scholarly journals In VitroSusceptibility ofMadurella mycetomatisto Posaconazole and Terbinafine

2011 ◽  
Vol 55 (4) ◽  
pp. 1771-1773 ◽  
Author(s):  
Alex van Belkum ◽  
Ahmed H. Fahal ◽  
Wendy W. J. van de Sande
Keyword(s):  
Clinical Outcome ◽  
Safety Profile ◽  
Poor Clinical Outcome ◽  
Highly Active ◽  
Excellent Safety Profile ◽  
Madurella Mycetomatis ◽  
Therapeutic Alternatives

ABSTRACTPresently, therapy of eumycetoma in Sudan is still based on surgery combined with prolonged ketoconazole therapy. This usually results in a poor clinical outcome. To determine if posaconazole and terbinafine could offer better therapeutic alternatives, thein vitrosusceptibilities of 34Madurella mycetomatisstrains were determined. It appeared that posaconazole was highly active againstM. mycetomatisbut terbinafine was only moderately active. Since posaconazole has an excellent safety profile, it might provide an important alternative in mycetoma therapy.

scholarly journals Madurella mycetomatis Is Not Susceptible to the Echinocandin Class of Antifungal Agents

2010 ◽  
Vol 54 (6) ◽  
pp. 2738-2740 ◽  
Author(s):  
Wendy W. J. van de Sande ◽  
Ahmed H. Fahal ◽  
Irma A. J. M. Bakker-Woudenberg ◽  
Alex van Belkum
Keyword(s):  
Aspergillus Fumigatus ◽  
Antifungal Agents ◽  
Recurrent Infections ◽  
Madurella Mycetomatis ◽  
High Doses ◽  
Therapeutic Alternatives ◽  
Therapeutic Responses

ABSTRACT Eumycetoma caused by Madurella mycetomatis is treated surgically and with high doses of ketoconazole. Therapeutic responses are poor, and recurrent infections are common. In search of therapeutic alternatives in the treatment of mycetoma, we determined the in vitro susceptibilities of M. mycetomatis isolates against caspofungin, anidulafungin, and micafungin. As a comparator fungus, Aspergillus fumigatus was used. Minimal effective concentrations (MECs) and MICs were assessed and compared to those of ketoconazole. M. mycetomatis isolates were not susceptible to the echinocandins.

scholarly journals LncRNA RHPN1-AS1 promotes cholangiocarcinoma progression and predicts poor clinical outcome through miR-345-5p/YAP1 axis

2020 ◽  
Author(s):  
Lifeng Ma ◽  
Tao Li ◽  
Guochao Liu ◽  
Jianlong Wang ◽  
Zhaoqiang Yin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Clinical Practice ◽  
Clinical Outcome ◽  
Carcinoma Cell ◽  
Poor Clinical Outcome ◽  
Xenograft Growth ◽  
Poor Outcome ◽  
New Strategies

Abstract Background LncRNAs have proven to be involved in the initiation and progression of cholangiocarcinoma (CCA), although the mechanism by which this occurs remains unknown. Methods The current study reveals that RHPN1-AS1 was overexpressed in CCA patient samples, which predicted poor outcome of CCA patients. RHPN1-AS1 increased in vitro pancreatic carcinoma cell proliferation as well as promoted xenograft growth in vivo. Mechanistically, DANCR upregulated expression of YAP1 by competitively binding to miR-345-5p. Importantly, RHPN1-AS1 level was positively correlated with YAP1 expression level in CCA tissues. Moreover, YAP1 overexpression could predicted a poor outcome of CCA patients. Results Taken together, our results suggested that RHPN1-AS1 might be a remarkable biomarker to evaluate prognosis in CCA. Conclusion The RHPN1-AS1/YAP1 axis may provide new strategies for CCA clinical practice.

scholarly journals OC-8722 THE GENERATION AND TESTING OF A GENETICALLY ATTENUATED MALARIA PARASITE (GAP) VACCINE

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A18.1-A18
Author(s):  
Shahid Khan ◽  
Keyword(s):  
Phase I ◽  
Safety Profile ◽  
Gene Deletion ◽  
Conditional Release ◽  
The Us ◽  
Controlled Human Malaria Infection ◽  
Humanised Mice ◽  
Excellent Safety Profile ◽  
Gene Deletion Mutant

BackgroundImmunisation with radiation-attenuated Plasmodium falciparum sporozoites (SPZ) (Sanaria PfSPZ Vaccine) can protect >90% of vaccinees against controlled human malaria infection (CHMI) and protects against naturally-transmitted P. falciparum in Africa for at least 6 months. Immunisation with sporozoites of genetically attenuated parasites (GAPs), which completely arrest after liver-cell invasion can be potentially safer and more potent than irradiated sporozoite vaccines. As part of a collaboration between two Dutch research groups (LUMC and Radboud University) and the US company, Sanaria, we describe the generation and first-in-man testing of a GAP vaccine,MethodsWe screened single and multiple gene deletion parasites in order to identify parasites that can invade hepatocytes but are unable to complete liver-stage development. Informed by rodent studies we created P. falciparum double gene-deletion mutant, Δb9Δslarp; sporozoites of this line were infective to human hepatocytes in vitro and to humanised mice but they completely arrest after invasion. PfΔslarpΔb9 PfSPZ (Sanaria PfSPZ-GA1 Vaccine) was manufactured in compliance with cGMPs and released for human clinical trials in the EU under a conditional release GMO license. This GAP vaccine was used to perform phase I (safety) and phase 2a (efficacy) clinical CHMI trial in the Netherlands.ResultsIn a dose escalating phase I clinical trial, the vaccine showed an excellent safety profile. All adverse events related to the vaccine were mild (grade 1). Based on this indication of safety, vaccine efficacy was examined by CHMI; 48 subjects were subsequently enrolled into phase 2a study and were immunised with either PfSPZ-GA1 or PfSPZ Vaccine or saline placebo.ConclusionsIn conclusion, PfSPZ-GA1 Vaccine is the first injectable genetically attenuated malaria vaccine assessed in humans. The accomplishment to manufacture, obtain regulatory approval and to demonstrate an excellent safety profile for this vaccine is unprecedented and holds a promise for PfSPZ vaccines with increased potency.

scholarly journals OC-0463: In vitro prediction of DNA repair defects reveals association with poor clinical outcome in HNSCC

2017 ◽  
Vol 123 ◽  
pp. S246-S247
Author(s):  
P. Essers ◽  
C. Verhagen ◽  
M. Van der Heijden ◽  
M. Van den Brekel ◽  
H. Bartelink ◽  
...  
Keyword(s):  
Dna Repair ◽  
Clinical Outcome ◽  
Poor Clinical Outcome

scholarly journals The safety of a therapeutic product composed of a combination of stem cell released molecules from adipose mesenchymal stem cells and fibroblasts

2020 ◽  
Vol 6 (7) ◽  
pp. FSO592
Author(s):  
Greg Maguire ◽  
Peter Friedman
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Safety Profile ◽  
Human Fibroblasts ◽  
Cellular Tissue ◽  
Adipose Mesenchymal Stem Cells ◽  
Excellent Safety Profile

Aim: We sought to determine the safety profile of a therapeutic candidate composed of the released molecules from a combination of human adipose-derived mesenchymal stem cells and fibroblasts. Although stem cells, their progenitor cells and the molecules that are released from these cells have some demonstrated therapeutic value, much more needs to learn about the efficacy, mechanism of action and the safety profiles of these stem cell-based therapeutics. Methods: A number of cellular, in vitro, in vivo and human studies were performed to analyze cellular, tissue and systemic safety profiles of the combinatorial product. Results: At the levels tested in this study, ranging from demonstrated therapeutic doses to supratherapeutic doses, the combinatorial product demonstrated an excellent safety profile in all in vitro, cellular, tissue and systemic studies. Conclusions: We found evidence that a therapeutic candidate composed of the molecules released from human adipose-derived mesenchymal stem cells and human fibroblasts has an excellent safety profile, and that the product warrants further studies for safety and efficacy where dosing may include topical application, injection and oral application.

scholarly journals Methylene Blue has a potent antiviral activity against SARS-CoV-2 in the absence of UV-activation in vitro

2020 ◽  
Author(s):  
Valeria Cagno ◽  
Chiara Medaglia ◽  
Andreas Cerny ◽  
Thomas Cerny ◽  
Caroline Tapparel ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Antiviral Activity ◽  
Broad Spectrum ◽  
Safety Profile ◽  
Uv Light ◽  
Malaria Treatment ◽  
Virucidal Activity ◽  
Blood Products ◽  
Excellent Safety Profile

ABSTRACTMethylene blue is an FDA and EMA approved drug with an excellent safety profile. It displays broad-spectrum virucidal activity in the presence of UV light and has been shown to be effective in inactivating various viruses in blood products prior to transfusions. In addition, its use has been validated for methemoglobinemia and malaria treatment. Here we show the virucidal activity of methylene blue at low micromolar concentrations and in the absence of UV activation against SARS-CoV2.

scholarly journals Up-regulation of inflammation-related LncRNA-IL7R predicts poor clinical outcome in patients with cervical cancer

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Yangyang Fan ◽  
Yan Nan ◽  
Juanjuan Huang ◽  
Hui Zhong ◽  
Weidong Zhou
Keyword(s):  
Cervical Cancer ◽  
Clinical Outcome ◽  
Cox Regression ◽  
Proliferation Index ◽  
Poor Clinical Outcome ◽  
Clinical Role ◽  
Ki 67 ◽  
Cox Regression Analysis

The long-term chronic inflammation of cervical intraepithelial neoplasia (CIN) induces the initiation and progression of cervical cancer. Long non-coding RNAs (LncRNAs) are being identified to be involved into inflammation and carcinogenesis and could function as cancer biomarkers in clinical. However, the significance of inflammation-related LncRNA (e.g. LncRNA-IL7R) in cervical cancer is limited. We, here, investigated the clinical role of inflammation-related LncRNA-IL7R (Lnc-IL7R) in healthy cervical tissue (n=15), CIN 1/2/3 (n=35), cervical cancer (n=70), and clarified its function via knockdown in vitro and in vivo. The results showed that the expression of Lnc-IL7R was increased from normal tissues to neoplastic lesions and cervical cancer. Up-regulated Lnc-IL7R positively correlated to tumor size, International Federation of Gynaecology and Obstetrics (FIGO) stage, and lymph node metastasis (LNM). Patients with high expression of Lnc-IL7R had poor prognosis with short overall survival (OS) time, and Cox regression analysis revealed that Lnc-IL7R could be independent prognostic factor for cervical cancer. Moreover, knockdown of Lnc-IL7R by two different siRNAs in cervical cancer cell lines Hela and SiHa induced impaired cell vitality and caspase-3-dependent apoptosis in vitro. Furthermore, inhibition of Lnc-IL7R in vivo significantly restricted the tumor growth with decreased expressions of proliferation index Ki-67 and Lnc-IL7R. These data indicated that Lnc-IL7R predicts a poor clinical outcome of cervical cancer patients, and knockdown of Lnc-IL7R is amenable to the treatment of cervical cancer.

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