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Biomedical subjects

W F Whitmore

Publications and source records attributed to W F Whitmore.

At least 145 records · Page 8Linked to original sources

Cell surface antigens of human bladder cancer defined by mouse monoclonal antibodies.

Mouse monoclonal antibodies were obtained by immunization with cultured human bladder cancer or lysates of bladder papilloma. They identify 11 distinct antigenic systems as defined by serological analysis of cultured cells and studies of antigen distribution in normal and neoplastic tissues. The most restricted of these antigens, Om5, defines a subset of bladder tumors. Om5 is not detected in normal bladder urothelium or in any other normal or malignant tissue. T101 and JP165 are also subset markers for bladder cancer that are not detected in normal tissues. T16, T43, T87, and J143 (antigens represented on many cultured cells) are found in specific areas of the normal urinary tract and in a distinctive range of other normal and malignant cell types--e.g., T16 expression in pluristratified epithelium of skin, exocervix, and esophagus. T138 antigen is also a common feature of cultured cell lines, but its expression in sections of normal tissues is restricted to endothelial cells. In contrast, T110 is poorly represented on cultured cells but can be detected in culture supernatants. Localization of T110 in normal tissues showed that it is a component of the extracellular matrix. All determinants detected by this series of antibodies are heat labile and not related to A, B, H, I, Lewis blood group antigens. Six of the antibodies immunoprecipitated glycoproteins from radiolabeled cell lysates: AbT16 (Mrs 48,000 and 42,000), AbT87 (Mr 60,000), AbT43 (Mr 85,000), AbJ143 (Mr 140,000, 120,000, 60,000), AbT43 (Mr 85,000), AbJ143 (Mr 140,000, 120,000, and 30,000), and AbT110 (Mr 240,000).

Antibodies, Monoclonal↗

VP-16-213 and cisplatin in the treatment of patients with refractory germ cell tumors.

Twenty-two patients with progressive or relapsing germ cell tumors and one patient without prior treatment received VP-16-213 (etoposide) 100 mg/m2 on days 1-5 and cisplatin 20 mg/m2 days 1-5 every 4 weeks. Three complete remissions and one partial remission were seen in five patients who previously achieved a complete remission to a cisplatin-based regimen. A partial remission was observed in a previously untreated patient with widely metastatic extragonadal choriocarcinoma. No complete remissions and two partial remissions were seen in 14 patients who did not achieve a previous complete remission to cisplatin-based combination chemotherapy. Four patients remain free of disease, including one complete responder and three patients treated after resection of a solitary recurrence. Myelosuppression was universal and two very heavily pretreated patients died with leukopenia and presumed infection. VP-16-213 plus cisplatin may be an effective salvage regimen for patients relapsing after a complete remission, but is probably ineffective if the patient has not achieved a prior complete remission.

Adult↗

Immunoanatomic dissection of the human urinary tract by monoclonal antibodies.

The immunoanatomy of the human kidney and urinary tract has been analyzed by a panel of mouse anti-human monoclonal antibodies that define specific domains and structures. The differentiation antigens detected by these monoclonal antibodies represent a series of glycoproteins characteristic of different cell types. They differ from the blood group antigens and appear to be distinct from other antigens previously described within the kidney or urinary tract. The antigens recognized by these monoclonal antibodies represent an immunohistologic dissection of the human nephron. These antibodies have a broad range of potential applications in studying embryogenesis and pathogenesis of nonneoplastic and neoplastic diseases of the human kidney and urothelium.

Antibodies, Monoclonal↗

Orchiectomy alone in the treatment of clinical stage I nonseminomatous germ cell tumor of the testis.

Forty-five patients with clinical stage I nonseminomatous germ cell tumor of the testis (NSGCTT) were entered in a prospective clinical trial to receive no treatment other than orchiectomy until clinical evidence of relapse. Of this group, 36 patients (80%) have been continuously free of disease for a median duration of 19.5 months after orchiectomy. Nine patients (20%) have relapsed, eight within seven months of orchiectomy. Seven of nine relapsing patients have been rendered free of disease with chemotherapy and/or surgery for a median duration of seven months (range, one to 33 months) after completion of treatment; the other two patients are presently under treatment although one has progressive disease. The relapse rate was higher in patients with embryonal carcinoma than in those with teratocarcinoma, 57% versus 17%. These preliminary results imply that the omission of routine lymphadenectomy or lymph-node irradiation in clinical stage I NSGCTT deserves further trial.

Adolescent↗

The treatment of extragonadal seminoma.

Primary extragonadal seminoma (EGS) is a rare tumor of young adults that often presents with bulky primary tumors and metastatic disease. Long-term survival is inadequate with conventional therapy consisting of radiotherapy with or without surgery. The charts of 21 patients with EGS treated initially either with conventional therapy (group I) or with multimodality therapy including initial chemotherapy with high doses of cisplatin followed by either radiotherapy or surgery or both (group II) were reviewed. Five of the ten patients in group I developed recurrent disease and four of them eventually died of disease. Only one of 11 patients in group II died of metastatic disease and the remaining patients are free of disease with 19+ to 46+ months of follow-up. Of the six patients from group II who underwent surgical resection of apparently residual disease after chemotherapy but prior to radiotherapy, five were found to have completely necrotic tumor and one had microscopic disease on histologic examination, proving the efficacy of chemotherapy. Combined modality therapy including initial chemotherapy containing high doses of cisplatin provided rapid reduction in tumor burden and the results appeared superior to treatment that did not include initial chemotherapy.

Adult↗

RNA and DNA content of isolated nuclei from bladder irrigation specimens as measured by flow cytometry.

Cell nuclei were isolated from bladder irrigation specimens from urologic patients having neoplastic disease and distinct aneuploid tumor populations with ploidy levels greater than 2. 0c . The isolated nuclei were subsequently stained with acridine orange, and their fluorescence was measured by flow cytometry. The RNA-DNA frequency distributions of nuclei were compared to those of whole, intact cells from the identical specimens. A comparison of RNA content revealed distinct subpopulations of aneuploid G1 tumor cells with different RNA content. The low and high RNA subpopulations were present in both whole cells and intact nuclei. The overall profile regarding ploidy levels of tumors as well as cell cycle distributions were comparable in both whole cells and nuclei. The resolution of DNA content, however, was significantly better in nuclei preparations. This fact made it easier to distinguish aneuploid cells with near-diploid values of DNA content.

Aneuploidy↗

Natural history and staging of prostate cancer.

The natural history and staging of prostatic cancer, directly or indirectly, involve natural expectancy of the host, malignant potential of the tumor, extent of the tumor, and response of the tumor to treatment. Discussion of these topics is followed by a description of the systems of clinical staging of the disease.

Aged↗

Status of integrated irradiation and cystectomy for bladder cancer.

The rationale and representative results of integrated irradiation and cystectomy for bladder cancer are reviewed and an hypothesis regarding the mechanism and benefits of such treatment formulated. The basis for uncertainty regarding the value of preoperative irradiation is outlined and a perspective on the resolution of this uncertainty provided.

Combined Modality Therapy↗

Some effects of inhibitors of polyamine synthesis on experimental prostatic cancer.

Difluoromethylornithine (DFMO) and methylglyoxal-bis(guanyl-hydrazone) (MGBG), inhibitors of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AMDC), respectively, were tested in two experimental prostatic cancer models. DFMO resulted in a reduction in tumor size in both the rapidly growing R-3327 rat prostatic adenocarcinoma (30.5 +/- 15 versus 61 +/- 9.5 in control animals) and the human DU-145 adenocarcinomas (1.7 ml versus 3.3 ml in control animals) in nude mice. MGBG was tested only in the rat tumor, where it induced a reduction of 22.9 +/- 9.5 ml versus 61 +/- 9.5 in control animals in tumor size but was highly toxic. Flutamide or 9-B-D-arabinofuranosyladenine (Ara-A) proved ineffective per se in reducing tumor growth of the human DU-145 or of the R-3327-G strain, respectively, but increased the efficacy of DFMO against the DU-145 tumor had a high level of ODC which was reduced by DFMO of by Ara-A; the R-3327 tumor had a low level of ODC which was too low to be decreased by DFMO.

Adenine↗

Effects of alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) on the growth of experimental renal adenocarcinoma in mice.

alpha-Difluoromethylornithine (DFMO) and methylglyoxal bis-(guanylhydrazone) (MGBG) were tested against a murine renal adenocarcinoma, because polyamines are necessary for neoplastic cell growth and because human renal adenocarcinomas contain higher levels of spermidine than do normal renal cells; MGBG inhibits spermidine synthesis and has some activity against human renal tumors; DFMO irreversibly inhibits ornithine decarboxylase, the first rate-limiting enzyme controlling polyamine biosynthesis; and DFMO promotes intracellular accumulation of MGBG in experimental tumor models and human leukemia. DFMO (2%) in drinking water, MGBG (15 mg/kg i.p.), or a combination of DFMO and MGBG was administered daily to BALB/c mice (n = 80) with intrarenal transplants of renal adenocarcinoma cells. At 28 days, renal carcinomas weighed 64 and 73% less, respectively, in DFMO- and DFMO-MGBG-treated mice than in control animals (p less than 0.01). MGBG alone had no antigrowth effect. DFMO-MGBG reduced the total metastatic index (total number of metastases/total number of animals) to 1.2 versus 3.6 in control animals (p less than 0.01) and increased survival by 12.3 +/- 1.5 (S.E.) days, from 30.8 to 42.5 days (p less than 0.05). Compared with control, DFMO-, or MGBG-treated animals, DFMO-MGBG exposure reduced tumor growth and the number of metastases, prevented metastases in some animals (47%), and increased survival of mice bearing renal adenocarcinomas. DFMO also appeared to selectively increase the uptake of [14C]MGBG by tumor tissue, which may help to explain the enhanced synergistic antigrowth effect of DFMO and MGBG against this murine renal adenocarcinoma.

Adenocarcinoma↗

A technique of ilioinguinal lymph node dissection for carcinoma of the penis.

A technique has been described for ilioinguinal lymph node dissection that provides good exposure for both the pelvic and inguinal dissections and circumvents the anatomic barrier presented by the inguinal ligament. It also enables one to evaluate the pelvic lymph nodes unilaterally or bilaterally prior to the inguinofemoral dissection if one elects to do so. A limited experience demonstrates the practical feasibility of this procedure. Although the results with this technique compare favorably with those of other techniques, experience is too small to permit categoric assessment of its relative advantages and disadvantages.

Adult↗