摘要:

AbstractA total of 211 patients with limited small cell lung cancer were assessed retrospectively for long-term toxicities, treatment-related deaths, and second primaries. All had received treatment with various combinations of doxorubicin, vincristine, cispla-tin, lomustine, cyclophosphamide, and etoposide with or without split-course thoracic radiotherapy (4,000 cGy/10 fractions) and/or split-course prophylactic cranial irradiation (3,600 cGy/10 fractions). Sixty-eight (32%) ofthe patients survived longer than 1.5 years and formed the basis of this study. Debilitating pulmonary, cardiac, and neurologic toxicity was noted in 12%, 14%, and 15%, respectively, of long-term survivors. These complications were the result of aggressive combined modality therapy. Certain drugs appeared to cause additive toxicity when combined with radiation. Three patients developed new primary tumors of squamous cell origin. Attention must be directed to defining the safest way to employ aggressive combined modality treatment for these patients.

ISSN:0735-7907    

DOI:10.3109/07357908809078033

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractWe studied the effects of short-term dietary restriction on the survival of 3-4-month-old tumor-free and tumor-bearing Fisher rats. The diet-restricted food regimen consisted of alternate day ad libitum feeding followed by alternate day fasting. Diet-unrestricted control rats were fed ad libitum daily. Six tumor-free rats on the diet-restricted regimen compensated for the dietary restriction by an increase in food consumption during the alternate feeding days, and lost an average of only 2-3% of their weight in 13 days. Six tumor-free rats on a daily ad libitum feeding regimen gained an average of 6.8% in 15 days. The above dietary-restricted regimen was initiated 1 week before 24 rats were inoculated intraperitoneally with 15 million Mat 13762 ascites tumor cells. Sixteen of 24 (66.7%) diet-restricted tumor-bearing hosts and 5/24 (20.8%) diet-unrestricted tumor-bearing hosts survived at 9 days after tumor inoculation (p<0.005). Twelve of 24 (50%) diet-restricted tumor-bearing hosts, and 3 of 24 (12.5%) diet-unrestricted tumor-bearing hosts, survived at 10 days after tumor inoculation (p<0.025). Thus, the survival of tumor-bearing rats was enhanced by short-term relatively mild dietary restrictions. We suggest that relatively mild dietary restrictions should be included in clinical trials designed to inhibit cancer growth and enhance the survival of human cancer patients.

ISSN:0735-7907    

DOI:10.3109/07357908809078034

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractLewis lung carcinoma (LLC) induces a range ofhemopoietic alterations in its murine host including progressive anemia, thrombocytopenia, splenomegaly, neutrophilia, and marrow and splenic myeloid hyperplasia. Concentrations of both pluripotent and committed marrow hemopoietic progenitors is increased and the cycling fraction of granulocyte-macrophage progenitors is accelerated. We have developed a way to study whether these hemopoietic effects become long-term consequences of cancer, using LLC-bearing mice with advanced tumor treated with the antineoplastic agent tiazofurin, 2-β-D-ribofuranosyl-thiazole-4-carboxyamide, NSC 286193 (TZ). LLC mice were treated with a single dose of TZ either 150, 300, or 600 mg/kg, intraperitoneally on day 6 posttumor implant when lung metastases are present and all hemopoietic effects of the tumor are recognizable. Even a single dose of 150 mg/kg of TZ produced a significant survival advantage, and 600 mg/kg resulted in 30% of the animals remaining disease free during a 5-month follow-up. A 6-week treatment schedule was devised, administering TZ intraperitoneally, 600 mg/kg, weekly beginning on day 6. In this group, median survival was not reached after 9 months of follow-up. The only evidence of myelotoxicity produced by intermittent administration of TZ was a mild anemia which was fully reversible 2 weeks after discontinuance of the drug. No difference in white blood cell count, differential count, or platelet count was detected in tumor bearers and controls treated with TZ. Both pluripotent and committed marrow hemopoietic precursors remained unchanged in TZ-LLC, TZ-controb and untreated controls throughout treatment and 2 weeks thereafter. This study demonstrates that TZ-cured LLC mice are suitable to explore late hemopoietic effects of cancer.

ISSN:0735-7907    

DOI:10.3109/07357908809078035

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractRabbit polyclonal antibodies (pAb) were raised against a yeast ras-related protein YP20 and shown to be immunoreactive with human normal as well as altered Ha-ras and Ki-ias p21 gene products using immunoblotting and immunoprecipitation techniques. The p21 protein revealed by anti-YP20 antibodies comigrates with p21 protein detected by anti-p21 monoclonal antibody (Cetus Diagnostics). These pAbs were tested against a panel of human acetone-fixed tumor cell lines and malignant effusions and nonfixed fresh-frozen tissue sections obtained from cancer patients by the indirect immunofluorescence assay (IFA). Twelve of sixteen (75%) sarcoma and carcinoma cells lines and one fibroblast cell line were stained by the anti-YP20 pAb. The binding occurred most commonly in the cytoplasm. Six of eight fresh-frozen colon and breast cancer tissue sections were immunostained and normal sections from these organs or skin showed only low level of binding to thepAbs. Four of five malignant effusions were distinctively immunostained. These antibodies are suggested to serve as additional probes for assessing the expression of ras gene-related proteins in human malignancy.

ISSN:0735-7907    

DOI:10.3109/07357908809078036

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractThere is a recent increased incidence of cancer of the pancreas that is more marked in men. Over 21,000 patients per year develop this disease. It currently ranks as the fourth most common cause of cancer-related mortality in the United States and is the second most common gastrointestinal malignancy (1,2). Because of its inaccessible location in the body, lesions are not diagnosed until they are quite advanced. As a result, survival rates are low, with less than 2% of patients surviving 5 years (1). The death rate from cancer of the pancreas has risen from 10/100,000 in 1940 to 40/100,000 in 1960, to greater than 70/100,000 in the 1980s.

ISSN:0735-7907    

DOI:10.3109/07357908809078037

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractINTRODUCTIONThe interactions between cells and their extracellular matrices are controlled by various intracellular and exogenous signals. The control of these interactions by polypeptide growth factors appears to involve different levels of regulation. Growth factors can, in addition to the regulation of cell proliferation, direct cell migration and movement, alter the production of different connective tissue components, and regulate extracellular proteolysis. Of particular interest are the autocrine and paracrine growth factors produced by both normal and malignant cells (1-5).

ISSN:0735-7907    

DOI:10.3109/07357908809078038

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractINTRODUCTION AND BACKGROUND Our understanding of carcinogenesis in liver and other tissues has progressed steadily with the use of a sequential analytical approach (1-5). Persistent nodule hepatocytes which are potential precursors for cancer were shown to be resistant in vivo relative to the surrounding hepatocytes to cytotoxic and mitoinhibitory effects of hepatocarcinogens and hepatotoxins (6,7). A working hypothesis was that one population of initiated hepatocytes has this resistance property (1,3-9). To test this hypothesis of resistant hepatocytes as products of initiation with Farber and co-workers (1,9-13), we used single exposures to a variety of chemical carcinogens as initiators. This work showed that focal populations of hepatocytes were present in the liver after initiation which were resistant to cytotoxic and mitoinhibitory effects of 2-acetylaminofiuorene (2-AAF) and were manifest as nodular proliferations in response to resistance-selection with 2-AAF (9-14) or lasiocarpine (15). The resistant hepatocyte (RH) model became a useful bioassay for initiation (1,4,5). From these studies, a number of important conclusions about initiation could be reached: (a) cell proliferation of hepatocytes (within 3 days of initiating chemical exposure) is essential for initiation to occur (10-14), (b) the original clone of resistant hepatocytes after initiation is projected to be at most only a few cells in size (1,16), (c) these resistant hepatocyte nodules generated by initiation and resistance-selection are a rare event (1) or about 1 RH clone per 105or 106total hepatocytes exposed to an initiating carcinogen in vivo (1,4,5). In spite of the fact that resistant hepatocytes in persistent nodules arising after both initiation and resistant-selection could be readily studied biochemically, functionally (biologically), or histopathologically 07-31), initiated (resistant) hepatocytes induced by initiation alone without selection were not yet analyzable (1,4,5).

ISSN:0735-7907    

DOI:10.3109/07357908809078039

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractThe discovery of the Philadelphia chromosome as a marker for chronic myelogenous leukemia (CML) in 1960 represented an important scientific breakthrough (1). It established for the first time that a specific chromosomal abnormality was associated with a specific malignancy. Unfortunately, this major event did not translate into direct clinical benefits for patients with this disease. Over the next 20-25 years, our understanding continued to grow while our clinical approach remained essentially unchanged. We know that the Philadelphia chromosome is the result of a translocation (2) and we understand the nature of aberrant and complex translocations (3). A consistent molecular event associated with the Philadelphia chromosome has been characterized (4,5). We understand that Philadelphia-negative CML may have the same molecular basis as Philadelphia-positive CML (6) and the relationship between this disease and Philadelphia-positive acute lymphoblastic leukemia (ALL) has also been clarified (7,8).

ISSN:0735-7907    

DOI:10.3109/07357908809078040

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractINTRODUCTION In the untreated state, patients with chronic myelogenous leukemia (CML) generally are asymptomatic and do not require urgent or intensive therapy. Resolution of the signs and symptoms of the disease using standard therapies is achievable without significant toxicity or risk to the patient. However, unlike acute myelogenous leukemia (AML), where true remissions can be obtained, in CML, despite attaining“hematologic”remission, persistence of the abnormal malignant clone as evidenced by the presence of the Philadelphia chromosome-positive (Ph+) cells is characteristic. Eventually all patients with CML, despite control of their disease in the chronic state, will enter a blastic or terminal phase resembling acute leukemia which, for the most part, is resistant to therapy. Patients with CML can expect a median survival of approximately 36-40 months (1) which has not changed appreciably in the last five decades. The recognition of this has led to the pursuit of more aggressive therapy using chemotherapy, immunotherapy, and chemoradiotherapy with marrow transplantation. This review focuses on the treatment of CML in the chronic phase, the use of aggressive therapy to obtain true remission and possible cure, and the therapeutic options available to patients who have entered the blastic phase.

ISSN:0735-7907    

DOI:10.3109/07357908809078041

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor

摘要:

AbstractOncologists point with pride to developments in the management of small cell lung cancer as an example of the heights modern cancer therapy has reached. Immediate improvement in both the control of cancer-related symptoms and survival are obvious in this deadly and common solid tumor affecting nearly 40,000 Americans annually.

ISSN:0735-7907    

DOI:10.3109/07357908809078042

出版商:Taylor&Francis    

年代:1988

数据来源: Taylor