Combination treatment of cancer cells with pan-Akt and pan-mTOR inhibitors: effects on cell cycle distribution, p-Akt expression level and radiolabelled-choline incorporation.

abstract：:Based on the high response rates seen among patients with colon cancer receiving high dose Melphalan with autologous marrow infusion, the Southwest Oncology Group conducted a Phase II trial of the compound at a conventional dose. The initial starting dose of 40 mg/m2 was reduced to 30 mg/m2 after severe myelotoxicity ...

journal_title：Investigational new drugs

authors： Knight WA 3rd,Goodman P,Taylor SA,Macdonald JS,Coltman CA Jr,Constanzi JJ,Baker LH

更新日期：1990-01-01 00:00:00

abstract：:Herein we describe a series of multifunctional 5-aminolevulinic-acid (ALA) prodrugs for photodynamic dependent and independent cancer therapy (PDT). We studied the cell-death mechanisms in glioblastoma U251 cells treated with four ALA-prodrugs: (1) AlaAcBu, that releases ALA, acetaldehyde, and butyric acid; (2) AlaFaB...

journal_title：Investigational new drugs

authors： Berkovitch-Luria G,Weitman M,Nudelman A,Rephaeli A,Malik Z

更新日期：2012-06-01 00:00:00

abstract：:Transcription factor Specificity protein 1 (Sp1) and its downstream target survivin (inhibitor of apoptosis protein), play major roles in the pathogenesis of various cancers. Ewing Sarcoma (ES) is a common soft tissue/bone tumor in adolescent and young adults. Overexpression of survivin is also linked to the aggressiv...

journal_title：Investigational new drugs

authors： Shelake S,Sankpal UT,Paul Bowman W,Wise M,Ray A,Basha R

更新日期：2017-04-01 00:00:00

abstract：BACKGROUND AND RATIONALE:Bortezomib (PS-341, VELCADE®) is a selective inhibitor of the 26S proteasome, an integral component of the ubiquitin-proteasome pathway. This phase II study evaluated the activity and tolerability of bortezomib in unresectable hepatocellular carcinoma (HCC) patients. METHODS:The primary endpoi...

journal_title：Investigational new drugs

authors： Kim GP,Mahoney MR,Szydlo D,Mok TS,Marshke R,Holen K,Picus J,Boyer M,Pitot HC,Rubin J,Philip PA,Nowak A,Wright JJ,Erlichman C

更新日期：2012-02-01 00:00:00

abstract：:T cells are important effectors in anti-tumor immunity, and aberrant expression of B7 family members may contribute to tumor evasion. In this study, we analyzed expression of costimulatory molecules on human hematologic tumor cells and explored whether B7-H3, a member of the B7 superfamily, is an effective target for ...

journal_title：Investigational new drugs

authors： Sun X,Yu Y,Ma L,Xue X,Gao Z,Ma J,Zhang M

更新日期：2020-06-01 00:00:00

abstract：BACKGROUND:This study investigated the activity of MK-2206, an AKT inhibitor, in metastatic or recurrent nasopharyngeal carcinoma (NPC). METHOD:Oral MK-2206 at a dose of 200 mg was administered on days 1, 8, 15 and 22 of a 28-day cycle until progression. Plasma EBV DNA clearance during the first month of treatment was...

journal_title：Investigational new drugs

authors： Ma BB,Goh BC,Lim WT,Hui EP,Tan EH,Lopes Gde L,Lo KW,Li L,Loong H,Foster NR,Erlichman C,King AD,Kam MK,Leung SF,Chan KC,Chan AT

更新日期：2015-08-01 00:00:00

abstract：:Myricetin is a naturally omnipresent benzo-α-pyrone flavonoids derivative; has potent anticancer activity. Receptor tyrosine kinases family provides the decisive role in cancer initiation and progression. These receptors have recently caught the attention of the researchers as an attractive target to combat cancer, ow...

journal_title：Investigational new drugs

authors： Singh P,Bast F

更新日期：2015-06-01 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：PURPOSE:The transcription factor nuclear factor-kB (NFkB) is implicated in gastric cancer carcinogenesis and survival, and its inhibition by proteosome inhibition is associated with preclinical gastric cancer anti-tumor activity. We examined the single agent efficacy of bortezomib, a selective proteasome inhibitor, in ...

journal_title：Investigational new drugs

authors： Shah MA,Power DG,Kindler HL,Holen KD,Kemeny MM,Ilson DH,Tang L,Capanu M,Wright JJ,Kelsen DP

更新日期：2011-12-01 00:00:00

abstract：:Hepatocellular carcinoma (HCC) is the most prevalent type of tumor among primary liver tumors and is the second highest cause of cancer-related deaths worldwide. Current therapies are controversial, and more research is needed to identify effective treatments. A new synthetic compound, potassium 5-cyano-4-methyl-6-oxo...

journal_title：Investigational new drugs

authors： da Silva EFG,Lima KG,Krause GC,Haute GV,Pedrazza L,Catarina AV,Gassen RB,de Souza Basso B,Dias HB,Luft C,Garcia MCR,Costa BP,Antunes GL,Basso LA,Donadio MVF,Machado P,de Oliveira JR

更新日期：2020-12-01 00:00:00

abstract：:Thirty-two patients with advanced epidermoid carcinoma of the esophagus were treated with ifosfamide (1.50 gm/m2 daily x 5 days) with uroprotective mesna in a phase II study. Eighteen patients were previously untreated. Of 28 evaluable patients, two (7%) had partial remissions lasting 2+ and 6+ months. Toxicity was pr...

journal_title：Investigational new drugs

authors： Nanus DM,Kelsen DP,Lipperman R,Eisenberger M

更新日期：1988-09-01 00:00:00

abstract：:Coptis chinensis Franch. has been extensively used in traditional Chinese medicine. The chemical structure of oxyepiberberine, as an alkaloid isolated from Coptis chinensis Franch., has been previously studied. However, anti-cancer effects and underlying mechanisms of oxyepiberberine need to be explored. This study ai...

journal_title：Investigational new drugs

authors： Ning H,Lu W,Jia Q,Wang J,Yao T,Lv S,Li Y,Wen H

更新日期：2020-09-30 00:00:00

abstract：:Background This open-label, first-in-human, phase 1 study evaluated AMG 232, an oral selective MDM2 inhibitor in patients with TP53 wild-type (P53WT), advanced solid tumors or multiple myeloma (MM). Methods In the dose escalation (n = 39), patients with P53WT refractory solid tumors enrolled to receive once-daily AMG ...

journal_title：Investigational new drugs

authors： Gluck WL,Gounder MM,Frank R,Eskens F,Blay JY,Cassier PA,Soria JC,Chawla S,de Weger V,Wagner AJ,Siegel D,De Vos F,Rasmussen E,Henary HA

更新日期：2020-06-01 00:00:00

abstract：:Background The hexapeptide 4A6 (Ac-Thr(tBu)-His(Bzl)-Thr(Bzl)-Nle-Glu(OtBu)-Gly-Bza) was isolated from a peptide library constructed to identify peptide-based transport inhibitors of multidrug resistance (MDR) efflux pumps including P-glycoprotein and Multidrug Resistance-associated Protein 1. 4A6 proved to be a subst...

journal_title：Investigational new drugs

authors： Oerlemans R,Berkers CR,Assaraf YG,Scheffer GL,Peters GJ,Verbrugge SE,Cloos J,Slootstra J,Meloen RH,Shoemaker RH,Dijkmans BAC,Scheper RJ,Ovaa H,Jansen G

更新日期：2018-10-01 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：:SHetA2 is a small molecule flexible heteroarotinoid (Flex-Het) with promising cancer prevention and therapeutic activity. Extensive preclinical testing documented lack of SHetA2 toxicity at doses 25 to 150 fold above effective doses. Knowledge of the SHetA2 molecular target(s) that mediate(s) the mechanism of SHetA2 a...

journal_title：Investigational new drugs

authors： Benbrook DM,Nammalwar B,Long A,Matsumoto H,Singh A,Bunce RA,Berlin KD

更新日期：2014-06-01 00:00:00

abstract：:9-Aminocamptothecin (9-AC) is a water-insoluble camptothecin derivative that demonstrated broad activity in pre-clinical studies. In vitro, greater anti-tumor efficacy can be achieved with prolonged administration. A minor response was observed in gastric cancer in a phase I study. We conducted a phase II study of 9-A...

journal_title：Investigational new drugs

authors： Kindler HL,Avadhani A,Wade-Oliver K,Karrison T,Mani S,Vokes EE

更新日期：2004-08-01 00:00:00

abstract：:LY2457546 is a potent and orally bioavailable inhibitor of multiple receptor tyrosine kinases involved in angiogenic and tumorigenic signalling. In biochemical and cellular assays, LY2457546 demonstrates potent activity against targets that include VEGFR2 (KDR), PDGFRβ, FLT-3, Tie-2 and members of the Eph family of re...

journal_title：Investigational new drugs

authors： Burkholder TP,Clayton JR,Rempala ME,Henry JR,Knobeloch JM,Mendel D,McLean JA,Hao Y,Barda DA,Considine EL,Uhlik MT,Chen Y,Ma L,Bloem LJ,Akunda JK,McCann DJ,Sanchez-Felix M,Clawson DK,Lahn MM,Starling JJ

更新日期：2012-06-01 00:00:00

abstract：:Background PF-06650808 is a novel anti-Notch3 antibody-drug conjugate (ADC) able to deliver an auristatin-based cytotoxic payload to target cells. In this first-in-human, dose-finding, phase I study (NCT02129205), we investigated safety, pharmacokinetics, immunogenicity, and preliminary antitumor activity of single-ag...

journal_title：Investigational new drugs

authors： Rosen LS,Wesolowski R,Baffa R,Liao KH,Hua SY,Gibson BL,Pirie-Shepherd S,Tolcher AW

更新日期：2020-02-01 00:00:00

abstract：:Over forty papers describing correlations between in vitro human tumor sensitivity to a variety of chemotherapeutic agents and the in vivo response of patients to those agents have been published since the publication in 1978 by Salmon and Hamburger of their results of a human tumor colony-forming chemosensitivity ass...

journal_title：Investigational new drugs

authors： Bradley EC,Issell BF,Hellman R

更新日期：1984-01-01 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：BACKGROUND:Therapeutic approaches to marginal zone B-cell lymphoma (MZL) continue to evolve. Localized MZL responds favorably to local treatments, including surgery and/or local radiation therapy. However, MZL manifests as a disseminated disease in one-third of the cases at diagnosis. Moreover, relapses involving dista...

journal_title：Investigational new drugs

authors： Oh SY,Kim WS,Lee DH,Kim SJ,Kim SH,Ryoo BY,Kang HJ,Choi YJ,Chung JS,Kim HJ,Suh C

更新日期：2010-04-01 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：INTRODUCTION:This multicenter, open-label, phase II study was carried out to compare the efficacy and safety of cilengitide (EMD 121974), a selective inhibitor of the cell-surface integrins αVβ3 and αVβ5, with that of docetaxel in patients with advanced non-small-cell lung cancer (NSCLC). METHODS:Patients (n = 140) wi...

journal_title：Investigational new drugs

authors： Manegold C,Vansteenkiste J,Cardenal F,Schuette W,Woll PJ,Ulsperger E,Kerber A,Eckmayr J,von Pawel J

更新日期：2013-02-01 00:00:00

abstract：:Ninhydrin (2,2-dihydroxy-1,3-indane dione) was evaluated for its antitumor and cytotoxic properties in Ehrlich ascites carcinoma cell (EAC Cell)-bearing mice. The rationale behind this study has been mainly the literature reports of its characteristic interference with DNA synthesis and calcium homeostasis. Antitumor ...

journal_title：Investigational new drugs

authors： Qureshi S,Al-Shabanah OA,Al-Bekairi AM,Al-Harbi MM,Al-Gharably NM,Raza M

更新日期：2000-08-01 00:00:00

abstract：:Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse ...

journal_title：Investigational new drugs

authors： Izzedine H,Gueutin V,Gharbi C,Mateus C,Robert C,Routier E,Thomas M,Baumelou A,Rouvier P

更新日期：2014-08-01 00:00:00

abstract：:Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumo...

journal_title：Investigational new drugs

authors： Schwartsmann G,DiLeone LP,Horowitz M,Schunemann D,Cancella A,Pereira AS,Richter M,Souza F,da Rocha AB,Souza FH,Pohlmann P,De Nucci G

更新日期：2006-09-01 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：:A retrospective cohort study was performed to investigate the effectiveness of preemptive postsurgical therapy with cetuximab for patients with a major risk of recurrence or metastasis after clinical complete resection of primary oral squamous cell carcinoma (OSCC). The study period was from 2007 to 2019 for patients ...

journal_title：Investigational new drugs

authors： Fukumoto C,Sawatani Y,Shiraishi R,Zama M,Shimura M,Hasegawa T,Komiyama Y,Fujita A,Wakui T,Kawamata H

更新日期：2021-01-15 00:00:00

abstract：:CP-4126 is a gemcitabine (2',2'-difluorodeoxycytidine; dFdC) 5' elaidic acid ester. The purpose of this dose-escalating study was to assess safety, pharmacokinetics (PK) and preliminary antitumor activity of the oral formulation and to determine the recommended dose (RD) for phase II studies. The study had a two-step ...

journal_title：Investigational new drugs

authors： Stuurman FE,Voest EE,Awada A,Witteveen PO,Bergeland T,Hals PA,Rasch W,Schellens JH,Hendlisz A

更新日期：2013-08-01 00:00:00