Abstract：
:Transport of folates and antifolates in most cells is mediated by the reduced folate carrier (RFCI), an anion exchanging concentrative process, which is opposed by independent exit pump(s) that are directly coupled to energy metabolism. The balance of these processes governs the free intracellular folate level that is the substrate for folylpolyglutamate synthetase and determines the rate of metabolism of many folates and antifolates to polyglutamate derivatives. The RFCI has a high affinity for new-generation antifolates, but the relationship between transport and polyglutamylation for all these compounds has not, as yet, been defined. Analysis of mutations in RFCI indicate highly selective functional changes in binding affinity and/or carrier mobility, raising the possibilities that (1) enhanced transport and accumulation of natural folates can result in resistance to antifolate inhibitors of purine and pyrimidine synthesis by blocking their polyglutamylation to active derivatives, or by competition at the target enzyme site without substantial changes in antifolate transport, and (2) transport-related resistance to one antifolate might not produce comparable cross-resistance to another. Impaired export pump function, which results in enhanced accumulation of folates in cells and inhibition of antifolate polyglutamylation, represents another potential mechanism of resistance to new-generation antifolates. Folate receptor-mediated transport is another route of entry of folates and antifolates into cells, but its importance has not been well-defined. Finally, a low pH transport mechanism is present in a variety of mammalian cell lines. However, its relationship to RFCI and other low pH epithelial transporters and its ability to transport new-generation antifolates remain to be established.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Sierra EE,Goldman IDsubject
Has Abstractpub_date
1999-04-01 00:00:00pages
11-23issue
2 Suppl 6eissn
0093-7754issn
1532-8708journal_volume
26pub_type
杂志文章,评审abstract：:Maintenance therapy using rituximab is currently under consideration as a means of prolonging remission in patients with indolent non-Hodgkin's lymphoma. A phase II trial using rituximab as first-line therapy followed by maintenance treatment was carried out in patients with previously untreated indolent non-Hodgkin's...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：2004-02-01 00:00:00
abstract：:Patients with advanced colorectal cancer were randomized to receive either fluorouracil (5-FU) 370 mg/m2 IV days 1 to 5 followed by weekly applications of 5-FU 600 mg/m2 or the same doses of 5-FU preceded by folinic acid 200 mg/m2. Because of toxicity, the weekly 5-FU dose in the combination treatment schedule was red...
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：1992-04-01 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：:Long-term survival is occasionally observed in patients with neoplastic meningitis (NM) accompanying breast cancer (13% one-year and 6% 2-year survival), melanoma, and lymphoma, but in general the survival of most patients is short and averages only 3 to 4 months. The incidence of NM appears to be increasing, in part ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2006.04.016
更新日期：2006-06-01 00:00:00
abstract：:Breast cancer patients undergoing therapeutic regimens of high-dose chemotherapy (HDCT) with circulating progenitor cell support often develop anemia. As a general consideration in the transplantation setting, red blood cell transfusions are normally required in patients who have passed the myeloablative phase after H...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/sonc.2002.33529
更新日期：2002-06-01 00:00:00
abstract：:Colorectal cancer is the third most common cause of cancer-related death in both men and women. Surgery is the primary form of treatment, with greater than 90% of patients surviving 5 years or more. The remaining patients have metastatic disease, for which treatment options are limited. The fluoropyrimidine, 5-fluorou...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1997-12-01 00:00:00
abstract：:The epidemiologic studies relevant to the hypothesis that exposure to tamoxifen is associated with risk of cancer of the endometrium and perhaps other organs are described, summarized, and evaluated. One large body of data comes from the randomized trials of tamoxifen as a therapeutic agent against established breast ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1997-02-01 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：:In non-small cell lung cancer (NSCLC), the first immune checkpoint inhibitor to be approved by the US Food and Drug Administration was nivolumab, based on a survival advantage over docetaxel in recurrent squamous NSCLC, a difficult-to-treat histology. In addition, several other immune checkpoint inhibitors are also in...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2015.09.019
更新日期：2015-10-01 00:00:00
abstract：:Combination antimicrotubule therapy with estramustine phosphate (EMP) and vinblastine has reproducible activity in metastatic hormone-refractory prostate cancer (HRPC) with an objective response rate of 31%. Although paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 24-hour infusion was inactive in HR...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:The combination of paclitaxel and carboplatin is now established as the standard first-line chemotherapy regimen for advanced ovarian cancer. Ways in which this standard therapy can be further improved are being investigated, and several approaches have been taken. One approach is to integrate a different cytotoxic ag...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2006.03.015
更新日期：2006-04-01 00:00:00
abstract：:The natural history of squamous cell head and neck cancer is well understood. Locoregional approaches to salvage therapy for this disease have curative potential, primarily because distant metastases are uncommon. Before proceeding with salvage treatment, however, clinicians should identify the extent of disease and d...
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 data suggest a synergistic antiproliferative effect of different cytokines. In four clinical studies chronic myelogenous leukemia (CML) patients were treated with interferon (IFN)-alpha alone or IFN-alpha combined with either low-dose IFN-gamma or tumor necrosis factor (TNF)-alpha. The best response was achie...
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：1992-04-01 00:00:00
abstract：:Improving local tumor control is a goal of modern radiotherapy that will directly impact a majority of cancer patients. Numerous attempts to develop radiosensitizing agents have, however, met with limited clinical success. Recent advances in gene therapeutic approaches have allowed researchers to combine gene therapy ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1997-12-01 00:00:00
abstract：:The human gammaherpesvirus family includes Epstein-Barr virus (EBV) and human herpesvirus (HHV)-8, also known as Kaposi sarcoma-associated herpesvirus (KSHV). In human immunodeficiency virus (HIV)-infected patients, both EBV and KSHV have been implicated in the development of a wide range of tumors. KSHV-associated di...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2014.12.026
更新日期：2015-04-01 00:00:00
abstract：:Compelling data implicate angiogenesis and tumor-associated neovascularization as a central pathogenic step in the process of tumor growth, invasion, and metastasis. These complex processes involve multiple steps and pathways dependent on the local balance between positive and negative regulatory factors, as well as i...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1997-04-01 00:00:00
abstract：:The goal of this National Cancer Institute-sponsored phase I trial is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7-week total) intravenous paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combined with standard curative radiotherapy (RT) for pre...
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：: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：BACKGROUND:Patients with severe renal impairment or undergoing hemodialysis are usually excluded from clinical trials. Available data regarding safety and activity of systemic therapies (ST) in hemodialyzed patients are scarce. METHODS:Clinical data were searched through PubMed database until April 2020 according to P...
journal_title：Seminars in oncology
pub_type： 杂志文章
doi：10.1053/j.seminoncol.2020.05.001
更新日期：2020-01-01 00:00:00
abstract：:Cancer cells that express excessive levels of Bcl-2 pose a major problem in the delivery of curative therapy. Most treatments for such cancer involve chemotherapy to induce the apoptotic process. While these therapies often result in disease control for periods of time, failure to initiate apoptosis as a result of acq...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2004.10.014
更新日期：2004-12-01 00:00:00
abstract：:Platelet-derived microparticles (PMPs) represent the most abundant microparticle (MP) subtype. Their presence reflects platelet activity, physiopathology, and the thrombotic state of cancer patients. The quantity and composition of PMPs strictly depends on the way MPs were generated. Because platelets play a key role ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2014.04.010
更新日期：2014-06-01 00:00:00
abstract：:Hypoxic areas are a characteristic property of solid tumors. Hypoxia results from an imbalance between the supply and consumption of oxygen. Major pathogenetic mechanisms for the emergence of hypoxia are (1) structural and functional abnormalities in the tumor microvasculature; (2) an increase in diffusion distances; ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1016/s0093-7754(01)90210-6
更新日期：2001-04-01 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：: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：:Almost 125 years after the first documented case, pulmonary metastasectomy is still poorly understood. No other organ is subject to the wide histologic variety of metastatic insults, and this fact has complicated a complete exposition of when pulmonary metastasectomy may be beneficial. Many physicians still consider p...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2007.03.004
更新日期：2007-06-01 00:00:00
abstract：:Phase I trials of the intraperitoneal (IP) administration of cisplatin have demonstrated that the drug can be safely delivered by this route with a major increase in exposure (approximately tenfold to 15-fold) of the cavity to the cytotoxic agent compared with that of the systemic circulation. Phase I trials of IP cis...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1989-08-01 00:00:00
abstract：:Postmenopausal patients with advanced measurable and/or evaluable breast cancer entered a phase II trial of multiple agent cytotoxic therapy combined with endocrine therapy. Cycles of PNMF (prednimustine, novantrone, methotrexate, and 5-fluorouracil) were repeated every 4 weeks as follows: P, 100 mg/m2 PO on days 1 to...
journal_title：Seminars in oncology
pub_type： 杂志文章
doi：
更新日期：1986-03-01 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：:The goal of this National Cancer Institute-sponsored phase I trial is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7 weeks total) intravenous paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when combined with standard, curative-intent radiation t...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章
doi：
更新日期：1997-08-01 00:00:00
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
