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M A Friedman

Publications and source records attributed to M A Friedman.

At least 73 records · Page 4Linked to original sources
PubMed1992

Trans-retinoic acid and related differentiation agents.

Interest in retinoids as therapeutic agents has developed as a result of the observations of remission induction with all-trans retinoic acid (tRA) in patients with acute promyelocytic leukemia (APL), and of high objective response rates noted with the combination of cis-retinoic acid (cRA) with interferon-alpha in squamous cell carcinomas of skin and cervix. The therapeutic experience with RA in APL is discussed in this article from the perspectives of new information concerning retinoid biology, observations related to the development of the retinoid syndrome, complex pharmacology of this agent, and possible explanations for development of retinoid resistance. The current National Cancer Institute-supported drug development strategy for RA used alone or in combination with other differentiating agents, and the potential therapeutic uses in cancer for other retinoids are also discussed.

Animals↗
PubMed1991

Thalamo-cortical processing of vibrissal information in the rat. I. Intracortical origins of surround but not centre-receptive fields of layer IV neurones in the rat S1 barrel field cortex.

The receptive fields of cells restricted to the D1 cortical barrel territory in the S1 cortex of the rat were examined before and after substantial lesions of the D2 barrel. We tested 131 cells (N = 62, unlesioned controls; N = 69, lesioned animals) for modal latency and response magnitude to standard vibrissal deflections of 1.14 degrees. Lesions ranged in size to encompass 22-95% of the volume of the D2 barrel hollow and 5-75% of its neighbouring septal region, as calculated from cytochrome oxidase and Nissl staining of alternate sections. Negligible loss (mean 1.1%) of other barrel hollows and their septal regions (6.3%) occurred. A mean loss of 58% of the D2 barrel hollow and 27% of its accompanying septa was paralleled by a highly significant deficit in response magnitude (57.3%; p less than 0.005) of D1 barrel cells to D2 vibrissal stimulation, when compared with controls. The best-fit relationship between deficit and volumetric loss of the D2 barrel hollow was linear (regression coefficient -0.91). In the extreme case where 95% loss of D2 barrel hollow occurred, there was a 92% deficit in response of D1 barrel cells to the D2 input. No significant loss in response magnitude to other vibrissae, including the principal D1 input, occurred. Postlesioned animals exhibited some increase in excitability to the D1 vibrissa, and to vibrissae whose principal barrel territories were undamaged (delta, gamma, C1). Lesioning of the D2 barrel caused a highly significant mean increase (60%) in latency of residual responses to stimulation of the D2 vibrissal input (15.2 ms controls; 24.3 ms experimentals). No significant changes in response latency to other vibrissae compared to controls occurred. These results suggest that an intact D2 barrel is essential for the generation of responses of D1 barrel cells by the D2 vibrissa, and further imply that surround receptive fields of layer IV barrel cells are largely generated intracortically by barrel-to-barrel relay. The implications of these findings to cortical processing of tactile information and plasticity in the somatosensory system are discussed.

Afferent Pathways↗
PubMed1991

Commentary concerning demonstration of safety and efficacy of investigational anticancer agents in clinical trials.

Expeditious clinical development and approval of new drugs that are beneficial to patients are matters of high priority. There has been a great deal of discussion within the oncology community about what should constitute evidence of effectiveness of new anticancer agents for purposes of drug approval. This commentary is intended to illustrate a variety of end points that can lead to approval of new anticancer agents for specific clinical situations. Although the ultimate hope of antineoplastic therapy is prolongation of life, there are other effects of anticancer drugs that constitute clear clinical benefit and represent evidence of effectiveness. The guiding principle is that the beneficial effects obtained from a new drug should sufficiently outweigh the adverse effects such that the potential risk:benefit ratio achieved by an individual patient is favorable. The assessment of a new drug should flexibly evaluate safety and efficacy in the context of the specific clinical condition being treated. Early discussions with the Food and Drug Administration (FDA) and the National Cancer Institute (NCI) are recommended to identify prospectively the end points and trial designs needed to demonstrate effectiveness of a new drug. The general principles discussed will likely apply to the drug approval process for other medical disciplines as well.

Antineoplastic Agents↗
PubMed1990

Opportunities in clinical trials. Adjuvant breast cancer.

Breast cancer is the most common cancer in women in the US, with approximately two-thirds of patients presenting with tumors confined to the breast alone or breast and ipsilateral axillary lymph nodes. Although all of these women can be rendered free of detectable breast cancer by local therapeutic modalities, many will experience recurrences regionally or at distant sites. Nearly all patients who have distant recurrences will subsequently die of breast cancer. Although metastatic breast cancer responds to a variety of hormonal and chemotherapeutic interventions, it is rare that such therapy is curvative. Hence, there has been great interest in studying adjuvant systemic therapies. There is now a long clinical trial experience with adjuvant therapy in breast cancer that provides an extensive background for implementing recent advances in molecular and cellular biology in the clinical setting. Predictably, these laboratory-clinical correlations will provide important leads for future generations of randomized adjuvant trials, both by helping to target new therapies for particular subsets of patients and by identifying prognostic groups. In this report, current efforts in adjuvant therapy trials and laboratory-clinical correlations being conducted in conjunction with those trials are described.

Breast Neoplasms↗
PubMed1990

The distribution of [14C]acrylamide in rainbow trout studied by whole-body autoradiography.

The distribution of [2,3-14C]acrylamide was studied in fingerling rainbow trout by whole-body autoradiography. Fish weighing approximately 7 g were injected ip with 3.2 mg/kg [14C]acrylamide (0.1 microCi/g). One group of fish was kept in a fresh flowing water tank and frozen in dry ice/hexane 22 hr after injection; another group was placed in a separate tank of fresh flowing water and frozen 120 hr after treatment. A third group of fish served as nontreated controls. The autoradiographs of the fish at 22 hr show the highest concentration of radioactivity in the kidney, urinary bladder, blood, gallbladder, intestinal contents, and lens of eye. Lesser amounts of radioactivity are seen in the CNS, liver, and gills. Very low concentrations are seen in muscle. By 120 hr the only high concentrations are seen in gallbladder and lens of the eye. Lesser amounts are seen in the sclera, vertebrae, CNS, kidney, wall of intestine, and discrete spots in subcutaneous tissue presumed to be chromatophores. Low amounts are seen in muscle, the tissue usually consumed by man.

Acrylamide↗
PubMed1989

Oncology.

Explore the source record for details and available documents.

Humans↗
PubMed1989

Adjuvant multimodality treatment of rectal cancer.

It has long been recognized that curative surgery as the sole treatment for rectal cancer yields disappointing results. There is now a growing body of evidence from prospective randomized clinical trials to support the role of adjuvant therapy for patients whose primary tumour has spread through the rectal wall or has associated lymph node involvement. Carefully planned radiation therapy with adequate doses and fields can reduce the risk of locoregional failure. Chemotherapeutic agents delivered either systemically or regionally may also contribute to better disease control and survival. A number of diagnostic and therapeutic issues still need to be addressed in order to use the available adjuvant treatment methods most appropriately. Efforts to refine patient selection, to enhance therapeutic effect and to minimize toxicity are likely to improve the outlook for patients with resectable rectal cancer.

Antineoplastic Agents↗
PubMed1989

Locally advanced breast cancer current status and future directions.

Patients described as having locally advanced breast cancer comprise a heterogeneous group of patients with variable clinical presentations. Systematic evaluation of patients with these presentations has been limited, with much of our current understanding based on retrospective reviews. Prospective pilot studies have demonstrated the feasibility of multimodality therapy. However, there have been few well-conducted randomized trials in this setting. Comparison of results among studies is made difficult by the varying eligibility criteria and the way in which the data are reported. The use of common and consistent definitions of operable and inoperable disease is necessary for a more uniform understanding of the therapeutic interventions necessary for a given patient within this broad category of Stage III or locally advanced breast cancer. There are a variety of opportunities for clinical research activities in this group of patients including tests of hormonal recruitment or synchronization, high dose chemotherapy requiring autologous bone marrow transplantation, perioperative or preoperative chemotherapy, and alternating chemotherapy with short course radiotherapy. The integration of clinical information with biological characteristics of the tumor such as cytokinetics, oncogene amplification, and hormone receptors will be an important and necessary focus of future investigation in this disease.

Breast Neoplasms↗
PubMed1989

Treatment of patients with advanced colorectal carcinomas with fluorouracil alone, high-dose leucovorin plus fluorouracil, or sequential methotrexate, fluorouracil, and leucovorin: a randomized trial of the Northern California Oncology Group.

We compared the effectiveness of fluorouracil (5-FU) alone (arm A), high-dose leucovorin plus 5-FU (arm B), and sequential methotrexate, 5-FU, and leucovorin (arm C) for treatment of patients with advanced colorectal carcinomas who had not received prior chemotherapy. Arm A consisted of infusions of 5-FU at 12 mg/kg/d intravenously (IV) for 5 days followed by weekly infusions of 5-FU at 15 mg/kg; arm B consisted of leucovorin infusions at 200 mg/m2/d IV plus infusions of 5-FU at 400 mg/m2/d IV on days 1 through 5 of a 28-day cycle; arm C consisted of methotrexate at 50 mg/m2 orally every 6 hours for five doses followed by infusions of 5-FU, 500 mg/m2 IV, and leucovorin, 10 mg/m2 orally, every 6 hours for five doses every other week. A total of 265 patients were entered into the trial, of whom 249 (94%) were fully evaluable. The objective response rate (complete [CR] plus partial [PR] responses) was 17.3% on arm A, 18.8% on arm B, and 19.8% on arm C (log-rank test, P greater than .4). The median time to failure was 138 days on arm A, 166 days on arm B, and 182 days on arm C (log-rank test, P values of arm A v B = .06; arm A v arm C = .04). Median survival was 345 days on arm A, 324 days on arm B, and 356 days on arm C (log-rank test, P greater than .4). Treatment with 5-FU alone was significantly more dose intensive and more toxic than either of the experimental combinations. The rates of grade 3 or greater nonhematologic toxicity were 42.3% on arm A, 24.3% on arm B, and 14.3% on arm C. Hematologic toxicity was milder but had the same pattern. This study indicates that these regimens of high-dose leucovorin plus 5-FU and sequential methotrexate, 5-FU, and leucovorin are not more effective than is 5-FU alone for treatment of patients with colorectal carcinomas when 5-FU is administered at high-dose intensity.

Adult↗