摘要:

Since dose intensity of doxorubicin is correlated with the clinical response of patients with sofl tissue sarcomas and since doxorubicin dose intensity niay be compromised in conibiiiation chemotherapy, we evaluated the use of recoinbinant granulocyte-macrophage colony-stiniulating factor (rGM-CSF) to ameliorate niyelosuppression and allow doxorubicin dose escalation in a phase I trial utilizing the MAID combination [Mesna 2.5 g/m2/day×4 days, Adrianiyciii (doxorubicin) 15 mg/m2/day×4 days, ifosfaniide 2.0 g/m2/day×3 days, dacarbazine 250 mg/m2/day×4 days; to be repeated every 21 days]. Thirteen patients were treated. The doxorubicin dose for the first 6 patients was at the standard dose of 15 mg/m2/day×4 days (level I), while the doxorubicin dose for the next 7 patients was escalated by 25% to 18.75 mg/m2/day×4 days (level 2). tGM-CSF was given at 5μg/kg/day, days 5-14. All patients experienced moderate to severe tiyelosuppression, with all patients at dose level 2 requiring doxorubicin dose reduction to dose level I or lower by their third course of treatment. rGM-CSF failed to allow sustained escalation of the doxorubicin dose in the MAID reginien.

ISSN:0735-7907    

DOI:10.3109/07357909609076895

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Appropriate staging procedures for patients with hormone-refractory prostate cancer are poorly defined. In particular, there are no studies correlating prostate-specific antigen (PSA) with more traditional methods of staging. We have evaluated the abdominal/pelvic CT scan, bone scan, and PSA results following initial diagnosis of hot-nione-refractory prostate cancer in 177 consecutive patients (median age = 63.1 years, range 45-80). Thirty-four patients (19.2%) had nteasurable lesions (≥2 cm) on CT scan cotnpatible with inetastatic disease. Of the patients with measurable lesions, 29/34 (85.3%) had iztroperitoneal and/or- pelvic adenopathy; 5 patients (14.7%) had measurable lesions in the liver. Other- sites of metastatic disease were detected in less tkari 1% of the patients receiving scans. All patients had bone scan abriormalities compatible with metastatic disease. Results of these imaging studies were then compared to PSA serum concentration (Abbott IMx). The mean PSA concentration was not direrent in those patients with soft tissue disease as compared to those without soft tissue involvement and there was no correlation between PSA concentration and the presence or absence of measurable soft tissue disease. In contrast to previously published studies in hormone-naile prostate cancer patients, these studies in hormone-refractory patients indicate that the detection of metastatic disease by standard radiological procedures camot be predicted by measurement of serum PSA.

ISSN:0735-7907    

DOI:10.3109/07357909609076896

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

To identify genes associated with tumor metastasis, we prepared 5 cDNA libraries using mRNA from normal ovaries, paired primary and metastatic ovarian tumors, as well as paired cultured ovarian tumor cells. By differential screening, we identified 12 clones, which can be divided into 3 classes based on hybridization to various probes. Class 1 clones showed no reaction with the normal probe, slight or no reaction with the primary probe, but high reaction with the metastatic probe. Class 2 clones showed some reaction with normal and primary probes, but showed stronger reaction with the metastatic probe. Class 3 clones showed strong hybridization to the normal probe, slight or no reaction with the primary probe, and did not hybridize with the metastatic clone. These clones were further analyzed by determination of DNA sequence. One of the class 1 clones (clone I) was identified as ferritin heavy chain. Northern blot analysis showed higher expression of ferritin H-chain in metastatic samples compared to primary tumor in 16/23 pairs of samples analyzed so far.

ISSN:0735-7907    

DOI:10.3109/07357909609076897

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We reviewed all reported cases of Burkitt's lymphoma and/or Burkitt's leukemia (BLL) occurring following therapy for Hodgkin's disease. In addition to the case described in this report, a total of 19 patients have been previously reported. The male/female ratio was 3.75. Treatment for Hodgkin's disease included chemotherapy combined with radiation therapy in 15 patients, chemotherapy in 3 patients, and radiation therapy alone in 1 patient. Median interval between Hodgkin's disease and the diagnosis of BLL was 97 months. Patient characteristics are similar to those with de novo BLL. Bone marrow, abdomen, central nervous system, as well as extranodal organs were commonly involved. Typical cytogenetic translocations seen in patients with primary BLL were found in 6 patients, but 5 of these patients had additional cytogenetic abnormalities. Only 2 patients achieved complete remission after chemotherapy. The mechanism for the development of BLL after treatment for Hodgkin's disease is unknown. Although the majority of cases have been seen in patients treated with combined-modality therapy, the role of previous therapy in causing this complication cannot be assessed in this study.

ISSN:0735-7907    

DOI:10.3109/07357909609076898

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield alpha particles and recoiling lithium-7 nuclei. High-grade astrocytomas, glioblastoma multiforme, and metastatic brain tumors constitute a major group of neoplasms for which there is no effective treatment. There is growing interest in using BNCT in combination with surgery to treat patients with primary, and possibly metastatic brain tumors. For BNCT to be successful, a large number of10B atoms must be localized on or preferably within neoplastic cells, and a sufficient number of thermal neutrons must reach and be absorbed by the10B atoms to sustain a lethal10B (n,α)7Li reaction. Two major questions will be addressed in this review. First, how can a large number of10B atoms be delivered selectively to cancer cells? Second, how can a high fluence of neutrons be delivered to the tumor? Two boron compounds currently are being used clinically, sodium borocaptate (BSH) and boronophenylalanine (BPA), and a number of new delivery agents are under investigation, including boronated porphyrins, nucleosides, amino acids, polyamines, monoclonal and bispecific antibodies, liposomes, and epidermal growth factor. These will be discussed, and potential problems associated with their use as boron delivery agents will be considered. Nuclear reactors, currently, are the only source of neutrons for BNCT, and the fission process within the core produces a mixture of lower-energy thermal and epithermal neutrons, fast or high (>10,000 eV) energy neutrons, and gamma rays. Although thermal neutron beams have been used clinically in Japan to treat patients with brain tumors and cutaneous melanomas, epithermal neutron beams should be more useful because of their superior tissue-penetrating properties. Beam sources and characteristics will be discussed in the context of current and future BNCT trials. Finally, the past and present clinical trials on BNCT for brain tumors will be reviewed and the future potential of BNCT will be assessed.

ISSN:0735-7907    

DOI:10.3109/07357909609076899

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

First-line treatment of malignant gliomas invariably includes surgery when feasible, and often adjuvant radiotherapy with or without chemotherapy; at progression or recurrence, the only remaining possibility is chemotherapy. While the role of first-line treatment has been established by many randomized studies, second-line treatment is not as well defined. To analyze the difficulties encountered with cytotoxic drugs in relation to both the blood-brain barrier and drug resistance, we examined the results obtained by single-agent chemotherapy, drug combinations, and biological response modifiers. Our findings confirmed that the nitrosoureas are the most active substances at the time of recurrence; these agents give an approximately 30% global response rate, with about 20 weeks' survival. Although no comparative randomized studies regarding single- versus multiple-agent chemotherapy are available, the latter approach, including nitrosourea, can obtain an up to 40% rate of response, with survival ranging from 30 to 50 weeks. The role of interferons has been very controversial; individually, alpha- and beta-interferons seem to give a 20% response rate, with 20 weeks' survival. To date, they have never been used in combination with cytotoxic drugs, but they may prove synergistic without increasing toxicity. Studies addressing the quality of life of these patients are not available, and it is clear that we need more basic research in this field.

ISSN:0735-7907    

DOI:10.3109/07357909609076900

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909609076901

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909609076902

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0735-7907    

DOI:10.3109/07357909609076903

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

This brief review article deals with the subject of anticarcinogenic activity of protease inhibitors (PI). Three basic premises are made: (1) Although PI are prevalent constituents of dietary staples such as soy products, which have been epidemiologically associated with reduced cancer incidences at multiple target sites, they are unlikely to be the active anticarcinogenic entities. Cooked soy products, which are devoid of PI activity, are equally as effective at reducing cancer development as raw soy products. Isoflavones are likely to represent major chemopreventive agents in soy, although other constituents may well contribute. (2) Although supplementation of diets with PI (natural or synthetic), or direct topical administration, results in lower cancelincidences in many experimental models in vivo, this effect appears to be indirect. Dietary PI are, in general, poorly absorbed from the GI tract, and never reach target organs in any measurable quantity. The most attractive hypothesis is that dietary PI could induce synthesis and distribution of endogenous PI (acute-phase readouts), which have widespread effects on cell growth and behavior. Effects of topical administration of PI also encompass prominent anti-inflammatory effects. (3) A spectrum of PI inhibit in vitro transformation induced by a variety of carcinogenic agents. Their effects can be grouped into three basic categories, affecting: (a) signal transduction pathways; (b) DNA repair processes; and (c) nuclear proteases. I suggest that the nuclear multicatalytic protease activity, in particular the chymotrypsin-like activity, represents an important cellular target for which considerable anecdotal support can be garnered.

ISSN:0735-7907    

DOI:10.3109/07357909609076904

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor