Stathmin 1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours.

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 highly expressed in ACC patients, and STMN1 silencing reduces the clonogenicity and migration of ACC cell lines. However, the prognostic significance of STMN1 and its therapeutic potential remain undefined in ACC. In the present study, STMN1 mRNA levels were significantly higher (p < 0.05) in ACC patients, especially in an advanced stage, and correlated with BUB1B and PINK1 expression, the prognostic-related genes in ACC. In paediatric tumours, high STMN1 expression was observed in both adrenocortical carcinoma and adrenocortical adenoma patients. Among the adult malignant tumours, STMN1 level was an independent predictor of survival outcomes (overall survival: hazard ratio = 6.08, p = 0.002; disease-free survival: hazard ratio = 4.65, p < 0.0001). Paclitaxel, a microtubule-stabilizing drug, reduces the activation of STMN1 and significantly decreases cell migration and invasion in ACC cell lines and ACC cells from secondary cell culture (all p < 0.0001). In summary, STMN1 expression may be of great value to clinical and pathological findings in therapeutic trials and deserves future studies in ACC.

journal_name

Invest 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

doi

10.1007/s10637-019-00846-9

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

899-908

issue

3

eissn

0167-6997

issn

1573-0646

pii

10.1007/s10637-019-00846-9

journal_volume

38

pub_type

杂志文章
  • A new synthetic HDAC inhibitor, MHY218, induces apoptosis or autophagy-related cell death in tamoxifen-resistant MCF-7 breast cancer cells.

    abstract::Acquired resistance to tamoxifen (Tam) is a critical problem in breast cancer therapy. Therefore, new potential strategies for Tam-resistant breast cancer are needed recently. In this study, we synthesized a novel histone deacetylase (HDAC) inhibitor, MHY218, for the development of potent inhibitors of HDAC and evalua...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-011-9752-z

    authors: Park JH,Ahn MY,Kim TH,Yoon S,Kang KW,Lee J,Moon HR,Jung JH,Chung HY,Kim HS

    更新日期:2012-10-01 00:00:00

  • TRAIL shows potential cardioprotective activity.

    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

    pub_type: 杂志文章

    doi:10.1007/s10637-010-9627-8

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

    更新日期:2012-06-01 00:00:00

  • Circadian rhythm and seasonal dependence in the toxicological response of mice to epirubicin.

    abstract::Compared to doxorubicin, equimolar epirubicin toxicity is reduced by about 50% by the epimerization of a hydrogen and hydroxyl group at the 4' position of the anthracycline sugar moiety. The circadian timing of doxorubicin administration markedly affects its lethal and sub-lethal bone marrow and gut toxicities in mice...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00173645

    authors: Mormont MC,von Roemeling R,Sothern RB,Berestka JS,Langevin TR,Wick M,Hrushesky WJ

    更新日期:1988-12-01 00:00:00

  • Phase II trial of PCNU in breast carcinoma.

    abstract::The Eastern Cooperative Oncology Group undertook a limited institution phase II study of PCNU in advanced, metastatic breast cancer. The study was limited to patients treated with 1 to 2 prior chemotherapy regimens. Accrual goals were 30 patients but the study was terminated after 10 patients had no response, with a r...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00170866

    authors: Rubins JM,Taylor SG 4th

    更新日期:1989-07-01 00:00:00

  • Primary tumor, lung and kidney retention and antimetastasis effect of NAMI-A following different routes of administration.

    abstract::Imidazolium-trans-dimethylsulfoxideimidazoletetrachlororuthenate (NAMI-A) is a ruthenium compound effective on solid tumor metastases. In this study, we evaluated the effects of different routes of administration of NAMI-A on the distribution to primary tumor, lungs and kidneys in BD2F1 hybrids with Lewis lung carcino...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1023/a:1022916310694

    authors: Cocchietto M,Zorzet S,Sorc A,Sava G

    更新日期:2003-02-01 00:00:00

  • Lack of effects of recombinant human interleukin-4 on in vitro colony formation of freshly explanted human tumor cells.

    abstract::Interleukin-4 is a highly pleiotropic T-cell derived lymphokine that has been reported to stimulate a host cell-mediated antitumor response. Recombinant human interleukin-4 (rhuIL-4) is currently undergoing clinical phase I trials. We have studied the growth modulating effects of rhuIL-4 on a variety of freshly explan...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00944180

    authors: Hanauske AR,Degen D,Marshall MH,Trotta PP,Von Hoff DD

    更新日期:1992-11-01 00:00:00

  • Phase II trial of topotecan in advanced gastric cancer: a Southwest Oncology Group study.

    abstract::Topotecan (NSC 609099) is a camptothecin analogue that demonstrated activity against a variety of human tumors in preclinical studies. A phase II trial was performed with topotecan given to patients with locally advanced or metastatic adenocarcinoma of the stomach. Topotecan was administered IV Bolus over 30 minutes o...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1005899720463

    authors: Benedetti JK,Burris HA 3rd,Balcerzak SP,Macdonald JS

    更新日期:1997-01-01 00:00:00

  • Gemcitabine and radiosensitization in human tumor cells.

    abstract::Gemcitabine is a nucleoside analogue with excellent clinical activity against solid tumors. Within the cell, gemcitabine is rapidly phosphorylated to its active di- and triphosphate metabolites. Cytotoxicity with gemcitabine appears to be related to multiple effects on DNA replication, where gemcitabine triphosphate c...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,评审

    doi:10.1007/BF00194528

    authors: Shewach DS,Lawrence TS

    更新日期:1996-01-01 00:00:00

  • Phase II trial of ifosfamide in epidermoid carcinoma of the esophagus: unexpectant severe toxicity.

    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

    pub_type: 杂志文章

    doi:10.1007/BF00175406

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

    更新日期:1988-09-01 00:00:00

  • A phase II trial of oral etoposide with mitoxantrone and ifosfamide/mesna consolidated with intravenous etoposide, methylprednisolone, high-dose arabinoside, and cisplatin as salvage therapy for relapsing and/or refractory lymphomas.

    abstract:PURPOSE:To evaluate the response to oral Etoposide when combined with mesna, ifosfamide, and mitoxantrone in patients with relapsed and/or refractory lymphoma. To evaluate response and its duration after administration of intravenous Etoposide, methylprednisolone, high-dose cytosine arabinoside, and cisplatin (ESHAP) a...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00873962

    authors: Romaguera JE,Rodriguez MA,Hagemeister FB,McLaughlin P,Swan F,Moore DF Jr,Sarris AH,Younes A,Hill D,Cabanillas F

    更新日期:1994-01-01 00:00:00

  • Effect of ketoconazole on the pharmacokinetics of axitinib in healthy volunteers.

    abstract:OBJECTIVE:Axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, is metabolized primarily by cytochrome P450 (CYP) 3A with minor contributions from CYP1A2, CYP2C19, and glucuronidation. Co-administration with CYP inhibitors may increase systemic expos...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s10637-010-9511-6

    authors: Pithavala YK,Tong W,Mount J,Rahavendran SV,Garrett M,Hee B,Selaru P,Sarapa N,Klamerus KJ

    更新日期:2012-02-01 00:00:00

  • CPBMF65, a synthetic human uridine phosphorylase-1 inhibitor, reduces HepG2 cell proliferation through cell cycle arrest and senescence.

    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

    pub_type: 杂志文章

    doi:10.1007/s10637-020-00941-2

    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

  • Phase I dose-finding and pharmacokinetic trial of orally administered indibulin (D-24851) to patients with solid tumors.

    abstract::Indibulin is a synthetic small molecule which antitumor activity is based upon destabilization of microtubules. The primary study objectives were to determine the impact of fasted and fed condition on pharmacokinetic parameters, as well as the maximum tolerated dose of the oral drinking solution of indibulin administe...

    journal_title:Investigational new drugs

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1007/s10637-006-9027-2

    authors: Kuppens IE,Witteveen PO,Schot M,Schuessler VM,Daehling A,Beijnen JH,Voest EE,Schellens JH

    更新日期:2007-06-01 00:00:00

  • Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplifi

    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

    pub_type: 杂志文章

    doi:10.1007/s10637-009-9324-7

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

    更新日期:2010-12-01 00:00:00

  • A phase I study of vitamin E, 5-fluorouracil and leucovorin for advanced malignancies.

    abstract::Six patients with incurable malignancies were originally treated with vitamin E, 3200 IU/day for fourteen days, followed by the same dose of vitamin E daily plus LCV (20 mg/m2 i.v. bolus daily x 5) with 5FU (425 mg/m2 i.v. bolus immediately following LCV). The same schedule of LCV and 5FU was repeated 4 weeks later, t...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1023/a:1006484031959

    authors: Blanke CD,Stipanov M,Morrow J,Rothenberg M,Chinery R,Shyr Y,Coffey R,Johnson DH,Leach SD,Beauchamp RD

    更新日期:2001-01-01 00:00:00

  • A phase I evaluation of the combination of vinflunine and erlotinib in patients with refractory solid tumors.

    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

    pub_type: 杂志文章

    doi:10.1007/s10637-010-9427-1

    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

  • Macromolecular DNA-damage in murine and human leukemic and lymphoid cells after in vitro exposure to ASTA Z 7557 (INN mafosfamide).

    abstract::Cyclophosphamide (CPA) is widely used against leukemic and lymphoproliferative diseases, but in vitro studies on response to this agent so far have been limited to instable derivatives with poor galenic properties. ASTA Z 7557 is a newly synthesized "activated cyclophosphamide" that circumvents the need for hepatic ac...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00232346

    authors: Osieka R,Pannenbäcker R,Schmidt CG

    更新日期:1984-01-01 00:00:00

  • AN-7, a butyric acid prodrug, sensitizes cutaneous T-cell lymphoma cell lines to doxorubicin via inhibition of DNA double strand breaks repair.

    abstract::We previously found that the novel histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) had greater selectivity against cutaneous T-cell lymphoma (CTCL) than SAHA. AN-7 synergizes with doxorubicin (Dox), an anthracycline antibiotic that induces DNA breaks. This study aimed to elucidate the m...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-017-0500-x

    authors: Moyal L,Goldfeiz N,Gorovitz B,Rephaeli A,Tal E,Tarasenko N,Nudelman A,Ziv Y,Hodak E

    更新日期:2018-02-01 00:00:00

  • Alterations in human circulating and bone marrow mononuclear cell polyamine levels in hematologic malignancies as a consequence of difluoromethylornithine administration.

    abstract::The effect of administering increasing intravenous doses of difluoromethylornithine on human tumor cell polyamine levels was determined in patients with hematologic malignancies. Difluoromethylornithine from 5.5. to 64 gm/m2 per day was administered to nine patients with refractory acute leukemia or multiple myeloma. ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00195371

    authors: Maddox AM,Freireich EJ,Keating MJ,Frasier-Scott KF,Haddox MK

    更新日期:1988-06-01 00:00:00

  • Effect of alisertib, an investigational aurora a kinase inhibitor on the QTc interval in patients with advanced malignancies.

    abstract::Aims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50 ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-017-0498-0

    authors: Zhou X,Nemunaitis J,Pant S,Bauer TM,Patel M,Sarantopoulos J,Craig Lockhart A,Goodman D,Huebner D,Mould DR,Venkatakrishnan K

    更新日期:2018-04-01 00:00:00

  • Distribution, elimination, metabolism and bioavailability of hexamethylenebisacetamide in rats.

    abstract::Hexamethylenebisacetamide (HMBA), an in vitro differentiating agent, was studied for its pharmacodynamic actions in animals. Plasma stability, organ distribution, excretion, oral bioavailability, and estimates of pharmacokinetic parameters and acute lethality were determined in rats. The single dose intraperitoneal LD...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00179430

    authors: Litterst CL,Roth JS,Kelley JA

    更新日期:1985-01-01 00:00:00

  • A pilot study for the early assessment of the effects of BMS-754807 plus gefitinib in an H292 tumor model by [(18)F]fluorothymidine-positron emission tomography.

    abstract::BMS-754807 is an inhibitor of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor that also represses aurora kinase. Cancers that express high levels of IGF-1/IGF-1R are sensitive to BMS-754807; however, it shows limited efficacy in non-small cell lung cancer (NSCLC) in which IGF-1R-driven signals may ...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-012-9874-y

    authors: Lee SJ,Kim EJ,Lee HJ,Kim SY,Oh SJ,Ryu JS,Moon DH,Ahn JH,Kim SW

    更新日期:2013-06-01 00:00:00

  • Absolute and relative activities of platinum-complexes on human tumors as evaluated by an antimetabolic in vitro assay.

    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

    pub_type: 杂志文章

    doi:10.1007/BF00175294

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

    更新日期:1987-01-01 00:00:00

  • First-line combination chemotherapy with mitoxantrone and cyclophosphamide in advanced breast cancer.

    abstract::In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone; dihydroxyanthracenedione) 16 mg/m2 i.v. Drug treatment was repeated every 3-4 weeks, for a maximum of 12 cycles. The overall response rate w...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00174165

    authors: Periti P,della Cuna GR,Pannuti F,Mazzei T,Preti P,Martoni A,Mini E

    更新日期:1985-01-01 00:00:00

  • A dose escalation, safety, and tolerability study of MN-029 in patients with advanced solid tumors.

    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

    pub_type: 杂志文章,多中心研究

    doi:10.1007/s10637-009-9264-2

    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

  • Phase II study of didemnin B in advanced colorectal cancer.

    abstract::Didemnin B is a depsipeptide derived from a Caribbean tunicate (sea squirt) that has demonstrated antineoplastic activity against a variety of murine tumor models, including the L1210 and P388 leukemia, the B16 melanoma, and M5076 sarcoma cell lines. Based on these data, we designed a phase II trial in which 15 patien...

    journal_title:Investigational new drugs

    pub_type: 临床试验,杂志文章

    doi:10.1007/BF00877248

    authors: Jones DV Jr,Ajani JA,Blackburn R,Daugherty K,Levin B,Patt YZ,Abbruzzese JL

    更新日期:1992-08-01 00:00:00

  • A pilot study of S-1 plus cisplatin versus 5-fluorouracil plus cisplatin for postoperative chemotherapy in histological stage IIIB-IV (M0) gastric cancer.

    abstract:BACKGROUND:Although its efficacy is unproven, 5-fluorouracil plus cisplatin (FP) is used to prevent postoperative relapse in gastric cancer. We investigated the safety and feasibility of S-1 plus cisplatin (SP) vs. FP for stage IIIB-IV (M0) gastric cancer. METHODS:Following curative resection, 41 stage IIIB-IV (M0) ga...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-010-9515-2

    authors: Lee SS,Jeung HC,Chung HC,Noh SH,Hyung WJ,Ahn JY,Rha SY

    更新日期:2012-02-01 00:00:00

  • Preliminary pharmacokinetic and bioanalytical studies of SJG-136 (NSC 694501), a sequence-selective pyrrolobenzodiazepine dimer DNA-cross-linking agent.

    abstract::SJG-136 is a synthetic pyrrolobenzodiazepine (PBD) dimer in which two DNA-alkylating subunits are linked through an inert propanedioxy tether. Biophysical and biochemical studies of SJG-136 have shown a remarkable affinity for DNA and potent cytotoxicity in vitro. On this basis, together with its unique sequence selec...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1023/B:DRUG.0000026249.97007.60

    authors: Wilkinson GP,Taylor JP,Shnyder S,Cooper P,Howard PW,Thurston DE,Jenkins TC,Loadman PM

    更新日期:2004-08-01 00:00:00

  • Phase I trial of 4-demethoxydaunorubicin (idarubicin) with single oral doses.

    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

    pub_type: 杂志文章

    doi:10.1007/BF00175378

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

    更新日期:1984-01-01 00:00:00

  • Effectiveness of cetuximab as preemptive postsurgical therapy for oral squamous cell carcinoma patients with major risk: a single-center retrospective cohort study.

    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

    pub_type: 杂志文章

    doi:10.1007/s10637-021-01062-0

    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