Proteasome inhibition and mechanism of resistance to a synthetic, library-based hexapeptide.

abstract：:Twenty-four patients with advanced epidermoid carcinoma of the esophagus were treated with trimetrexate (TMTX), a lipid soluble non-classical antifol. Patients were given TMTX 8 mg/m2 intravenously day 1-5 every 28 days. In nine of these patients the dose was escalated to 12 mg/m2 day 1-5 every 28 days. Three patients...

journal_title：Investigational new drugs

authors： Alberts AS,Falkson G,Badata M,Terblanche AP,Schmid EU

更新日期：1988-12-01 00:00:00

abstract：:A series of novel 5-(4-methyl-benzylidene)-thiazolidine-2,4-dione derivatives 6 (a-d) and 7 (a-g) were synthesized with different substituted aromatic sulfonyl chlorides (R-SO(2)-Cl) and alkyl halides (R-X) and were characterized by (1)H NMR, LC/MS, FTIR and elemental analyses. All the compounds synthesised were evalu...

journal_title：Investigational new drugs

authors： Chandrappa S,Benaka Prasad SB,Vinaya K,Ananda Kumar CS,Thimmegowda NR,Rangappa KS

更新日期：2008-10-01 00:00:00

abstract：PURPOSE:To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and tolerability of MN-209, a novel vascular disrupting agent, in patients with advanced solid tumors. STUDY DESIGN:MN-029 was administered weekly for three consecutive weeks out of four; two cycles were planned. Dose escalation ...

journal_title：Investigational new drugs

authors： Traynor AM,Gordon MS,Alberti D,Mendelson DS,Munsey MS,Wilding G,Gammans RE,Read WL

更新日期：2010-08-01 00:00:00

abstract：:We have previously shown that the insulinotropic imidazoline compound RX871024 induces death of insulinoma MIN6 cells, an effect involving stimulation of c-Jun N-terminal kinase (JNK) and caspase 3. It has also been reported that AMP-activated protein kinase (AMPK) activates JNK and induces β-cell death. Here we show ...

journal_title：Investigational new drugs

authors： Zaitseva II,Zaitsev SV,Berggren PO

更新日期：2016-08-01 00:00:00

abstract：:Twenty-four evaluable patients with epithelial ovarian cancer resistant to primary therapy, or relapsing after response to initial therapy, were treated with acivicin utilizing a daily X 5 schedule. One patient achieved a partial response lasting five months; the remaining 23 patients showed no objective response. Pro...

journal_title：Investigational new drugs

authors： McGuire WP,Blessing JA,DiSaia PJ,Buchsbaum HJ

更新日期：1986-01-01 00:00:00

abstract：:Fifteen patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck received a 5 day continuous I.V. infusion of 6-thioguanine repeated every five weeks. Dose limiting toxicity was primarily hematological with grade III/IV leucopenia and thrombocytopenia seen in seven patients. Nausea and vo...

journal_title：Investigational new drugs

authors： Kruter F,Eisenberger M,Sinibaldi V,Engstrom C,Jacobs M,Abrams J,Belani C,Gray W,Krasnow S

更新日期：1992-07-01 00:00:00

abstract：:Background Treatment of recurrent, unresectable granulosa cell tumor (GCT) of the ovary can be challenging. Given the rarity of the tumor, alternative therapies have been difficult to evaluate in large prospective clinical trials. Currently, to our knowledge, there are no reports of the use of immune checkpoint inhibi...

journal_title：Investigational new drugs

authors： How JA,Jazaeri A,Westin SN,Sood AK,Ramondetta LM,Xu M,Abonofal A,Karp DD,Subbiah V,Stephen B,Rodon JA,Yang F,Naing A

更新日期：2021-01-07 00:00:00

abstract：INTRODUCTION:Heat shock protein 90 (Hsp90) has been studied as a therapeutic target in many cancers. In preclinical trials, the Hsp90 ATPase inhibitor ganetespib demonstrated potent inhibition of solid tumor growth, with superior potency than prior Hsp90 inhibitors. Given the promising preclinical outcome and favorable...

journal_title：Investigational new drugs

authors： Thakur MK,Heilbrun LK,Sheng S,Stein M,Liu G,Antonarakis ES,Vaishampayan U,Dzinic SH,Li X,Freeman S,Smith D,Heath EI

更新日期：2016-02-01 00:00:00

abstract：:Angiogenesis is recognized as an important biological process that allows growth of a tumor beyond an initial small size. PTK787/ZK222584, a potent orally active angiogenesis inhibitor capable of inhibiting all known isoforms of Vascular Endothelial Growth Factor (VEGF) receptor, belongs to the class of aminophthalazi...

journal_title：Investigational new drugs

authors： Sharma S,Freeman B,Turner J,Symanowski J,Manno P,Berg W,Vogelzang N

更新日期：2009-02-01 00:00:00

abstract：BACKGROUND:We evaluated the efficacy and safety of cetuximab in combination with XELOX [XELoda® (capecitabine) and OXaliplatin] in advanced gastric cancer (AGC) patients. The objectives were to evaluate overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety of cetuximab plus XEL...

journal_title：Investigational new drugs

authors： Kim C,Lee JL,Ryu MH,Chang HM,Kim TW,Lim HY,Kang HJ,Park YS,Ryoo BY,Kang YK

更新日期：2011-04-01 00:00:00

abstract：:Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be required for tumor invasion, tumor-induced angiogenesis and vascular invasion. A synthetic hydroxamate, batimastat (also known as BB-94), inhibits MMPs by binding the zinc ion in the active site of the MMP. ...

journal_title：Investigational new drugs

authors： Wojtowicz-Praga S,Low J,Marshall J,Ness E,Dickson R,Barter J,Sale M,McCann P,Moore J,Cole A,Hawkins MJ

更新日期：1996-01-01 00:00:00

abstract：:Menogaril, a semisynthetic anthracycline antibiotic, was administered to patients with metastatic adenocarcinoma of the prostate. Forty-five patients with measurable disease and 45 patients with evaluable disease received 150-200 mg/m2 over 1 hour every 28 days. There were three partial responses (PR) among 87 patient...

journal_title：Investigational new drugs

authors： Taylor SA,Blumenstein BA,Stephens RL,Crawford ED,Pistone B,Hill JB

更新日期：1994-01-01 00:00:00

abstract：:Recent clinical trials carried out in patients with advanced cancer have shown that recombinant TRAIL administration is usually safe and well tolerated when used either alone or in association with chemotherapeutic drugs. Notably, anticancer chemotherapy can be associated to cardiomiopathy. We have here demonstrated t...

journal_title：Investigational new drugs

authors： Toffoli B,Bernardi S,Candido R,Zacchigna S,Fabris B,Secchiero P

更新日期：2012-06-01 00:00:00

abstract：:Neuroblastoma is an extracranial, solid, and heterogeneous malignancy in children. The conventional therapeutic modalities are mostly ineffective and thus new therapeutic strategies for malignant neuroblastoma are urgently warranted. We examined the synergistic efficacy of combination of sorafenib (SF) and genistein (...

journal_title：Investigational new drugs

authors： Roy Choudhury S,Karmakar S,Banik NL,Ray SK

更新日期：2010-12-01 00:00:00

abstract：:Idarubicin, a new analogue of daunorubicin, was administered to 27 patients with advanced breast cancer in a phase II trial. The drug was given orally at a dose of 30-35 mg/m2 every 3 weeks. Twenty-two patients were evaluable for response. All evaluable patients were previously treated with one or more chemotherapeuti...

journal_title：Investigational new drugs

authors： Lopez M,Di Lauro L,Papaldo P,Lazzaro B,Ganzina F,Di Pietro N

更新日期：1986-01-01 00:00:00

abstract：:Fourteen patients with active chronic lymphocytic leukemia who had failed prior therapy were treated with progressive doses of weekly intravenous colchicine beginning at 2 mg and escalating as high as 7 mg in a single injection. Responses were seen in two of 14, with a lessening of adenopathy and splenomegaly. Toxicit...

journal_title：Investigational new drugs

authors： Weick JK,Livingston RB,Van Slyck EJ

更新日期：1983-01-01 00:00:00

abstract：PURPOSE:To investigate the safety, optimal dosing, pharmacokinetics and clinical activity of a regimen of navitoclax (ABT-263) combined with gemcitabine in patients with solid tumors. EXPERIMENTAL DESIGN:Patients with solid tumors for which gemcitabine was deemed an appropriate therapy were enrolled into one of two di...

journal_title：Investigational new drugs

authors： Cleary JM,Lima CM,Hurwitz HI,Montero AJ,Franklin C,Yang J,Graham A,Busman T,Mabry M,Holen K,Shapiro GI,Uronis H

更新日期：2014-10-01 00:00:00

abstract：:XK-469 is advancing to Phase I clinical trials. Preclinical studies were carried out to assist in clinical applications. DOSE-SCHEDULE ROUTE TESTING: Single dose i.v. treatment with XK-469 produced lethality (LD20 to LD100) above 142 mg/kg. Optimum treatment required total dosages of 350 to 600 mg/kg. Furthermore, hig...

journal_title：Investigational new drugs

authors： Polin L,White K,Kushner J,Paluch J,Simpson C,Pugh S,Edelstein MK,Hazeldine S,Fontana J,LoRusso P,Horwitz JP,Corbett TH

更新日期：2002-02-01 00:00:00

abstract：:Drug lag, which delays patients' access to medicinal products, is typically associated with pharmaceutical regulations. To shorten drug lag, health authorities may establish new policies to liberalize the regulations, a step that is important in countries, such as Taiwan, with consumer demand for imported novel therap...

journal_title：Investigational new drugs

authors： Sun IC

更新日期：2019-10-01 00:00:00

abstract：BACKGROUND:To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology. METHODS:Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily....

journal_title：Investigational new drugs

authors： Galsky MD,Von Hoff DD,Neubauer M,Anderson T,Fleming M,Nagarwala Y,Mahoney JM,Midwinter D,Vocila L,Zaks TZ

更新日期：2012-04-01 00:00:00

abstract：:Background Older non-small cell lung cancer (NSCLC) patients under erlotinib are reported to experience more acute toxicity. We hypothesized that modifications in erlotinib pharmacokinetics might explain this observation. Methods A monocentric prospective clinico-pharmacological study included stage IIIb/IV NSCLC cons...

journal_title：Investigational new drugs

authors： Bigot F,Boudou-Rouquette P,Arrondeau J,Thomas-Schoemann A,Tlemsani C,Chapron J,Huillard O,Cessot A,Vidal M,Alexandre J,Blanchet B,Goldwasser F

更新日期：2017-04-01 00:00:00

abstract：:We have developed a specific and sensitive method aiming at docetaxel (Taxotere) determination in plasma of treated patients. This involved solid-phase extraction of 1 ml of plasma onto carboxylic acid (CBA) grafted silica cartridges followed by reversed-phase liquid chromatography with UV detection. The best selectiv...

journal_title：Investigational new drugs

authors： Ardiet CJ,Tranchand B,Zanetta S,Guillot A,Bernard E,Peguy M,Rebattu P,Droz JP

更新日期：1999-01-01 00:00:00

abstract：:Fluorinated pyrimidines, particularly 5-fluorouracil (FUra), have been the subject of intense and almost continuous basic and clinical study since development in the late 1950's by Dr. Charles Heidelberger. Despite this intensive effort, the most important mechanisms by which FUra influences tumor growth in individual...

journal_title：Investigational new drugs

authors： Kovach JS,Beart RW Jr

更新日期：1989-04-01 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：: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：:To explore the clinical significance of the level of HER2/neu gene amplification in a homogenous cohort of 33 patients with HER2-positive metastatic breast cancer (MBC) and available tumor samples treated with a trastuzumab-based regimen, we retrospectively performed dual-color fluorescence in-situ hybridization test ...

journal_title：Investigational new drugs

authors： Gullo G,Bettio D,Torri V,Masci G,Salvini P,Santoro A

更新日期：2009-04-01 00:00:00

abstract：:Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellula...

journal_title：Investigational new drugs

authors： Dredge K,Hammond E,Davis K,Li CP,Liu L,Johnstone K,Handley P,Wimmer N,Gonda TJ,Gautam A,Ferro V,Bytheway I

更新日期：2010-06-01 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：:Osimertinib is a molecularly targeted agent used to treat non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) T790M mutation. However, its efficacy and safety profile when patients have poor performance status (PS) is unknown. Therefore, we conducted an open-label, multi-center,...

journal_title：Investigational new drugs

authors： Nakashima K,Ozawa Y,Daga H,Imai H,Tamiya M,Tokito T,Kawamura T,Akamatsu H,Tsuboguchi Y,Takahashi T,Yamamoto N,Mori K,Murakami H

更新日期：2020-12-01 00:00:00

abstract：:Cancer is one of the major causes of death for non-transmissible chronic diseases worldwide. Conventional treatments including surgery, chemotherapy and external beam radiotherapy are generally far from curative. Complementary therapies are attempted for achieving more successful treatment response. Systemic targeted ...

journal_title：Investigational new drugs

authors： Cona MM,Wang H,Li J,Feng Y,Chen F,de Witte P,Verbruggen A,Ni Y

更新日期：2012-10-01 00:00:00