Search PubMed⌕ Search

Biomedical subjects

M A Friedman

Publications and source records attributed to M A Friedman.

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

Adjuvant therapy for breast cancer patients with negative lymph nodes.

Although approximately 50,000 cases of axillary node-negative breast cancer are diagnosed in the United States annually, the natural history of this heterogeneous disease is incompletely defined. Several series have reported 5-year relapse-free and overall survival ranging from 56% to 89% and 74% to 92%, respectively. Tumor necrosis and anaplastic morphology correlate with early treatment failure. The estrogen receptor and size of the primary tumor are probably also predictive of clinical course. Thus far, perioperative cyclophosphamide is the only systemic treatment demonstrated to prolong survival in a statistically significant fashion. Several ongoing studies are investigating the role of tamoxifen or cytotoxic chemotherapy, or both, in prospective randomized trials. However, too few patients with insufficient follow-up have been analyzed to permit definitive conclusions or recommendations.

Antineoplastic Agents↗
PubMed1985

A reevaluation of nonhormonal cytotoxic chemotherapy in the treatment of prostatic carcinoma.

The palliative role of nonhormonal cytotoxic chemotherapy in the treatment of endocrine-resistant prostatic carcinoma has not been established. Conventional means of quantifying tumor response are most frequently not applicable in this disease because of the lack of measurable objective parameters to allow for a reliable estimation of antitumor effects. While this problem is not unique to prostatic carcinoma, this review illustrates its magnitude in this disease. Only approximately 5% of patients studied fulfill the various criteria for complete response (CR), partial response (PR), or both, while the vast majority of patients reported as responders are actually in the stable disease category. Stable disease is highly questionable as an indicator of antitumor response and should not be used as a criterion for response in conventional phase II studies unless it is convincingly demonstrated that it occurs as a result of treatment. A study design that may allow a more reliable assessment of the value of the stable disease category is described in the text. More effective means for assessing tumor responses and better instruments to measure aspects of quality of life are needed. Review of several prospective randomized clinical trials showed that no treatment program tested during the last decade resulted in a survival advantage when compared with a concurrently treated control group. Furthermore, in two such trials, four different single chemotherapeutic agents widely used in the treatment of this disease (cyclophosphamide, 5-fluorouracil, estramustine phosphate, and streptozocin) either alone or in combination, did not produce any prolongation of survival when compared to a no chemotherapy (standard treatment) control arm. Survival curves for endocrine-resistant patients fall within a relatively narrow and possibly predictable range that may be used as an additional endpoint in conjunction with response (CRs and PRs only) in phase II trials. More definitive evidence of therapeutic efficacy in this disease should derive from phase III trials using survival as one of the major endpoints. Because of the poor results observed with chemotherapy thus far, we suggest that the appropriate control arm for phase III testing in endocrine-resistant patients continues to be a no chemotherapy control arm consisting of a best symptomatic care or a uniformly applied second-line endocrine manipulation.

Antineoplastic Agents↗
PubMed1984

The distribution of [14C]caprolactam in male, female and pregnant mice.

The distribution of [14C]caprolactam was studied by whole-body autoradiography in male, female and 14.5-day-pregnant mice. This technique does not allow translocation or removal of soluble compounds from the sites of localization. Pregnant mice were frozen 20 min and 1, 3, 9 and 24 hr after oral administration of the compound. The non-pregnant mouse was frozen 3 hr after oral dosing; two male mice were frozen 20 min and 9 hr after intravenous administration. Radioactivity was rapidly absorbed from the stomach and distributed throughout the entire animal, including the foetuses. There was efficient elimination by the kidney and liver. Material secreted by the liver into bile and intestinal contents appeared not to be reabsorbed via the enterohepatic circulation. The kinetics of distribution and elimination appeared to be the same in male, female and pregnant animals. The only sites of retention of radioactivity after 24 hr were the umbilical cords, amnion, yolk sac, maternal lens, maternal Harderian gland and maternal liver. The distribution into and removal from the foetuses was typical of molecules that diffuse freely across the placenta. There was no retention of radioactivity in any foetal tissue. With the possible exception of some residual activity in the nasal epithelium, no localization was seen that would suggest a site of toxic action of caprolactam.

Animals↗
PubMed1984

Hepatic arterial chemotherapy for colorectal cancer metastatic to the liver.

Hepatic metastases of colorectal origin are resistant to radiation and immunotherapy. Traditional intravenous chemotherapy produces responses in 10% to 30% of patients, and surgical resection is feasible in approximately 20% of patients who have a solitary or unilobar lesion. Infusion of cytotoxic agents into the hepatic artery, introduced 2 decades ago, is the most promising form of therapy for unresectable hepatic metastases. Fluorouracil, floxuridine, and mitomycin have been most commonly administered by hepatic arterial infusion. The recent development of a totally implantable pump has allowed prolonged ambulatory infusion of chemotherapeutic agents into the hepatic artery. We review the recent data on the pharmacology, therapeutic outcome, administration techniques, and complications of hepatic arterial chemotherapy. Future trials in this area should use uniform stratification variables and standardized criteria for evaluating response, time to progression, and survival.

Antineoplastic Agents↗
PubMed1983

Chemotherapy of disseminated gastric cancer. A joint effort of the Northern California Oncology Group and the Japanese Gastric Cancer Chemotherapy Group.

A consortium of Northern California and Japanese investigators studied 142 patients with advanced gastric adenocarcinoma. Patients were randomized to one of two combination chemotherapy programs in each nation (one common therapy shared and one therapy unique to each nation). Median duration of survival ranged between 5 and 45 weeks, depending on performance status, extent of disease, and chemotherapy program. More importantly, there was considerable comparability with respect to toxicity and outcome between patients in the US and Japan. Overall median survival was 26 weeks for Japanese and 27 weeks for US patients. This study helps provide the basis for future comparative multinational trials.

Adenocarcinoma↗
PubMed1983

5-Fluorouracil + Oncovin + Adriamycin + mitomycin C (FOAM): an effective program for breast cancer, even for disease refractory to previous chemotherapy. A Northern California Oncology Group (NCOG) Study.

One hundred and thirty-one patients (118 evaluable) with disseminated breast cancer were treated with a combination of 5-fluorouracil + Oncovin + Adriamycin + mitomycin C (FOAM). The objective response rate for 82 evaluable patients whose disease was refractory to previous CMF or L-PAM chemotherapy was 35%; that for 36 evaluable patients who had not previously received chemotherapy, 56%. The hematologic toxicity of this therapy was generally mild and acceptable. It is believed that FOAM is an effective therapy for patients whose tumors are resistant to CMF.

Adult↗
PubMed1983

Concentration-dependent elicitation of dermal sensitization in guinea pigs treated with 2,4-toluene diisocyanate.

2,4-Toluene diisocyanate (TDI) can cause pulmonary sensitization and allergic skin reactions. Since many commercial materials contain TDI, the present study was designed to determine the concentration-dependent elicitation of dermal sensitization in guinea pigs treated with TDI. Young adult guinea pigs received two open, epicutaneous induction applications (25 microliters) of 8,20, or 40% TDI in n-butyl ether on two separate areas. Five days later, animals were challenged with 0.0, 0.025, 0.05, 0.1, 0.2, and 0.4% TDI (25 microliter per concentration site). All challenge applications except the 0.0% solution elicited a positive response in 75 to 100% of the animals, and the severity of the skin reactions was dependent on the concentrations of the challenge and induction application. In another study at lower doses, animals received a total induction application (25 microliters per each of two sites) of either 4 or 8% TDI and were challenged with 0.0, 0.006, 0.012, 0.025, 0.05, and 0.1% of TDI (25 microliters per site). TDI did not elicit a sensitization response at challenge concentrations up to 0.012% (total application of 3 micrograms) when a 4% induction application was used, while a challenge concentration of 0.025% (total application of 6.25 micrograms) elicited a sensitization response in 63% of the animals. At the 8% induction application (total application of 4000 micrograms), all challenges, except the 0.0% indicated sensitization, and the intensities of the skin reactions were correlated with the challenge concentrations and the induction application. In conclusion, the results demonstrate that TDI produced sensitization at dilute induction concentrations and that the severity of the dermal response was correlated with the concentration used at induction and challenge. Furthermore, no observed effect levels were determined below which the challenge concentration did not elicit a dermal hypersensitivity reaction. When 4% TDI was applied at induction, no observed effect was seen with a dermal challenge application of 3 micrograms whereas an effect was seen with 6.25 micrograms (in 25 microliters) when n-butyl ether was the solvent.

Animals↗
PubMed1983

How accurate are computed tomographic scans in assessment of changes in tumor size?

The computed tomographic scan plays an integral part in the diagnosis and management of tumors; however, its potential has not yet been fully exploited. With a computer-assisted volume determination method, the reproducibility of derived volume calculations was assessed, and radiologists' standard interpretations of interval change on serial scans were compared with the investigators' calculations of tumor volume change. Interobserver reproducibility of tumor volume calculations of the mean of two repeated volume determinations was satisfactory (mean of 3 percent, median of 1 percent). There were 29 comparisons (47 scans of 19 patients with liver tumors) of computed tumor changes with the radiologists' computed tomographic reports of consecutive scans. In only 41 percent (12 of 29) of the cases did the radiologists' interpretations and the computer-assisted volume determinations agree. It is concluded that objective computer-assisted volume determination provides a potentially more sensitive assessment of tumor change and that such precise, specific, reproducible determination of tumor volume should further clinical research and improve patient care.

Adult↗
PubMed1983

Effect of dietary administration of the rubber curative trithiocyanuric acid to the rat.

Trithiocyanuric acid (TCY) is a rubber curative of low oral and dermal toxicity and with a low potential for eye and skin irritation. This study determined the effects of TCY on Sprague-Dawley rats at levels of 0.0, 625, 2500 and 5000 ppm in the diet for 2-30 days. While there were some effects on body-weight gain and survival at the higher levels of intake, the main effects concerned unusual lesions of the pinna and the distal portions of the tail. Purplish discolorations of the ear margin and tip of the tail were noted in some animals on the 2500- and 5000-ppm diets. The tail lesion was evident microscopically at day 16 only in the 5000-ppm group and consisted of congestion of the vasculature in the subepidermal connective tissue with focal necrosis of the distal tail segment. By day 16 the ear lesion was also microscopically identifiable only in the group on the 5000-ppm diet. It was found in 33% of these animals at day 8 and in 67% at day 16 and consisted of a localized cellulitis characterized by moderate infiltrates of polymorphonuclear leucocytes in the epidermal and subepidermal tissues. The lesions caused by high levels of TCY were apparently site-specific, since histopathological examination of selected internal organs did not detect any lesions. The no-effect levels determined were 2500 ppm for microscopic lesions during an 8-16-day treatment period and 625 ppm for gross pathological lesions in a 30-day feeding study.

Animals↗
PubMed1983

Metabolism, disposition and excretion of [14C]melamine in male Fischer 344 rats.

The metabolism, excretion and disposition of melamine were determined after administration of a single oral dose of 0.025 mCi (0.38 mg) [14C]melamine to adult male Fischer 344 rats. Within the first 24 hr, 90% of the administered dose was excreted in the urine. Negligible radioactivity appeared in breath and faeces. There was little difference in blood, liver or plasma concentrations of 14C, suggesting that melamine distributes in body water. The only organs showing radioactivity levels much higher than plasma were the kidney and bladder. The bladder level was by far the highest, a finding probably due either to back diffusion from urine or to contamination of bladder tissue with urine. Virtually no residual radioactivity was observed in tissues examined at 24 hr or later. The elimination-phase half-life calculated from plasma data, 2.7 hr, was in good agreement with the urinary-excretion half-life of 3.0 hr. The renal clearance of melamine was 2.5 ml/min. Radioactivity in plasma or urine co-chromatographed with that of the dosing solution, indicating that melamine is not metabolized in the male Fischer 344 rat.

Animals↗
PubMed1983

Primary hepatocellular cancer--present results and future prospects.

Hepatocellular cancer is an enormously difficult clinical problem. This review provides an overview of selected basic and applied aspects of the care of hepatoma patients. Important pathophysiologic and prognostic features are now recognized. Initially, chemotherapy programs focused on the use of those agents commonly employed for gastrointestinal neoplasms (fluoropyrimidines, anthracyclines and alkylators). When employed as a conventional intravenous bolus, only Adriamycin is a reproducibly effective agent. However, because of the unique dual vascular supply of the liver and tumor, the use of intraarterial (IA) infusion chemotherapy has become more popular. In this regard, of promise are the application of IA FUDR and Adriamycin, the use of totally implanted infusion systems, and hepatic artery embolization. Furthermore, combinations of whole liver irradiation with chemotherapy seem efficacious. New directions for the therapy of hepatoma patients will focus on superior drug-radiation combinations, exploration of isotopic immunoglobulin, and hormonal therapy. There is currently no standard therapy for hepatoma patients, but prospects for the future have never been so bright.

Administration, Oral↗
PubMed1983

Hepatic intraarterial chemotherapy--current status and future prospects--"If you have a short sword, take a step forward".

The use of hepatic intraarterial (IA) chemotherapy for patients with unresectable liver malignancy has become an increasingly popular mode of therapy. Advances in the understanding of antineoplastic pharmacology, catheter placement technique, and infusion pump design have renewed interest in this approach. Despite inadequacies of the historical data, it appears that IA therapy may be superior to conventional intravenous therapy for patients who have disease limited to the liver, especially from colorectal and hepatocellular malignancies. Unanswered are questions concerning which is the best drug (or drugs) for IA therapy, how to properly integrate IA therapy with surgery and radiation, and how to select patients likely to respond. This renovated technology offers a bright promise for the future of clinical oncology.

Carcinoma, Hepatocellular↗
PubMed1982

Hormone receptors in hepatoblastoma: a demonstration of both estrogen and progesterone receptors.

A case of mixed hepatoblastoma occurring in a four-year-old girl is described. Light and electron micrographs illustrate a predominant mesenchymal component and a less conspicuous epithelial element. The tumor contained specific cytosolic protein receptors for estrogen and progesterone. The estrogen receptor titer was 10.5 fmol/mg cytosol protein and the progesterone receptor titer was 62.2 fmol/mg cytosol protein.

Carcinoma, Hepatocellular↗
PubMed1982

Primary hepatocellular carcinoma. Present state of the disease and prospects for the future.

Primary hepatocellular cancer is a common and virulent malignancy found all over the world. New insights into this disease are being provided by evaluation of the impact of epidemiologic data (hepatitis viral exposure, race, sex, HLA typing, and environmental factors). An enhanced appreciation of the biochemical modulators of hepatocellular cancer metabolism is now also possible. The limited success of current therapies is far from satisfactory, but prospects for the future seem more varied and promising than ever before.

Carcinoma, Hepatocellular↗