infarction. The presence of complex stenoses has also been found to increase the risk of future myocardial infarction. Plaque morphology thus appears to significantly affect the prognosis of patients with coronary disease and should be carefully evaluated in interpretation of all coronary angiograms. 相似文献
40.