The PIT method: an automated in vitro technique for drug toxicity testing.

abstract：BACKGROUND:TAS-102 is a nucleoside antitumor agent consisting of trifluridine (FTD) and tipiracil hydrochloride (TPI). We investigated the recommended dose (RD) of TAS-102 plus irinotecan for metastatic colorectal cancer refractory to 5-fluorouracil (5-FU) and oxaliplatin. METHODS:This study was used a escalated dose ...

journal_title：Investigational new drugs

authors： Doi T,Yoshino T,Fuse N,Boku N,Yamazaki K,Koizumi W,Shimada K,Takinishi Y,Ohtsu A

更新日期：2015-10-01 00:00:00

abstract：:Studies with CGP 41 251 (I), an N-benzoylstaurosporine derivative and PKC-alpha inhibitor, revealed that oral administration of 400 microg/day of the compound to wild type mice on four successive days reversed multi drug resistance (Killion et al. Oncology Research 7: 453-459, 1995). In our study, the same regimen of ...

journal_title：Investigational new drugs

authors： van Gijn R,van Tellingen O,Haverkate E,Kettenes-van den Bosch JJ,Bult A,Beijnen JH

更新日期：1999-01-01 00:00:00

abstract：:Receptor tyrosine kinases (RTKs) modulate a variety of cellular events, including cell proliferation, differentiation, mobility and apoptosis. In addition, RTKs have been validated as targets for cancer therapies. Microtubules are another class of proven targets for many clinical anticancer drugs. Here, we report that...

journal_title：Investigational new drugs

authors： Zhang J,Zhou J,Ren X,Diao Y,Li H,Jiang H,Ding K,Pei D

更新日期：2012-04-01 00:00:00

abstract：:Background This first-in-human phase 1 study assessed the safety of TAS-114, a novel deoxyuridine triphosphatase inhibitor, combined with S-1 to determine its maximum tolerated dose (MTD) and recommended dose (RD). Methods In this dose-escalation study with a 3 + 3 design, TAS-114 and S-1 were concurrently administere...

journal_title：Investigational new drugs

authors： Doi T,Yoh K,Shitara K,Takahashi H,Ueno M,Kobayashi S,Morimoto M,Okusaka T,Ueno H,Morizane C,Okano N,Nagashima F,Furuse J

更新日期：2019-06-01 00:00:00

abstract：:TNF-alpha may improve drug delivery to tumors by alteration of vascular permeability. However, toxicity precludes its systemic administration in patients. NGR-TNF comprises TNF coupled to the peptide CNGRC, which is a ligand for CD13. CD13 is expressed on tumor vasculature. Therefore, to assess the efficacy of NGR-TNF...

journal_title：Investigational new drugs

authors： van Laarhoven HW,Gambarota G,Heerschap A,Lok J,Verhagen I,Corti A,Toma S,Gallo Stampino C,van der Kogel A,Punt CJ

更新日期：2006-01-01 00:00:00

abstract：:An in vitro assay, which evaluates drug effect on 3H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activiti...

journal_title：Investigational new drugs

authors： Daidone MG,Silvestrini R,Zaffaroni N,Grignolio E,Landoni F

更新日期：1987-01-01 00:00:00

abstract：PURPOSE:Epidermal growth factor receptor (EGFR) inhibition may overcome chemotherapy resistance by inhibiting important anti-apoptotic signals that are constitutively activated by an overstimulated EGFR pathway. METHODS:This phase I dose escalation trial assessed the safety and efficacy of vinflunine, a novel vinca al...

journal_title：Investigational new drugs

authors： Sanoff HK,Davies JM,Walko C,Irvin W,Buie L,Keller K,Ivanova A,Chiu WK,O'Neil BH,Stinchcombe TE,Dees EC

更新日期：2011-10-01 00:00:00

abstract：:In vitro cytotoxicity and xanthine oxidase inhibition capabilities were investigated for five palladium (II) chelate complexes. The palladium complexes were synthesized by starting from S-alkyl-thiosemicarbazones where the alkyl component is methyl, ethyl, propyl or butyl. The solid complexes are characterized by elem...

journal_title：Investigational new drugs

authors： Özerkan D,Ertik O,Kaya B,Kuruca SE,Yanardag R,Ülküseven B

更新日期：2019-12-01 00:00:00

abstract：:The discovery of multiple putative therapeutic targets and multiple putative agents for these targets in prostate cancer in the coming years poses significant challenges for clinical trial design. This is especially true for cytostatic agents that are not expected to lead to frank tumor shrinkage or declines in the PS...

journal_title：Investigational new drugs

authors： Stadler W

更新日期：2002-05-01 00:00:00

abstract：:Interleukin-4 (IL-4) is a pleiotropic cytokine affecting growth and differentiation of various cell types as well as regulating other cytokines. To study the effect of IL-4 on AIDS-related Kaposi's sarcoma (AIDS-KS) cells, we first examined the tumor cells for IL-4 receptor (IL-4R) expression. KS cells express a singl...

journal_title：Investigational new drugs

authors： Cai J,Zheng T,Murphy J,Waters CA,Lin GY,Gill PS

更新日期：1997-01-01 00:00:00

abstract：PURPOSE:This study investigated the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic (PK) profiles of DHP107, a novel oral paclitaxel containing neither Cremophor EL nor P-glycoprotein (P-gp) inhibitor. PATIENTS AND METHODS:Patients with advanced solid tumors refractory to all standard t...

journal_title：Investigational new drugs

authors： Hong YS,Kim KP,Lim HS,Bae KS,Ryu MH,Lee JL,Chang HM,Kang YK,Kim H,Kim TW

更新日期：2013-06-01 00:00:00

abstract：:Adrenocortical carcinoma (ACC) is an aggressive endocrine cancer with few molecular predictors of malignancy and survival, especially in paediatric patients. Stathmin 1 (STMN1) regulates microtubule dynamics and has been involved in the malignant phenotype of cancer cells. Recently, it was reported that STMN1 is highl...

journal_title：Investigational new drugs

authors： Dos Santos Passaia B,Lima K,Kremer JL,da Conceição BB,de Paula Mariani BM,da Silva JCL,Zerbini MCN,Fragoso MCBV,Machado-Neto JA,Lotfi CFP

更新日期：2020-06-01 00:00:00

abstract：:Clinically relevant resistance to the currently approved camptothecins, irinotecan and topotecan, is poorly understood but may involve increased expression of ATP-dependent drug transporters such as ABCG2 (breast cancer resistant protein, BCRP). Gimatecan (ST1481) is a lipophilic 7-substituted camptothecin derivative ...

journal_title：Investigational new drugs

authors： Gounder MK,Nazar AS,Saleem A,Pungaliya P,Kulkarni D,Versace R,Rubin EH

更新日期：2008-06-01 00:00:00

abstract：:Ergot alkaloids are psychoactive and vasoconstricting agents of the fungus Claviceps purpurea causing poisoning such as ergotism in medieval times (St. Anthony's Fire). This class of substances also inhibits tumor growth in vitro and in vivo, though the underlying mechanisms are unclear as yet. We investigated six erg...

journal_title：Investigational new drugs

authors： Mrusek M,Seo EJ,Greten HJ,Simon M,Efferth T

更新日期：2015-02-01 00:00:00

abstract：BACKGROUND:The primary objective of this Phase I study was to determine the maximum tolerated dose (MTD) and recommended phase II dose for Tomudex and Doxorubicin when given in combination to patients with advanced metastatic cancer. The secondary objective was to assess the toxicity profile. PATIENTS AND METHODS:Star...

journal_title：Investigational new drugs

authors： Bjarnason GA,Charpentier D,Wong R,Goel R,Douglas L,Walsh W,Matthews S,Dent S,Seymour L,Winquist E

更新日期：2005-01-01 00:00:00

abstract：:We studied the effect of riccardin D, a macrocyclic bisbibenzyl, which was isolated from the Chinese liverwort plant, on human leukemia cells and the underlying molecular mechanism. Riccardin D had a significant antiproliferative effect on human leukemia cell lines HL-60, K562 and its multidrug resistant (MDR) counter...

journal_title：Investigational new drugs

authors： Xue X,Qu XJ,Gao ZH,Sun CC,Liu HP,Zhao CR,Cheng YN,Lou HX

更新日期：2012-02-01 00:00:00

abstract：:Antiprogestins have been largely utilized in reproductive medicine, yet their repositioning for oncologic use is rapidly emerging. In this study we investigated the molecular mediators of the anti-ovarian cancer activity of the structurally related antiprogestins RU-38486, ORG-31710 and CDB-2914. We studied the respon...

journal_title：Investigational new drugs

authors： Goyeneche AA,Seidel EE,Telleria CM

更新日期：2012-06-01 00:00:00

abstract：:Spirogermanium (NSC 192965) is a new metallic investigational anticancer drug of novel heterocyclic structure. Although its mode of action has not been fully elucidated, it appears that spirogermanium is not a phase or cell cycle specific drug and inhibits DNA, RNA and protein synthesis, the protein synthesis being th...

journal_title：Investigational new drugs

authors： Slavik M,Blanc O,Davis J

更新日期：1983-01-01 00:00:00

abstract：:A series of 96 diarylamidine (and diarylimidazoline) derivatives were evaluated for their inhibitory effects on the growth and DNA synthesis of murine leukemia L1210 cells. The amidino- and imidazolino-substituted aryl moieties of the compounds consisted of phenyl, indole, indene, benzofuran, benzo[b]thiophene or benz...

journal_title：Investigational new drugs

authors： Balzarini J,de Clercq E,Dann O

更新日期：1983-01-01 00:00:00

abstract：:Epidermal growth factor receptor (EGFR) gene mutations activate the KRAS-RAF-MEK-ERK pathway in lung cancer cells. EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib induce apoptosis of cancer cells, but prolonged treatment is often associated with acquired resistance. Here, we identified a novel MEK1/2 inhibito...

journal_title：Investigational new drugs

authors： Song JY,Kim CS,Lee JH,Jang SJ,Lee SW,Hwang JJ,Lim C,Lee G,Seo J,Cho SY,Choi J

更新日期：2013-12-01 00:00:00

abstract：:Breast cancer is commonly treated with anti-estrogens or aromatase inhibitors, but resistant disease eventually develops and new therapies for such resistance are of great interest. We have previously isolated several tamoxifen-resistant variant sub-lines of the MCF-7 breast cancer cell line and provided evidence that...

journal_title：Investigational new drugs

authors： Leung E,Rewcastle GW,Joseph WR,Rosengren RJ,Larsen L,Baguley BC

更新日期：2012-12-01 00:00:00

abstract：:Mitonafide is the lead compound of a new series of antitumor drugs, the 3-Nitronaphthalimides, which have shown antineoplastic activity in vitro as well as in vivo. This phase I Mitonafide study in non-small cell lung cancer using a 120-hour continuous infusion (120 h. C.I.) schedule of administration was designed to ...

journal_title：Investigational new drugs

authors： Rosell R,Carles J,Abad A,Ribelles N,Barnadas A,Benavides A,Martin M

更新日期：1992-08-01 00:00:00

abstract：:Peloruside A is a microtubule-stabilizing agent that is currently under investigation as a potential anticancer agent. Peloruside A binds to a site on β-tubulin that is distinct to that of the taxanes (paclitaxel and docetaxel) and the epothilones. An attractive clinical quality of microtubule-stabilizing agents is th...

journal_title：Investigational new drugs

authors： Chan A,Singh AJ,Northcote PT,Miller JH

更新日期：2015-06-01 00:00:00

abstract：BACKGROUND:Dacomitinib (PF-00299804) is an oral, irreversible, small molecule inhibitor of human epidermal growth factor receptor-1, -2, and -4 tyrosine kinases. METHODS:This phase I, open-label, dose-escalation study (clinicaltrials.gov: NCT00783328) primarily evaluated the safety and tolerability of dacomitinib by d...

journal_title：Investigational new drugs

authors： Takahashi T,Boku N,Murakami H,Naito T,Tsuya A,Nakamura Y,Ono A,Machida N,Yamazaki K,Watanabe J,Ruiz-Garcia A,Imai K,Ohki E,Yamamoto N

更新日期：2012-12-01 00:00:00

abstract：:An inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that typically develops in the lungs and seldom in the head and neck region. It is often related to the anaplastic lymphoma kinase (ALK) fusion gene. Crizotinib, a first-generation ALK inhibitor, has been shown to have a notable response in pat...

journal_title：Investigational new drugs

authors： Honda K,Kadowaki S,Kato K,Hanai N,Hasegawa Y,Yatabe Y,Muro K

更新日期：2019-08-01 00:00:00

abstract：:There is no effective systemic therapy for disseminated metastatic melanoma. Data suggest that endothelin may play a role in pathophysiology of melanoma and that the dual endothelin receptor antagonist bosentan may have anti-tumor activity. This multicenter, open-label, single-arm, prospective, proof-of-concept study ...

journal_title：Investigational new drugs

authors： Kefford R,Beith JM,Van Hazel GA,Millward M,Trotter JM,Wyld DK,Kusic R,Shreeniwas R,Morganti A,Ballmer A,Segal E,Nayler O,Clozel M

更新日期：2007-06-01 00:00:00

abstract：:Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib tre...

journal_title：Investigational new drugs

authors： Yamamoto Y,Okamoto I,Otsubo K,Iwama E,Hamada N,Harada T,Takayama K,Nakanishi Y

更新日期：2015-10-01 00:00:00

abstract：:Flavone acetic acid (FAA) was incubated for 1 to 48 hr with 3 established human colon cancer cell lines endowed with distinct degrees of phenotypic properties. All 3 lines responded to FAA in almost identical fashion; when incubated with the drug for only 1 hr, an initial decrease in survival was observed for concentr...

journal_title：Investigational new drugs

authors： Drewinko B,Yang LY

更新日期：1986-01-01 00:00:00

abstract：:Twenty-four patients with a variety of solid tumors entered a Phase I trial with 4-demethoxydaunorubicin, a new analogue of daunorubicin. The drug was given as a single oral dose of 10-60 mg/m2 repeated every 3-4 weeks. Leukopenia was the dose-limiting toxicity. Other toxic effects included mild to moderate nausea and...

journal_title：Investigational new drugs

authors： Kaplan S,Sessa C,Willems Y,Pacciarini MA,Tamassia V,Cavalli F

更新日期：1984-01-01 00:00:00

abstract：:Purpose The aim of this study is to detect apoptotic and cytotoxic/antiproliferative effects of a ligand substance and its metal derivatives. The substances were investigated by using an h-ras oncogene transformed rat embryo fibroblast cell line (5RP7). Methods The cytotoxic influences of dipyrido[3,2-a:2',3'c]phenazi...

journal_title：Investigational new drugs

authors： Kaplan A,Benkli K,Koparal AT

更新日期：2018-10-01 00:00:00