Abstract:
:Lactoferrin has gained extensive attention due to its ample biological properties. In this study, recombinant human lactoferrin carrying humanized glycosylation (rhLf-h-glycan) expressed in the yeast Pichia pastoris SuperMan5, which is genetically glycoengineered to efficiently produce functional humanized glycoproteins inclosing (Man)5(GlcNAc)2 Asn-linked glycans, was analyzed, inspecting its potential toxicity against cancer cells. The live-cell differential nuclear staining assay was used to quantify the rhLf-h-glycan cytotoxicity, which was examined in four human cell lines: acute lymphoblastic leukemia (ALL) CCRF-CEM, T-cell lymphoblastic lymphoma SUP-T1, cervical adenocarcinoma HeLa, and as control, non-cancerous Hs27 cells. The defined CC50 values of rhLf-h-glycan in CCRF-CEM, SUP-T1, HeLa, and Hs27 cells were 144.45 ± 4.44, 548.47 ± 64.41, 350 ± 14.82, and 3359.07 ± 164 µg/mL, respectively. The rhLf-h-glycan exhibited a favorable selective cytotoxicity index (SCI), preferentially killing cancer cells: 23.25 for CCRF-CEM, 9.59 for HeLa, and 6.12 for SUP-T1, as compared with Hs27 cells. Also, rhLf-h-glycan showed significant antiproliferative activity (P < 0.0001) at 24, 48, and 72 h of incubation on CCRF-CEM cells. Additionally, it was observed via fluorescent staining and confocal microscopy that rhLf-h-glycan elicited apoptosis-associated morphological changes, such as blebbing, nuclear fragmentation, chromatin condensation, and apoptotic bodies in ALL cells. Furthermore, rhLf-h-glycan-treated HeLa cells revealed shrinkage of the microfilament structures, generating a speckled/punctuated pattern and also caused PARP-1 cleavage, a hallmark of apoptosis. Moreover, in ALL cells, rhLf-h-glycan altered cell cycle progression inducing the G2/M phase arrest, and caused apoptotic DNA fragmentation. Overall, our findings revealed that rhLf-h-glycan has potential as an anticancer agent and therefore deserves further in vivo evaluation.
journal_name
Invest New Drugsjournal_title
Investigational new drugsauthors
Nakamura-Bencomo S,Gutierrez DA,Robles-Escajeda E,Iglesias-Figueroa B,Siqueiros-Cendón TS,Espinoza-Sánchez EA,Arévalo-Gallegos S,Aguilera RJ,Rascón-Cruz Q,Varela-Ramirez Adoi
10.1007/s10637-020-01020-2subject
Has Abstractpub_date
2020-10-16 00:00:00eissn
0167-6997issn
1573-0646pii
10.1007/s10637-020-01020-2pub_type
杂志文章abstract::Chloroquinoxaline sulfonamide (CQS) has been developed to the clinical trial stage based on its activity in the Human Tumor Colony Forming Assay (HTCFA). In the HTCFA, CQS demonstrated inhibition of colony formation against breast, lung, melanoma and ovarian carcinomas. The mechanism of action of CQS is unknown. It do...
journal_title:Investigational new drugs
pub_type: 杂志文章,评审
doi:10.1007/BF00873904
更新日期:1993-02-01 00:00:00
abstract:PURPOSE:Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested uti...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9766-6
更新日期:2012-12-01 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
pub_type: 杂志文章
doi:10.1007/s10637-019-00840-1
更新日期:2020-06-01 00:00:00
abstract::A retrospective analysis was performed on the medical charts of 160 cancer patients who received esorubicin (ESO or 4'deoxydoxorubicin) in a Phase I clinical trial. The purpose of the review was to characterize the incidence of local venous reactions to this investigational doxorubicin (DOX) analog. The impact of prop...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00217666
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:Hepatobiliary cancers respond poorly to cytotoxic chemotherapy. We evaluated the activity and safety of ixabepilone, an epothilone B analogue which stabilizes microtubules, in a phase II trial in patients with advanced cancers of the gallbladder, bile duct, and liver. METHODS:Eligible patients had previously-u...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9297-6
更新日期:2010-12-01 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
pub_type: 杂志文章
doi:10.1007/s10637-010-9554-8
更新日期:2012-02-01 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
pub_type: 临床试验,杂志文章
doi:10.1007/BF00210790
更新日期:1996-01-01 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
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-015-0307-6
更新日期:2016-02-01 00:00:00
abstract::This study was conducted to assess the efficacy and toxicity of suramin administered using a fixed dose schedule in patients with advanced renal cell carcinoma. Fourteen eligible patients with advanced renal cell carcinoma were enrolled and treated on a fixed dose schedule of suramin administered over 12 weeks. Surami...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1006331518952
更新日期:1999-01-01 00:00:00
abstract::alpha-Difluoromethylornithine (DFMO) is a known irreversible inhibitor of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Cyclosporine (CsA) has been reported to inhibit ODC activity in vitro. In the present study, we compared the effects of DFMO and CsA on growth, survival, and poly...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/BF00175295
更新日期:1987-01-01 00:00:00
abstract::Withaferin A (WA), a steroidal lactone derived from the plant Vassobia breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti-angiogenic properties against cancer growth. In this study, we identified several key underlying mechanisms of anticancer action of WA in glioblastoma cells. WA was f...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9888-5
更新日期:2013-06-01 00:00:00
abstract::Colon cancer is the third most malignant neoplasm in the world and it remains today an important cause of death, especially in western countries. In this study, we have evaluated the chemopreventive efficacy of morin on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in 1,2-dimethylhydra...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9136-1
更新日期:2009-02-01 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::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
更新日期:2012-10-01 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
pub_type: 杂志文章
doi:10.1007/s10637-010-9627-8
更新日期:2012-06-01 00:00:00
abstract:PURPOSE:A phase I study of intraperitoneal paclitaxel (ip PTX) combined with gemcitabine (GEM) plus nab-paclitaxel (nab-PTX) (GnP) was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) in pancreatic cancer patients with peritoneal metastasis in first-line setting. METHODS:Based on t...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-020-00982-7
更新日期:2020-08-08 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
pub_type: 杂志文章,多中心研究
doi:10.1007/s10637-006-9014-7
更新日期:2007-06-01 00:00:00
abstract:BACKGROUND:BTH1677 is a beta glucan pathogen associated molecular pattern (PAMP) currently being investigated as a novel cancer therapy. Here, the initial safety and pharmacokinetic (PK) results of BTH1677 in healthy subjects are reported. SUBJECTS AND METHODS:In the Phase 1a single-dosing study, subjects were randomi...
journal_title:Investigational new drugs
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10637-016-0325-z
更新日期:2016-04-01 00:00:00
abstract:PURPOSE:Cytotoxic and anti-angiogenic drugs are efficacious in malignancies. This trial was undertaken to evaluate the toxicity of a novel regimen combining docetaxel and lenalidomide. PATIENTS AND METHODS:Patients with advanced solid tumors were eligible. Docetaxel was administered on day 1, and lenalidomide was give...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-008-9200-x
更新日期:2009-10-01 00:00:00
abstract::Sorafenib, an orally active multi-kinase inhibitor approved for the treatment of hepatocellular carcinoma (HCC), is primarily metabolized both via cytochrome P450 3A4 isoform (CYP3A4) and UGT1A9. Due to the contribution of these two biotransformation pathways, sorafenib is considered to be less susceptible than other ...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-010-9514-3
更新日期:2011-12-01 00:00:00
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
更新日期:1997-01-01 00:00:00
abstract::PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wildtype lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on pri...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-012-9847-1
更新日期:2013-02-01 00:00:00
abstract::Pharmacological intervention to reduce CRC mortality entails the use of oral agents that can avert carcinogenesis. Silibinin, a major component of silymarin isolated from Silybum marianum (L.) was found to possess attractive remedial features. An in vivo study was designed to elucidate the effect of silibinin on the f...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9237-5
更新日期:2010-06-01 00:00:00
abstract::Transforming growth factor-beta (TGF-β) signaling pathway plays pivotal roles in various types of cancer. TGF-β receptor 2 (TGFβR2) contains a kinase domain that phosphorylates and activates the downstream of the TGF-β signaling pathway. Our previous microarray analysis revealed marked changes in miR-181a expression i...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-018-0695-5
更新日期:2019-10-01 00:00:00
abstract::Gemcitabine is a deoxycytidine (dCyd) analog with activity in leukemia and solid tumors, which requires phosphorylation by deoxycytidine kinase (dCK). Decreased membrane transport is a mechanism of resistance to gemcitabine. In order to facilitate gemcitabine uptake and prolong retention in the cell, a lipophilic pro-...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-009-9377-7
更新日期:2011-06-01 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
pub_type: 杂志文章
doi:10.1007/BF00172014
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1007/BF00874443
更新日期:1994-01-01 00:00:00
abstract::P-cadherin is frequently up-regulated in solid tumors such as gastric, colon, lung, pancreatic and breast cancers. Although P-cadherin promotes cadherin-mediated cell adhesion, the gastric cancer-linked regulation of P-cadherin has not been extensively investigated. In this study, we found epigenetic regulation of P-c...
journal_title:Investigational new drugs
pub_type: 杂志文章
doi:10.1007/s10637-011-9710-9
更新日期:2012-08-01 00:00:00
abstract::Androgen receptors are present in both pancreatic cancer tissue and cell lines. Flutamide is a potent antiandrogen widely used in clinical practice for patients with metastatic prostate cancer. This Phase II trial was undertaken to evaluate the impact of flutamide in patients with advanced pancreatic adenocarcinoma wh...
journal_title:Investigational new drugs
pub_type: 临床试验,杂志文章
doi:10.1023/a:1005989519350
更新日期:1997-01-01 00:00:00
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
更新日期:2003-02-01 00:00:00