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  • 1
    Digitale Medien
    Digitale Medien
    s.l. : American Chemical Society
    Journal of medicinal chemistry 23 (1980), S. 682-684 
    ISSN: 1520-4804
    Quelle: ACS Legacy Archives
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    ISSN: 1573-904X
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract We have used modified standard methods and derived new formulae to quantitate cell permeability (P), cell/media partitioning (λ), and intracellular sequestration or binding rate constants (m) for cultured S49 murine lymphoma cells in suspension. Using 15 standard compounds and anticancer drugs, we found quantitative relationships among log P, log PO (octanol/pH 7.4 buffer partition coefficient), and molecular weight (MW) such that logP = −4.5 + 0.56log (PO(MW)−1/2). A good correlation among P, λ, and MW was also determined with λ = 0.67 + 5890 gm1/2 cm−1 sec (P (MW)1/2). These studies show that there is a strong partitioning (λ) dependence to molecular weight and permeability that can be predicted even for known carrier-transported and biotransformable compounds. Furthermore, results of this study show that the slope of the plot of permeability and lipophilicity is not necessarily unity as has been postulated from the results of other studies.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 13 (1985), S. 387-403 
    ISSN: 1573-8744
    Schlagwort(e): cerebrospinal fluid ; pharmacokinetics ; ACNU ; DFMO ; MGBG ; beagle dogs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Two mathematical approaches are described to approximate the distribution of compounds (e.g., drugs) in the cerebrospinal fluid (CSF) downstream of or distal to both the ventricular injection site and the cisterna magna sampling site. The first approach uses a graphic representation and is, in essence, model independent;the second approach considers the geometry and physiology of CSF distribution and clearance. In all studies, radiolabeled inulin was used as an “internal standard” since it is not metabolized and is eliminated from the CSF primarily by bulk flow. Temporal comparison of the study compound to radiolabeled inulin in the cisternal CSF allowed testing of these models in beagle dogs. One use of this data is in the estimation of the drug exposure integral for antineoplastic drugs administered in the CSF to treat leptomeningeal neoplasia.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    ISSN: 1573-8744
    Schlagwort(e): brain capillary permeability ; capillary permeability coefficient ; brain tumor chemotherapy ; blood-brain barrier
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Capillary permeability was analyzed in both normal rat brain and intracerebral 9L gliosarcoma tumor and in rhesus monkey brain using a newly derived formula for the capillary permeability coefficient (P).The Pvalue for isotopic urea and sodium was less in monkey brain than in rat brain. The Pvalue for tumor was 1 log unit higher in tumor for all but the most rapidly transported drugs. Amphotericin B increased the normal brain Pvalue for galactitol but not for urea. Glucocorticoids did not alter brain Pvalues for sucrose or urea. Using P,drugs can be categorized in terms of blood-brain barrier (BBB) exclusion, slow BBB passage, moderate BBB passage, and rapid BBB passage. The technique described in this article is applicable to the study of regional differences in brain capillary permeability associated with disease states.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 257-296 
    ISSN: 1573-8744
    Schlagwort(e): chemotherapy ; pharmacokinetics ; brain tumors ; modeling ; solid tumors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract It is apparent that chemotherapy against malignant brain tumors is generally ineffective. While some agents are more effective than others, none appreciably alters the clinical course of and the poor prognosis for patients with brain tumors. Even though new and more effective agents are being or will be developed, chemotherapy depends as much on the delivery of drug as it does on the drug used. Therefore, we have defined factors that we believe are of primary importance in drug delivery to brain tumors, and, using computer simulation, we have modeled the effects of these factors. In this article we discuss (a) the extent of the “breakdown” in the blood-brain barrier (BBB) that accompanies the development of malignant tumors in the brain, (b) factors that influence drug transport from tumor capillaries to tumor cells at varying distances from the capillaries, (c) the problems inherent in drug delivery from a well-vascularized tumor outward to normal brain tissue that might harbor malignant cells but that does not have leaky vessels (i.e., normal BBB), and (d) the difficulties in drug delivery from a well-perfused, highly permeable outer tumor shell to a central, poorly perfused tumor core.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Pharmaceutical research 3 (1986), S. 302-306 
    ISSN: 1573-904X
    Schlagwort(e): dibromodulcitol ; bioassay ; cytotoxicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Dibromodulcitol (DBD) is a halogenated hexitol active against animal and human brain tumors in vivo. In aqueous solution, DBD is transformed to products with different cytotoxicities. We studied the in vitro activation and inactivation of DBD with a bioassay in 9L rat brain tumor cells. We developed a mathematical model to calculate the rate constants of activation and inactivation. The kinetics of the activation and inactivation of DBD transformation products in cell culture medium were exponential, with rate constants of 0.139 and 0.0189 hr−1, respectively. The maximum cell kill was caused by DBD that had been preincubated in medium for 13–16 hr. Thus cell kill is not caused by parent drug but by active transformation products.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Publikationsdatum: 2010-01-04
    Print ISSN: 1535-3893
    Digitale ISSN: 1535-3907
    Thema: Chemie und Pharmazie
    Publiziert von American Chemical Society
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Publikationsdatum: 2012-11-16
    Beschreibung: Abstract 3670 Background: Diagnosis of cancer during pregnancy is emotionally stressful for the patient and her family and presents challenges for the medical team including how to best minimize risk of adverse fetal events while still ensuring the best disease outcome for the woman. Cancer is diagnosed during 0.1% of pregnancies with lymphoma being the 4th most common cancer effecting 1 in 6000 pregnancies (Brenner, B et al, The Lancet, 2012 & Pereg, D et al, Haematologica, 2007). This prevalence is anticipated to grow given the shift towards increasing average age at time of pregnancy. The overall rarity of this presentation and the variance of the histological diagnoses have prevented the conduction of large prospective clinical trials, and thus no stringent management algorithms exist. Methods: From 2005 women with a diagnosis of lymphoma during pregnancy were consented and enrolled into this IRB-approved prospective database trial. Patients received multidisciplinary care including counseling and co-management with our maternal-fetal medicine and reproductive medicine collaborators. Results: A total of 19 patients (pts) were consented with full treatment (tx) and fetal outcome data available for 16. The median age of the women was 30 (20–38) years with a slightly lower median age for the classical Hodgkin lymphoma (HL) pts of 28.5 (20–35) years. Ten pts had HL (6 early stage [ES], 2 advanced stage [AS], 2 relapsed), while the remaining 9 had NHL (3 [2 ES, 1 AS] diffuse large B-cell lymphoma [DLBCL], 1 ES anaplastic lymphoma kinase [ALK]-positive LBCL, 1 primary CNS DLBCL, 1 AS follicular lymphoma [FL] with transformation to DLBCL, 1 ES FL, 1 AS MALT, and 1 ALK+ anaplastic LCL). Fifteen pts had diagnoses made of initial or relapsed disease during pregnancy at a median of 18 (3–34) weeks (wks) gestation with 33% during 1st trimester, 54% during 2nd trimester, and 13% during 3rd trimester. Four pts with chronic oligomenorrhea with baseline negative serum pregnancy tests became pregnant while on tx (ABVD, rituximab plus gemcitabine, R-CHOP, and maintenance rituximab) with fetal loss in all 4 with spontaneous abortions from wk 8 to 26 and an elective abortion at wk 6. Four pts of the 15 pts deferred start of tx until after delivery (ES HL and ES primary mediastinal DLBCL pts, a relapsed HL pt, and a ES FL grade 3B pt diagnosed respectively at wks gestation of 31, 34, 14, and 27) and the 3 pts for whom outcome data is available have durable complete remissions (CRs) at a median of 25 (5–52) months (mos) of follow-up with babies born at a median of 35 (31–37) wks at a median birth weight of 2381 (1814–3004) grams with 75% being above the 50% weight percentile. Ten pts started tx while pregnant (80% during 2nd/3rd trimester) at a median of 18 (11–29) wks (ABVD/AVD in 5, R-CHOP/AVD in 1, R-CHOP in 2, HCVAD in 1, and DeAngelis regimen in 1) with all but 1 pt having MRIs and ultrasounds for staging. Seven of these pts delivered babies at a median of 37 (33–39) weeks with 57% delivered at term, a median birth weight of 2948 (2494–3061) grams with 50% being above the 50% weight percentile, and no fetal malformations. At a median of 20.5 (8–53) mos of follow-up 60% of the pts who received tx while pregnant are free of progression while 2 HL pts (1 ES HL pt 22 months after delivery) died from disease progression and 2 pts are on active treatment for relapsed disease (HL and ALK+ LBCL). Three pts experienced fetal loss including a AS HL pt with SVC syndrome necessitating intubation with prolonged ICU care (spontaneous abortion at 23 wks), a AS HL pt who started ABVD at 14 wks of gestation (stillbirth of twins at 26 wks), and the pt with CNS DLBCL who initiated the DeAngelis regimen with high dose methotrexate at 13 wks (elective abortion at 19 wks). Conclusions: Given the rarity of the diagnosis of lymphoma during pregnancy our series to our knowledge represents one of the largest single center prospective clinical studies. Our data highlight that ABVD, R-CHOP, and HCVAD can be given with excellent outcomes for pt and fetus at a preferred start of 2nd trimester or later, although 1 pt with symptomatic HL did start ABVD early at 11 wks of gestation with preservation of positive outcomes. These findings also emphasize the importance of co-management through all the steps of treatment with a maternal-fetal medicine colleague. Furthermore, we show the need to counsel oligomenorrheic pts on the risk of still becoming pregnant and perform assessments to rule-out pregnancy beyond the baseline pre-tx visit. Disclosures: Fanale: Millennium: Research Funding; MedImmune: Research Funding; Novartis: Honoraria, Research Funding, Travel Expenses, Travel Expenses Other; Genentech: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel Expenses, Travel Expenses Other; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel Expenses Other; Onyx: Research Funding; Allos: Membership on an entity's Board of Directors or advisory committees. Lai:Celgene: Membership on an entity's Board of Directors or advisory committees. Younes:Seattle Genetics, Inc.: Consultancy, Research Funding; Millennium: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria; Affimed: Research Funding; Gilead: Research Funding; Johnson & Johnson: Research Funding.
    Print ISSN: 0006-4971
    Digitale ISSN: 1528-0020
    Thema: Biologie , Medizin
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Publikationsdatum: 1980-06-01
    Print ISSN: 0022-2623
    Digitale ISSN: 1520-4804
    Thema: Chemie und Pharmazie , Medizin
    Publiziert von American Chemical Society
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Publikationsdatum: 1993-07-26
    Print ISSN: 0014-5793
    Digitale ISSN: 1873-3468
    Thema: Biologie , Chemie und Pharmazie
    Standort Signatur Erwartet Verfügbarkeit
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