Abstract:
PURPOSE:Cisplatin and radiation therapy remain the current standard for treating locally advanced SCCHN. Novel treatment approaches are needed, especially in patients with human papilloma virus (HPV)-negative disease who have worse outcomes despite multimodality therapy. METHODS:Using our institutional review board approved database, we obtained twenty oropharyngeal squamous cell carcinoma (SCC) tissue samples: ten p16 positive, ten p16-negative. Because p16 expression is strongly associated with HPV positivity in oropharyngeal SCC, p16 status was used as a marker of HPV. We subsequently analyzed, via immunohistochemistry, heat shock protein 90 (HSP90) protein levels. Using HPV-positive and HPV-negative SCC cell lines, we compared baseline HSP90 expression levels and the effect of the HSP90 inhibitor ganetespib on viability and apoptosis. Clonogenic survival of HPV-negative cells treated with ganetespib, radiation therapy, and/or cisplatin was then investigated. We characterize the effects of ganetespib on proteins that are thought to drive DNA damage resistance in HPV-negative cells. RESULTS:HSP90 expression was significantly higher in p16-negative compared with p16-positive samples (p = 0.016) and in HPV-negative cell lines compared with positive cells. Ganetespib increased cytotoxicity and induced apoptosis in HPV-negative more than positive cells. Adding ganetespib to cisplatin and/or radiation therapy in HPV-negative cells further decreased clonogenic survival. Finally, ganetespib downregulated expressions of EGFR, ERK, AKT, p53, and HIF-1α. CONCLUSIONS:Ganetespib inhibited HPV-negative SCCHN viability and potentiated cell kill when combined with cisplatin or radiation therapy in vitro. With HSP90 expression higher in HPV-negative cells and in p16-negative patients, further exploration of the clinical activity of HSP90 inhibitors in SCCHN is warranted.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Patel K,Wen J,Magliocca K,Muller S,Liu Y,Chen ZG,Saba N,Diaz Rdoi
10.1007/s00280-014-2584-8subject
Has Abstractpub_date
2014-11-01 00:00:00pages
1015-22issue
5eissn
0344-5704issn
1432-0843journal_volume
74pub_type
杂志文章abstract::Methotrexate and methotrexate polyglutamates were quantitatively determined in red blood cells from 12 children with acute lymphoblastic leukemia who were treated with MTX (15-20 mg/m2 per week) and daily 6-mercaptopurine orally during the steady-state period of erythrocyte MTX concentration (ery-MTX). The terminal de...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257362
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:S-1 and gemcitabine (GS) combination therapy is a promising treatment for advanced biliary tract cancer (BTC). However, systemic administration of GS is associated with a high rate of grade 3 and 4 neutropenia. Hepatic arterial infusion (HAI) of gemcitabine may overcome this problem. We conducted a prospective ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2704-0
更新日期:2015-04-01 00:00:00
abstract:PURPOSE:Hypoxic tumor cells overexpressing hypoxia-inducible factor 1alpha (HIF-1alpha) are generally resistant to chemo/radiotherapy. We have reported that Se-methylselenocysteine (MSC) therapeutically enhances the efficacy and selectivity of irinotecan against human tumor xenografts. The aim of this study was to deli...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1238-8
更新日期:2010-10-01 00:00:00
abstract::Selective protection of the normal host tissues from the toxic effects of anticancer agents would allow the use of higher, probably more effective, doses of the drugs. It has been demonstrated that delayed high-dose uridine administration after 5-fluorouracil decreases the extent of myelosuppression and causes faster ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685843
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are key drugs in the treatment of non-small cell lung cancer (NSCLC) harboring EGFR activating mutations. We assessed the efficacy and safety of one EGFR tyrosine kinase inhibitor, erlotinib, in elderly Japanese patients with EGFR-mutated NSCLC....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-015-2784-x
更新日期:2015-07-01 00:00:00
abstract::The development of nitrosoureas has switched from more lipophilic derivatives to congeners with higher water-solubility, since this property was presumably associated with a decrease in myelosuppression. We have compared the therapeutic efficacy of clinically well-known lipophilic nitrosoureas BCNU, CCNU, and MeCCNU w...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254194
更新日期:1983-01-01 00:00:00
abstract::cis-Diammine-1,1-cyclobutane dicarboxylate platinum II (CBDCA, JM8), an analogue of cisplatin showing reduced toxicity in preclinical studies, was evaluated in 60 patients. Doses were given initially every 3 weeks and escalated from 20 to 520 mg/m2. Following this, doses were given every 4 weeks and escalated from 300...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257742
更新日期:1982-01-01 00:00:00
abstract:PURPOSE:Trifluorothymidine (TFT) is a fluoropyrimidine that is part of the novel combination metabolite TAS-102, in which TFT is combined with a potent thymidine phosphorylase inhibitor (TPI). TAS-102 is currently tested as an orally chemotherapeutic agent in different schedules in a phase I study. In its monophosphate...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0033-4
更新日期:2006-01-01 00:00:00
abstract::Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0148-7
更新日期:2006-08-01 00:00:00
abstract::The 9L gliosarcoma growing subcutaneously in the hind leg of the Fisher 344 rat contains major areas of severe (< 5 mmHg) hypoxia, making up about 49% of the tumor. Intravenous administration of an ultrapurified polymerized bovine hemoglobin solution (8 ml/kg) along with normal air breathing reduces the percentage of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00686024
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:Recently, based on results of the PACIFIC trial, durvalumab after chemoradiotherapy (CRT) became the standard therapy for unresectable stage III non-small cell lung cancer (NSCLC). However, in the PACIFIC trial, patients were recruited and randomized after CRT, and certain patients were considered ineligible af...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03885-4
更新日期:2019-08-01 00:00:00
abstract:PURPOSE:The antifolate pralatrexate (10-propargyl-10-deazaaminopterin, PDX) demonstrates greater in vitro and in vivo antitumor efficacy than methotrexate. Preclinical models indicated that the efficacy of pralatrexate may be enhanced by coadministration with probenecid. The aim of this phase I study was to determine t...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0080-x
更新日期:2006-05-01 00:00:00
abstract:PURPOSE:PF-00337210 is an oral, highly selective vascular endothelial growth factor receptor (VEGFR) inhibitor. We evaluated a composite of biomarkers in real time to identify the recommended phase 2 dose (RP2D) and preliminary anticancer activity of PF-00337210. PATIENTS AND METHODS:Patients (Pts) with advanced cance...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-2958-1
更新日期:2016-03-01 00:00:00
abstract:BACKGROUND:Bevacizumab is approved for various cancers. This analysis aimed to comprehensively evaluate bevacizumab pharmacokinetics and the influence of patient variables on bevacizumab pharmacokinetics. METHODS:Rich and sparse bevacizumab serum concentrations were collected from Phase I through IV studies in early a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3079-6
更新日期:2016-08-01 00:00:00
abstract:PURPOSE:To evaluate the safety and efficacy of the combination of cisplatin on day 1 and docetaxel on days 1, 8 and 15 every 4 weeks for the treatment of previously untreated patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:A group of 38 patients with advanced or metastatic NSCLC who had not rece...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-004-0810-5
更新日期:2004-08-01 00:00:00
abstract::Melphalan (L-PAM) pharmacokinetics were investigated in nine ovarian cancer patients before and after cisplatin (DDP) treatment. When L-PAM was given 24 h before DDP, the elimination half-life (t 1/2 beta), plasma clearance (Clp), and volume of distribution (Vd beta) of L-PAM were, respectively: 46.4 +/- 6.7 min, 20.5...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254189
更新日期:1988-01-01 00:00:00
abstract::The nephrotoxic interaction between cis-diamminedichloroplatinum (CDDP) and amikacin (AMI) was studied in rats. Following a single dose of CDDP (5 mg/kg i.v.), AMI (60 mg/kg s.c.) was given for 14 days. When given alone CDDP caused a 40% fall in the glomerular filtration rate (GFR), whereas AMI alone had no effect on ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257319
更新日期:1988-01-01 00:00:00
abstract::The initial results from the Children's Cancer Study Group (CCSG) study on vindesine are the subject of this report. Vindesine was shown to be active in the treatment of acute lymphocytic leukemia (ALL) in children in a phase-II clinical trial conducted by the CCSG. A phase-II trial is now in progress. The aim of this...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257193
更新日期:1979-01-01 00:00:00
abstract::Larotaxel (XRP9881, RPR109881), a novel semi-synthetic taxoid that shares a mode of action with the taxanes docetaxel and paclitaxel, was active in preclinical studies against a broad spectrum of tumour cells and tumour models refractory/resistant to taxanes, and have demonstrated clinical activity in taxane pre-treat...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1014-9
更新日期:2009-12-01 00:00:00
abstract::We established an etoposide (VP-16)-resistant human small-cell lung cancer cell line (H69/VP) by stepwise exposure to VP-16. The resistance of H69/VP to VP-16 was 9.4-fold that of the parent cell line (H69/P). H69/VP showed cross-resistance to Adriamycin (ADM), (4S)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino) c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897284
更新日期:1990-01-01 00:00:00
abstract::Plasmatic and salivary concentrations of 5-FU were investigated in ten patients given 5-day continuous infusions of 5-fluorouracil (5-FU) (1 g/m2/day). Measurable concentrations of salivary 5-FU were scattered ranging from 6 to 100 ng/ml. Between individual 5-FU concentrations in saliva and plasma the coefficient of c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00300243
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:5-Fluorouracil is the most commonly used drug for the treatment of colon cancer, yet clinical resistance to this drug is frequently observed in patients making this drug ineffective. Thus, identification of gene responsible for 5-FU resistance is of utmost importance. METHODS:Cellular cytotoxicity and expressi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2794-8
更新日期:2015-09-01 00:00:00
abstract:PURPOSE:Artemisinins are now established drugs for treatment of malaria. These agents have been shown to possess impressive anti-cancer properties. We have investigated the role of artemisone (ATM), a novel derivative of artemisinin (ART) in a cancer setting both alone and in combination with established chemotherapeut...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1355-4
更新日期:2011-03-01 00:00:00
abstract:PURPOSE:Malignant gliomas display aggressive local behavior and are not cured by existing therapy. Etoposide, a topoisomerase-II-inhibitor agent, is one of the most active and useful antineoplastic agents. However, etoposide is not usually used on these tumors. We undertook an in vitro study to prove that etoposide is ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050713
更新日期:1998-01-01 00:00:00
abstract::The primary development of clinical resistance to 1-beta-D-arabinofuranosyl cytosine (ara-C) in leukemic blast cells is expressed as decreased cellular concentrations of its active anabolite. Correlations exist between the cellular concentrations of 1-beta-D-arabinofuranosyl cytosine 5'-triphosphate (ara-CTP) in leuke...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257619
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate safety and toxicity of chronomodulated capecitabine administered in the morning and at noon according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of first-line XELOX chemotherapy in patients with metastatic colorectal cancer. METHODS:A total...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3067-x
更新日期:2016-07-01 00:00:00
abstract::A total of 23 patients were treated at five dose escalations with high-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. The maximum tolerated doses of cyclophosphamide, cisplatin, and melphalan were 5,625, 180, and 80 mg/m2, respectively. The dose-limiting toxicity was c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00435840
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to evaluate a phenotypic cell panel with tumor cells from various patients and normal cells for preclinical profiles of antitumor efficacy and toxicity of anticancer drugs. METHODS:The antitumor activity of fourteen anticancer drugs was tested in over one hundred tumor samples from pa...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-011-1746-1
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND:Pre-clinical activity of SSG against melanoma and renal cancer has been identified recently although the drug's mechanism of action and activity against tumors of additional histological-types remain undefined. METHODS:The effects of SSG and SSG combination with other agents on DU145 human prostate carcinom...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0378-3
更新日期:2007-08-01 00:00:00
abstract:OBJECTIVE:To characterize the population pharmacokinetics of plitidepsin (Aplidin) in cancer patients. METHODS:A total of 283 patients (552 cycles) receiving intravenous plitidepsin as monotherapy at doses ranging from 0.13 to 8.0 mg/m(2) and given as 1- or 24-h infusions every week; 3- or 24-h infusion biweekly; or 1...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s00280-008-0841-4
更新日期:2009-06-01 00:00:00