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排序方式: 共有1326条查询结果,搜索用时 15 毫秒
71.
Ganesan Vaidyanathan Donna J. Affleck Kevin L. Alston Michael R. Zalutsky 《Journal of labelled compounds & radiopharmaceuticals》2007,50(3):177-182
Radioiodinated MIBG has shown considerable promise as an imaging agent for cardiac and oncologic applications, and also as a targeted radiotherapeutic for treating patients with neuroendocrine tumors. This radiolabeled agent, synthesized at a no‐carrier‐added level, has demonstrated advantages over the carrier‐added preparation in preliminary clinical studies. Earlier we developed a silicon precursor from which both radioiodinated MIBG and the α‐particle‐emitting 211At analog [211At]MABG could be synthesized at a no‐carrier‐added level. In order to increase the practicality of this approach, we have developed a synthesis of a tin precursor in two steps from a readily available starting material. This tin precursor, N, N′‐bis(tert‐butyloxycarbonyl)‐3‐(trimethylstannyl)benzylguanidine (Bis‐Boc MTMSBG) was evaluated for the synthesis of n.c.a. [*I]MIBG and [211At]MABG via halodestannylation. The radiochemical yields were 83 ± 9% (n=7), 30 ± 21% (n=2), 77 ± 2% (n=2), and 66 ± 7% (n=4) for labeling with 131I, 124I, 125I, and 211At, respectively. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
72.
73.
Ganesan S Travis SP Ahmad T Jazrawi R 《Current opinion in investigational drugs (London, England : 2000)》2002,3(9):1297-1300
Tumor necrosis factor-alpha (TNF alpha) is one of several pro-inflammatory cytokines that have been implicated in the pathogenesis of Crohn's disease (CD). Treatment with antibodies to TNF alpha has been shown to reduce mucosal inflammation in the disease, promote tissue healing, achieve and maintain remission, improve the CD activity index (CDAI) and improve the quality of life. The first part of this article reviews the role of TNF alpha in CD. 相似文献
74.
Protein kinase C (PKC)-dependent regulation of voltage-gated Ca (Ca(v); with alpha(1)beta1Balpha2/delta subunits) channel 2.3 was investigated using phorbol 12-myristate 13-acetate (PMA), or by M(1) muscarinic receptor activation in Xenopus oocytes. The inward Ca(2+)-current with Ba(2+) (I(Ba)) as the charge carrier was potentiated by PMA or acetyl-beta-methylcholine (MCh). The inactivating [I(inact)] and non-inactivating [I(noninact)] components of I(Ba) and the time constant of inactivation tau(inact) were all increased by MCh or PMA. This may be a PKC-dependent action since the effect of MCh and PMA was blocked by Ro-31-8425 or beta-pseudosubstrate. MCh effect was blocked by atropine, guanosine-5'-O-(2-thiodiphosphate) trilithium (GDPbetaS) or U-73122. The effect of MCh but not PMA was blocked by the inhibition of inositol-1,4,5-trisphosphate (IP3) receptors, intracellular Ca(2+) ([Ca(2+)](i)) or the translocation of conventional PKC (cPKC) with heparin, BAPTA and betaC2.4, respectively. While a lower concentration (25 nM) of Ro-31-8425 blocked MCh, a higher concentration (500 nM) of Ro-31-8425 was required to block PMA action. This differential susceptibility of MCh and PMA to heparin, BAPTA, betaC2.4 or Ro-31-8425 is suggestive of the involvement of Ca(2+)-dependent cPKC in MCh action, whereas cPKC and Ca(2+)-independent novel PKC (nPKC) in PMA action. PMA led to additional increase in I(Ba) that was already potentiated by preadministered MCh (1 or 10 microM), leading to the suggestion that differential phosphorylation sites for cPKC and nPKC may be present in the alpha(1)2.3 subunit of Ca(v) 2.3 channels. 相似文献
75.
Using controlled in vivo and in vitro pharmacological methods, we evaluated the safety of papaya (Carica papaya) consumption in pregnancy with reference to its common avoidance during pregnancy in some parts of Asia. Ripe papaya (Carica papaya L. (Caricaecae) blend (500 ml/l water) was freely given to four groups of Sprague-Dawley rats at different stages of gestation (days 1-5, 6-11, 12-17 and 1-20). The control group received water. The effect of ripe papaya juice and crude papaya latex on pregnant and non-pregnant rats' uteri was also evaluated using standard isolated-organ-bath methods. The daily volumes (ml) of ripe papaya blend consumed by the treated group were significantly (P<0.05) more than water consumed by the control (control 40.3 (sd 11.6) v. treated 64 (sd 19.0)). There was no significant difference in the number of implantation sites and viable fetuses in the rats given ripe papaya relative to the control. No sign of fetal or maternal toxicity was observed in all the groups. In the in vitro study, ripe papaya juice (0.1-0.8 ml) did not show any significant contractile effect on uterine smooth muscles isolated from pregnant and non-pregnant rats; conversely, crude papaya latex (0.1-3.2 mg/ml) induced spasmodic contraction of the uterine muscles similar to oxytocin (1-64 mU/ml) and prostaglandin F(2 alpha) (0.028-1.81 microm). The response of the isolated rat uterine smooth muscles to 0.2 mg crude papaya latex/ml was comparable to 0.23 microm prostaglandin F(2 alpha) and 32 mU oxytocin/ml. In the 18-19 d pregnant rat uterus, the contractile effect of crude papaya latex was characterized by tetanic spasms. The results of the present study suggest that normal consumption of ripe papaya during pregnancy may not pose any significant danger. However, the unripe or semi-ripe papaya (which contains high concentration of the latex that produces marked uterine contractions) could be unsafe in pregnancy. Though evaluation of potentially toxic agents often relies on animal experimental results to predict risk in man, further studies will be necessary to ascertain the ultimate risk of unripe papaya-semi-ripe papaya consumption during pregnancy in man. 相似文献
76.
Riddle PJ Echeta CB Manek S Lavery BA Charnock FM Mackenzie I Ganesan TS 《Clinical oncology (Royal College of Radiologists (Great Britain))》2002,14(1):54-61
We report a retrospective study of 47 consecutive patients with uterine sarcoma treated at the Churchill Hospital in Oxford between 1990-1998. The mainstay of treatment was surgery with adjuvant chemotherapy and radiotherapy reserved for selected patients with early stage disease. Overall 1 and 2 year survival was 49% and 30% respectively compared with 73% and 55% in the group who received adjuvant chemotherapy/radiotherapy. Median survival was 11 months for the group as a whole compared to 32.9 months in the adjuvant therapy group. This is a retrospective review with small numbers and considerable selection bias, however, given the poor survival of patients with this disease, adjuvant treatment should be considered in future trials of patients with uterine sarcoma. 相似文献
77.
78.
Risperidone is an atypical anti-psychotic medication with both 5HT2 receptor and D2 dopamine receptor antagonism. Its use has been reported to be generally safe with very few gastro-intestinal (GI) adverse or side effects. In this paper, we describe a case of megacolon associated with the use of risperidone. A 44-year-old man suffering from schizophrenia was treated with risperidone and developed gross abdominal distension after twenty-five days. Abdominal X-ray and colonoscopy showed megacolon. He improved following a surgical decompression and a reduction of risperidone dosage. We discuss the neuro-electro-physiological mechanisms of gastro-intestinal motility and conclude that the risperidone-associated megacolon may be dose-related and that there should be a heightened awareness of such possible GI complication when using risperidone. 相似文献
79.
Propper DJ Levitt NC O'Byrne K Braybrooke JP Talbot DC Ganesan TS Thompson CH Rajagopalan B Littlewood TJ Dixon RM Harris AL 《British journal of cancer》2000,82(11):1776-1782
BW12C (5-[2-formyl-3-hydroxypenoxyl] pentanoic acid) stabilizes oxyhaemoglobin, causing a reversible left-shift of the oxygen saturation curve (OSC) and tissue hypoxia. The activity of mitomycin C (MMC) is enhanced by hypoxia. In this phase II study, 17 patients with metastatic colorectal cancer resistant to 5-fluorouracil (5-FU) received BW12C and MMC. BW12C was given as a bolus loading dose of 45 mg kg(-1) over 1 h, followed by a maintenance infusion of 4 mg kg(-1) h(-1) for 5 h. MMC 6 mg m(-2) was administered over 15 min immediately after the BW12C bolus. The 15 evaluable patients had progressive disease after a median of 2 (range 1-4) cycles of chemotherapy. Haemoglobin electrophoresis 3 and 5 h after the BW12C bolus dose showed a fast moving band consistent with the BW12C-oxyhaemoglobin complex, accounting for approximately 50% of total haemoglobin. The predominant toxicities--nausea/vomiting and vein pain--were mild and did not exceed CTC grade 2. Liver 31P magnetic resonance spectroscopy of patients with hepatic metastases showed no changes consistent with tissue hypoxia. The principle of combining a hypoxically activated drug with an agent that increases tissue hypoxia is clinically feasible, producing an effect equivalent to reducing tumour oxygen delivery by at least 50%. However, BW12C in combination with MMC for 5-FU-resistant colorectal cancer is not an effective regimen. This could be related to drug resistance rather than a failure to enhance cytotoxicity. 相似文献
80.
Evaluation of toremifene for reversal of multidrug resistance in renal cell cancer patients treated with vinblastine 总被引:8,自引:0,他引:8
Braybrooke JP Vallis KA Houlbrook S Rockett H Ellmén J Anttila M Ganesan TS Harris AL Talbot DC 《Cancer chemotherapy and pharmacology》2000,46(1):27-34
Purpose: Expression of P-glycoprotein (Pgp), which confers the multidrug resistance (MDR) phenotype, is thought to contribute to
the insensitivity of renal cell cancer (RCC) to chemotherapy. The development of Pgp inhibitors for clinical application has
been hampered by unacceptable toxicity at doses required to achieve adequate cellular concentration. Toremifene is able to
reverse MDR and sensitise RCC to vinblastine in vitro. However, in vivo toremifene is tightly bound to serum proteins, in
particular the acute phase protein α1-acid glycoprotein (AAG), which may limit tissue availability. In this phase I–II study we assessed the tolerability of short
courses of high dose toremifene in combination with vinblastine and evaluated the key determinants of MDR reversal in vivo.
Methods: Twenty-seven patients with metastatic RCC received escalating doses of oral toremifene for 3 days every 2 weeks in combination
with vinblastine 6 mg/m2 i.v. on day 3 of each cycle. The serum concentration of toremifene, its metabolites and AAG were measured and the effect
of patients' serum on inhibition of Pgp in vitro was determined. Results: Twenty-six patients were evaluable for response. Eight patients (31%) had stable disease and 18 patients (69%) progressive
disease. The mean serum concentration of toremifene at 780 mg daily for 3 days was 7.82 μM [standard deviation (SD) 2.48, range 2.50 to 14.70], which exceeds that known to reverse MDR in vitro. The serum concentration
of the major metabolite of toremifene, N-demethyltoremifene, which also reverses MDR, was 5.13 μM (SD 1.78, range 1.80 to 9.00). In 60% of patients the pre-treatment AAG concentration was above that known to block the effects
of toremifene in vitro. However, addition of serum from patients on toremifene to MCF-7 adr cells in vitro inhibited Pgp-mediated
efflux of rhodamine 123. Conclusions: We have shown that short course, high-dose toremifene in combination with vinblastine is generally well tolerated and that
the concentration of toremifene required to reverse MDR in vitro is achievable in vivo.
Received: 7 July 1999 / Accepted: 15 November 1999 相似文献