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Biomedical subjects

R R Bahnson

Publications and source records attributed to R R Bahnson.

At least 37 records · Page 2Linked to original sources

Surgical resection for management of renal cancer with hepatic involvement.

PURPOSE: More than 900 patients who underwent hepatic resections were reviewed to identify those whose liver resections were due to involvement by renal cell carcinoma. MATERIALS AND METHODS: Three patients with direct hepatic extension of the renal cell cancer underwent radical nephrectomy with en bloc partial hepatectomy, while 1 with a metachronous recurrence 3 years after nephrectomy underwent right triple lobe hepatectomy. There were no postoperative complications. RESULTS: Of the en bloc resections 2 showed sarcomatoid features on histopathological examination. These patients experienced rapid disease progression and died. The remaining 2 patients with typical clear cell carcinoma have no evidence of disease. CONCLUSIONS: Experience with these 4 patients has demonstrated that hepatic resection is technically feasible and associated with acceptable morbidity rates. Surgical management should be considered in patients with the uncommon presentation of renal cell carcinoma and localized hepatic involvement.

Adult↗

Intravesical recombinant tumor necrosis factor in the treatment of superficial bladder cancer: an Eastern Cooperative Oncology Group study.

We tested and proved the safety of recombinant human tumor necrosis factor given intravesically weekly for 11 weeks (dwell time 2 hours) for the treatment of superficial bladder cancer in 8 men and 1 woman 46 to 87 years old (mean age 69 years). Cohorts of 3 patients received 200, 400 and 1,000 micrograms. recombinant human tumor necrosis factor. The maximal tolerated dose was not achieved. There were 9 episodes of urological symptoms, 8 of flu-like symptoms, 4 of headache and 3 of chest tightness. Hematological and gastrointestinal toxicities were minor, and no renal toxicity was encountered. Recombinant human tumor necrosis factor was safe to administer at doses up to 1,000 micrograms. We hope that recombinant human tumor necrosis factor in conjunction with other antitumor agents will lead to a new, effective treatment for superficial bladder cancer.

Administration, Intravesical↗

Adjuvant chemotherapy for bladder cancer. Standard of care or unproven therapy?

The failure of radical cystectomy to cure the majority of patients with muscle invasive transitional cell carcinoma of the bladder has prompted clinical trials evaluating adjuvant chemotherapy. No properly conducted prospective trials are available to support unequivocally the application of pre- or postsurgical chemotherapy. A large trial comparing chemotherapy with no chemotherapy and standard treatment (cystectomy) is nearing completion. The results will determine whether or not adjuvant chemotherapy becomes the standard of care.

Carcinoma, Transitional Cell↗

Subcellular localization of metallothionein IIA in human bladder tumor cells using a novel epitope-specific antiserum.

Human metallothioneins (hMTs) are a family of highly homologous proteins thought to be critical in cellular protection against toxins. The comparative function of individual isoforms is, however, obscure. Antibodies to individual MT isoforms might help clarify this issue but their generation has been challenging. We now describe a strategy that has successfully produced an epitope-specific antiserum to a major human isoform, hMT IIA. The immunogen, a conjugated tridecyl amino acid synthetic peptide unique to residues 8-20 in hMT IIA (AAGDSCTCAGSCK), yielded an antiserum (B2) that reacted specifically with hMT IIA in a concentration- and titer-dependent manner and showed no reactivity with human or rabbit liver MT I or horse MTs. This antiserum recognized rabbit liver MT II and, surprisingly, also reacted weakly with chicken MT. MT amino acid sequence comparisons and peptide blocking studies suggested aspartate-11 and threonine-14 are important antigenic determinants for B2. Using confocal immunofluorescence microscopy and B2 antiserum, we observed nuclear localization of hMT IIA with human bladder T24 tumor cells in exponential growth but more cytoplasmic localization at confluence. These results suggest the subcellular location of hMT IIA is a function of cell density in T24 bladder carcinoma cells. The general approach of epitope-specific antibodies may be useful for the generation of antibodies to other MT isoforms and for studying the role of individual MT isoforms in biology and toxicology.

Amino Acid Sequence↗

Absence of immunohistochemical metallothionein staining in bladder tumor specimens predicts response to neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy.

Pre-chemotherapy bladder tumor tissue was retrospectively analyzed in 21 patients treated with neoadjuvant cisplatin, methrotrexate and vinblastine. Immunohistochemical staining for 2 proposed mediators of drug resistance, p-glycoprotein and metallothionein, was performed and compared to chemotherapeutic response and survival. There was no significant relationship between staining for p-glycoprotein and the response to chemotherapy or survival. Patients with no detectable staining for metallothionein were statistically more likely to sustain a complete pathological response (p = 0.029) after chemotherapy than those with any detectable staining. No relationship between metallothionein immunostaining and survival was apparent. This study offers further evidence linking metallothionein in tumor resistance to cisplatin containing chemotherapy regimens.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Survival of men with clinically localized prostate cancer detected in the eighth decade of life.

We reviewed our experience with the management of men 70 to 79 years old with clinically localized prostate cancer to determine whether surgical candidates were likely to die of intercurrent disease soon after the disease was diagnosed. Of 101 men in the eighth decade of life who were surgical candidates by all criteria other than patient age 44 underwent radical prostatectomy, whereas 57 were managed by medical therapy including observation, radiation therapy and/or androgen deprivation. Five patients died in the surgical group at a median followup of 59 months, only 1 of whom died of intercurrent disease. Among 15 deaths in the medical group metastatic prostate cancer was the most common cause and all deaths from prostate cancer occurred more than 3 years after diagnosis. Survival for the surgical group was significantly better than that for the medical group during followup (p < 0.01 log-rank test). We conclude that men at our institution who underwent radical prostatectomy in the eighth decade of life did not frequently die of intercurrent disease, and experienced acceptable morbidity and mortality rates. We believe that men with localized prostate cancer should not be denied a radical operation based on age alone.

Age Factors↗

Human metallothionein isoform gene expression in cisplatin-sensitive and resistant cells.

Overexpression of metallothioneins (MTs) has been observed in some cis-diamminedichloroplatinum (CDDP)-resistant cells. We have developed oligonucleotide probes for each of the six non-neuronal human MT (hMT) isoforms and used them to assay hMT isoform expression in three pairs of CDDP-resistant and -sensitive human carcinoma cell lines, i.e., SCC25/CP versus SCC25 cells, H69/CP versus H69 cells, and SW2/CP versus SW2 cells. We found a 9-fold increase in basal hMT-IIa mRNA levels and a 5-fold increase in hMT-le mRNA levels in SCC25/CP cells, compared with SCC25 cells. Nuclear run-on studies also revealed a 3-fold increase in hMT-IIa transcription rate. Basal hMT-IIa steady state mRNA levels were 2-3.6-fold greater in H69/CP and SW2/CP cells, compared with their parental cells. No significant basal expression of hMT-Ia, -Ib, -If, or Ig was detected in any cells, suggesting that overexpression of these isoforms was not commonly associated with the CDDP-resistant phenotype. Levels of constitutively expressed hMT isoforms, as well as hMT-If, could be elevated by treatment of all cells with 100 microM zinc. The universal overexpression of hMT-IIa suggests a role of this particular isoform in CDDP resistance. Using our isoform-specific hMT-IIa probe and the demethylating agent 5'-azacytidine (AZC), we found that AZC pretreatment increased basal hMT-IIa mRNA levels in SCC25 but not SCC25/CP cells, suggesting that DNA hypomethylation was responsible for higher basal hMT-IIa mRNA levels in SCC25/CP cells. AZC had little or no effect on hMT-If or -Ig expression. Limited restriction analysis by methylation-sensitive enzymes, however, revealed no obvious differences in the methylation status of the hMT-IIa promoter in either SCC25 or SCC25/CP cells.

Azacitidine↗

Carcinoma of prostate metastatic to parotid gland.

A rare case of prostate cancer with metastasis to the parotid salivary gland is reported. The prostatic origin of the mass was proven by incisional biopsy and immunohistochemical staining for prostate-specific antigen. Additional studies of the tumor included ultrastructural and quantitative deoxyribonucleic acid (DNA) analysis.

Adenocarcinoma↗

Recurrent transitional cell carcinoma in an ileal conduit treated by sandwich chemotherapy and surgical resection.

Recurrent transitional cell carcinoma in a ureteroileal conduit following radical cystectomy is rare. The prognosis for these patients is uniformly poor. We report on a patient with transitional cell carcinoma in an ileal conduit treated by chemotherapy and partial excision of the ileal conduit. He was without evidence of disease 4 1/2 years after completion of therapy.

Carcinoma, Renal Cell↗

Immunological effects of treatment with sequential administration of recombinant interferon gamma and alpha in patients with metastatic renal cell carcinoma during a phase I trial.

Many anticancer mechanisms of the interferons have been proposed but none have been associated with clinical response to date. The biological activities of the interferons in vivo have included effects upon the natural killer cell, T- and B-lymphocytes, and macrophages. This report details a prospective study of the immunological effects on peripheral blood mononuclear cells of sequentially administered recombinant (r) interferon (IFN) gamma and rIFN alpha in 28 patients with metastatic renal cell carcinoma. Natural killer cell activity, T-cell phenotype (CD4, CD8, CD56, CD16, CD4/HLA-DR, CD8/HLA-DR, CD56/HLA-DR) and 2',5'-oligoadenylate synthetase were measured prior to therapy, during therapy, and following completion of treatment. Statistical analysis of all parameters was performed for the entire group, by individual patient, by dosage, by time, and by clinical response. An overall significant depression in natural killer cell activity and in the percentage of circulating CD56, CD16, and CD8+ cells were noted. Significant increases in 2',5'-oligoadenylate synthetase and in the percentage of circulating CD4 cells were also noted. Although an association between the magnitude of change in percentage of CD16+ cells and 2',5'-oligoadenylate synthetase and dosage of rIFN gamma and rIFN alpha, respectively, was observed, optimal biological dose of this sequence of rIFNs could not be determined due to the limited number of patients. A decrease in the percentage of circulating CD8+ cells was observed among patients with objective clinical response (partial and complete). Sequentially administered rIFN gamma and rIFN alpha can modulate immunological parameters in vivo in patients with metastatic renal cell carcinoma. A fall in percentage of circulating CD8+ cell is associated with response and suggests that this sequence of rIFN alpha and rIFN gamma might influence T-cell mediated antitumor activity.

2',5'-Oligoadenylate Synthetase↗

Interferon-induced reversible acute renal failure with nephrotic syndrome.

Although there has been considerable experience with interferons in clinical trials during the past decade, acute renal failure as a side effect of interferon treatments has rarely been reported. We report a case in which acute renal failure with nephrotic syndrome was associated with therapy with two types of interferons. We note incomplete return of renal function upon withdrawal of therapy.

Acute Kidney Injury↗

Quantitative DNA analysis of small renal cortical neoplasms.

DNA aneuploidy is common in large renal cortical neoplasms (RCNs), but the incidence in small RCNs is not known. This study was undertaken to investigate whether the traditional 3.0-cm size distinction between small (benign) and large (malignant) tumors might have an objective correlate in the form of abnormal DNA content. Quantitative DNA analysis was performed retrospectively, by image analysis, on 59 RCNs measuring 5.0 cm or less from 30 nephrectomy specimens with solitary tumors and 17 with multiple tumors. DNA indices and the proportion of cells with DNA content greater than that of the G0/G1 population were evaluated with respect to tumor size, stage, and histologic parameters. There was a relationship between the presence of detectable nondiploid stem lines (NDSLs) and tumor size, stage, nuclear grade, and proportion of non-G0/G1 cells, but not histologic pattern. The relationship of NDSLs to tumor size was more apparent in the solitary tumor group, while the relationship of a high proportion of non-G0/G1 cells to tumor size was stronger in the multiple tumor group. Our results show that the incidence of NDSLs increases with tumor size and nuclear grade, and suggest that as RCNs enlarge, the emergence of NDSLs heralds potential biologic aggressiveness. Further, solitary tumors and multiple synchronous tumors may be biologically different in terms of etiologic factors and growth potential.

Adenoma↗

Immunohistochemical localization of metallothionein in transitional cell carcinoma of the bladder.

Metallothionein is a metal binding protein thiol found in high concentrations in the liver and kidney. Recent evidence has linked overexpression of cellular metallothionein with tumor cell resistance to chemotherapeutic drugs, such as alkylating agents and cis-diamminedichloroplatinum (II) (cisplatin). We studied the metallothionein content of 9 human transitional cell carcinomas of the bladder with immunohistochemical methods. All tumors stained positive for metallothionein and the staining was localized almost exclusively to the cytoplasm. Uroepithelium displaying dysplastic changes or carcinoma in situ demonstrated the greatest intensity of staining, while staining in the invasive portions of the tumor was weak and variable. These findings were of interest, since combination chemotherapy of invasive transitional cell carcinoma of the bladder often is ineffective against carcinoma in situ. Normal uroepithelium stained strongly in all 3 patients who experienced disease progression and death, and in only 1 of the 5 who are currently without evidence of disease.

Aged↗