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Biomedical subjects

D E Brenner

Publications and source records attributed to D E Brenner.

85 records · Page 5Linked to original sources
PubMed1982

CT of peritoneal mesothelioma: analysis of eight cases.

In order to define the computed tomographic appearance of mesothelioma, eight patients with histologically proven peritoneal mesotheliomas had computed tomography (CT) performed during the course of their disease. CT findings for all cases were analyzed for evidence of tumor involvement in the peritoneum, mesentery, liver, bone, lymph nodes, and lower pleural space, and for ascitic and pleural fluid. CT findings included evidence of peritoneal involvement (7/8 patients, 88%), ascites (6/8, 75%), mesenteric involvement (6/8, 75%), pleural involvement (4/7, 57%), bone destruction (2/8, 25%), peritoneal mass (1/8, 12%), and retroperitoneal lymph node involvement (1/8, 12%). On the basis of diffuse mesenteric and peritoneal involvement and high incidence of ascites, CT may suggest the diagnosis of peritoneal mesothelioma; however, it may be difficult to differentiate from carcinomatosis, gastrointestinal malignancies, ovarian carcinomas, and, rarely, lymphomas. It is important to suggest the diagnosis of peritoneal mesothelioma because special stains and electron microscopy are necessary for pathologic diagnosis. Experience suggests that CT may be useful in suggesting the diagnosis and biopsy site, and after response to therapy of peritoneal mesothelioma.

Adult↗
PubMed1977

Plasma prostaglandins in hypercalcemic patients with neoplastic disease.

Peripheral plasma prostaglandin E (PGE) determinations were performed on a series of 79 patients with solid tumor neoplasms and correlated with their serum calcium levels. Fourteen patients were hypercalcemic and 11 of these had significant elevations in circulating plasma PGE. Ten of the hypercalcemic group had extensive metastases to bone. These findings support the recently developed hypothesis that prostaglandins are causally related to the genesis of hypercalcemia in malignancy.

Adult↗
PubMed1977

Immunosuppression and human cancer: role of prostaglandins.

Prostaglandins, unsaturated fatty acid derivatives with diversified pharmacologic activity, have been implicated in the pathophysiology of many diseases. Prostaglandin E (PGE) levels were measured by radioimmunoassay in the plasma of 41 normocalcemic patients with various stages of malignancies. Delayed hypersensitivity was assessed by a battery of six recall skin test antigens (ST) and by Dinitrochlorobenzene (DNCB) sensitization and challenge. Twenty-five patients with one or more positive skin tests had a mean PGE level of 87+/-8 pg/ml, whereas 16 patients with negative ST had a mean PGE level of 96+/-12 pg/ml. Twenty-one DNCB negative patients had a mean PGE level of 98+/-12 pg/ml and eight totally anergic patients had a mean PGE of 96+/-12 pg/ml. All PGE values were within the normal range and there was no statistical difference between the four groups. (p less than 0.1). We concluded that circulating PGE does not correlate with the non-specific immunosuppression seen in cancer patients.

Adult↗
PubMedDate not supplied

Carcinoma of the cervix--a review.

Carcinoma of the cervix is the fourth most common neoplasm in women. The mortality from this tumor has dropped with the advent of Papanicolaou smears and routine periodic screening, particularly in high risk populations. Diagnosis and staging includes a careful physical examination, the use of colposcopy, directed biopsy, intravenous urogram and cystoscopy. Computed tomography and lymph-angiography may be helpful for detection of iliac or paraaortic lymph nodes. Early, noninvasive stages of this disease (CIN) may be treated with cryosurgery or laser vaporization. Carcinoma in situ (CIS) and microinvasive carcinoma is usually treated with simple hysterectomy for cure. More advanced invasion localized to the cervix may be treated with radical hysterectomy or radiation therapy with 90% of patients surviving 5 years. More advanced tumors are treated with external and intracavitary radiation therapy. For patients with paraaortic lymph node involvement or recurrent tumor, 5-year survival is less than 10%. Chemotherapy may provide some palliation to patients with recurrent tumors but does not increase long term survivorship.

Adult↗
PubMedDate not supplied

Cellular pharmacology of doxorubicinol alone and combined with verapamil in pancreatic cancer cell lines.

The cellular accumulation/retention and cytotoxicity of doxorubicinol (DOXOL) were determined in three pancreatic cancer cell lines, which display primary or intrinsic resistance to doxorubicin (DOX). The studies reported here were performed in the presence and in the absence of verapamil, a calcium antagonist which we have previously shown to potentiate the cytotoxicity of DOX in our panel of pancreatic cancer cell lines. The accumulation/retention of DOXOL, as assayed by HPLC, was not enhanced by 6.6 microM verapamil in these cell lines. No aglycone metabolites were detected in any of the cell lines. The DOXOL cytotoxicity was enhanced 2.0 to 2.9-fold in two of the cell lines. The dose-related accumulation of DOX, as compared to that of DOXOL, was 7.5 to 10-fold greater at 0.1 microM, 3.6 to 6.5-fold greater at 1.0 microM, and 1.9 to 2.4-fold greater at 10 microM. In contrast, for two of our more sensitive cell lines, DOX was 25 to 27 times more cytotoxic than DOXOL. The present study suggests that (a) verapamil's effect on the cytotoxicity of DOX is not mediated by changes in the accumulation/retention nor the cytotoxicity of DOXOL; (b) metabolism of DOXOL does not influence its cytotoxicity nor that of DOX; and (c) DOXOL'S lower antitumor potency as compared to DOX cannot be fully explained by differences in intracellular accumulation.

Adenocarcinoma↗
PubMedDate not supplied

Dissociation of the verapamil-induced enhancement of doxorubicin's cytotoxicity from changes in cellular accumulation or retention of doxorubicin in pancreatic cancer cell lines.

The poor response of pancreatic adenocarcinoma to conventional chemotherapy has prompted us to search for innovative treatment approaches. Verapamil, a calcium channel blocker, has been reported to increase the doxorubicin sensitivity of several tumor models with acquired resistance, often in association with decreased efflux resulting in increased net accumulation/retention of doxorubicin. The cell lines used in the present study, PANC-1 of human origin and two cell lines of hamster origin, WD PaCa and PD PaCa, exhibit primary or intrinsic doxorubicin resistance. Verapamil caused a dose-dependent enhancement of doxorubicin's cytotoxicity in the pancreatic cancer-cell lines studied. In PANC-1, WD PaCa, and PD PaCa, respectively, the enhancement was 10.4-, 281.01-, and 15.8-fold at 6.6 microM verapamil and 1.1-, 8.8-, and 6.3-fold at 1.0 microM verapamil. Of note is the finding that the verapamil enhancement of sensitivity to doxorubicin was most marked in our most drug resistant cell line (WD PaCa). However, minimal to no effect on the accumulation or retention of doxorubicin was documented. In addition, the intracellular metabolism of doxorubicin was not found to be altered by verapamil. The present study raises questions concerning the nature and mechanism(s) of primary anthracycline resistance.

Adenocarcinoma↗
PubMedDate not supplied

Facile and definitive determination of human adriamycin and daunoribicin metabolites by high-pressure liquid chromatography.

Adriamycin and eight metabolites were separated and characterized with an ammonium formate/tetrahydrofuran solvent system on a muBondapak-Phenyl column. Danorubicin and seven daunorubicin metabolites were separated and characterized by the same method. Adriamycin and its major metabolite, adriamycinol, were extracted with 50-70% efficiency from human plasma with chloroform/2-propanol (1:1) and quantified against a daunorubicin internal standard. Urinary concentrations of parent drug, adriamycinol, and the 4-O-sulfate were determined as well. Daunorubicin and daunorubicinol were extracted from human plasma and quantified against an adriamycinol internal standard. The fluorescence detection system has a detection limit of 1.0 pmol, and levels as low as 25 mmol/ml are measurable in plasma.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Doxorubicin and dactinomycin therapy for advanced sarcomas.

Doxorubicin and dactinomycin were administered to 25 patients with advanced sarcomas. Twenty-one were evaluable for response. There were six responses (two complete and four partial) (28%) and eight improvements. Responders survived longer than nonresponders, while those with improvements had intermediate survival. Toxic effects included leukopenia in 35% of administered courses, mucositis in 50% of the patients, and congestive heart failure in 21% of the patients. Plasma doxorubicin kinetics did not correlate with excess toxic effects in four patients studied. The response rates and durations of survival obtained with this combination are comparable to those obtained with doxorubicin alone. The marked increase in toxicity makes this combination less desirable than treatment with doxorubicin alone.

Adolescent↗
PubMedDate not supplied

Mutual kinetic interaction between 5-fluorouracil and bromodeoxyuridine or iododeoxyuridine in dogs.

The pharmacokinetics of 5-fluorouracil (FUra) were studied alone and in the presence of either bromodeoxyuridine (BrdUrd) or iododeoxyuridine (IdUrd) in five mixed breed hounds. FUra was administered intravenously over 1 min as a 5 mg/kg dose in all three treatments. BrdUrd or IdUrd was infused intravenously at 2.5 mg/hr.kg x 6 hr and FUra was given 3 hr into the 6-hr infusion of thymidine analog. Serial blood samples were obtained for 3 hr prior to and after FUra dosing. Plasma concentrations of FUra, BrdUrd and bromouracil (BrUra), and IdUrd and iodouracil (IUra) were measured by reversed-phase HPLC. Concomitant administration of BrdUrd or IdUrd resulted in substantial changes in the kinetics of FUra. In particular, the total plasma clearance of FUra was decreased and area under the plasma concentration-time curve was increased. There were also significant changes in the volume of distribution steady-state, and in the mean residence time and half-life of FUra. The data show that FUra had little or no effect on the disposition of BrdUrd or IdUrd. In contrast, FUra had a significant effect on the disposition of BrUra and IUra going to form catabolic products. The observed pharmacokinetic interaction in dogs is probably due to a competition between BrUra (or IUra) and FUra for the rate-limiting catabolic enzyme, dihydropyrimidine dehydrogenase. This kinetic interaction was mutual and of a smaller magnitude for FUra + BrdUrd than for FUra + IdUrd.

Animals↗