Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Univariate and multivariate analyses were performed on data from 370 5-fluorouracil (5-FU)-resistant advanced colorectal cancer patients treated with oxaliplatin (Eloxatin)/5-FU+/-folinic acid (FA) to identify prognostic factors for oxaliplatin-based treatment. The response rate was 14.6% (95% confidence interval (CI): 11.0-18.2%), median time to progression was 4.3 months (95% CI: 3.9-4.7), and median overall survival 9.7 months (95% CI: 8.5-10.8). Multivariate analysis indicated < 2 prior chemotherapy regimens, bi-weekly treatment administration schedule (versus tri-weekly) and continuous chronomodulated delivery (CCM) as significantly associated (P < 0.05) with a higher overall response rate. Performance status (PS) < 2, having only one involved organ, biweekly schedule and CCM were associated (P < 0.05) with a longer time to progression. Good PS, one involved organ, low alkaline phosphatase (AP) serum levels, bi-weekly schedule and CCM were significantly correlated with longer overall survival, while confirming the efficacy of oxaliplatin/5-FU+/-FA in this indication.
 ...
PMID:Factors predicting for efficacy of oxaliplatin in combination with 5-fluorouracil (5-FU)+/-folinic acid (FA) in a compassionate-use cohort of 370 5-FU-resistant advanced colorectal cancer (CRC) patients. 1109 7

A statistical analysis was performed on the patient data collected from two compassionate-use programmes using oxaliplatin (Eloxatin(R)) + 5-fluorouracil (5-FU) +/- folinic acid (FA), to identify predictive factors for oxaliplatin-based salvage treatment in patients with 5-FU-resistant advanced colorectal cancer (ACRC). 481 5-FU-resistant ACRC patients, most with performance status < or = 2, > or = 3 involved sites, and > or = 2 prior lines of chemotherapy, received oxaliplatin + 5-FU +/- FA. Prognostic factors associated with overall response rate (ORR), time to progression (TTP) and overall survival (OS) were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The ORR was 16% (95% CI: 13-20), the median TTP was 4.2 months (95% CI: 3.4-4.6), and the median OS was 9.6 months (95% CI: 8.6-10.6). The multivariate analysis indicated poor (> or = 2 WHO) performance status (PS), a large number of prior chemotherapy regimens (> or = 3), a low baseline haemoglobin level (< 10 g/dl), and a triweekly (vs biweekly) treatment administration schedule as significantly associated (P< 0.05) with a lower ORR. Sex (male), number of organs involved (> or =3) and alkaline phosphatase (AP) level (> or = 2 x the upper limit of normal) were associated (P< 0.05) with shorter TTP. Poor PS, a large number of organs involved, and elevated AP were independently and significantly correlated with shorter OS. Our analysis identified a relationship between efficacy results of oxaliplatin + 5-FU +/- FA treatment in 5-FU-resistant ACRC patients and baseline prognostic factors related to PS, extent of disease and number of prior regimens.
 ...
PMID:Factors predicting efficacy of oxaliplatin in combination with 5-fluorouracil (5-FU) +/- folinic acid in a compassionate-use cohort of 481 5-FU-resistant advanced colorectal cancer patients. 1150 88

The main toxicity of Oxaliplatin, a major drug in the treatment of metastatic colorectal carcinoma, is neurologic. Severe sinusoidal lesions of the liver have been recently described in patients receiving pre-operative (neoadjuvant) oxaliplatin-containing chemotherapy, but their clinical relevance is unknown. Four patients with metastatic colon cancer receiving oxaliplatin, 5 fluorouracil and elvorin, developped a progressive increase in gammaglutamyl transpeptidase and alkaline phosphatase, contrasting with tumour regression established by CT-scan and decrease in serum carcinoembryonic antigen concentrations. Histological examination of liver biopsies showed sinusoidal dilatation in all cases, with perisinusoidal fibrosis and centrilobular vein lesions in 3, peliosis in 1 (in a patient receiving oxaliplatine by intraarterial hepatic route), and nodular regenerative hyperplasia in 1. The patient with peliosis developped ascites, and died from hepatic failure, despite withdrawal of the drug. The patient with nodular regenerative hyperplasia developped jaundice, ascites and severe infection following a right hepatectomy. In the three surviving patients, liver function tests improved after the withdrawal of oxaliplatin, and, in one, deteriorated again after reintroduction of the drug. The prevalence of liver sinusoid lesions induced by oxaliplatin-containing chemotherapeutic regimens is probably underestimated. Careful monitoring of gamma-glutamyl transpeptidase and alkaline phosphatase is mandatory in treated patients, especially in those receiving adjuvant therapy, in whom significant sequelae could occur despite initially asymptomatic lesions.
 ...
PMID:Severe sinusoidal lesions: a serious and overlooked complication of oxaliplatin-containing chemotherapy? 1718 76

Oxaliplatin is a third-generation platinum complex, and has a broad spectrum of antitumor activity. Such platinum complexes with the DACH carrier ligand have recently received increasing attention since they show efficacy against cisplatin-resistant cell lines. As the foremost indication of antitumor activity of platinum drugs is the formation of adducts with genomic DNA, calf thymus DNA-oxaliplatin adducts were the major target in this study. Calf thymus DNA was incubated with oxaliplatin, resulting in the formation of a large number of platinum-DNA adducts. Treated DNA was digested into the dinucleotides with a combination of enzymes, namely, benzonase, alkaline phosphatase, and nuclease S1. Using a high-performance liquid chromatography, we carried out the separation of individual platinum-DNA adducts which were concurrently identified using electrospray ionization ion trap mass spectrometry (MS). Both 1,2-intrastrand and 1,2-interstrand cross-linked adducts were found; however, those of the intrastrand nature have a considerably higher abundance than those of the interstrand cross-links. Among them, d(GpG)-oxaliplatin was the most abundant bifuctional adduct. To a lesser extent, a few monofunctional adducts were detected as well. MS(n) experiments served to ascertain the detailed structures of oxaliplatin adducts of dinucleoside monophosphates and of dinucleotides.
 ...
PMID:Separation and characterization of oxaliplatin dinucleotides from DNA using HPLC-ESI ion trap mass spectrometry. 1870 62

Oxaliplatin, [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II) shows a great efficiency against colorectal cancer. Although the mode of action of oxaliplatin is not yet understood, it is commonly accepted that binding of oxaliplatin to DNA prevents DNA synthesis and alters protein to DNA binding. In order to elucidate the modified DNA-protein interaction and thus to understand the mechanisms leading to cellular misinterpretation of DNA information and apoptosis, we have identified the preferential binding sites and the dynamics of the oxaliplatin-DNA intrastrand and interstrand adducts at the oligomer level using high-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS) and HPLC/inductively coupled plasma-MS for quantitative studies. We used a combination of benzonase, alkaline phosphatase and Nuclease S1 for digestion. This digestion procedure allows the study of platinated oligomeric nucleotides and more complex interstrand adducts. The digestion products were mostly chromatographically separated and characterized using HPLC/ESI-ion trap MS/MS experiments. We could show that the adducts to guanine and adenine are quite dynamic; that is, the ratios are changing for several days. In addition, the resulting adducts provide evidence for the action of the digesting enzymes and indicate that the adduct spectrum at the oligomeric level is different to that at the commonly studies dinucleotide level.
 ...
PMID:Structures of oxaliplatin-oligonucleotide adducts from DNA. 2301 59