Search results for "Xenograft"

Combination of the mTOR inhibitor ridaforolimus and the anti-IGF1R monoclonal antibody dalotuzumab: preclinical characterization and phase I clinical…

2014

Abstract Purpose: Mammalian target of rapamycin (mTOR) inhibition activates compensatory insulin–like growth factor receptor (IGFR) signaling. We evaluated the ridaforolimus (mTOR inhibitor) and dalotuzumab (anti-IGF1R antibody) combination. Experimental Design: In vitro and in vivo models, and a phase I study in which patients with advanced cancer received ridaforolimus (10–40 mg/day every day × 5/week) and dalotuzumab (10 mg/kg/week or 7.5 mg/kg/every other week) were explored. Results: Preclinical studies demonstrated enhanced pathway inhibition with ridaforolimus and dalotuzumab. With 87 patients treated in the phase I study, main dose-limiting toxicities (DLT) of the combination were p…

Activity of the antiestrogenic cajanin stilbene acid towards breast cancer

2014

Antiestrogenic therapy is a mainstay for estrogen receptor (ERα)-positive breast cancer. Due to the development of resistance to established antihormones such as tamoxifen, novel compounds are required. The low abundant cajanin stilbene acid (CSA) recently isolated by us from Pigeon Pea (Cajanus cajan) has structural similarities with estrogen. We analyzed the cytotoxic and anticancer activity of CSA in ERα-positive and -negative human breast cancer cells in vitro, in vivo and in silico. CSA exerts anticancer and antiestrogenic activities towards ERα-positive breast cancer, and it showed cytotoxicity towards tamoxifen-resistant MCF-7 cells, implying that CSA may be active against tamoxifen-…

A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid …

2016

Abstract Activation of AKT signaling by PTEN loss or PIK3CA mutations occurs frequently in human cancers, but targeting AKT has been difficult due to the mechanism-based toxicities of inhibitors that target the inactive conformation of AKT. Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule inhibitor of AKT that preferentially targets active phosphorylated AKT (pAKT) and is potent in cell lines with evidence of AKT activation. In this phase I study, ipatasertib was well tolerated; most adverse events were gastrointestinal and grade 1–2 in severity. The exposures of ipatasertib ≥200 mg daily in patients correlated with preclinical TGI90, and pharmacodynamic studies co…

A poorly differentiated synovial sarcoma (SYT/SSX1) expresses neuroectodermal markers: a xenografts and in vitro culture study.

2004

Synovial sarcoma (SS) is a neoplasm that poses diagnostic problems, due to its histologic heterogeneity. The poorly differentiated variant, in particular, may be histologically indistinguishable from other small round cell tumors. Detection of the synovial sarcoma-associated t(X;18) or SYT-SSX fusion transcripts may be necessary to confirm the diagnosis of SS in difficult cases. Most of SS carry a t(X;18) in about one third of cases as the sole cytogenetic abnormality. We evaluated a case of poorly differentiated synovial sarcoma and their derived tumors in nude mice xenografts and cell cultures. We used a panel of antibodies (including those to intermediate filament, nerve-sheath associate…

Evaluation of the antiproliferative, proapoptotic, and antiangiogenic effects of a double-stranded RNA mimic complexed with polycations in an experim…

2015

Objective To assess the antiproliferative, proapoptotic, and antiangiogenic effects of the double-stranded RNA mimic polyinosine-polycytidylic acid (pIC) complexed with polyethylenimine [pIC PEI ] in xenografted human leiomyomas. Design Heterologous leiomyoma mouse model. Setting University-affiliated infertility center. Animal(s) Ovariectomized and hormone-replaced nude mice (n = 16) who received human leiomyoma fragment transplantation. Intervention(s) Leiomyoma fragments placed in the peritoneum of 5-week-old nude female mice and treated with the vehicle (n = 8) or 0.6 mg/kg [pIC PEI ] (n = 8) for 4 weeks. Main Outcome Measure(s) The size of the leiomyoma implants, and cellular prolifera…

Improving ovarian tissue cryopreservation for oncologic patients: slow freezing versus vitrification, effect of different procedures and devices.

2013

Objective To compare slow freezing (SF) with four vitrification techniques (VT) for cryopreservation of ovarian tissue (OT) and to evaluate the best protocol for human OT in a xenograft model. Design Experimental study. Setting University hospital. Patient(s) Patients undergoing fertility preservation. Animal(s) Ovariectomized nude mice. Intervention(s) Cryopreservation of bovine OT after SF and four VTs (VT1, VT2, VT3, and VT4) by combining two cryoprotectant vitrification solutions (VS1 and VS2) and two devices (metallic grid and ethyl vinyl acetate bag), after which the cryopreservation of human OT by SF and VT1 and xenograft into nude mice. Main Outcome Measure(s) Follicular densities, …

Comparison of the effect of ginger and aloe vera mouthwashes on xerostomia in patients with type 2 diabetes: A clinical trial, triple-blind

2021

Background Ginger and aloe vera are two medicinal herbs mostly used to produce mouthwash. This study aimed to compare the effects of ginger and aloe vera mouthwashes on the xerostomia in patients referred to Bandar Abbas diabetes clinic (Iran). Material and Methods In this triple-blind clinical trial, three groups (n=35 patients in each group) were studied. One group was given aloe vera mouthwash, the other group used ginger mouthwash, and the control group was only given normal saline. All the mouthwashes were used 20 ccs three times daily for 14 consecutive days. The symptoms and severity of xerostomia were measured before and after the intervention by the questionnaire proposed by Fox et…

Folate-targeted supramolecular vesicular aggregates as a new frontier for effective anticancer treatment in in vivo model.

2012

Abstract Supramolecular vesicular aggregates (SVAs), made up by self-assembling liposomes and polyasparthydrazide co-polymers conjugated to folic acid molecules were extensively investigated in this manuscript as potential active targeting formulation for anticancer drug delivery. Folate-targeted systems (FT-SVAs) were used to treat breast cancer and to further proof the potential in vivo administration of these systems for the therapeutic treatment for several aggressive solid tumors. The physicochemical and technological parameters of FT-SVAs are suitable for their potential in vivo administration. The chemotherapeutic activity of GEM-loaded FT-SVAs was increased during in vivo experiment…

MP-03.04 The Combination Treatment of Bicalutamide Plus Carbidopa Significantly Enhances the in vivo Antitumor Activity on LNCaP Castration-resistant…

2011

Synthesis of 131I-labeled glucose-conjugated inhibitors of O6-methylguanine-DNA methyltransferase (MGMT) and comparison with nonconjugated inhibitors…

2006

O 6 -Substituted guanine derivatives are powerful agents used for tumor cell sensitization by inhibition of the DNA repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT). To provide targeted accumulation of MGMT inhibitors in tumor tissue as well as tools for in vivo imaging, we synthesized iodinated C 8 -alkyl-linked glucose conjugates of 2-amino-6-(5-iodothenyl)-9H-purine (O 6 -(5-iodothenyl) guanine, ITG) and 2-amino-6-(3-iodobenzyloxy)-9H-purine (O 6 -(5-iodobenzyl) guanine, IBG). These compounds have MGMT inhibitor constants (IC 5 0 values) of 0.8 and 0.45 μM for ITGG and IBGG, respectively, as determined in HeLa S3 cells after 2-h incubation with inhibitor. To substantiate tha…