Abstract:
:Navelbine (NVB) or 5' nor-anhydro-vinblastine was shown to present a broader antitumor activity and to induce fewer side effects than vinblastine (VBL) or vincristine (VCR). The possible mechanisms of these differences were analyzed with in vitro methods. At substoichiometric concentrations, the three drugs inhibit microtubule assembly. NVB, in comparison with VCR and VBL, is shown to have a lower inhibitory effect. At stoichiometric concentrations, the three drugs are able to induce tubulin aggregation into spirals and paracrystals. This process involves a microtubule-associated protein (MAPs) family referred to as Tau and is inhibited by another MAPs family referred to as MAP2. However, dramatic quantitative and qualitative differences are observed between NVB and VLB or VCR in TAU-induced aggregation of tubulin. The rate and extent of NVB-induced tubulin aggregation is much lower. With NVB, only certain TAU isoforms are able to induce paracrystals, while all TAU isoforms may contribute to VCR-induced or VBL-induced paracrystals. The TAU isoforms that are not able to induce crystallization with NVB, at least in a certain range of concentrations, are probably involved in mitotic microtubules--the hypothetical antitumoral target of vinca alkaloids (VAS). The present work shows for the first time that an anticancer drug is able to discriminate between the various types of microtubules. A next step will be to investigate whether this property is limited to a modulating effect of the various TAU isoforms on the affinity of VAS for tubulin. These biochemical investigations will be extended to tubulins extracted from tumor cell lines in order to further discriminate NVB from the other VAS.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Fellous A,Ohayon R,Vacassin T,Binet S,Lataste H,Krikorian A,Couzinier JP,Meininger Vsubject
Has Abstractpub_date
1989-04-01 00:00:00pages
9-14issue
2 Suppl 4eissn
0093-7754issn
1532-8708journal_volume
16pub_type
杂志文章abstract::Patients diagnosed with germ cell tumors (GCT) are relatively young, and most are rendered disease-free by primary treatment. Also, second-line therapies in nearly all instances are potentially curative. Therefore, the schedule and modalities of follow-up testing are important issues in detecting recurrence of GCT and...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1016/s0093-7754(03)00098-8
更新日期:2003-06-01 00:00:00
abstract::The current resurgence in the use of nomograms as diagnostic and prognostic tools has legitimate roots in their effectiveness in facilitating communication between the doctor and patient. By returning to a more classical approach to nomography, graphical insights can further enlighten the patient beyond what can be ac...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/j.seminoncol.2009.12.003
更新日期:2010-02-01 00:00:00
abstract::First-line therapy for men with metastatic or recurrent prostate cancer following definitive local therapy is medical or surgical castration. Though effective initially in most patients, the majority of tumors develop castration resistance, necessitating the addition of further therapy. The historic treatment paradigm...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2013.04.015
更新日期:2013-06-01 00:00:00
abstract::Session V of the Colloquium was chaired by Professors Teresa López-Fernández of Spain and Grzegorz Opolski of Poland. The 3 speakers addressed cardio-oncology issues as they relate to both clinical studies and real life situations. Professor Susan Dent discussed cardio-oncology networks for patients, emphasizing the i...
journal_title:Seminars in oncology
pub_type:
doi:10.1053/j.seminoncol.2019.01.004
更新日期:2019-12-01 00:00:00
abstract::Thus, many interesting and promising techniques are now available for the study of potential prognostic factors in esophageal carcinoma, and the results may supplement the information that is obtained by routine histopathologic analysis. It may become possible to define subgroups of patients with lower risk tumors, fo...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1994-08-01 00:00:00
abstract::In vitro uptake and retention of 3H-cytosine arabinoside (ara-C) was studied in 68 acute myelogenous leukemia (AML) patients (ten were studied twice) treated with a regimen containing conventional (54 patients) or high doses (24) of ara-C. Drug uptake and retention after four hours were measured following 30 minutes e...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::Many cytotoxic therapies are available for patients with metastatic breast cancer, but response rates are low and acquired or de novo resistance is virtually universal. Among the agents that are used in the treatment of pretreated metastatic breast cancer are vinorelbine, gemcitabine, nab-paclitaxel, pemetrexed, plati...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2011.04.005
更新日期:2011-06-01 00:00:00
abstract::Radiation is an effective modality to aid in symptom management of patients with metastatic disease. The type and duration of treatment depends on the Karnofsky performance status (KPS) of the patient and type and status of the cancer. Abbreviated treatment regimens may be favored in this patient population. They prov...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2004.11.013
更新日期:2005-04-01 00:00:00
abstract::Bendamustine has clinical potential in the treatment of low-grade non-Hodgkin's lymphoma (NHL). As a single agent, bendamustine has been used in two studies in patients with relapsed or refractory low-grade NHL. When bendamustine 120 mg/m(2) was given on days 1 and 2, the overall response rate was 73% with complete re...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.34877
更新日期:2002-08-01 00:00:00
abstract::The optimal management of early stage ovarian cancer with poor prognostic features remains controversial. On the basis of results of studies in advanced ovarian cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with a platinum agent has become part of adjuvant chemotherapy trials i...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2000-06-01 00:00:00
abstract::The side effects of cisplatin (75 mg/m2) in combination with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (175 mg/m2 over 3 hours) are expected to be more severe and frequent than those of carboplatin (area under the concentration-time curve of 5) in combination with the same dose of paclitaxel, but...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1997-10-01 00:00:00
abstract::In this feasibility study, a 3-hour infusion of 225 mg/m2 paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was combined with carboplatin dosed to an area under the concentration-time curve of 6 to treat patients with stage T2N0, T1-2N1, or T3N0-1 (excluding superior sulcus tumors) non-small cell lung ca...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated substantial single-agent activity against both minimally pretreated and resistant metastatic breast cancer. Evaluation of paclitaxel-based combinations has demonstrated appreciable activity, but also toxicity, for the paclitaxel/doxorubic...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::Coelomic epithelial carcinoma of the ovary, the most common cause of death from cancer of the female genital tract in the United States, presents most commonly as advanced (stage III or IV) disease. Management consists of aggressive surgical cytoreduction followed by combination chemotherapy, until recently, a platinu...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1995-12-01 00:00:00
abstract::The current study was conducted to determine the risk of adverse outcomes among patients with monoclonal gammopathy of undetermined significance (MGUS) of the IgM class. Two hundred thirteen patients with IgM MGUS were identified in southeastern Minnesota from 1960 to 1994. The primary end point was progression to lym...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/sonc.2003.50062
更新日期:2003-04-01 00:00:00
abstract::The purpose of this review is to demonstrate a successful use of preclinical models of bladder cancer to confirm the therapeutic potential of new promising drug candidates. The bladder has long been thought to be an ideal target for investigating therapies. When developing a new antineoplastic pharmaceutical agent, th...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2012.08.006
更新日期:2012-10-01 00:00:00
abstract::HER2 is a transmembrane growth factor receptor found in normal and malignant breast epithelial cells. Phosphorylation of the intracellular tyrosine kinase results in intracellular signaling and activation of genes involved in cell growth. Overexpression of HER2 has independent prognostic significance in early breast c...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:2001-12-01 00:00:00
abstract::Fludara I.V. (fludarabine phosphate) (9-beta-D-arabinosyl-2-fluoroadenine, F-ara-A) is an adenine nucleoside analogue resistant to adenosine deaminase that shows promising therapeutic activity in the clinical treatment of lymphocytic hematologic malignancies. F-ara-A is transported into cells, where it is converted to...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1990-10-01 00:00:00
abstract::From this brief review is should be evident that the hereditary varieties of common cancers are characterized by a high degree of genetic heterogeneity. The specific types of hereditary cancers can be identified by focusing on the histologic types and sites of involvement, not only of the primary neoplasm, but also of...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1978-03-01 00:00:00
abstract::Experimental and clinical observations of the proliferation of cancer cells and their responses to cytotoxic drugs already have had an impact on the design of anticancer therapies and it is possible that further understanding of the natural history of tumors will enable better treatments to be developed. This review a...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1997-08-01 00:00:00
abstract::Etoposide is one of the few cancer chemotherapy agents that is schedule-dependent in both preclinical and clinical studies. A randomized trial of etoposide as initial therapy in extensive small cell lung cancer (SCLC) demonstrated the superiority of a 5-day course versus the same total dose administered over 24 hours....
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::The targeting of molecular abnormalities in neoplasms may provide an opportunity to improve the selectivity of cancer therapy. Ras mutations are a common genetic event in human cancers. Other genetic changes in tumors can signal through ras-dependent pathways as well. The targeting of ras through the inhibition of Ras...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1016/s0093-7754(01)90286-6
更新日期:2001-10-01 00:00:00
abstract::Thus far the development of adjuvant therapies in melanoma has suffered greatly from the lack of effective drugs in stage IV melanoma. Chemotherapy, cytokines, vaccines, and combinations of drugs have been used with minimal success. This has led to adjuvant therapies that are not used uniformly or widely because of th...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2010.09.009
更新日期:2010-10-01 00:00:00
abstract::Ifosfamide was developed by investigators at Asta-Werke in Germany. Its chemical structure differs from that of cyclophosphamide by the transposition of one of the side chain chloroethyl groups to the ring nitrogen. In several preclinical models, ifosfamide had greater activity than cyclophosphamide. It produced less ...
journal_title:Seminars in oncology
pub_type: 历史文章,杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::This presentation represents consensus recommendations for the treatment of patients with Waldenstrom's macroglobulinemia (WM), which were prepared in conjunction with the second International Workshop held in Athens, Greece during September 2002. The faculty adopted the following statements for the management of pati...
journal_title:Seminars in oncology
pub_type: 共识发展会议,杂志文章,评审
doi:10.1053/sonc.2003.50039
更新日期:2003-04-01 00:00:00
abstract::Adrenocortical cancer (ACC) is a rare, challenging disease with a broad range of clinical presentations. Often presenting in an advanced stage with a large, locally invasive primary tumor or with Cushing's syndrome, it requires a multidisciplinary approach to treatment. We discuss controversies in the evaluation and m...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2010.10.011
更新日期:2010-12-01 00:00:00
abstract::This randomized, multinational, multicenter study was designed to determine the response rate of gemcitabine monotherapy and cisplatin/etoposide combination therapy in chemotherapy-naive patients with advanced, recurrent, and/or metastatic non-small cell lung cancer (stage IIIA [if inoperable], IIIB, or IV). One group...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1997-06-01 00:00:00
abstract::For patients whose breast cancers are not responsive to endocrine therapy, there are a large number of cytotoxic drugs that will induce a response. In spite of the introduction of new, very active drugs such as the taxanes, vinorelbine, capecitabine, gemcitabine, and trastuzumab, the anthracyclines are still as active...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2004.09.018
更新日期:2004-12-01 00:00:00
abstract::Distant metastasis is the major cause for therapeutic failures in Clinical oncology. Active immunotherapy in the adjuvant setting of patients with low tumor volume would contribute to further reduction of the remaining tumor and establish long-lasting immunity that could protect the patient from recurrence of disease....
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-02-01 00:00:00
abstract::Over the last 40 years the National Cancer Institute (NCI) has created a vibrant public-private partnership for the implementation of NCI-sponsored cooperative group (Network) clinical trials throughout the United States and Canada. Over these four decades, the cancer clinical trials process has become more complex mo...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2015.07.011
更新日期:2015-10-01 00:00:00