Preclinical analysis of radiolabeled anti-GD2 immunoglobulin G.

Background: Unlabeled murine monoclonal anti-GD2 immunoglobulin (Ig)G (14G2a) reactive with nervous system diganglioside and neuroblastoma, melanoma, and small cell lung carcinoma produces tumor regression. However, serious acute abdominal pain, paresthesia, hypotension and hypertension, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and occasional motor weakness occur. Studies in preclinical animal models can elucidate the mechanism of the observed neurotoxicity and lead to anti-GD2 antibody treatment with a higher therapeutic ratio.

Intralesional radiolabeled human monoclonal IgM in human tumor xenografts.

Background And Purpose: Intralesional (i.l.) administration of radiolabeled human monoclonal IgM could provide a new method for increasing the radiation dose delivered to a tumor without exceeding normal tissue tolerance.

Deprenyl stimulates the release of luteinizing hormone from the pituitary in vitro.

The direct effects of deprenyl on the pituitary were investigated by measuring the release of luteinizing hormone (LH) from the pituitary glands of male Sprague-Dawley rats in vitro. Basal release of LH was determined by incubating the pituitaries in Krebs-Ringer Henseleit (KRH) solution with 0, 0.1, 1, or 10 mM of deprenyl for 1 h.

Chronic hyperprolactinemia and changes in dopamine neurons.

The tuberoinfundibular dopaminergic (TIDA) system is known to inhibit prolactin (PRL) secretion. In young animals this system responds to acute elevations in serum PRL by increasing its activity. However, this responsiveness is lost in aging rats with chronically high serum PRL levels.

Tyrosine hydroxylase and DOPA decarboxylase activities in the medical preoptic area and arcuate nucleus during the estrous cycle: effects of aging.

HPLC and Palkovits' microdissection technique were used to measure activities of two catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH) and dopa decarboxylase (DD), in the medial preoptic area (MPA) and arcuate nucleus (AN), both of which are involved in LH regulation. The measurements were made during an 8-h period at 1200, 1400, 1600, 1800, and 2000 h on the days of proestrus and diestrus in young (4-5-month-old) rats. Similar measurements were made at 1400, 1600, 1800, and 2000 h in middle-aged (8-10-month-old) proestrous rats and in 18-22-month-old persistently diestrous rats.

Proposal for translational analysis and development of clinical radiolabeled immunoglobulin therapy.

Background And Purpose: Radiolabeled immunoglobulin therapy (RIT) can be a selective, effective, low-toxicity outpatient cancer therapy. A consensus on the best approach for the preclinical and clinical development of RIT reagents needs to be developed. We report the M.

Carpal tunnel syndrome: which electrodiagnostic path should we follow? A prospective study of 100 consecutive patients.

We prospectively studied 100 consecutive patients (200 hands) sent to our Neurophysiopathology Service for a suspected Carpal Tunnel Syndrome (C.T.S.

Maleimido derivatives of diethylenetriaminepentaacetic acid and triethylenetetraaminehexaacetic acid: their synthesis and potential for specific conjugation with biomolecules.

Immunoconjugates sometimes suffer changes in immunoreactivity and tumor targeting because the chelators used interfere with antigen binding. To try to circumvent such problems, two new homobifunctional chelating agents, 2,6-bis[p-[(beta-maleimidopropionyl) amino]benzyl]diethylenetriamine- N,N,N',N",N"-pentaacetic acid (MPBz-DTPA) and 2,9-bis [p-(beta-maleimidopropionyl)amino]benzyl] triethylenetetraamine-N,N,N',N',N",N"-hexaacetic acid (MPBz-TTHA), were synthesized for chelation of 111In and 90Y metal ions. Each of the new chelators contains two maleimido functional groups substituted at the carbon backbone.

Intraperitoneal indium-111- and yttrium-90-labeled human IgM (AC6C3-2B12) in nude mice bearing peritoneal carcinomatosis.

Unlabelled: Radiolabeled monoclonal antibodies are utilized increasingly for the diagnosis and treatment of human cancer. Tumor targeting of radiolabeled human monoclonal IgM improves with compartmental administration and might be useful for the diagnosis or treatment of peritoneal carcinomatosis.

Methods: A human monoclonal antibody IgM lambda (AC6C3-B12) reactive with human adenocarcinomas was conjugated to isothiocyanato-2-benzyl-3-methyl-diethylenetriamine-penta-a cetic acid and labeled with either 111In or 90Y.

Hematologic side effects of radiolabeled immunoglobulin therapy.

Radiolabeled immunoglobulin therapy (RIT) is a new cancer treatment that is more selective than its predecessors. Its dose-limiting normal tissue side effect is bone marrow toxicity, and hematopoietic stem cell damage appears to be its most significant mechanism. Platelet consumption in irradiated normal liver tissues and apoptosis of circulating peripheral blood lymphocytes are other, less important, hematologic side effects.

Synthesis, biodistribution, and estrogen receptor scintigraphy of indium-111-diethylenetriaminepentaacetic acid-tamoxifen analogue.

This study was aimed at developing a hydrophilic diethylenetriaminepentaacetic acid-tamoxifen (DTPA-Tam) analogue for use in imaging estrogen receptor positive (ER+) lesions. In rat uterine cytosol, the IC50 of DTPA-Tam conjugate was 1 microM and of tamoxifen, 2 microM. Biodistribution, autoradiography, and radionuclide imaging of 111In-DTPA-Tam in breast-tumor-bearing rats showed that tumor-to-tissue ratios increased steadily between 30 min and 48 h.

HSP70-1 promoter region alleles and susceptibility to rheumatoid arthritis.

The distribution of HSP70-1 promoter alleles was studied in 90 adult Caucasian RA patients (65 European and 25 Asian Indian) and 113 normal control (60 European and 53 Asian Indian). The HSP70-1 promoter alleles were defined by oligonucleotide typing of polymerase chain (PCR)-amplified genomic DNA. The prevalence of HSP70-1 promoter allele "B" was significantly (p < 0.

Review of five consecutive studies of radiolabeled immunoglobulin therapy in Hodgkin's disease.

Recurrent Hodgkin's Disease (HD) provides unique opportunities to improve radiolabeled immunoglobulin therapy (RIT). Normal tissue toxicity after RIT is limited to bone marrow damage and is well documented and quantified in HD patients. Anti-antibody formation is rare in patients with HD, allowing for multiple RIT cycles.

Preclinical analysis of intraperitoneal administration of 111In-labeled human tumor reactive monoclonal IgM AC6C3-2B12.

An IgM lambda human tumor cell-reactive monoclonal antibody was developed that reacts with cells of ovarian cancer, colorectal cancer, breast cancer, and certain other malignancies. The monoclonal antibody AC6C3-2B12, which was obtained from a recent recloning, was purified from tissue culture supernatants and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-PAGE. An animal model was developed in which human tumors grew either as solid peritoneal metastases or as s.

Results of a study to correlate serum prostate specific antigen and reproductive hormone levels in patients with localized prostate cancer.

This cross-sectional study was undertaken to determine whether serum hormones (free testosterone, androstenedione, luteinizing hormone, or prolactin) have any influence on serum prostate specific antigen (PSA) levels in patients with stage A-C prostate cancer. Blood samples were collected prior to any treatment in 36 patients; in 19 (group 1), three blood samples were collected 10 minutes apart between 9:00 AM and 9:30 AM for each patient and pooled together to avoid diurnal and episodic variation in serum testosterone values. In the remaining patients, only one sample could be collected (group 2).

Survival of patients with resistant Hodgkin's disease after polyclonal yttrium 90-labeled antiferritin treatment.

Purpose: A follow-up study was initiated of patients with Hodgkin's disease who were treated with yttrium 90-labeled antiferritin. Prescription method, pharmacokinetics, acute and late side effects, and survival were evaluated.

Methods: Patients had measurable disease and failed > or = two multiagent chemotherapy regimens previously (N = 44).

Cyclic changes in the release of norepinephrine and dopamine in the medial basal hypothalamus: effects of aging.

Push-pull perfusion and HPLC were used to measure the release of norepinephrine (NE) and dopamine (DA) in the medial basal hypothalamus of young (4-5 months old), middle-aged (8-10 months old), and old (22-24 months old) rats. In the young animals, the afternoon of proestrus was characterized by a gradual increase in NE release and a simultaneous gradual decrease in DA release. The peak in NE release and the nadir in DA release occurred at about the time when the proestrous surges in serum LH and PRL are known to occur.

Temporal (circadian) and functional relationship between prostate-specific antigen and testosterone in healthy men.

Objectives: To study the circadian relationship between serum prostate-specific antigen (PSA) and total testosterone in men without clinically evident prostate disease.

Methods: Blood samples were collected every 3 hours for 24 hours (eight per subject) from 11 clinically healthy men, ages 46 to 72 years. PSA was also monitored once a week for 6 weeks in 16 additional healthy men.

Tumor targeting and pharmacokinetics of unmodified and modified F(ab)2 fragments of an anti-CEA murine monoclonal antibody (Immu-14).

Pharmacokinetic studies were performed with two different 111In-labeled F(ab)2 fragments of an anti-CEA murine monoclonal immunoglobulin G (Immun-14). Unmodified F(ab)2 and modified Fab-BMH-Fab fragments were compared in nude mice bearing a LS-174T human colon carcinoma tumor xenograft. Tumor accumulation is significantly higher for modified fragments than for unmodified fragments at all time points.

Biodistribution and tumor localization of 111In-labeled unmodified and modified F(ab')2 fragments of human monoclonal IgM (16.88) in a nude mouse model.

Unmodified F(ab')2 and modified Fab'-BMH-Fab' fragments of human monoclonal IgM (16.88) were compared for biodistribution and tumor localization in nude mice bearing LS-174T human colon carcinoma xenografts. Although both unmodified and modified fragments of IgM cleared rapidly from the blood, the radioactivity retentions for each fragment in liver and kidney were significantly different.

Measurement of weekly prostate specific antigen levels in patients receiving pelvic radiotherapy for nonprostatic malignancies.

Purpose: To study the response of nonmalignant prostatic tissue to ionizing irradiation in terms of the resultant changes in serum prostate specific antigen (PSA) levels.

Methods And Materials: Weekly serum PSA values were determined during radiotherapy (RT) in nine patients ("treatment group") without clinical evidence of prostate cancer (PC), and who received pelvic RT for other indications. Slopes for the rate of change in PSA was determined using model: log PSA = beta 0 + beta 1*week + beta 2*week2 + error.

Liver toxicity induced by combined external-beam irradiation and radioimmunoglobulin therapy.

High-dose radiation therapy for liver metastases of gastrointestinal malignancies might be improved by combining external-beam irradiation and radioimmunoglobulin therapy. We studied the liver toxicity of the proposed combination in healthy beagle dogs. A total dose of 30 Gy to the whole liver, delivered in 2-Gy fractions over 3 weeks, resulted in mild, temporary veno-occlusive disease (VOD) in three of three dogs.

Deprenyl reinitiates estrous cycles, reduces serum prolactin, and decreases the incidence of mammary and pituitary tumors in old acyclic rats.

The purpose of this study was to investigate the effects of long term treatment with deprenyl, a monoamine oxidase-B inhibitor, on estrous cyclicity, serum PRL, incidence of mammary and pituitary tumors, and monoamine metabolism in the medial basal hypothalamus (MBH) and striatum (ST) of old female rats. Acyclic female Sprague-Dawley rats (15-16 months old) were treated sc with 0, 0.25, or 2.

Major histocompatibility-encoded human proteasome LMP2. Genomic organization and a new form of mRNA.

LMP2 is one of the two proteasome subunits encoded by genes in the major histocompatibility complex class II region. Here we report the genomic organization of human LMP2 gene. Sequence analysis of polymerase chain reaction-amplified cDNA from a number of lymphoblastoid cell lines demonstrated two forms of LMP2 mRNA, one (LMP2.