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R K Chiou

Publications and source records attributed to R K Chiou.

46 records · Page 3Linked to original sources

Comparison of fresh tissue incubation assay and the in vivo localization of monoclonal antibodies to renal cell carcinoma.

Few in vitro tests currently available are able to accurately predict the in vivo localization of monoclonal antibodies (Mabs) to cancer. We report on a fresh tissue incubation assay (FTIA) and compare the results of this assay to the in vivo localization of renal cell carcinoma (RCC)-reactive Mab A6H and control Mab AFP-22 to RCC and non-RCC xenografts implanted in nude mice. Both the FTIA and in vivo localization study demonstrated highly selective uptake of A6H in RCC but not in non-RCC xenografts. Radioimmunoscintigraphy using A6H clearly visualized RCC xenografts in every attempt, while AFP-22 did not highlight any of the tumor xenografts. The results demonstrate that FTIA may be a useful in vitro assay for selecting Mabs for in vivo application, and that radioimmunoscintigraphy is a potentially useful tool in detecting cancer sites.

Animals↗

Radioimmunoscintigraphy and radioimmunotherapy of renal cell carcinoma xenografts.

From a panel of monoclonal antibodies (MAb) reactive with human renal cell carcinoma generated by this laboratory, three (designated A6H, C5H, and D5D) were selected for in vivo studies with a nude mouse xenograft model. These studies included 131I- and 111In-labeled MAb radioimmunoscintigraphy and 131I-labeled MAb radioimmunotherapy. In the imaging studies, these radiolabeled MAb allowed visualization of subcutaneous xenografts larger than 40 mg and subrenal capsule xenografts smaller than 20 mg. Comparisons of tumor to non-tumor tissue radiolabel distribution yielded unusually high ratios and depended on the MAb-xenograft combination. The 111In-radiolabeled A6H showed increased accumulation in the liver compared with 131I-A6H, but this still did not necessitate background subtraction for good visualization of small, subrenal capsule renal cell carcinoma xenografts. Radioimmunotherapy studies with 131I-A6H in BALB/c nu/nu mice bearing established renal cell carcinoma xenografts showed a prolonged (greater than 90 days) regression in tumor burden and possible "cures," whereas three sets of control mice showed progressive and rapid increases in tumor size. These studies indicated that MAb, which show good tissue biodistribution and high imaging sensitivity, could also be capable of delivering effective radiotherapy to the tumor when "human equivalent" radiolabeled-MAb doses are used.

Animals↗

Endoscopic treatment of complete urethral obstruction using thin trocar.

We used an endoscopic thin trocar to reestablish the continuity of the completely obliterated urethra in 2 patients. In 1 man the obstruction resulted from a pelvic fracture and in 1 woman from early removal of the urethral catheter after a bladder neck reconstruction. We found this technique safe and effective, and we consider it to represent an improvement over previously described methods of endoscopic treatment of the obliterated urethra.

Adult↗

Localization of human renal cell carcinoma xenografts with a tumor-preferential monoclonal antibody.

We previously described an immunoglobulin G1 monoclonal antibody (UMVA-RCC-A6H) that is highly reactive with human renal cell carcinoma (RCC) and has little cross-reactivity to other cell types both normal and malignant. In efforts detailed herein, radiolabeled A6H selectively localized to RCC xenografts and provided high resolution images of the xenografts. Also, A6H clearly discriminated between RCC xenografts and other human tumor xenografts. Consistent images of RCC xenografts (greater than 60 mg) were obtained without background subtraction. The amount of radiolabeled A6H in the tumor usually ranged from five to twenty times that of the blood. Normal mouse tissues, abscesses, and other human tumor xenografts contained less radiolabel per mg than did blood. A control monoclonal antibody of the same isotype failed to exhibit any localization in xenografts or normal tissues. Approximately 40% of the radiolabeled A6H dose per g was localized in the RCC xenograft 2 days after injection, although at the time of imaging about 60% of the radiolabel remaining in the mouse was associated with the xenograft. These results demonstrate that a RCC restrictive monoclonal antibody does specifically localize to RCC xenografts and supports the hope that this approach may have clinical value for diagnosis, staging, or treatment.

Animals↗

Monoclonal antibodies to human renal cell carcinoma: recognition of shared and restricted tissue antigens.

Monoclonal antibodies (MABs) reactive with human renal cell carcinoma (RCC) were generated following immunization of mice with either RCC homogenates, RCC cell lines, or fetal kidney homogenates. The characteristics of four highly reactive immunoglobulin G1 MABs, designated UMVA-RCC-A6H, UMVA-RCC-A36, UMVA-RCC-C5H and UMVA-RCC-D5D are presented. The screening process consisted of a cell binding enzyme-linked immunosorbent assay and immunohistological examination of tumor, normal, and fetal tissue sections. The MABs illustrated various degrees of antigen restriction: A6H identified an antigen common to RCC, some lung and colon carcinomas, the proximal renal tubules but no other normal tissues; A36 reacted with most human tumors, the renal tubules, and many other normal tissues; C5H reacted with nearly every human cancer but of the normal tissues, only the renal glomerulus shared this antigen; D5D was very restrictive, reacting with many although not all RCC and no other cancers or normal tissues with the exception of an occasional reactivity with a Bowman's capsule. Metastatic RCC and RCC xenografts expressed these antigens. None of the MABs participated in complement-mediated cytotoxicity. In immunoprecipitation studies with L-[methyl-3H]methionine and [3H]glucosamine-HCl metabolically labeled RCC cells, C5H was shown to be associated with an antigen of Mr 115,000.

Animals↗

Monoclonal antibodies in human renal cell carcinoma and their use in radioimmune localization and therapy of tumor xenografts.

A series of monoclonal antibodies (Mabs) to human renal cell carcinoma (RCC) material was developed. Two Mabs (D5D and A6H) that showed especially restrictive reactivities were radiolabeled with iodine 131 and tested in nude mice bearing human tumor xenografts for their ability to specifically localize RCC. Extensive studies of tissue radioactive uptake indicated that these Mabs could specifically localize RCC tumors with some mice achieving high tumor:blood ratios ranging from 15 to 60. Scintigraphic scanning revealed specific and consistent detection of RCC xenografts. Finally, preliminary results indicate that larger intravenous doses of radiolabeled RCC Mabs were effective as radioimmune therapy in inhibiting RCC xenograft growth. Mabs can be produced that are highly restrictive to human RCC and may be useful clinically for radioimmunoscintigraphy or therapy.

Animals↗

Endoscopic re-establishment of urethral continuity after traumatic disruption of the membranous urethra.

We report 3 cases of complete traumatic disruption of the membranous urethra treated by transurethral section of the scar tissue with transvesical endoscopic guidance and digital rectal control. Postoperatively, the patients required an average of 3 subsequent urethrotomies. They remain well, continent and free of voiding symptoms for 28, 11 and 14 months after re-establishment of urethral continuity. We suggest that this treatment be considered as an alternative to conventional surgical repair, particularly in elderly and other high risk patients.

Adult↗