Abstract:
PURPOSE:The effect of an anticancer treatment on tumor cell proliferation in vitro can be described as a three-dimensional surface where the inhibitory effect is related to drug concentration and treatment time. The analysis of this kind of response surface could provide critical information: for example, it could indicate whether a prolonged exposure to a low concentration of an anticancer agent will produce a different effect from exposure to higher concentrations for a shorter period of time. The parametric approach available in the literature was not flexible enough to accommodate the behavior of the response surface in some of the data sets collected as part of our research programs. Therefore, a new, general, nonparametric approach was developed. METHODS:The response surface of the inhibition of cell-based tumor growth was described using a radial basis function neural network (RBF-NN). The RBF-NN was trained using regularization theory, which provided the initialization of a constrained quadratic optimization algorithm that imposes monotonicity of the surface with respect to both concentration and exposure time. RESULTS:In the two analyzed cases (doxorubicin and flavopiridol), the proposed method was accurate and reliable in describing the inhibition surface of tumor cell growth as a function of drug concentration and exposure time. Residuals were small and unbiased. The new method improved on the parametric approach when the relative importance of drug concentration and exposure time in determining the overall effect was not constant across the experimental data. CONCLUSIONS:The proposed RBF-NN can be reliably applied for the analysis in cell-based tumor growth inhibition studies. This approach can be used for optimizing the administration regimens to be adopted in vivo. The use of this methodology can be easily extended to any cell-based experiment, in which the outcome can be seen as a function of two experimental variables.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Germani M,Magni P,De Nicolao G,Poggesi I,Marsiglio A,Ballinari D,Rocchetti Mdoi
10.1007/s00280-003-0688-7keywords:
subject
Has Abstractpub_date
2003-12-01 00:00:00pages
507-13issue
6eissn
0344-5704issn
1432-0843journal_volume
52pub_type
杂志文章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:PURPOSE:Acute kidney injury (AKI) is a common and serious adverse effect of cisplatin-based chemotherapy. However, traditional markers of kidney function, such as serum creatinine, are suboptimal, because they are not sensitive measures of proximal tubular injury. We aimed to determine whether the new urinary biomarker...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-015-2880-y
更新日期:2015-11-01 00:00:00
abstract::The discovery of targetable mutations, which cause gene rearrangement, led to a major advancement in the treatment of patients with non-small cell lung cancer (NSCLC), and cancers with such mutations can be paired with drugs which specifically target them. c-ros oncogene (ROS1) positive NSCLC is one molecular subtype ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00280-019-03902-6
更新日期:2019-10-01 00:00:00
abstract:PURPOSE:Preclinical research and prior clinical observations demonstrated reduced toxicity and suggested enhanced efficacy of cisplatin due to folic acid and vitamin B12 suppletion. In this randomized phase 2 trial, we evaluated the addition of folic acid and vitamin B12 to first-line palliative cisplatin and gemcitabi...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00280-018-3588-6
更新日期:2018-07-01 00:00:00
abstract:PURPOSE:We have developed and evaluated a CNS-targeted chemotherapy regimen based on the pharmacokinetic properties of the individual drugs in the combination. PATIENTS AND METHODS:In a twin-track study, 16 patients with secondary CNS lymphoma (SCNSL) and 8 with primary CNS lymphoma (PCNSL) were treated with IDARAM wh...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s00280-003-0737-2
更新日期:2004-04-01 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:PURPOSE:Based on the promising results of a Phase I study with a combination of gemcitabine and DTIC performed in advanced soft tissue sarcoma (ASTS) patients, and due to the limited efficacy of second or third line therapies in those patients, we designed a Phase II study to determine the activity of this new regimen....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-006-0263-0
更新日期:2007-02-01 00:00:00
abstract:PURPOSE:Fenretinide is a synthetic retinoid with activity in prostate cancer and other cell lines. The aim of this study was to assess the efficacy and tolerability of fenretinide in chemotherapy-naïve men with hormone refractory prostate cancer. METHODS:Eligibility criteria included hormone refractory prostate cancer...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-009-1228-x
更新日期:2010-10-01 00:00:00
abstract:PURPOSE:Little information is available about changes in renal function after cisplatin-based chemotherapy (CBCT) in patients with a solitary kidney. The authors evaluated the renal safety and efficacy of CBCT after nephroureterectomy for upper urinary tract-urothelial carcinoma (UUT-UC). METHODS:The data of patients ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1349-2
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:Although cisplatin is an important agent in non-small-cell lung cancer (NSCLC), de novo resistance is common and acquired resistance emerges rapidly during therapy. Proposed mediators of platinum resistance include the protein kinase C (PKC) signal transduction pathway and associated c-FOS overexpression. While...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800100293
更新日期:2001-07-01 00:00:00
abstract::Studies are described in which a new folate analogue, edatrexate (EDX), in combination with the vinca alkaloids, vinblastine (VBL), navelbine (NVB) or vindesine (DVA) was evaluated against E0771 mammary adenocarcinoma, T241 fibrosarcoma and the Lewis lung tumor. Each of the four agents when given individually to anima...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685901
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer. METHODS:Patients had measurable or evaluable lesions according to the Japanes...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-009-1114-6
更新日期:2010-05-01 00:00:00
abstract::The activity of CD437¿6-[3-(1-adamantyl)-4 hydroxyphenyl]-2-naphthalene carboxylic acid¿, a relatively selective activator of RAR-gamma, was evaluated against four human ovarian-carcinoma cell lines : PE01, PE04 (a Pt-resistant in vivo-derived counterpart of PE01), PE01CDDP (a Pt-resistant in vitro-derived model of PE...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050841
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:This study evaluated the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of erlotinib when combined to irinotecan and capecitabine in pre-treated metastatic colorectal cancer patients. METHODS:Five dose level combinations with irinotecan (from 180 to 240 mg/m(2), day 1, q21), capecitabine (1,...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0852-1
更新日期:2009-06-01 00:00:00
abstract::A series of in vitro cytotoxicity studies were performed to achieve pharmacologic reversal of resistance to the alkylating agent mitomycin (MMC) in L-1210 leukemia cells. A multidrug-resistant (MDR), P-glycoprotein-positive cell line, RL-1210/.1 [11], was exposed to potential MDR modulators in the absence or presence ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685114
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:To evaluate the efficacy and safety of preoperative radiotherapy with capecitabine and mitomycin C in patients with locally advanced rectal cancer. METHODS:A prospective, open-label, non-randomized, phase II study was performed on 49 patients with locally advanced rectal cancer. Preoperative radiotherapy was c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00280-010-1469-8
更新日期:2011-09-01 00:00:00
abstract:PURPOSE:Although irinotecan monotherapy is often used in third-line treatment after the failure of taxanes in Japanese clinical practice, its survival benefit is still unclear. The aim of this study is to investigate the efficacy and safety of irinotecan monotherapy as third-line treatment. METHODS:Clinical data from ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3138-z
更新日期:2016-10-01 00:00:00
abstract::The therapeutic efficacy of PTT.119, p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl, was evaluated using the transplantable L1210 leukemia and Ridgway osteogenic sarcoma tumor lines and the spontaneous C3H/StRos mammary tumor and AKR leukemia tumor models. Given in a single i.p. dose at 5-10 mg/kg on day 2 or...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF02897202
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Irinotecan-induced gut toxicity is mediated in part by Toll-Like receptor 4 (TLR4) signalling. The primary purpose of this preclinical study was to determine whether blocking TLR4 signalling by administering (-)-naloxone, a TLR4 antagonist, would improve irinotecan-induced gut toxicity. Our secondary aim was to...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3223-3
更新日期:2017-02-01 00:00:00
abstract:PURPOSE:Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excis...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0703-0
更新日期:2008-12-01 00:00:00
abstract:PURPOSE:This study aimed at investigating the anti-tumor effect of arsenic sulfide (As2S2) against liver cancer both in vivo and in vitro and to elucidate its underlying mechanisms. METHODS:Cell viability of the human hepatocellular carcinoma cell lines SMMC-7721, BEL-7402, HepG2 were measured by CCK-8 assay. The effe...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3755-9
更新日期:2019-03-01 00:00:00
abstract::OSI-7836 (4'-thio-beta-D-arabinofuranosylcytosine) is a novel nucleoside analog in phase I clinical development for the treatment of cancer. As with other nucleoside analogs, the proposed mechanism of action involves phosphorylation to the triphosphate form followed by incorporation into cellular DNA, leading to cell ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-004-0844-8
更新日期:2005-03-01 00:00:00
abstract:PURPOSE:To review the 20 years of experience at M. D. Anderson Cancer Center with a combined-modality approach against inflammatory breast carcinoma. PATIENTS AND METHODS:A total of 178 patients with inflammatory breast carcinoma were treated in the past 20 years at M. D. Anderson Cancer Center by a combined-modality ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050664
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:Chemotherapy dosing in neonates represents a major clinical challenge because of a lack of clinical pharmacology information in this patient population. In this study, we investigate the use of cisplatin dose adaptation based on therapeutic drug monitoring in a 2-week-old neonate with localized hepatoblastoma. ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-018-3625-5
更新日期:2018-08-01 00:00:00
abstract:PURPOSE:The aim of the study was to assess the clinical activity and toxicity of oxaliplatin and leucovorin in combination with bolus and continuous infusional 5-fluorouracil administered every 2 weeks (modified FOLFOX-6 regimen) to patients with adenocarcinoma of an unknown primary site (ACUP). METHODS:Previously unt...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2904-7
更新日期:2016-01-01 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:PURPOSE:The aims of this dose-escalating phase I study were to determine the maximum tolerable dose (MTD) and recommended dose (RD) of 5-fluorouracil (5-FU), docetaxel, and nedaplatin (UDON) combination therapy for future phase II studies, and to evaluate the safety and efficacy of this regimen in patients with untreat...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-015-2799-3
更新日期:2015-08-01 00:00:00
abstract:PURPOSE:To explore the clinical significance of plasma D-dimer increase for transcatheter arterial chemoembolization (TACE) in patients with primary liver cancer (PLC). METHODS:The clinical data of 80 PLC patients who underwent TACE in our hospital from January 2015 to January 2017 were collected, including the plasma...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03778-6
更新日期:2019-04-01 00:00:00
abstract::To predict the clinical effect on leukemic disease of a combination regimen developed to circumvent multidrug resistance (MDR), we tested various antitumor agents in the presence and absence of AHC-52, a sensitizing agent for multidrug-resistant cells, in the i.v.-i.v. model of murine leukemia. In this model system, s...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689959
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:Although chemotherapeutic protocols that include chloroethylnitrosoureas (CENUs), such as 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), have been a mainstay of treatment for glioblastomas, the clinical outcomes ha...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050023
更新日期:2000-01-01 00:00:00