The hepatic stem cell niche: identification by label-retaining cell assay.

Unlabelled: Label retention assays remain the state-of-the-art approach to identify the location of intraorgan epithelial stem cell niches, in situ and in vivo. They are commonly used in organs with rapid cell turnover but have not been applied to the liver, where cell turnover is very slow. We used a sublethal dose of acetaminophen administered coincident with bromodeoxyuridine to load possible hepatic stem cells in mice with label and then administered a second, sublethal chase of acetaminophen to accomplish "washout" of label from transit amplifying cell populations.

Radioimmunotherapy for model B cell malignancies using 90Y-labeled anti-CD19 and anti-CD20 monoclonal antibodies.

In recent years, radioimmunotherapy (RIT) with beta(-) particle emitting radionuclides targeting the CD20 antigen on B cells in the treatment of non-Hodgkin's lymphoma has provided the most compelling human clinical data for the success of RIT. CD19, like CD20, is an antigen expressed on the surface of cells of the B lineage, and CD19 may provide an alternative target for radioimmunotherapy of B cell neoplasms. CD19 has been largely overlooked as a target for conventional 131I RIT, because the antigen rapidly internalizes upon binding of antibody, resulting in catabolism and significant release of 131I.

Relative therapeutic efficacy of (125)I- and (131)I-labeled monoclonal antibody A33 in a human colon cancer xenograft.

Unlabelled: A33, a monoclonal antibody that targets colon carcinomas, was labeled with (125)I or (131)I and the relative therapeutic efficacy of the 2 radiolabeled species was compared in a human colon cancer xenograft system.

Methods: Nude mice bearing human SW1222 colon carcinoma xenografts were administered escalating activities of (125)I-A33 (9.25-148 MBq) or (131)I-A33 (0.

An alpha-particle emitting antibody ([213Bi]J591) for radioimmunotherapy of prostate cancer.

A novel alpha-particle emitting monoclonal antibody construct targeting the external domain of prostate-specific membrane antigen (PSMA) was prepared and evaluated in vitro and in vivo. The chelating agent, N-[2-amino-3-(p-isothiocyanatophen-yl)propyl]-trans-cyclohexane-1, 2-diamine-N,N',N',N'',N''-pentaacetic acid, was appended to J591 monoclonal antibody to stably bind the 213Bi radiometal ion. Bismuth-213 is a short-lived (t 1/2 = 46 min) radionuclide that emits high energy alpha-particles with an effective range of 0.

131I radioimmunotherapy and fractionated external beam radiotherapy: comparative effectiveness in a human tumor xenograft.

Unlabelled: This article compares the effectiveness of radiation delivered by a radiolabeled monoclonal antibody, 131I-labeled A33, that targets colorectal carcinoma, with that of 10 fractions of conventional 320 kVp x-rays.

Methods: Human colorectal cancer xenografts (SW1222) ranging between 0.14 and 0.

Rapid and specific targeting of monoclonal antibody A33 to a colon cancer xenograft in nude mice.

Monoclonal antibody (mAb) A33 detects a glycoprotein homogeneously expressed by > 95% of human colon cancers and by normal colon cells. The A33 antigen is not secreted or shed and after mAb A33 binds to antigen on the cell membrane, a fraction of membrane-bound mAb A33 is internalized into endosomes. Phase I 131I-mAb A33 biodistribution studies have shown consistent, specific tumor-targeting, and phase I radioimmunotherapy trials with 131I- or 125I-mAb A33 have demonstrated antitumor effects.

Enhanced antitumor activity of combination radioimmunotherapy (131I-labeled monoclonal antibody A33) with chemotherapy (fluorouracil).

Monoclonal antibody (mAb) A33 reacts with an antigen expressed by >95% of colon cancer and normal colon epithelial cells. An earlier Phase I trial of 131I-labeled mAb A33 (131I-mAb A33) demonstrated bone marrow suppression as the dose-limiting toxicity, and although modest antitumor effects were seen, no normal colon toxicity was observed. In this study, a nude mouse model was used to test whether combinations of low-dose 131I-mAb A33 (0.

Enhancement of radiation dose to the nucleus by vesicular internalization of iodine-125-labeled A33 monoclonal antibody.

Unlabelled: In radioimmunotherapy, the emission characteristics of the radioisotope is critical in determining the radiation dose to the tumor compared to normal organs. If antibodies internalize and transport low-energy electron emitting isotopes close to the tumor cell nucleus, an improved therapeutic advantage is achieved.

Methods: Using fluorescent microscopy, we studied the subcellular distribution of an internalizing antibody, A33, which detects a restricted determinant on colon cancer cells.

Right ventricle wall motion abnormalities in patients treated with chemotherapy.

Doxorubicin is a cytotoxic agent used in the treatment of patients with various malignancies. Its clinical value is limited by a dose-related cardiotoxicity. Wall motion was analyzed in 52 patients during different stages of treatment.

Which factors influence age at onset and rate of progression in Huntington's disease?

Fifty-one families of patients affected with Huntington's chorea were interviewed with respect to age at onset, symptoms at onset and course of the disease. The interview further comprised questions pertinent to line of transmission, socio-economic status, housing, previous illnesses and pregnancy and stillbirth. Since the study was set up as a fishing expedition detailed quantitative information was gathered on many life-style factors including eating, drinking and smoking habits.

Jaw, blink and corneal reflex latencies in multiple sclerosis.

Jaw, blink and corneal reflexes, which all involve the trigeminal system, were recorded in 54 patients with multiple sclerosis; thirty-seven of these patients were classified as having definite multiple sclerosis and 17 as indefinite multiple sclerosis, according to Schumacher's criteria. The jaw reflex was abnormal less frequently than either of the other two reflexes, but in four cases it was the only abnormal reflex found. Testing a combination of two or three trigeminal reflexes did not yield a higher incidence of abnormalities than testing the blink or corneal reflex alone.