Cisplatin dmso
Received 9 15 98; accepted 12 2 98. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Supported in part by NIH Grants CA 72217 and CA 76581 and NIH Training Grant GM-07767 and by NIH Grants AR 20557 and CA46592 to the University of Michigan Core Flow Cytometry Facility. 2 To whom requests for reprints should be addressed, at 4713 Upjohn Center, University of Michigan Medical Center, 1310 East Catherine, Ann Arbor, MI 48109-0504. Phone: 734 ; 763-5810; Fax: 734 ; 763-3438; E-mail: dshewach umich.
CISPLATIN BINDING TO CELLULAR DNA nuclear [CDDP] to come to a steady state ; . Afterward, the rate of cisplatin uptake is the same as for thiol-blocked cells. Since total cellular thiol concentration has not been measured experimentally, the model gives useful information about the contribution of cellular sulfhydryls. Figure 4 also includes a plot of calculated thiol concentration remaining after 2 h versus [CDDP]. It appears that the concentration of cisplatin must exceed 8 M to reduce the concentration of thiol groups by 90% during the 2-h incubation period. If the thiol groups are blocked by other reagents, so S0 0, the entire cisplatin is effective in binding to DNA. Figure 5 shows changes over time, from calculations assuming [CDDP] 7 M and the thiol concentration as either 0 or 2 mM. The same values for rate constants were used as in the calculations of Fig. 4. With no available thiol S0 0 ; , the amount of Pt bound to DNA is close to a linear function of time, with a slope of 1.5 Pt atoms 106 nt min. With S0 2 mM, the slope starts out very small and rises with time. Even at t 2 h, the slope is much smaller than the slope with S0 0, even though three-quarters of the thiol groups have been saturated by Pt as shown in Fig. 5 ; . For larger times, the slope increases to approach 1.5 Pt atoms 106 nt min. The average slope with S0 2 mM about 0.2 Pt atoms 106 nt min. The slope calculated from the experimental data Fig. 2, open squares ; is 0.46 0.11, but the scatter in the data is too large to warrant fine tuning of the parameters in the calculation to get better agreement with this number. With S0 0, the slope calculated from the experimental data is 1.3 0.2 Fig. 2, closed squares ; , fairly close to what we calculated 1.4 ; . The scatter in the data for S0 0 is less serious than for S0 2 mM, largely because the quantities measured are bigger. Our model is too simple to account for the apparent rate changes found experimentally Fig. 2 ; . The value of kb we used, 8 105 M 1 h 1, several orders of magnitude larger than the rate constant reported Bose et al., 1997 ; for reaction of CDDP with cysteine or glutathione Dedon and Borch, 1987 ; . It is likely, however, that the compound in the cell has been aquated to Pt NH3 ; 2 H2O ; Cl, and the rate constant for the reaction of Pt NH3 ; 2 H2O ; Cl with cysteine is given Bose et al., 1997 ; only as "fast". Recently, it has been shown that, for binding to DNA, the doubly aquated compound has a rate constant 2 orders of magnitude higher than Pt NH3 ; 2 H2O ; Cl, and this should also hold for binding to thiols Legenre et al., 2000 ; . It should be emphasized that a large value of kb is demanded by the experimental results. The large increase in the slope of Fig. 1 left panel ; shows that the intracellular thiols are becoming nearly saturated when Pe 5 M. [P] is fairly constant, the concentration of free thiols decreases according to: ln kb[P]t. Assuming [P] 3 M calculations show [P] is somewhat more than half of Pe at [S] S0 0.1 for t 2 h requires that kb be 4 105 M 1 h The effects of the cytoprotective agents can also be interpreted in the context of this model. WR-1065 or mesna enters the cells rapidly Souid et al., 1999, 2001 ; , thus effectively adding to the original concentration of thiols. Figure 6 shows the calculated amount of platination after a 2-h incubation as a function of the added thiol. The total thiol concentration at time 0 is equal to the added concentration plus 2.0 mM, an approximate amount of endogenous cellular thiols Reedijk and Teuben, 1999 ; . Because of the scattered data in Table 3, we did not attempt to adjust parameters to get close agreement with experimental results. The effect of added thiols is small probably undetectable ; when the added concentration is 0.3 mM first point ; , but the Pt -DNA adducts are reduced to a small fraction of its original value for added thiol concentrations exceeding 4 mM Fig. 6 ; . In conclusion, it is well known that endogenous thiols intercept.
Carboplatin and cisplatin
CYTOKINES SUCH AS tumor necrosis factor TNF- ; have been shown to have both endothelium-dependent and -independent vasodilator properties 14, 36 ; . Such properties imply an important role for TNF induced vascular responses in cases in which plasma TNFlevels are elevated such as sepsis endotoxemia, vascular damage associated with hypertension, and obesity 5, 8, 39 ; . Indeed, the vasodilator effects of TNF- may be responsible for the marked hypotension seen in septic shock. The endothelium-dependent component has been attributed to activation of endothelial nitric oxide NO ; synthase, generation of NO, and relaxation of vascular smooth muscle 3, 34 ; . The endotheliumindependent component of TNF induced vasodilation has not been characterized. In other systems, TNF- has been shown to stimulate a membrane-associated, neutral-optimum pH.
Figure 5. Formation and repair of specific DNA adducts in CD34 and CD34 cells after exposure to melphalan or cisplatin ex vivo. Cells were isolated from CB and exposed to melphalan 5 g mL ; for one hour or cisplatin 10 g mL ; for 2 hours and then replaced to fresh medium. Cell aliquots were taken at different time points after treatment and specific DNA adducts were measured by ICA analysis using antimelphalan-DNA or anticisplatin G-G ; antibodies as described in "Materials and methods.
Cisplatin-Based Chemotherapy: The first double-blind trial compared granisetron hydrochloride tablet 1 mg bid, relative to placebo historical control ; , in 119 cancer patients receiving high-dose cisplatin mean dose 80 mg m2 ; . At 24 hours, granisetron hydrochloride tablets 1 mg bid was significantly P 0.001 ; superior to placebo historical control ; in all efficacy parameters: complete response 52% ; , no vomiting 56% ; and no nausea 45% ; . The placebo rates were 7%, 14%, and 7%, respectively, for the three efficacy parameters.
Function, accompanied by SBP in one patient, was infrequent, even in Child-Pugh class C patients, in whom the risk per session was 8.3% and the overall incidence during the course of treatment under 20%. Furthermore, the 30-day mortality after a session of TACE was under 5% in this group. In individual patients, further deterioration did not necessarily follow additional treatment sessions, implying that hepatic decompensation was not the consequence of cumulative exposure to doxorubicin or cisplatin, but more likely due to variable degrees of ischaemic injury sustained by non-tumorous liver tissue from session to session. Actuarial survival rates at 12, 24 and 36 months were 50.0%, 29.0% and 14.8%, respectively. A trend between longer-term survival and initial Child-Pugh status was apparent, in that most patients who survived at least 36 months were initially Child-Pugh class A and none were class C. Conversely, such a trend was not evident with regard to initial tumour size. Some 25% of patients who survived for this time had been treated for a HCC 4 cm in diameter, while 50% had HCCs 47 cm in diameter and 25% had an HCC 8 cm in diameter. These survival rates, occurring in exclusively cirrhotic patients predominantly with large tumours, are similar to those reported in a similarly treated group of mostly noncirrhotic patients with small HCCs, 24 and compare favourably with those in untreated, historical controls. We conclude that multi-agent TACE with lipiodol, doxorubicin and cisplatin provides a useful antitumour effect, even in cirrhotic patients with large HCCs. This can be achieved with little time spent in hospital. These findings are especially important in view of the lack of alternative treatment options of proven benefit in this latter group. The incidence of clinically significant deterioration in hepatic function due to ischaemia of non-tumorous liver is acceptably low, even in Child-Pugh class C patients and cladribine.
Cisplatin solution storage
1407 Our institution uses the chemotherapy combination of mitomycin C, vinblastine and cisplatin MVP ; for the treatment of mesothelioma. We report here our experience with this combination of drugs in a large series of patients with mesothelioma in whom data were collected prospectively from the time of their first referral. This report is an update of the outcome of this group and an assessment of prognostic factors.
The project is based on Robert Putnam's concept that trade policy is the result of a two level game: the structure and dynamics of the process at the national level and the interaction among the national players at the supranational level. While the international policy process has been extensively documented and analyzed, remarkably little is known about the nature of the process at the first level. Yet the process at the national level is an essential component of the final outcome, i.e. the international agreement at the conclusion of the negotiations. Indeed, in the case of the two largest trading powers, the US and the EU, the domestic process has arguably been the major determinant of both the agenda and the dynamics of the international process and thus the final outcome. Since the Uruguay Round trade policy has become far more complex in recent years, both in terms of the range of issues involved and the participation of new actors, it is thus extremely important to enhance our understanding of the actors and institutions that shape and constrain trade policy formulation at the national level. To this end policy memoranda were commissioned for a group of eight countries in the Western Hemisphere: Argentina, Brazil, Canada, Chile, Colombia, Mexico, United States and Uruguay. A number of questions were posed concerning the nature of the process and the resulting memos are published here. Rather than trying to summarize the analyses, it is probably more useful to highlight some of the main features of the differing policy templates and to raise a few questions about the possible evolution in the structure and content of the process. This project is just a first step in what, we hope, will be further research in this important but unexplored subject. As readers will note after perusing the eight papers, there is considerable diversity in the policy process among these countries in terms of procedures for consultation; groups included; scheduling; institutional arrangements; and so on. Yet there is a clear dividing line between the two North American industrialized countries -Canada and the United States- and the six other Latin American countries. The former, unlike the latter, have established institutional arrangements involving both legislative bodies and a wide range of interested parties or stakeholders, including business, farmers, labor, NGO's and academics. There are very marked differences in the consultative process as between Canada and the United States, however, that are based on the differences in basic governance i.e. a parliamentary versus a presidential system. This is worth noting and suggests that governance -including constitutions- should also be regarded as one of the determinants of the policy-process. In a domain as broad and complex as trade policy today it may and clofarabine.
Cisplatin pemetrexed nsclc
Events. However, our data suggest that the nurse service is clinically effective. Service provision is different from showing that a type of service is potentially effective. We found that nearly 20% of patients seen by the nurse had to be seen by a general practitioner as well. Whether this is sustainable in terms of cost effectiveness is still not clear. Our data suggest that referral rates may fall as nurses become more experienced: in the second half of the trial only 17.7% of nurses' patients had to be seen by the doctor, compared with 21.3% in the first half. Cost effectiveness goes beyond the immediate cost of a nurse or general practitioner. We should take into account factors such as the improvements that could be made by changing the way current services are provided. For example, in minor illness there might be little to choose in terms of cost between a nurse and a general practitioner, but doctors' time might be better used in seeing patients with more complex problems or extending other services.
28.05.2002 Type Species Strain Sex Number of animals Vehicle Exposure time Method Year GLP Test substance Remark Source Reliability 28.05.2002 Type Species Strain Sex Number of animals Vehicle Exposure time Method Year GLP Test substance Remark : : : other mouse and clofibrate.
60. The Appeal Panel considered that the Appraisal Committee had not given appropriate consideration to the issue of whether a chemoradiotherapy regimen of carboplatin alone was as effective as cisplatin, or that a regimen consisting of carboplatin plus fluorouracil would necessarily be suitable for the population identified in the decision problem in whom cisplatin was contra-indicated. The Panel found that, as a result, the Committee's conclusions were perverse in proposing a `carboplatin-based' regimen for those in whom cisplatin was contra-indicated.
Severe RV volume overloading causing overt right heart failure was present in each of these dogs. Cardiocyte morphology. Cardiocyte dimensions were evaluated in terms of cellular length and width. As and clorazepate
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Accordingly, 1 ; cytogam has market exclusivity for use in lung, liver, pancreas, and heart transplants until december 2005; 2 ; respigam has market exclusivity for its currently licensed indication through january 17, 2003; 3 ; ethyol has market exclusivity for its currently licensed chemoprotective indication for patients with ovarian cancer through december 2002, and for its radioprotective indication through june 2006; and 4 ; neutrexin had market exclusivity for its currently licensed pcp indication through december 200 ethyol has also been designated as an orphan drug for use as a chemoprotective agent for use with cyclophosphamide in the treatment of advanced ovarian carcinoma, as a chemoprotective agent for use with cisplatin in the treatment of metastatic melanoma, for the treatment of myelodysplastic syndromes, and for the reduction of the incidence and severity of cisplatin-induced toxicities and clove.
Cisplatin and taxol for ovarian cancer
However, other risk factors include: age older than 60 years ; weakened immune system diseases of the colon such as inflammatory bowel disease and colorectal cancer ; intestinal surgery cancer chemotherapy with medications, such as 5-fluorouracil and cisplatin pseudomembranous colitis is more common in certain people in hospitals and nursing homes, often when they're receiving drugs or undergoing surgery in which antibiotics are part of the treatment regimen.
Tigation in phase II III trials combined with standard chemotherapy and radiotherapy, as radiosensitizers, in patients with head and neck Table II ; , lung, renal, gastric and prostate cancer. These agents can improve the efficacy of platinoids, taxanes and anthracyclines cytotoxic; these groups of cytostatics are the most effective in salivary gland malignancy 49 50. Cetuximab IMC-225 ; , a chimeric monoclonal antibody that specifically binds to the EGFR with high affinity, overcomes resistance to cisplatin in cisplatin-refractory advanced head and neck squamous cell carcinoma 51. Protein kinase A inhibitors and VEGFR inhibitors have a synergistic effect in combination with EGFR inhibitors 52 53; multitarget therapy seems very interesting. COX-2 inhibitors enhance antitumoural activity of EGFR and HER-2 neu inhibitors 54 55. COX-2 inhibitors, show promise in combination with radiation therapy and inhibit angiogenesis 56 57. The HER2 oncogene is differently expressed in salivary gland malignancies 58-60 Table III its overexpression correlates with poor prognosis. We have monoclonal antibodies and tyrosine kinase inhibitors for the erbB-2 receptor which could be used alone or in combination for salivary gland malignancies and codeine.
Compared to standard treatment 73% versus 52% on days 15, 89% versus 78% on day 1 and 75% versus 56% on days 25 ; [11]. Complete response from nausea was not significantly different. In both studies adverse effects were mild and not significantly different between the two groups of patients. In conclusion, in both studies aprepitant significantly increased antiemetic efficacy and its combination with a 5-HT3 antagonist and dexamethasone should be considered the new standard option for the prevention of cisplatin-induced acute emesis. An analysis of an extension of the two studies, in which multiple cycles maximum 6 ; were permitted, confirmed that the aprepitant combination is significantly superior during all six cycles of chemotherapy [12]. Given the different antiemetic regimens employed for acute prophylaxis, one can question whether a significant component of the improved efficacy of the aprepitant-containing arms during the delayed phase was due to a carryover effect from the different control rates during day one. A subsequent analysis of the combined database from these two phase III trials strongly suggests that aprepitant provided protection against delayed vomiting regardless of response in the acute phase [13]. In patients with acute vomiting, the proportion of patients with delayed vomiting was 85% and 68% in the control and aprepitant arms, respectively. In patients with no acute vomiting, the proportion with delayed vomiting was 33% and 17% on the control and aprepitant arms, respectively. Unfortunately, in both studies the treatment of choice for cisplatin-induced delayed emesis was not used. The MASCC has recommended that in patients receiving cisplatin treated with a combination of aprepitant, a 5-HT3-receptor antagonist and dexamethasone to prevent acute vomiting and nausea, the combination of dexamethasone and aprepitant is suggested to prevent delayed emesis, on the basis of its superiority to dexamethasone alone [14]. Our opinion is that in order to define the role of aprepitant in the prophylaxis of cisplatin-induced delayed emesis, it is necessary to carry out further studies in which all patients receive the same standard combination of aprepitant plus a 5-HT3 antagonist plus dexamethasone for the prevention of cisplatin-induced acute emesis, and, starting from 24 h after cisplatin administration, patients should be randomized to receive dexamethasone plus metoclopramide or ondansetron ; or dexamethasone plus aprepitant and cisplatin.
Etoposide with cisplatin
Etoposide and cisplatin chemotherapy
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