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 its 5'-triphosphate (F-ara-ATP), the principal active metabolite. Deoxycytidine kinase is the enzyme responsible for the initial step of this activation metabolism. The differential transport and phosphorylation of F-ara-A and accumulation of F-ara-ATP by normal and cancer cells may constitute the metabolic basis of its positive therapeutic index. The major action of F-ara-A is the inhibition of DNA synthesis. F-ara-ATP competes with deoxyadenosine triphosphate for incorporation into the A sites of the elongating DNA strand by DNA polymerases and terminates DNA synthesis at the incorporation sites. That action is potentiated by the decrease of cellular dATP that results from inhibition of ribonucleotide reductase by F-ara-ATP. In vitro experiments demonstrated that DNA polymerase delta is able to excise the incorporated F-ara-AMP residues from DNA with its 3' to 5' exonuclease activity. The terminal incorporation of F-ara-AMP into DNA results in deletion of genetic material. That mechanism may be responsible for the observed mutagenicity of Fludara I.V., and ultimately its cytotoxic action.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Plunkett W,Huang P,Gandhi Vsubject
Has Abstractpub_date
1990-10-01 00:00:00pages
3-17issue
5 Suppl 8eissn
0093-7754issn
1532-8708journal_volume
17pub_type
杂志文章,评审abstract：:Multiple myeloma (MM) is a heterogeneous disease for which several new treatments are available. Much has been learned about its biology over the past 15 years. We now understand that there are various subtypes of the disease, each one associated with different outcomes and clinical pathological features. While a deta...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2013.07.002
更新日期：2013-10-01 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：:Lung cancer is the leading cause of cancer death in the United States. Despite evidence of molecular abnormalities in biological specimens, progress in this disease is hampered by the lack of diagnostic markers useful for clinical practice. The majority of patients with lung cancer are still diagnosed at an advanced s...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2005.02.009
更新日期：2005-06-01 00:00:00
abstract：:Non-small cell lung cancer (NSCLC) remains a malignancy that is refractory to most currently available chemotherapeutic agents. The most frequently used systemic therapy is cisplatin-based combination therapy, which is not always suitable for patients with stage IV disease because of toxicity. Thus, any single agent w...
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：1998-08-01 00:00:00
abstract：:A phase I/II study was conducted to determine the response rate and the toxicity of escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus cisplatin with granulocyte colony-stimulating factor support in patients with untreated advanced head and neck carcinoma. Twenty-eight patients wi...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:Cisplatin is recognized as an active chemotherapeutic agent in a broad variety of human tumors. The severe emetic effects of cisplatin, however, result in both acute and delayed emesis syndromes causing considerable morbidity. Over the last decade, the standard of therapy for control of cisplatin-induced emesis has be...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1991-02-01 00:00:00
abstract：:The limited single-agent activity of cisplatin, its toxicity profile, and the inconvenience involved in hydrating patients has compelled researchers to investigate other treatments as possible alternative therapies in non-small cell lung cancer. More recently, interest has focused on the potential of nonplatinum combi...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1016/s0093-7754(01)90299-4
更新日期：2001-02-01 00:00:00
abstract：:One of the most known oncogenes is the epidermal growth factor receptor (EGFR) family. It activates multiple signaling cascades that promote carcinogenesis and immune evasion. Therefore, these molecules have been extensively targeted in cancer immunotherapy. Beyond EGFR signaling cascade inhibition, some of these agen...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2018.04.008
更新日期：2018-01-01 00:00:00
abstract：:To address the urgent need for novel therapies for multiple myeloma (MM), long-term research efforts have characterized the mechanisms whereby MM cells home to the bone marrow and adhere to bone marrow stromal cells and extracellular matrix proteins. Research also characterizes the functional sequelae of this binding ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/sonc.2002.34072
更新日期：2002-12-01 00:00:00
abstract：:Over the past three decades conceptual approaches to breast cancer have led to improvements in locoregional therapy and early diagnosis. Systematic screening programs with mammography reduce disease-specific mortality by 25% to 30%, while many patients with early breast cancer receive optimal breast-conserving treatme...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1999-08-01 00:00:00
abstract：:Acute lymphoblastic leukemia (ALL) 5-year survival rates are approaching 90% in children and 50% in adults who are receiving contemporary risk-directed treatment protocols. Current efforts focus not only on further improving cure rate but also on patient quality of life. Hence, all protocols decrease or limit the use ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2009.05.002
更新日期：2009-08-01 00:00:00
abstract：:Organ function preservation in patients with head and neck cancer can be achieved by intensity-modulated radiation therapy (IMRT). Much of the work on the physics of IMRT has been done for currently available IMRT systems. However, clinical data remain scarce. Before IMRT is accepted as a standard of care, more compre...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章,评审
doi：10.1053/j.seminoncol.2003.11.009
更新日期：2003-12-01 00:00:00
abstract：:Current data indicate that most elderly patients with acute myelogenous leukemia should be treated with intensive chemotherapy. Most should receive remission induction chemotherapy using cytarabine 100 to 200 mg/m2/d by constant intravenous infusion for five to seven days plus daunorubicin greater than or equal to 30 ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1989-02-01 00:00:00
abstract：:Approximately 60% of patients diagnosed with colorectal cancer (CRC) will go on to develop hepatic metastases. Although surgical resection is the only curative modality, a majority will not be able to undergo surgery. Alternative methods for treating this population have focused on the feasibility of hepatic arterial ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/sonc.2002.31680
更新日期：2002-04-01 00:00:00
abstract：:Colorectal cancer (CRC) is a common malignancy in the elderly. Randomized trials have demonstrated that adjuvant and palliative chemotherapy for CRC improves survival and quality of life. Unfortunately, there is a lack of evidence-based data about elderly patients to guide decisions regarding therapy. Clinical trials ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2008.08.004
更新日期：2008-12-01 00:00:00
abstract：:One of the new agents intensively studied in the last decade for the treatment of metastatic breast cancer is vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France). This vinca alkaloid produces response rates comparable to other single agents in women with m...
journal_title：Seminars in oncology
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:The benefits of radiation therapy (RT) as part of a treatment regimen for cancer must be weighed against the potential risk of harm to the patient and in the pregnant patient, the risk to the developing fetus. Information necessary for determining the potential effects of RT on the developing fetus include the gestati...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：2000-12-01 00:00:00
abstract：:In recent years, several new cytotoxic agents have been investigated for the management of non-small cell lung cancer (NSCLC), including the antimetabolic gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and the new multitargeted antifolate pemetrexed (Alimta, Eli Lilly and Company), which are both among ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1016/s0093-7754(03)00284-7
更新日期：2003-08-01 00:00:00
abstract：:Hypercalcemia of malignancy (HCM) is a potentially life-threatening complication of cancer resulting from increased bone resorption by osteoclasts. Clinical management of HCM primarily consists of intravenous rehydration therapy combined with pharmaceutical agents that decrease osteoclast activity. Several generations...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/sonc.2002.37417
更新日期：2002-12-01 00:00:00
abstract：:The purpose of this study is to evaluate the efficacy and safety of a biweekly neoadjuvant docetaxel/gemcitabine regimen in patients with histologically confirmed stage II and III breast cancer. In addition, a cDNA microarray study attempted to correlate pretreatment gene-expression profile with clinical and pathologi...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章
doi：10.1053/j.seminoncol.2004.03.025
更新日期：2004-04-01 00:00:00
abstract：:Gemcitabine is an active agent in non-small cell lung cancer, with single-agent treatment producing response rates of approximately 20% and median survivals of approximately 7 to 9 months. In a pilot trial in advanced non-small cell lung cancer, the gemcitabine/carboplatin combination produced a response rate of 43% a...
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：10.1053/sonc.2002.34276
更新日期：2002-06-01 00:00:00
abstract：:During the past decade, local control of primary sarcomas of the extremities by radiation and conservative surgery has supplanted more radical compartmental resections or amputations. Reviews of others and our published data show that the probability of achieving local control is highly dependent on achieving negative...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1997-10-01 00:00:00
abstract：:In April 1990, the Argentine Group for Treatment of Acute Leukemia began a multicenter trial for the treatment of previously untreated acute myeloblastic leukemia patients who were under 21 years of age. Initial treatment consisted of an 8-day induction phase with cytarabine together with idarubicin on days 3 to 5 and...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章,多中心研究
doi：
更新日期：1993-12-01 00:00:00
abstract：:Approximately 25% of all lung cancer cases diagnosed in 1993 were due to small cell lung cancer (SCLC). Approximately one third of all SCLC patients present with limited disease. Efforts to improve treatment results for patients with limited-stage SCLC include two recent meta-analyses of combined-modality treatment in...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1998-02-01 00:00:00
abstract：:Data from women with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III or IV) were analyzed to evaluate the pharmacokinetic/pharmacodynamic relationships of carboplatin-based combination chemotherapy. With the equation area under the plasma concentration versus time curve (AUC) =...
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：1994-10-01 00:00:00
abstract：:Over the past 5 years there has been a renewed interest in the use of monoclonal antibodies and immunoconjugates in the treatment of nonhematologic malignancies. This enthusiasm has stemmed from advances in recombinant technology allowing for the production of chimeric and humanized antibodies, from Food and Drug Admi...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：2000-12-01 00:00:00
abstract：:Lymphomas of the head and neck arise in Waldeyer's ring, the salivary glands, nasal cavity, paranasal sinuses, thyroid gland, and orbit. Though anatomically in close proximity, lymphomas arising in these sites have distinct clinical characteristics. Factors that appear to influence the pattern of disease include concu...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1999-06-01 00:00:00
abstract：:With the increasing numbers of breast cancers survivors, menopause, its symptoms, and its physical complications are becoming more prevalent problems in this patient population. Hormonal replacement, which has been the cornerstone therapy of menopausal related symptoms for decades, recently has been shown to increase ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2006.08.010
更新日期：2006-12-01 00:00:00
abstract：:Lymphoproliferative disorders are characterized by the abnormal accumulation of aberrant lymphocytes, which frequently interfere with the processes associated with immunologic response and hematopoiesis. Chronic lymphocytic leukemia (CLL) has traditionally been considered indolent, with a prolonged clinical course. Ho...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2006.01.026
更新日期：2006-04-01 00:00:00
abstract：:Two children with biopsy-proven LCH underwent successful hepatic transplantation for end-stage liver disease. These patients were thought not to have active LCH disease at the time of transplantation, although one had developed a new osteolytic lesion a few months before the operation and the other had suspicious oste...
journal_title：Seminars in oncology
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
