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Biomedical subjects

W F Whitmore

Publications and source records attributed to W F Whitmore.

At least 109 records · Page 6Linked to original sources
PubMed1986

Some aspects of clearance of mitoguazone in cancer patients and experimental cancer models.

Mitoguazone (methylglyoxal-bis(guanyl-hydrazone), MGBG) was studied by its first-pass mechanism in both cancer patients and experimental cancer models. It appears from the study that 90% of MGBG is cleared from the plasma within minutes. 24-h recovery in the urine, however, did not exceed 16% so that 84% of the drug seems to be bound to subcellular compartments. Tissue levels of MGBG in the normal prostate ranged higher than in experimental prostate cancer type 3327 M/G, i.e. enhanced clearance from cancer tissues: polyamine biosynthetic enzymes ornithine decarboxylase as well as S-adenosylmethionine decarboxylase are contrarily affected by MGBG.

Adenocarcinoma↗
PubMed1986

Cell surface antigens of human bladder tumors: definition of tumor subsets by monoclonal antibodies and correlation with growth characteristics.

Normal human urothelium and tumors of urothelial origin were analyzed with a panel of seven mouse monoclonal antibodies that identify surface antigens of cultured bladder cancer cell lines. Three categories of antigens were defined on the basis of differential expression on normal urothelium versus bladder tumors. Om5 (a category 1 antigen) is a highly restricted, differentiation antigen detected in the normal urothelium of 50-60% individuals. No other normal cell type in Om5- or Om5+ individuals expresses Om5. The incidence of Om5 expression in superficial bladder tumors is significantly higher (88%) than in normal urothelium, whereas its expression in invasive or metastatic tumors is far lower (20%), suggesting Om5 gain/loss in bladder tumors. Paired biopsies of normal urothelium and bladder tumors from the same individuals have shown Om5 induction in the superficial bladder tumors of Om5- individuals and Om5 loss in invasive bladder cancers of Om5+ individuals. Category 2 antigens (T43, T138, T23) are not expressed by normal urothelium or most superficial bladder tumors but are detected on a high proportion of invasive or metastatic bladder tumors, indicating that category 2 antigens are associated with late stages of tumor progression. Category 3 antigens (T16, T87, J143) provide lineage markers for normal or neoplastic cells of urothelial origin, being found on normal urothelium and virtually all bladder tumors. Thus, differential expression of category 1 and 2 antigens divide bladder tumors into distinct subsets, and these subsets correlate with pathological and clinical features of the disease.

Antibodies, Monoclonal↗
PubMed1985

The role of chemotherapy and surgery in the treatment of retroperitoneal metastases in advanced nonseminomatous testis cancer.

This study evaluates the effect of combination chemotherapy on retroperitoneal metastases from nonseminomatous germ cell tumors of the testis (NSGCTT). Sixty-six patients with Stage III or bulky Stage II NSGCTT with clinically documented retroperitoneal metastases first received systemic chemotherapy. Seventeen patients had minimal and 49 had advanced retroperitoneal metastases. The retroperitoneal metastases were classified as advanced if the patient had a palpable retroperitoneal mass, ureteral deviation on intravenous pyelogram, or a mass with a diameter greater than or equal to 5 cm documented by a computerized axial tomographic scan, a pedal lymphangiogram, or surgery. The patients with lesser but clinically evident retroperitoneal metastatic deposits were considered to have minimal retroperitoneal metastases. A complete remission of retroperitoneal metastatic deposits was achieved in 50 (76%) patients, with chemotherapy alone in 25 (38%), and with combined chemotherapy and surgery in 25 (38%). The resected deposits consisted of mature teratoma in 15 and malignant elements in 10. A complete remission using chemotherapy alone occurred in 13 of 17 (76%) with minimal and in 12/49 (24%) with advanced retroperitoneal metastases, and in 17/30 (57%) without and 8/36 (22%) with teratoma in the testis tumor. The data strongly implied that the bulk of the metastatic deposits was a more important prognostic variable than the histology of the primary tumor. The adverse relationship of a teratomatous differentiation on the response rates with chemotherapy alone was offset by the success of supplemental surgery. This study suggests the benefit of a postchemotherapy retroperitoneal lymph node dissection (RPLND) in patients with initially bulky retroperitoneal metastases (complete response [CR] increased from 24% to 67%; an additional 47% patients had no evidence of disease). The patients with minimal retroperitoneal metastases usually achieved a CR with chemotherapy alone. A routine RPLND after the chemotherapy is not indicated in patients with initially minimal retroperitoneal metastases.

Adult↗
PubMed1985

Endoscopic diagnosis and treatment of upper-tract urothelial tumors. A preliminary report.

The technique of transurethral ureteropyeloscopy allows many standard cystoscopic procedures to be extended into the upper urinary tract. This endoscopic method was used to evaluate 31 patients suspected to have urothelial malignancies of the ureter or renal pelvis. Twenty-eight of the patients had the procedure successfully completed (90%), 11 of whom were found to have urothelial tumors. Diagnostic ureteroscopic biopsy in three of these patients revealed high-grade, multifocal tumors and was followed by nephroureterectomy (two patients) or partial ureterectomy (one patient). However, in eight patients, ureteroscopy and biopsy revealed apparently localized, low-grade tumors which were treated by ureteroscopic fulguration or resection. The latter patients have undergone endoscopic surveillance every 3 months (average follow-up, 21 months). The technique of ureteropyeloscopy permits endoscopic access into the ureter and renal pelvis, enabling tissue diagnosis and better preoperative cancer staging without surgical exploration. Although follow-up is short, selected patients with low-grade tumors may be treated primarily by endoscopic means.

Aged↗
PubMed1985

Gleason grading of prostate cancer: a predictor of survival.

The Gleason grading system was employed in the pathologic assessment of 82 patients with carcinoma of the prostate diagnosed between 1962-1965 and subsequently followed to death. The data suggest that the Gleason grade gives long-term prognostic information independent of stage with a direct correlation between increasing Gleason grade and cancer death rate index. Furthermore, the sum of clinical stage plus Gleason grade is a more significant prognostic factor than either stage or grade alone.

Aged↗
PubMed1985

Experience with intravesical bacillus Calmette-Guèrin therapy of superficial bladder tumors.

Between March, 1978, and July, 1981, 86 patients with polychronotopic superficial papillary bladder tumors and concurrent carcinoma in situ were randomized to receive either transurethral resection alone (43) or TUR plus BCG (43). The results indicate that BCG is not only active in preventing recurrences of new tumors but also effective for the diffuse, flat carcinoma in situ.

Adult↗
PubMed1985

Randomized trial of cystectomy with or without preoperative radiotherapy for carcinoma of the bilharzial bladder.

A prospective randomized clinical trial was done for 92 patients with carcinoma of the bilharzial bladder who underwent radical cystectomy alone or with 2,000 rad preoperative radiation. The postoperative mortality and morbidity were similar in both groups. Patients were followed for a minimum of 60 months. Over-all, there was a marginal, statistically insignificant improvement in survival among patients receiving preoperative radiotherapy. Nevertheless, 2 subpopulations demonstrated significant improvement in survival following preoperative radiation, that is patients with high stage (P3 and P4) and high grade tumors.

Carcinoma, Squamous Cell↗
PubMed1985

The role of germinal epithelium and spermatogenesis in the privileged survival of intratesticular grafts.

The testis is an immunologically privileged site. Since earlier studies excluded testicular steroid production as an essential factor, the present study evaluates the role of germ cells and spermatogenesis in the privileged survival of allografts within the testis. We used a Sertoli cell-only testis model and adolescent unilateral cryptorchidism in inbred rats to eliminate germ cells and spermatogenesis selectively. Parathyroid allografts were implanted into these sites, normal testes and beneath the renal capsule (a nonprivileged site) in appropriately matched controls. With at least 15 rats in each group, privileged allograft survival was shown to be unaffected by eliminating germ cells and spermatogenesis (p less than .005). Experimental evidence suggests the presence of an active process which incidentally permits privileged allograft survival within the testis, but which exists teleologically to protect the developing sperm from autoimmune attack. This is in addition to the passive anatomical separation provided by the blood-testis barrier. Our cumulative data strongly implicates the Sertoli cell in this process.

Animals↗
PubMed1985

Estimation of ABO(H) isoantigen expression in bladder tumors.

ABO(H) isoantigen expression was estimated semiquantitatively with the red cell adherence test on single epithelial cell suspensions from 89 bladder tumor and 7 normal bladder specimens. Correlations of red cell adherence counts positive for antigen with the pathological findings of the bladder (histology and stage of tumor) were made in a blind fashion at the end of the study. The mean count positive for antigen from normal bladders was 86.0, which was significantly different (p less than 0.001) from those of muscle-invading lesions (12.6) and flat carcinoma in situ (21.6). This study shows a good correlation among the cell counts positive for antigen, histological findings and stage of disease, and provides the basis for a prospective study that may help to determine the role of ABO(H) isoantigen measurement in bladder tumor patients.

ABO Blood-Group System↗
PubMed1985

Intratubular malignant germ cells (carcinoma in situ) accompanying invasive testicular germ cell tumors.

We examined 111 radical orchiectomy specimens from patients with germ cell tumors of the testis treated between 1971 and 1981 for the presence of intratubular malignant germ cells (so-called carcinoma in situ) in adjacent testicular tissue. Of the specimens 12 were unevaluable because the entire specimen was tumor, while 36 of 44 cases of pure seminoma (82 per cent) and 41 of 55 mixed or nonseminomatous tumors (75 per cent) had intratubular malignant germ cells. Of the 22 cases without intratubular malignant germ cells 10 had severe atypia that suggested an earlier or borderline stage of development. These data support the contention that germ cell tumors originate as intratubular neoplasms or so-called carcinoma in situ in the seminiferous tubules.

Adolescent↗
PubMed1985

Immunohistologic dissection of the human kidney using monoclonal antibodies.

Nine murine monoclonal antibodies which detect differentiation antigens of the human kidney are described. Immunofluorescence and immunoperoxidase studies demonstrate that these antigens are expressed by different cell types comprising the nephron. Monoclonal antibody MA99 detects a glycoprotein complex of the glomerular basement membrane. Monoclonal antibody S4 detects a glycoprotein of 160,000 daltons (gp160) expressed by glomerular and proximal tubular epithelial cells. Monoclonal antibodies S23, S27 and S6 immunoprecipitate a glycoprotein of 120,000 daltons (gp120) found on cells of the proximal tubule and portions of Henle's loop. Monoclonal antibody C26 identifies a glycoprotein of 40,000 daltons (gp40) expressed by cells of the distal and collecting tubules. Monoclonal antibodies M2 and S8 are specific for A and B blood group antigens, respectively, found on cells of the collecting tubule in individuals of the respective blood type. This panel of antibodies is useful in the study of normal renal embryogenesis, microanatomy and physiology as well as pathological processes including tumors.

Animals↗
PubMed1985

Monitoring intravesical bacillus Calmette-Guerin treatment of bladder carcinoma with flow cytometry.

Flow cytometry of bladder irrigation specimens was studied in 22 patients with low stage bladder carcinoma who were treated by transurethral resection of visible tumor followed in 3 to 5 weeks by a course of intravesical bacillus Calmette-Guerin. The most informative examinations were just before the first bacillus Calmette-Guerin treatment, 6 weeks after completing a 6-week course of treatment (3 months) and at 9 months. Of the patients 10 had recurrent tumors after therapy; recurrence was anticipated correctly by flow cytometry at the 12-week followup examination in 6 of the 10 patients and suspected in another. Of 12 patients who remained clinically free of disease for a minimum of 15 months after bacillus Calmette-Guerin therapy flow cytometry identified correctly 7 at 12 weeks, while 1 had a partial response and the remaining 4 reverted to a negative status at 9 months. Of interest, only 4 of the 22 patients were free of disease by flow cytometry at the start of bacillus Calmette-Guerin treatment despite attempted ablation of the tumor by transurethral resection, suggesting that intravesical administration of bacillus Calmette-Guerin destroys existing carcinoma in situ in some cases.

BCG Vaccine↗
PubMed1985

Specificity analysis of mouse monoclonal antibodies defining cell surface antigens of human renal cancer.

Six mouse monoclonal antibodies (mAbs) defining separate systems of cell surface antigens of cultured human renal cancer were tested for reactivity with normal fetal and adult tissues and with neoplastic tissues. Five of the mAbs identified glycoproteins of Mr 160,000 (designated S4), Mr Mr 140,000 (F23), Mr 120,000 (S23 and S27), and Mr 115,000 (S22). The glycoprotein component of Mr 120,000 has been shown recently to be the adenosine deaminase binding protein (ADA-BP) and mAbS23 and mAbS27 define two distinct epitopes on ADA-BP. S22 was not detected on any normal fetal or adult tissues but was found on a subset of renal cancers. S4, F23, S23, and S27 defined distinct domains of the nephron: glomerulus (S4), proximal tubules (S4, F23, S23, and S27), and portions of Henle's loop (S23 and S27). mAbS4 also reacted with the interstitial matrix in the renal medulla and of other tissues, and mAbF23 reacted with fetal and adult fibroblasts. The S23 epitope of ADA-BP was expressed by placental trophoblasts and epithelial cells of breast, prostate, lung, and colon, whereas the S27 epitope was detected on a more limited range of cell types (trophoblasts and prostate epithelium). A panel of 20 renal cell carcinomas was typed for expression of these antigens; 7 phenotypes could be distinguished, with the S4+/F23+/S23+/S27+/S22+ or - phenotype (15 cases) being most common. The other antigenic system, V1, identified a heat-stable antigen that was widely expressed on cultured cell types but showed a restricted pattern of reactivity in tissues. V1 expression was limited to the adrenal cortex, Leydig cells, and the theca of ovarian follicles, and to adrenal cortical carcinomas.

Animals↗
PubMed1985

Effect of treatment on fertility and sexual function in males with metastatic nonseminomatous germ cell tumors of testis.

The effects of therapy on the sexual ability and fertility of sixty-seven patients with nonseminomatous germ cell tumors of the testis were analyzed. Ten of 38 patients had subfertile sperm counts before therapy. Normal ejaculation was preserved in only 7/61 patients who underwent retroperitoneal lymph node dissection. In five of these patients, sperm analysis was done after chemotherapy; all had complete azoospermia. An effort to restore ejaculation with imipramine yielded only minimal response in 4/9 patients who received this drug. No major long-term effects on the libido were observed.

Adolescent↗
PubMed1985

VAB-6 as initial treatment of patients with advanced seminoma.

Thirty patients with advanced seminoma were treated with VAB-6. Eighteen patients were previously untreated, eight had relapsed after radiation therapy, and four had persistent disease following chemotherapy and radiation therapy. Two patients had received prior high-dose cisplatin. Twenty-four (86%) of 28 evaluable patients achieved a complete remission. Four patients had relapsed. The median disease-free follow-up of patients achieving complete remission was 32+ months. VAB-6 is effective treatment for patients with advanced seminoma, and chemotherapy is recommended as the initial therapy in all patients with stage II seminoma with disease larger than 5 cm, extragonadal seminoma, and stage III seminoma.

Adult↗