摘要:

Specimens (173) were evaluated to assess the predictive value of cell viability as measured by Trypan Blue exclusion on colony formation in a human tumor cloning system. Overall, there was no significant correlation between Trypan Blue exclusion-determined viability and colony formation in soft agar for these specimens (p= 0.43). This lack of significant correlation was maintained for primary, metastatic, solid, and fluid tumor specimens. These data suggest that, in this soft agar system, specimens containing cells with low Trypan Blue exclusion viability should not be excluded from testing, and that it may not be advantageous to plate on the basis of "viable cells" as measured by Trypan Blue exclusion.

ISSN:0732-9482    

DOI:10.1089/cdd.1984.1.95

年代:1984

数据来源: MAL

摘要:

4'-(9-Acridinylamino)-methanesulfon-m-anisidide (m-AMSA) is an acridine compound that has been found useful in the systemic treatment of acute leukemia. This paper specifically investigates the CSF pharmacokinetics of m-AMSA following both intravenous and intraventricular administration in a subhuman primate model. Following intravenous administration, m-AMSA crossed the blood-brain barrier poorly; cerebrospinal fluid (CSF) concentrations were only 1-3% of systemic concentrations. Intraventricular administration of drug achieved high initial ventricular fluid concentrations, but the drug was rapidly cleared with a half-life of 115 min. Following 500 μg of intraventricular drug, CSF concentrations of m-AMSA remained above 1 μMfor only 6 h. These data suggest that m-AMSA has potential as an intrathecal agent against meningeal leukemia refractory to more conventional therapy, but detailed toxicology and neurohistopathology will be required before intra-CSF m-AMSA can be considered for human us

ISSN:0732-9482    

DOI:10.1089/cdd.1984.1.101

年代:1984

数据来源: MAL

摘要:

The drug-release properties of large unilamellar liposomes were measured at temperatures near the lipid's phase-transition temperature. The liposomes were formed from a mixture of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylglycerol (4:1 by weight) by the reverse-phase evaporation process. These liposomes captured 25-35% of the radiolabeled anticancer drug cytosine [3H]-1-β-arabinofuranoside in their aqueous compartment. They were stable in serum below the lipid's phase-transition temperature of 41°C. Complete drug release occurred within seconds after the liposomes reached a temperature of 43°C in serum. Addition of cholesterol or phosphatidylglycerol to the liposomal membrane reduced the drug-release temperature and broadened the range of drug release. These results show that suspensions of large unilamellar liposomes can be made to encapsulate a therapeutically useful quantity of drug that is rapidly and completely released at 43°C in se

ISSN:0732-9482    

DOI:10.1089/cdd.1984.1.109

年代:1984

数据来源: MAL

摘要:

A technique for insuring the controlled release of small amounts of macromolecules such as polypeptides from polymeric delivery systems is described. We show that incorporation of albumin in milligram quantities into these delivery systems can facilitate the sustained release of nanogram or microgram quantities of a model macromolecule such as inulin. The albumin-containing controlled-release polymers did not cause inflammation or tissue damage in two commonly used assay sites for certain biological growth factors such as tumor angiogenesis stimulators and inhibitors—the chick chorioallantoic membrane (CAM) and the rabbit cornea. The method reported here should be particularly suited to the delivery of purified growth factors which are active and usually obtainable in microgram or smaller amount

ISSN:0732-9482    

DOI:10.1089/cdd.1984.1.119

年代:1984

数据来源: MAL

摘要:

Monoclonal antibodies (MAb) and their F(ab')2fragments to human colorectal carcinoma (CRC) and human melanoma-associated antigens were conjugated to diethylenetriaminepentaacetic acid (DTPA) via an acylation reaction using cyclic DTPA dianhydride. Relative immunoreactivity of the F(ab')2fragments was as high as 70% when an average of only 0.7 DTPA molecules was conjugated per fragment, decreasing rapidly to less than 5% when 9.0 DTPA molecules were conjugated. The111In-labeled whole MAb in mice bearing human tumor xenografts showed higher concentrations in tumor, liver, kidney, and spleen 7 days after injection of MAb when compared with the same MAb labeled with131I. F(ab')2labeled with111In showed a marked persistence in the tumor-bearing mice with higher concentrations in all organs except blood, when compared with131I-labeled F(ab')2. Radioactivity was particularly high in the kidneys. Although images of human tumor xenografts were easily visualized using111I-labeled F(ab')23 days after injection, it was difficult to visualize tumor grafts with111In-labeled F(ab')2due to persistently high renal, liver, and background activity. Increased catabolism of the131I-labeled MAb may be the cause of the difference; but antibodies with high immunological activity are a necessity forin vivoimaging studies before firm conclusions can be drawn.

ISSN:0732-9482    

DOI:10.1089/cdd.1984.1.125

年代:1984

数据来源: MAL

ISSN:0732-9482    

DOI:10.1089/cdd.1984.1.137

年代:1984

数据来源: MAL

摘要:

The therapeutic advantage of intraarterial infusion chemotherapy depends upon delivery of a high drug concentration to the entire tumor bulk with maximum sparing of critical normal tissues. It is clear that successful application of regional therapy must include methodology to assess quantitatively and qualitatively the infused area.99mTc macroaggregated albumin (Tc-MAA) injected intraarterially is held on first pass in the arteriolar capillary bed, thus providing a map of blood flow distribution. Analog and digital planar images and single photon emission computed tomography (SPECT) after Tc-MAA injections provide static and transaxial tomographic images of head and neck intraarterial infusions. SPECT can be viewed as an endless movie-type display, thus producing a "rotating cimematic display." These radionuclide localization techniques provide a three-dimensional delineation of the tissues infused, including subsurface details not appreciated with dye injection alone. These procedures should be considered an integral part of intraarterial therapy of head and neck cancer.

ISSN:0732-9482    

DOI:10.1089/cdd.1984.1.145

年代:1984

数据来源: MAL

摘要:

This article summarizes studies conducted in children with acute lymphoblastic leukemia (ALL) who received intrathecal methotrexate (IT MTX) to prevent or treat central nervous system (CNS) leukemia.(1-7)To better understand the pharmacologic requirements of intrathecal chemotherapy directed against CNS leukemia, this report begins with a review of the pathophysiology of CNS leukemia and the clinical aspects of this disease manifestation that influence IT MTX therapy. The pharmacokinetics of IT MTX are then presented and the review is concluded with observations on the importance of the dosage regimen.

ISSN:0732-9482    

DOI:10.1089/cdd.1984.1.157

年代:1984

数据来源: MAL

摘要:

This is a review of implantable devices for chronic access and drug delivery to the central nervous system (CNS) via the cerebrospinal fluid, extracellular fluid, and vascular pathways. The current applications of such devices in the management of mycotic meningitis, meningeal leukemia and carcinomatosis, solid malignant tumors of the CNS, intractable cancer-associated pain, unresectable cystic tumors and in cytologic, pharmacologic, and experimental studies on the cerebrospinal fluid (CSF) are assessed. Specific attention is paid to the applications of the most commonly used device, a subcutaneous reservoir and pump (SRP), including its major uses and complications. A new system for local chemotherapy of malignant gliomas, the tumor cyst device (TCD), is also described.

ISSN:0732-9482    

DOI:10.1089/cdd.1984.1.169

年代:1984

数据来源: MAL