Search results for " therapeutics"
showing 10 items of 66 documents
Angiogenesis and vascular network of teratocarcinoma from embryonic stem cell transplant into seminiferous tubules
2009
Background: Carcinoma in situ (CIS) of the testis is considered to be a precancerous germinal cell lesion, but the precise cellular and molecular mechanisms underlying transformation of CIS into invasive pluripotent cancer cells remain to be elucidated. Moreover, a satisfactory animal model for the experimental study of germinal tumours has not been developed to date. METHODS: We have developed a tumour model that involves the microinjection of green fluorescent protein-labelled embryonic stem (ES) cells (which are functionally equivalent to CIS cells) into syngenic mouse seminiferous tubules, a unique cell microenvironment in which germinal cells mature and CIS arise. To characterise the v…
Posaconazole against Candida glabrata Isolates with Various Susceptibilities to Fluconazole
2008
ABSTRACT We investigated the in vitro activities of posaconazole (POS), fluconazole (FLC), amphotericin B (AMB), and caspofungin (CAS) against four clinical isolates of Candida glabrata with various susceptibilities to FLC (FLC MICs ranging from 1.0 to >64 μg/ml). POS MICs ranged from ≤0.03 to 0.5 μg/ml; AMB MICs ranged from 0.25 to 2.0 μg/ml, while CAS MICs ranged from 0.03 to 0.25 μg/ml. When FLC MICs increased, so did POS MICs, although we did not observe any isolate with a POS MIC greater than 0.5 μg/ml. Time-kill experiments showed that POS, FLC, and CAS were fungistatic against all isolates, while AMB at eight times the MIC was fungicidal against three out of four isolates of C. gl…
Posaconazole Activity against Candida glabrata after Exposure to Caspofungin or Amphotericin B
2008
ABSTRACT We evaluated the effects of sequential therapy with caspofungin (CAS) or amphotericin B (AMB) followed by posaconazole (POS) against Candida glabrata . The susceptibilities to POS of yeast cells pre-exposed to CAS or AMB were identical to those of untreated cells as shown by standard Clinical and Laboratory Standards Institute broth dilution, cell viability, and disk diffusion methods. We then investigated the activity of sequential regimens in an experimental model of disseminated candidiasis. CAS given at 1 mg/kg/day for 2 days followed by POS at either 15 or 30 mg/kg/day significantly reduced the counts compared to the controls, but this treatment was not superior to the use of …
Phase II dose escalation study of caspofungin for invasive Aspergillosis.
2011
ABSTRACT Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade ≥4 in 2 of 8 patients or ≥3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics w…
Poly-Xaa Sequences in Proteins - Biological Role and Interactions with Metal Ions: Chemical and Medical Aspects
2016
Background: The understanding of the bioinorganic and coordination chemistry of metalloproteins containing unusual poly-Xaa sequences, in which a single amino acid is repeated consecutively, is crucial for describing their metal binding-structure-function relationship, and therefore also crucial for understanding their medicinal potential. To the best of our knowledge, this is the first systematic review on metal complexes with polyXaa sequences. Methods: We performed a thorough search of high quality peer reviewed literature on poly-Xaa type of sequences in proteins, focusing on their biological importance and on their interactions with metal ions. Results: 228 papers were included in the…
Generación y caracterización de modelos en Drosophila de disfunción cardiaca en distrofia miotónica
2018
La tesis titulada "Generación y caracterización de los modelos de Drosophila de la disfunción cardíaca en la distrofia miotónica" se realiza mediante la combinación de tres artículos publicados. Después de la dificultad respiratoria, la disfunción cardíaca es la segunda causa más común de muerte asociada con la enfermedad neuromuscular distrofia miotónica (DM). A pesar de la participación central de la insuficiencia cardíaca en la DM, los estudios fisiopatológicos sobre los síntomas cardíacos han sido relativamente escasos porque pocos modelos murinos reproducen fielmente la enfermedad cardíaca. En consecuencia, solo un pequeño número de compuestos candidatos se han evaluado en este fenotip…
Impact of body weight, low energy diet and gastric bypass on drug bioavailability, cardiovascular risk factors and metabolic biomarkers: protocol for…
2018
IntroductionRoux-en-Y gastric bypass (GBP) is associated with changes in cardiometabolic risk factors and bioavailability of drugs, but whether these changes are induced by calorie restriction, the weight loss or surgery per se, remains uncertain. The COCKTAIL study was designed to disentangle the short-term (6 weeks) metabolic and pharmacokinetic effects of GBP and a very low energy diet (VLED) by inducing a similar weight loss in the two groups.Methods and analysisThis open, non-randomised, three-armed, single-centre study is performed at a tertiary care centre in Norway. It aims to compare the short-term (6 weeks) and long-term (2 years) effects of GBP and VLED on, first, bioavailability…
PROTACs: The Future of Leukemia Therapeutics
2022
The fight to find effective, long-lasting treatments for cancer has led many researchers to consider protein degrading entities. Recent developments in PROteolysis TArgeting Chimeras (PROTACs) have signified their potential as possible cancer therapies. PROTACs are small molecule, protein degraders that function by hijacking the built-in Ubiquitin-Proteasome pathway. This review mainly focuses on the general design and functioning of PROTACs as well as current advancements in the development of PROTACs as anticancer therapies. Particular emphasis is given to PROTACs designed against various types of Leukemia/Blood malignancies.
No findings of dental defects in children treated with minocycline
2004
Thanks to their broad antimicrobial spectrum, tetracyclines were found to be valuable for the treatment of many infections (10). Unfortunately, they irreversibly bind to calcifying tissues and are deposited along the incremental lines of dentine and enamel, causing defects and staining, from bright yellow to dark brown (3, 5, 8). According to the American Academy of Pediatrics, tetracyclines are not indicated for the treatment of common infections in children younger than 8 years of age. However, doxycycline (a tetracycline analogue) is recommended for treatment of Rocky Mountain spotted fever in children of any age (1). Minocycline has several advantages over other tetracyclines: it is bet…
An unexpected Dimroth rearrangement leading to annelated thieno[3,2-d][1,2,3]triazolo[1,5-a]pyrimidines with potent antitumor activity.
2013
An unusual Dimroth rearrangement occurring in the reaction leading to annelated thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidine core allowed the isolation of the linear isomer thieno[3,2-d][1,2,3]triazolo[1,5-a]pyrimidine. By decorating the linear isomer with the same chains that improved the biological activity of the angular isomers, new annelated thieno[3,2-d][1,2,3]triazolo[1,5-a]pyrimidines were designed and synthesized. They were selected by the Developmental Therapeutics Program (DTP) of the National Cancer Institute (NCI) for the anticancer screening against a panel of 60 human tumor cell lines. The biological results showed that the new derivatives exhibited strong antiproliferative …