Abstract：
:Purpose Among alkaloids, abundant secondary metabolites in plants, aporphines constitute a class of compounds with interesting biological activities, including anticancer effects. The present study evaluated the anticancer activities of 14 substances, including four aporphine derivatives acquired through the biomonitoring of (±)-apomorphine hydrochloride total synthesis from 2-phenethylamine and 3,4-dimethoxybenzaldehyde against head and neck squamous cell carcinoma (HNSCC). Methods The cytotoxic effects of compounds against a panel of HNSCC cell lines were determined by PrestoBlue cell viability assay, while the genotoxicity of substances was evaluated by micronucleus test. Cell death was detected by flow cytometry (Annexin V/7AAD) and western blot analysis was used to detect the presence of cleaved Caspase-3 molecules. Results The aporphine and isoquinoline derivatives APO, C1, and A5 significantly reduced HNSCC cell viability and promoted DNA damages in these cells. Further, by activating the Caspase-3 pathway, these substances were able to induce apoptosis. Conclusion Our results revealed that APO, C1, and A5 exhibit cytotoxic effects in HNSCC cells. The mechanisms of action appear to be partly via the generation of DNA damages and apoptosis induction through Caspase-3 pathway activation. This study provides preclinical data that suggest a potential therapeutic role for APO, C1, and A5 against head and neck cancer cells.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Rodrigues-Junior DM,de Almeida Pontes NM,de Albuquerque GE,Carlin V,Perecim GP,Raminelli C,Vettore ALdoi
10.1007/s10637-019-00784-6subject
Has Abstractpub_date
2020-02-01 00:00:00pages
70-78issue
1eissn
0167-6997issn
1573-0646pii
10.1007/s10637-019-00784-6journal_volume
38pub_type
杂志文章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
pub_type： 杂志文章
doi：10.1007/s10637-018-00715-x
更新日期：2019-10-01 00:00:00
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
更新日期：1984-01-01 00:00:00
abstract：INTRODUCTION:For decades, determination of the recommended Phase 2 dose (RP2D) was based on the toxicity (especially the maximum tolerated dose or MTD) experienced by patients enrolled in dose-escalating Phase 1 trials investigating anti-cancer agents. Recent studies suggest that this toxicity-based strategy is not sui...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-010-9574-4
更新日期：2012-04-01 00:00:00
abstract：INTRODUCTION:Multidrug resistance in cancer represents a major problem in chemotherapy. The present study was designed to assess the cytotoxicity of anthraquinones from Pentas schimperi, namely damnacanthal (1), damnacanthol (2), 3-hydroxy-2-hydroxymethyl anthraquinone (3) and schimperiquinone B (4) against nine drug-s...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-015-0268-9
更新日期：2015-08-01 00:00:00
abstract：:In a previous study we reported on the synthesis of 1,4-naphthoquinone-sulfides by thiolation of 1,4-naphthohydroquinones with primary aryl and alkyl thiols using laccase as catalyst. These compounds were synthesized as Vitamin K3 analogues. Vitamin K3 (VK3; 2-methyl-1,4-naphthoquinone; menadione) is known to have pot...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-019-00855-8
更新日期：2020-04-01 00:00:00
abstract：PURPOSE:To assess safety and efficacy of folinic acid, 5-fluorouracil, gemcitabine (FFG) and folinic acid, fluorouracil, oxaliplatin (FOLFOX4) regimens with added bevacizumab as first-line treatment in patients with advanced colorectal cancer (CRC). PATIENTS AND METHODS:Patients with Stage III unresectable or Stage IV...
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/s10637-010-9598-9
更新日期：2012-04-01 00:00:00
abstract：:Pictilisib (GDC-0941) is an oral class I phosphatidylinositol-3-phosphate kinase inhibitor. This phase Ia/Ib study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of pictilisib in monotherapy or in combination with carboplatin-paclitaxel and bevacizumab (CP + BEV) in Japanese patients wit...
journal_title：Investigational new drugs
pub_type： 杂志文章,多中心研究
doi：10.1007/s10637-016-0382-3
更新日期：2017-02-01 00:00:00
abstract：:3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or g...
journal_title：Investigational new drugs
pub_type： 临床试验,杂志文章
doi：10.1007/BF00198593
更新日期：1990-11-01 00:00:00
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journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00173763
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abstract：:B cell prolymphocytic leukemia (B-PLL) is a rare and aggressive disease that is associated with poor survival. Although initially asymptomatic patients do not require therapy, most patients will progress and inevitably require treatment. More than 50% of patients with B-PLL carry abnormalities in the TP53 tumor suppre...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-020-00902-9
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abstract：:This study was designed to test the hypothesis that specific inhibition of cathepsins B and L will cause death of neuroblastoma cells. Five compounds that differ in mode and rate of inhibition of these two enzymes were all shown to cause neuroblastoma cell death. Efficacy of the different compounds was related to thei...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-012-9826-6
更新日期：2013-02-01 00:00:00
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
更新日期：2004-08-01 00:00:00
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journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-008-9167-7
更新日期：2009-06-01 00:00:00
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journal_title：Investigational new drugs
pub_type： 杂志文章,多中心研究
doi：10.1007/s10637-012-9861-3
更新日期：2013-04-01 00:00:00
abstract：:Major discrepancies concerning risk-benefit assessments and regulatory actions are frequent among regulatory agencies. We explored the differences by scrutinizing a case of gemtuzumab ozogamicin (GO) in patients with acute myeloid leukaemia (AML). Assessment reports of GO were retrieved form the websites of the US Foo...
journal_title：Investigational new drugs
pub_type： 杂志文章,评审
doi：10.1007/s10637-012-9877-8
更新日期：2013-04-01 00:00:00
abstract：:The aim of this study was to determine the antitumor activity of irofulven when administered in combination with a variety of antimitotic agents. Irofulven in combination with either paclitaxel or docetaxel demonstrated synergistic activity in both the in vitro and in vivo studies. The majority of xenograft bearing an...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1023/a:1016201807796
更新日期：2002-08-01 00:00:00
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journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/BF00180811
更新日期：1996-01-01 00:00:00
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journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-011-9655-z
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journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-018-0711-9
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journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-015-0240-8
更新日期：2015-06-01 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
pub_type： 杂志文章
doi：10.1007/s10637-014-0092-7
更新日期：2014-08-01 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
pub_type： 临床试验,杂志文章
doi：10.1023/a:1006327302041
更新日期：1999-01-01 00:00:00
abstract：PURPOSE:DDB (dimethyl-4,4'-dimethoxy-5,6,5'6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate) is a synthetic hepatoprotectant which has been widely used to treat chronic viral hepatitis B patients in China for more than 20 years. In this study, we evaluated DDB as a multidrug resistance (MDR) chemosensitizing agent. MET...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-006-9001-z
更新日期：2007-04-01 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
pub_type： 杂志文章
doi：10.1007/s10637-020-01006-0
更新日期：2020-09-30 00:00:00
abstract：:Drug discovery involves various steps and is a long process being even more demanding for complex diseases such as cancer. Tumors are ensembles of subpopulations with different mutations, require very specific and effective strategies. Conventional drug screening technologies may not be adequate and efficient anymore....
journal_title：Investigational new drugs
pub_type： 杂志文章,评审
doi：10.1007/s10637-014-0081-x
更新日期：2014-12-01 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
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1007/s10637-013-9925-z
更新日期：2013-08-01 00:00:00
abstract：:Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and ...
journal_title：Investigational new drugs
pub_type： 杂志文章
doi：10.1007/s10637-019-00876-3
更新日期：2020-08-01 00:00:00
abstract：BACKGROUND:Gemcitabine (G) has shown activity in mantle cell lymphoma (MCL) as a single agent. The combination of mitoxantrone (M) and rituximab (R) is also active in MCL. The primary objective of this study was to determine the efficacy of G+M+R in relapsed or refractory MCL. PATIENTS AND METHODS:Sixteen patients wer...
journal_title：Investigational new drugs
pub_type： 杂志文章,多中心研究
doi：10.1007/s10637-008-9191-7
更新日期：2009-10-01 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
pub_type： 临床试验,杂志文章
doi：10.1007/BF00873122
更新日期：1992-07-01 00:00:00
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
更新日期：1994-01-01 00:00:00
