Abstract:
:Gonadotropin releasing hormone (GnRH) and its analogs inhibit the growth of hormone-dependent tumors in vivo and in vitro. The inhibition of growth and proliferation of tumor cells in vitro by GnRH and its analogs indicates that the tumor suppressing effect of the hormone is only partially due to suppression of pituitary gonadotropin release which reduces circulating steroid levels that are required for proliferation. Demonstration of GnRH-binding sites on some tumors suggests a direct inhibitory effect of GnRH and its analogs. However, the mechanism by which GnRH and its analogs inhibit tumor cell growth is not known. Our hypothesis is that the inhibition of growth and proliferation of tumor cells by GnRH and its analogs are mediated through down-regulation of its receptor expression. To test this hypothesis, mouse pituitary gonadotrope cell line (alphaT3-1) was selected as a model since this is the only cell line which expresses a sufficiently high level of GnRH receptors for precise measurements of the mRNA for the receptor. Addition of GnRH agonist (D-Lys6)GnRH to the cell cultures caused a time-dependent decrease in both cell growth, as measured by cell number, and cell proliferation, as measured by [3H]thymidine incorporation into DNA. After 1 h of treatment of alphaT3-1 cells with 1 microM of (D-Lys6)GnRH, the cell number was reduced to 83.0 +/- 13.4 compared to control, decreased to 75.1 +/- 3.2 at 2 h, 63.2 +/- 0.66 at 4 h and 52.2 +/- 0.87 at 24 h. This decrease in cell number was accompanied by a parallel decrease in [3H]thymidine incorporation into DNA. The inhibition of cell growth and [3H]thymidine incorporation by treatment with 1 microM of (D-Lys6)GnRH was sustained for at least 72 h. Inhibition of alphaT3-1 cell growth and [3H]thymidine incorporation was dose-dependent; thus 10(-9) M (D-Lys6)GnRH resulted in about 30% inhibition within 4h which was comparable to 10(-6) M (D-Lys6)GnRH, whereas 10(-12) M (D-Lys6)GnRH was ineffective. Measurement of mRNA for the GnRH receptor by Northern blot analysis showed a decrease in levels of mRNA by 5% within 2 h of treatment of alphaT3-1 cells with 1 microM (D-Lys6)GnRH, by 30% at 4 h and by 50% at 24 h. In conclusion these data demonstrate that treatment of alphaT3-1 cells with (D-Lys6)GnRH causes an inhibition of cell growth and proliferation, and down-regulates the GnRH receptor mRNA levels.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Kakar SS,Nath S,Bunn J,Jennes Ldoi
10.1097/00001813-199704000-00009subject
Has Abstractpub_date
1997-04-01 00:00:00pages
369-75issue
4eissn
0959-4973issn
1473-5741journal_volume
8pub_type
杂志文章abstract::The primary aim of this randomized trial was to determine response rate and progression-free survival following chemotherapy in patients with platinum-resistant recurrent ovarian cancer, who had been treated according to an ATP-based tumour chemosensitivity assay in comparison with physician's choice. A total of 180 p...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,随机对照试验
doi:10.1097/CAD.0b013e3281de727e
更新日期:2007-10-01 00:00:00
abstract::Glucocorticosteroids (GC) play an important role in the treatment of neuro-oncologic patients. GC are used for the management of malignant brain tumors, either primary of secondary, neoplastic epidural spinal cord compression (NESC), as adjuvant chemotherapy of some central nervous system tumors and perioperatively in...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199502000-00002
更新日期:1995-02-01 00:00:00
abstract::The goal of our study was to determine whether an apoptosis assay used after short-term drug exposure could predict selective toxicity to cancer cells. To this end we compared the effect of eight anticancer drugs and 10 toxic compounds without known antitumor activity in cultures of human breast cancer cells and norma...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200308000-00008
更新日期:2003-08-01 00:00:00
abstract::This study was performed to evaluate the role of protein kinase C (PKC) activity in the development of chemoresistance in clinical breast cancer cells. To simulate the clinical situation, native tumor cells derived from 10 patients with advanced breast cancer were brought into short-term cultures, and treated with ant...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200403000-00011
更新日期:2004-03-01 00:00:00
abstract::Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) is a colorectal cancer (CRC) stem cell marker. The role of Lgr5-expressing stem cells in resistance to chemotherapy is controversial. The notion that Lgr5-expressing cells are more chemotherapy resistant is supported by some data; other data do not sup...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000270
更新日期:2015-10-01 00:00:00
abstract::Thirty-three patients with advanced and refractory breast cancer were treated with two mitoxantrone-containing regimens (mitoxantrone plus mitomycin and mitoxantrone plus mitomycin plus methotrexate). All patients had received previous chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF); cyclophosp...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/00001813-199210000-00004
更新日期:1992-10-01 00:00:00
abstract::5-Fluorouracil, usually in combination with folinic acid, is widely used in the treatment of both colorectal and head and neck squamous cell cancer patients. Since 5-fluorouracil plus folinic acid and the antifolate thymidylate synthase inhibitor; raltitrexed have distinct mechanisms of action and toxicity profiles, w...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32809ef9b7
更新日期:2007-08-01 00:00:00
abstract::α-Lipoic acid (α-LA) is a biogenic antioxidant that has been used successfully in the treatment of diabetic polyneuropathy and its application to many oxidative stress-associated chronic diseases has increased. In this study, we investigated the effect of α-LA on colorectal cancer cell growth and its underlying mechan...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32836181eb
更新日期:2013-07-01 00:00:00
abstract::We recently established that NCPMF-60, a newly synthesized flavonoid, is an active cytotoxic component. The molecular mechanisms by which NCPMF-60 exerts its cytotoxic activity are currently unknown. In this study, we show that NCPMF-60 induces G2/M phase arrest and apoptosis in human hepatocellular carcinoma HepG2 ce...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3283405801
更新日期:2011-01-01 00:00:00
abstract::Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells. Its effect on pancreatic cancer is, however, unknown and the mechanism is unclear. The study aims to investigate its antitumor activity and underlying mechanisms in human pancreatic cance...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e3283212ade
更新日期:2009-02-01 00:00:00
abstract::Oxaliplatin (L-OHP), irinotecan (CPT-11) and 5-fluorouracil (5-FU) have shown their efficacy in metastatic colorectal cancer. The synergism of these drugs has been demonstrated in vivo and in vitro. The aim of this study was to determine the recommended dose of the triple combination of L-OHP, CPT-11 and CI 5-FU for a...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
doi:10.1097/01.cad.0000127146.50172.8a
更新日期:2004-06-01 00:00:00
abstract::Epirubicin is usually administered in combination with other cytotoxics. Few pharmacological studies address whether relevant clinical interactions occur in vitro between these drugs. This study investigated whether epirubicin interacted with other cytotoxics or anti-emetics. The following drugs were prepared at pharm...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199212000-00006
更新日期:1992-12-01 00:00:00
abstract::Venetoclax is a first-in-class orally available, B-cell lymphoma (BCL)-2 inhibitor indicated for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. We used a novel approach for evaluating venetoclax pharmacokinetics using only sparse sampling in 155 patien...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,多中心研究
doi:10.1097/CAD.0000000000000522
更新日期:2017-09-01 00:00:00
abstract::Trifluorothymidine (TFT) is a fluorinated thymidine analog that after conversion to its monophosphate derivative can inhibit thymidylate synthase (TS) and be incorporated into DNA. TFT is a good substrate for thymidine phosphorylase (TP), and the combination of TFT and a TP inhibitor (TPI), called TAS-102, has been de...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200503000-00007
更新日期:2005-03-01 00:00:00
abstract::The beta-carboline alkaloids are naturally existing plant substances. It is known that these alkaloids have a wide spectrum of neuropharmacological, psychopharmacological, and antitumor effects. Therefore, they have been traditionally used in oriental medicine for the treatment of various diseases including cancers an...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32832a2dd9
更新日期:2009-06-01 00:00:00
abstract::Low doses of drugs delivered at close, regular intervals are increasingly being used to manage patients with different neoplasms. Despite the good tolerability, treatment-related adverse events still occur following metronomic protocols. The aim of this study was to retrospectively investigate whether polymorphisms of...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000429
更新日期:2016-11-01 00:00:00
abstract::ET-743 is a marine anti-cancer drug and is currently in phase I trials in which the effect of combination therapies will be investigated. Its dose-limiting toxicity in patients is hepatotoxicity. In-vitro studies have shown that ET-743 is mainly metabolized by cytochrome P450 (CYP) 3A4, but also by 2C9, 2C19, 2D6 and ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/01.cad.0000180121.16407.38
更新日期:2005-10-01 00:00:00
abstract::C-reactive protein (CRP) is an independent prognostic factor for renal cell carcinoma (RCC). The aim of the present study was to investigate the overall prognostic impact of CRP in patients with metastatic RCC treated with sorafenib. Between April 2008 and December 2014, 40 consecutive patients with metastatic RCC wer...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000417
更新日期:2016-11-01 00:00:00
abstract::beta-Lapachone is a naturally occurring quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae) with cancer chemopreventive properties. The objective of the present study was to investigate the effect of beta-lapachone on the cell growth and apoptosis in human colon carcinoma tumor cell line HCT-116....
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200311000-00011
更新日期:2003-11-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) is the world's leading cause of cancer death and about 75% of all patients have advanced disease incurable with localized treatments (surgery and radiotherapy) alone. The aims of therapy in these are palliation of symptoms and extension of life. A substantial body of evidence has eme...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-200009000-00001
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abstract::The aim of this study was to evaluate the anticancer and antitumor activities of ceramide analog 315 in nude mice. Nude mice (n=10) were injected bilaterally with 5×10 MDA-MB-231 cells on each side. Tumors were allowed to form for 2 weeks. The mice were then divided into two groups (n=5 in each group). The control gro...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000675
更新日期:2018-10-01 00:00:00
abstract::Mistletoe extracts are frequently applied in adjuvant cancer treatment. The mistletoe lectins are especially suggested to mediate an antitumorous effect. During treatment with mistletoe lectin-rich extracts, anti-mistletoe lectin antibodies preferentially of the immunoglobulin G type are produced against mistletoe lec...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/00001813-199704001-00013
更新日期:1997-04-01 00:00:00
abstract::In this study, we investigated the putative cytotoxic effect elicited by the garlic-derived compound S-allylcysteine (SAC) in two human cancer cell lines (HCC827 and NCI-H1975) in order to develop an experimental approach to the therapeutic potential of this molecule for lung cancer. Cells were incubated for 24, 48 an...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000001015
更新日期:2021-02-01 00:00:00
abstract::The in-vitro growth inhibition of cancer and normal cell lines caused by mixed or covalently linked antimetabolites should clarify whether the conjugation of antimetabolites influences cell sensitivity and growth inhibition in a manner that differs from an equimolar mixture of the same antimetabolites or not. Growth i...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0b013e32835e5996
更新日期:2013-04-01 00:00:00
abstract::The goal of this study was to identify clinical characteristics and concurrent medications associated with an increased or decreased incidence of cisplatin-induced nephrotoxicity. The medical records for 62 subjects with head and neck cancer who received cisplatin 100 mg/m2 (day 1) plus fluorouracil 1000 mg/m2 (days 1...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,多中心研究
doi:10.1097/00001813-200602000-00013
更新日期:2006-02-01 00:00:00
abstract::The array of tools currently available and the aim of treatment make choosing the best therapeutic strategy in metastatic colorectal cancer (CRC) an increasing challenge worldwide. We present the case of a 53-year-old man with metachronous metastases (liver-only metastatic disease) treated with FOLFOXIRI as first-line...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/CAD.0000000000000761
更新日期:2019-04-01 00:00:00
abstract::Treatment failure of surgically treated gastric cancer is attributed to the spread of gastric cancer cells into the abdominal cavity and lymphatic or hematogenic canals. In the present study, local injection of mitomycin C bound to activated carbon (M-CH) combined with i.p. hyperthermic hypo-osmolar infusion (IPHHOI) ...
journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2002-04-01 00:00:00
abstract::The standard therapy for patients with aggressive lymphoma is cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemotherapy, which achieves a complete response in more than 60% of patients but is curative in only about 40-50%. More aggressive and/or dose-intensified chemotherapy regimens have failed to...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-200211002-00007
更新日期:2002-11-01 00:00:00
abstract::Chemotherapy is the only option of treatment for most patients presenting with a recurrent and/or metastatic head and neck squamous cell carcinoma. The triple association of cisplatin, 5-fluorouracile, and cetuximab is still the current standard for fit patients. Other schemes are currently being compared with this pr...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
doi:10.1097/CAD.0000000000000473
更新日期:2017-04-01 00:00:00
abstract::Dihydroartemisinin (DHA), a water-soluble active metabolite of artemisinin derivatives, is the safest and most effective antimalarial analog of artemisinin. In the present investigation, we assessed the apoptotic effect of DHA on leukemia HL60 cells and its regulation of transferrin receptor (TfR). Cell growth inhibit...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/cad.0b013e3282f3f152
更新日期:2008-03-01 00:00:00