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 acquired resistance limits the effectiveness of treatment for many common hematopoietic and solid malignancies, and ultimately death from the malignancy still occurs. Various anti-apoptotic proteins of the Bcl-2 family that localize to the mitochondria appear to be involved in this resistance mechanism. However, recent advances in the understanding of malignant cell biology, achieved through both genomics and proteomics, have made it possible to explore novel approaches directed at re-establishing sensitivity to chemotherapy, presenting an attractive strategy for cancer treatment. In this article we discuss how this may be achieved by lowering Bcl-2 anti-apoptotic protein expression using antisense oligonucleotides or, alternatively, by functionally antagonizing Bcl-2 using ligands of the mitochondrial benzodiazepine receptor.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Cotter FEdoi
10.1053/j.seminoncol.2004.10.014subject
Has Abstractpub_date
2004-12-01 00:00:00pages
18-21; discussion 33issue
6 Suppl 16eissn
0093-7754issn
1532-8708pii
S0093-7754(04)00491-9journal_volume
31pub_type
杂志文章,评审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：:Letrozole has proven efficacious in a variety of therapeutic scenarios, including that of extended adjuvant therapy following 5 years of tamoxifen treatment in postmenopausal women with estrogen-receptor-positive early breast cancer. The Breast International Group 1-98 trial (BIG 1-98) is the first to study the effica...
journal_title：Seminars in oncology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1053/j.seminoncol.2006.03.026
更新日期：2006-04-01 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：: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：:Non-small cell lung cancer (NSCLC) represents almost three quarters of all cases of lung cancer. Most NSCLC patients present with either locally advanced inoperable disease, stage IV metastatic disease, or comorbid medical conditions that make them unsuitable for curative resection. Among NSCLC patients in the United ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1995-08-01 00:00:00
abstract：:Richter syndrome (RS) is the development of an aggressive lymphoma in patients with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL). The incidence rate RS is ~0.5% per year of observation. Two biomarkers (NOTCH1 mutations and subset 8 configuration of the B-cell receptor) may help identifying...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2016.02.012
更新日期：2016-04-01 00:00:00
abstract：:Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecu...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2014.12.004
更新日期：2015-02-01 00:00:00
abstract：:Non-Hodgkin's lymphoma (NHL) is composed of a group of lymphoid malignancies that has been increasing in incidence at an annual rate of 4% to 7% over the last 20 years in both the United States and Europe. The reasons for this rise in incidence in NHL are not yet defined but most likely involve environmental exposures...
journal_title：Seminars in oncology
pub_type： 杂志文章
doi：10.1053/sonc.2002.30152
更新日期：2002-02-01 00:00:00
abstract：:Preclinical studies with zoledronic acid (Zometa; Novartis Pharmaceuticals Corp, East Hanover, NJ) have shown its potential in malignant bone disease. Clinical studies in the treatment of hypercalcemia of malignancy have been completed, as have phase I and II trials in patients with cancer and pre-existing bone metast...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章,随机对照试验,评审
doi：10.1016/s0093-7754(01)90260-x
更新日期：2001-04-01 00:00:00
abstract：:The epidemiologic literature suggests that environmental exposures, familial susceptibility, and cytogenetic changes affect AML risk in childhood and adulthood. Unfortunately, many studies are limited by inadequate sample sizes, imprecise case definition, or inadequate exposure measurement. Few studies have singled ou...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1987-12-01 00:00:00
abstract：:The results of recent clinical trials have shown that docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France), like paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ), has high levels of activity in patients with anthracycline-resistant breast cancer. Agents that are at least partially non-cross-resist...
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：:Docetaxel is a semisynthetic taxane that acts primarily by promoting microtubule assembly and preventing the depolymerization of assembled microtubules, thereby inducing mitotic block and inhibition of cell proliferation. This agent also induces apoptosis and appears to prevent angiogenesis. Although docetaxel has sho...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2005.04.002
更新日期：2005-04-01 00:00:00
abstract：:Studies in vitro and in animal models have helped define the mechanism of action of antiestrogens and the differences in the physical properties of the various antiestrogens. Tamoxifen is the most widely studied antiestrogen. A review of 45 separate studies has shown a response rate to tamoxifen in advanced breast can...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章
doi：
更新日期：1983-12-01 00:00:00
abstract：:Advanced-stage mantle cell lymphoma (MCL) is a disease for which no curative treatment strategy exists. Results with standard combination chemotherapy, with or without an anthracycline, are disappointing, and new and better therapies are needed. High-dose therapy and autologous stem-cell transplantation (ASCT) have be...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章,评审
doi：
更新日期：2002-02-01 00:00:00
abstract：:We studied the pharmacokinetics of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin administered in combination to 21 patients with advanced non-small cell lung cancer. Paclitaxel was administered as a 24-hour intravenous infusion at doses of 135 to 200 mg/m2. Carboplatin, dosed to a tar...
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：:Denileukin diftitox (ONTAK; Seragen Inc, San Diego, CA) is a fusion protein designed to direct the cytocidal action of diphtheria toxin to cells that overexpress the IL-2 receptor. The human IL-2 receptor exists in three isoforms: low (CD25), intermediate (CD122/CD132), and high (CD25/CD122/CD132) affinity. The high-a...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2005.12.017
更新日期：2006-02-01 00:00:00
abstract：:Although the benefit of adjuvant therapy for pancreas cancer is clear, the most effective therapy remains elusive. In the United States, combination therapy with chemotherapy and radiation remains the standard of care, while in other parts of the world the contribution of radiation is questioned. Clinical trials are r...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2007.05.006
更新日期：2007-08-01 00:00:00
abstract：:There is a spectrum of presentations of skeletal manifestations of malignancy that includes generalized osteopenia and hypercalcemia, focal osteolysis, focal osteogenesis, and osteomalacia and hypophosphatemia. In various preclinical animal models, parathyroid hormone-related protein (PTHrP) was seen to be produced by...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1016/s0093-7754(01)90226-x
更新日期：2001-08-01 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：: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：:Bone marrow transplantation (BMT) preparative regimens consisting of busulfan (Bu) and cyclophosphamide (Cy) were developed as an alternative to preparative regimens based on total body irradiation (TBI). Animal studies demonstrated that Bu had a high level of myeloablative and antileukemic activity, but little immuno...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1993-08-01 00:00:00
abstract：:Gemcitabine, a novel nucleoside analog, shows reproducible response rates of 20% and above in single-agent studies in non-small cell lung cancer. In the phase II studies reported, chemotherapy-naive patients received gemcitabine (starting doses, 800 to 1,250 mg/ m2) as a single agent on days 1, 8, and 15 of a 28-day c...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1996-10-01 00:00:00
abstract：:Preclinical models in vitro and in vivo have shown that tumor hypoxia alters the malignant cell phenotype, selecting for p53 mutations, stimulating angiogenesis and metastasis, and markedly reducing the efficacy of both radiotherapy and chemotherapy. Similarly, clinical studies measuring pretreatment tumor oxygen stat...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/sonc.2002.31531
更新日期：2002-02-01 00:00:00
abstract：:In a multicenter phase III trial, 267 patients with nonbulky metastatic colorectal cancer who had failed first-line 5-fluorouracil (5-FU) therapy were randomized to receive second-line treatment with either the new topoisomerase agent, irinotecan (Rhône-Poulenc Rorer, Antony, France), or a high-dose infusional 5-FU re...
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：1999-02-01 00:00:00
abstract：:High-dose interferon alfa (IFN alfa) therapy induces an overall response rate of 25% to 30% in unselected patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Up to 50% of patients with relatively preserved immune reactivity respond to treatment. However, when dosages of 20 x 10(6) units o...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1990-02-01 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：:This phase I study was designed to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with standard doses of cisplatin and etoposide for patients with untreated, extensive-stage small cell lung cancer. Secondary objectives were to determine the toxicities, response ...
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：:Interest in retinoids as therapeutic agents has developed as a result of the observations of remission induction with all-trans retinoic acid (tRA) in patients with acute promyelocytic leukemia (APL), and of high objective response rates noted with the combination of cis-retinoic acid (cRA) with interferon-alpha in sq...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1992-12-01 00:00:00
abstract：:Several new antimetabolites have been evaluated in clinical trials in recent years. Those with the most promising activity include the structurally related purine analogs fludarabine, 2-chlorodeoxyadenosine, and 2'-deoxycoformycin. These compounds have shown impressive activity against a broad spectrum of indolent lym...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1992-12-01 00:00:00
abstract：:Among the various deleterious effects of cancer chemotherapy, vascular toxicity is the least well recognized. This lack of recognition may be because the vasculotoxic phenomena are not unique to antineoplastic agents, can occur in patients without exposure to these agents, and the fact cancer itself may produce a hype...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2005.11.006
更新日期：2006-02-01 00:00:00
