Disease relevance of OAP

• Patients entering complete remission (CR) were given three consolidation courses of five-day OAP and randomized to maintenance chemotherapy alone (32 patients) or combined with BCG vaccine (24 patients) [1].
• For 160 previously untreated patients with acute myelogenous leukemia, there was no difference in remission rates (53% vs 43%) or median survival times (48 vs 47 weeks) between ten-day and five-day OAP [1].
• The relative importance of OAP in the genesis of clinically important arrhythmias awaits further investigation [2].
• METHODS: Human breast adenocarcinoma MCF-7/0 cells and a stably oxazaphosphorine-resistant subline thereof, MCF-7/OAP, were grown in the presence of 3-methylcholanthrene (3 microM), catechol (30 microM), or vehicle for 5 days [3].
• Stiffness of the medial (MCL) and lateral (LCL) collateral ligaments was compared between a group of 10 patients undergoing total knee arthroplasty for varus degenerative osteoarthritis (OAP), a group of 10 osteoarthritic cadaveric knees (OAC), and a group of 10 non-osteoarthritic cadaveric knees (NOA) [4].

High impact information on OAP

• To investigate additional ways c-Rel could regulate IL-2 gene expression, we determined whether c-rel overexpression could increase the activity of other transcription factors involved in IL-2 promoter regulation: NF-AT, Oct/OAP (ARRE-1), and AP-1 [5].
• OAP confers to Oct-2 responsivity to both TPA/Ca2+ and RA, since specific mutations of the AP-1/OAP-binding site significantly reduce the transactivation by Oct-2 in response to TPA and Ca2+ and abolish the inhibition by RA [6].
• Mutations of the genuine octamer-binding site abrogate both the binding of Oct-1 and Oct-2 and the TPA/Ca2+-induced transactivation of the OAP/octamer motif [6].
• We report that a constitutively active form of calcineurin partially substitutes for the Ca2+ co-stimulus required to activate the IL-2 promoter elements IL-2A (which binds the factors OAP and Oct-1) and IL-2E (which binds NF-AT), and completely substitutes for the Ca2+ co-stimulus required to stimulate an NF-kappa B-dependent element [7].
• In the first stage of the trial, patients with unfavorable prognosis (PPR less than .40) received AMSA-OAP for remission induction and patients with favorable prognosis (PPR greater than or equal to .40) received Adriamycin [Adria Laboratories, Columbus, OH] plus OAP (Ad-OAP) [8].

Chemical compound and disease context of OAP

• Sixteen elderly patients affected by acute non lymphoblastic leukaemia (ANLL) with a preexisting severe internal disease were treated with a low systemic toxicity drugs combination: OAP (Vincristine, Cytarabine and Prednisone) [9].
• The capsular polysaccharide of Neisseria meningitidis serogroup W135 is expressed in both O-acetyl-positive (OA+) and O-acetyl-negative (OA-) forms [10].

Biological context of OAP

• CN has recently been established as a key signaling enzyme in the T cell signal transduction cascade and an important regulator of transcription factors such as NF-AT and OAP/Oct-1, which are involved in the expression of a number of important T cell early genes [11].
• The numerous OA linkage studies that have now been performed have revealed a number of regions of the human genome that are likely to harbor genes predisposing to OA [12].
• Some of these studies suggest that genetic susceptibility may be more relevant to female OA than to male OA and that genes may have a greater role in OA development and progression at certain joint groups compared with others [12].
• These results indicate that the OA-sensitive protein phosphatase is involved in the regulation of channel activity, and suggest that both PP-1 and PP-2A are candidates responsible for the inhibition of channel activity through dephosphorylation of the PKA-mediated protein phosphorylation [13].

Anatomical context of OAP

• In response to digitalis, OAP occur in tissues of the specialized conducting systems of both ventricles and atria and, under the influence of tension, occasionally in ventricular myocardium [2].
• The stabilization of the primary OAP metabolites (MAFO), opens up new possibilities in clinical therapy and in preclinical tests, for examination in the clonogenic stem cell test, for in vitro purging in ABMT, and for the regional therapy of tumors [14].

Associations of OAP with chemical compounds

• Adults (274) with acute leukemia (AML) were randomly assigned to one of three treatment regimens: vincristine, prednisone, cytarabine--(1) 100 mg/sq m/day with cyclophosphamide (COAP); (2) 100 mg/sq m/day with daunorubicin (DOAP); and 200 mg/sq m/day (OAP) [15].
• The results were compared with those of a previous SWOG study in which cytarabine (200 mg per square meter of body area per day) was given for five days (five-day OAP) [1].
• In this Southwest Oncology Group (SWOG) study, 216 adults with acute leukemia were treated with ten-day chemotherapy consisting of vincristine sulfate (Oncovin), cytarabine (ara-C) (100 mg per square meter of body area per day by 24-hour infusion), and prednisone (ten-day OAP) [1].
• After nine months of complete remission, patients were randomized between late intensification with POMP (mercaptopurine + vincristine + methotrexate + prednisone) or continued maintenance with OAP (vincristine + cytosine arabinoside + prednisone) [16].
• Hence, the MCF-7/OAP ALDH-3 was judged to be a novel class 3 aldehyde dehydrogenase [17].

Other interactions of OAP

• Relative to MCF-7/0 cells, MCF-7/OAP cells stably overexpressed all but cytochrome P450 1A1 and were stably, more resistant to mafosfamide, melphalan and mitoxantrone, and more sensitive to EO9 [3].
• The development of the OAP cytostatics CP, IFO, TRO, and SUFO derives from the idea of applying the principle of transport form/active form to the highly reactive nitrogen mustard compounds [14].

Analytical, diagnostic and therapeutic context of OAP

• Moreover, quantitative PCR analysis showed 50% higher FLIP expression in RASF than in OASF [18].
• Genetic epidemiologic studies have demonstrated that primary OA has a major genetic component that segregates in families in a complex manner [12].

References