摘要:

AbstractThe mononuclear cell content and mononuclear cell function of human solid tumors were determined. Twenty‐eight primary, and 17 metastatic solid tumors, including 6 lymph node metastases, were obtained from 45 patients. Cells were released from the tumors by mincing, scraping, and sieving. Analysis of the cellular content was determined by light microscopy, and tumor lymphocyte function was determined by stimulation of blastogenesis with PHA, PWM, Con‐A, MLC, and SLO. A median of 3.3 × 107tumor cells with 12.5% viability was obtained per gram of tumor, and a median of 7.8 × 106lymphocytes with a viability of 96% and 0.35 × 106macrophages with a viability of 85% was also obtained per gram of tumor. Significant lymphocyte responses to various mitogens and antigens were obtained in 31–40% of the tumor lymphocyte preparations. From 9.4% to 23% had vigorous responses with a stimulation index greater than 10. Primary tumors contained significantly more lymphocytes than metastatic tumors; thus, the percent lymphocytes in primary tumors was 13.5% compared to 5% for metastatic tumors. In contrast, some of the lymphocyte responses were significantly greater for metastatic tumors than primary tumors. These data suggest that the direct study of lymphocytes infiltrating primary and metastatic tumors may be a useful approach to understanding tumor immunit

ISSN:0098-1532    

DOI:10.1002/mpo.2950020102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1976

数据来源: WILEY

摘要:

AbstractPharmacological data are currently available for a number of antineoplastic agents which have shown clinical activity in advanced breast carcincoma. Preclinical data reveal a relationship between therapeutic response and certain pharmacokinetic parameters such as time of effective cytotoxic exposure (Teff) and the product of concentration with time (Cxt). We have attempted to apply human pharmacologic data to get estimates of these parameters for 6 active agents in breast cancer, to relate them to response rates, and to suggest a method for estimating the role of individual drugs in a multidrug combination.The response rates for 6 single agents were obtained from literature review and related to estimates of Teffand Cxt. The Cxt‐response relations for single drugs were linear for cyclophosphamide, 5‐fluorouracil, and thiotepa; exponential for vincristine; and relatively flat for methotrexate and cytosine arabinoside. Most Teffvalues for the active single agents clustered about 15 hr/dose.From the graphs of response rate vs Cxt, the individual contribution of each agent in a combination study was estimated to arrive at a predicted response rate. The predicted response rates for the combination studies correlated with the actual response rates determined in the clinical study, for 6 of 6 nonrandomized studies and for 12 of 14 randomized studies analyzed. In 2 studies, deviations from the predicted response rate were attributed to differences in study design or analysis. There was no correlation between Teffand predicted response rate. Analyses of pharmacokinetic data may be useful to simulate combination chemotherapy studies to predict the effectiveness of clinical trials in breast cancer. Since the pharmacologic data were not obtained for any of the agents in the actual clinical trials done, we can only speculate on the usefulness of this method. We would encourage the prospective collection of this data in future clinical tra

ISSN:0098-1532    

DOI:10.1002/mpo.2950020103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1976

数据来源: WILEY

摘要:

AbstractAlthough these studies do not allow a definitive differentiation between the relative influence of chemotherapy and radiotherapy on mitogen‐induced lymphocyte transformation, the data suggested both radiotherapy and chemotherapy can cause depression; however, radiotherapy may have a more pronounced effect. The relationship between the absolute peripheral blood lymphocyte count and phytohemagglutin and pokeweed mitogen‐induced lymphocyte transformation was also analyzed. These data revealed that patients who are receiving or who have received intensive therapy may have normal peripheral absolute lymphocyte counts with impaired lymphocyte transformation. Serial studies of lymphocyte transformation were evaluated in 10 children with acute lymphoblastic leukemia who received both chemotherapy and radiother

ISSN:0098-1532    

DOI:10.1002/mpo.2950020104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1976

数据来源: WILEY

摘要:

AbstractThe effects of various concentrations of hydroxyurea (HU) on a human lymphoid cell line in exponential growth phase have been studied using a combination of methods, including determination of the total and viable cell counts; the cells' relative DNA content, measured in a flow microfluorimeter after staining with a fluorescent Feulgen technique; the mitotic index; and the percentage of cells incorporating thymidine‐3H (TdR‐3H) during brief and continuous exposure to the isotope both in the presence and absence of colcemid.A significant redistribution of the cells in the various phases of the cell cycle occurred during the first 24 hr of continuous treatment with 10‐3M and 10‐2MHU as follows: (1) division of cells in G2; (2) depletion of mid and late S phase cells due to early cell death; (3) movement of most G1cells at a normal rate into early S phase where they accumulate; and (4) arrest of the remaining cells in G1, which represented the surviving population after treatment for 96 hr or longer. After removal of the drug, the cell fraction blocked in early S phase progressed semisynchronously through S, but many of the cells were unable to complete division. Their capacity to recover depended on the drug concentration and duration of exposure, but in general the cellular injury caused by HU was more reversible than that caused by “equivalent” concentrations of arabino

ISSN:0098-1532    

DOI:10.1002/mpo.2950020105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1976

数据来源: WILEY

摘要:

AbstractSeventy‐one women with far‐advanced breast cancer resistant to standard chemotherapeutic agents were administered mitomycin C using an intermittent high dose schedule. One group consisted of 54 patients with measurable metastatic tumor; a second group consisted of 18 patients with nonmeasurable osseous metastases. Objective response rate in group 1 was 26% for an average duration of 2 1/2 months. Subjective response rate in group 2 was 44% for an average duration of 3 months. Response and toxicity data were similar to those of studies employing the less convenient protracted low‐dose schedule. Prior treatment with other alkylating agents did not adversely affect response. Further investigation into the role of mitomycin in combination chemotherapy programs is recomm

ISSN:0098-1532    

DOI:10.1002/mpo.2950020106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1976

数据来源: WILEY

摘要:

AbstractOne hundred forty‐three children with refractory lymphoblastic and undifferentiated leukemia (ALL/AUL) were treated with cytosine arabinoside (Ara‐C) and prednisone (Pred). The dose and duration of Ara‐C was escalated during induction depending on the response seen in the peripheral blood and/or bone marrow. For those achieving a remission, Ara‐C was also used to determine its maintenance capabilities. Of the 143 children, 79 attained a clinical remission, 45 having a complete bone marrow remission and 34 having a partial remission. Maintenance of remission with twice weekly Ara‐C was short and did not appear to depend on the amount of Ara‐C given during induction. The major toxicity of Ara‐C was mye

ISSN:0098-1532    

DOI:10.1002/mpo.2950020107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1976

数据来源: WILEY

摘要:

AbstractThe liver extended a minimum of 5 cm inferior to the right costal margin in 51% of the 504 patients studied. In 53% of these patients, experienced, mature physicians declared that the liver was not palpable on physical examination. In 3% of the cases, a mass was palpated which was believed to be liver by the examining physician but was found to be extrahepatic upon scanning and laparotomy.The unreliability of physical examination in determining whether or not the liver extends inferior to the costal margin in many instances is demonstrated.

ISSN:0098-1532    

DOI:10.1002/mpo.2950020108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1976

数据来源: WILEY

摘要:

AbstractCardiac infiltration by hematologic neoplasms leading to clinically significant cardiovascular disease is rare. Three such cases are described in this report, and it is suggested that rare manifestations of hematologic neoplasms may become more common in the future since these diseases are more amenable to therapy than heretofore. Cardiac involvement with hematologic neoplasms is of more than academic interest since this complication is likely to respond to radiotherapy.

ISSN:0098-1532    

DOI:10.1002/mpo.2950020109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1976

数据来源: WILEY

摘要:

AbstractFrom 1921 to 1973, 106 children with Hodgkin's disease under the age of 17 years were seen at Roswell Park Memorial Institute and were analyzed retrospectively. Evaluation was separated into three eras: 1921–1949 (early era), 1950–1964 (middle era), and 1965–1973 (recent era). In the early era, suboptimal radiation therapy was employed. In the middle era, radiation therapy techniques were improved, and single‐agent chemotherapy was introduced. In the recent era, multiagent chemotherapy routines were frequently used; aggressive external megavoltage radiation therapy became routine in conjunction with improvement in staging procedures. The best survival was observed in the recent era where five‐year survival of 96% was noted in early stage disease.Favorable prognostic features included: younger age group (5–9 years), female sex, lymphocytic predominant histology, early stage disease, and complete response to therapy. Nodular sclerosing and mixed cell types had an equal prognosis. The concept of involved area radiotherapy along with combination chemotherapy appears a reasonable approach in children and should be tested in a randomized study against more extensive radiotherapy techniques in early st

ISSN:0098-1532    

DOI:10.1002/mpo.2950020110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1976

数据来源: WILEY

摘要:

AbstractGentamicin in combination with cephalothin (Gent‐Ceph) or with chloramphenicol (Gent‐Chloro) was utilized in the treatment of 55 infections occurring in 49 cancer patients. Responses were obtained in 78% of the infections treated with Gent‐Ceph and in 64% of those treated with Gent‐Chloro. Pneumonia and septicemia were the most common infections in this study. Among the cases of pneumonia, 64% responded to Gent‐Ceph and 67% to Gent‐Chloro. Among the cases of septicemia, 88% responded to Gent‐Ceph and 50% to Gent‐Chloro. All of the identified organisms producing infection were gram‐negative bacilli. Of these, E. coli was the most common. All organisms were resistant to cephalothin in vitro, and only 41% of them were resistant to chloramphenicol. However, resistant organisms responded significantly better to the Gent‐Ceph combination (p<0.025). Also, response to therapy among patients with severe neutropenia (<100 neutrophils/mm3) was better for those patients treated with Gent‐Ceph (p = 0.07).The combination of gentamicin with cephalothin or with chloramphenicol did not increase the frequency of side effects expected from gentamicin alone. No significant hematological toxicity was seen among those patients treated with chloramphenicol. Gentamicin in combination with cephalothin or chloramphenicol is an effective and safe antibiotic combination against gram‐negative bacilli infections occurring in cancer patients. The efficacy of Gent‐Ceph in patients with severe neutropenia is

ISSN:0098-1532    

DOI:10.1002/mpo.2950020111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1976

数据来源: WILEY