scholarly journals In Vitro Sensitivity Testing in the Assessment of Anti-CLL Drug Candidates

10.5772/27087 ◽  
2012 ◽  
Author(s):  
Gnter Krause ◽  
Mirjam Kuckertz ◽  
Susan Kerwien ◽  
Michaela Patz ◽  
Michael Hallek
Keyword(s):  
Sensitivity Testing ◽  
Drug Candidates ◽  
In Vitro Sensitivity

Functional precision medicine in colorectal cancer based on patient-derived tumoroids and in-vitro sensitivity drug testing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15567-e15567
Author(s):  
Lars Henrik Jensen ◽  
Anders Kristian Moeller Jakobsen ◽  
Birgitte Mayland Havelund ◽  
Cecilie Abildgaard ◽  
Chris Vagn-Hansen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Primary Endpoint ◽  
Drug Testing ◽  
Progression Free Survival ◽  
Patient Specific ◽  
Precision Oncology ◽  
Sensitivity Testing ◽  
In Vitro Sensitivity

e15567 Background: Precision oncology based on in-vitro, functional assays has potential advantages compared to the much more common molecular approach, but the clinical benefit is unknown. We here report the results from the largest prospective interventional clinical trial testing the clinical outcome in colorectal cancer patients treated with drugs showing cytotoxic effect in matched patient-derived tumoroids. Methods: This single-center, phase II trial included patients with metastatic colorectal cancer previously exposed to all standard therapies. Specimens from one to three 18-16 G core needle biopsies were manually dissected, enzymatically treated, cultivated, and incubated to form 3D spherical microtumors, i.e. tumoroids. In the assay for in-vitro sensitivity testing, the tumoroids were challenged with single drugs and combinations thereof to determine patient-specific responses. Using tumoroid screening technology (IndiTreat, 2cureX, Copenhagen, Denmark), results were generated by comparing the sensitivity of the individual patient’s tumoroids with a reference panel from other patients. The testing included standard cytostatics and drugs with proven effect in previous early-phase clinical trials, a total of 15 drugs. The primary endpoint was the fraction of patients with progression-free survival (PFS) at two months. Based on placebo arms in randomized last-line trials, a minimal relevant difference of 20% (20% to 40%) was stated. Using Simon's two-stage design, a sample size of 45 patients was calculated with at least 14 PFS at two months (significance 5%, power 90%). Results: Ninety patients were enrolled from 9/2017 to 9/2020. Biopsies from 82 patients were obtained and sent for tumoroid formation of which 44 (54%, 95% CI 42-65) were successful and at least one treatment was suggested. Thirty-four patients initiated treatment according to the response obtained in the drug assays within a median of 51 days from inclusion (IQR 39-63). The primary endpoint, PFS at two months, was met in 17 of 34 patients (50%, 95%CI 32-68). There were no radiological responses. Median PFS was 81 days (95% CI 51-112) and median OS was 189 days (95% CI 103-277). Conclusions: Precision oncology using a functional approach with patient-derived tumoroids and in-vitro drug sensitivity testing seems feasible. The approach is limited by the fraction of patients with successful tumoroid development. The primary endpoint was met, as half of the patients were without progression at two months. Further clinical studies are justified. Clinical trial information: NCT03251612.

scholarly journals Relationship between Acute Suppurative Otitis Media and Chronic Secretory Otitis Media: Role of Antibiotics

1984 ◽  
Vol 77 (9) ◽  
pp. 754-757 ◽  
Author(s):  
Robert Mills ◽  
Ann Uttley ◽  
Michelle McIntyre
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
Secretory Otitis Media ◽  
Sensitivity Testing ◽  
Suppurative Otitis Media ◽  
In Vitro Sensitivity ◽  
Resistance To Penicillin

A total of 204 chronic middle ear effusions from 122 children have been studied. Bacteria were isolated from 30 effusions. The commonest species found were Strep. pneumoniae and H. influenzae. These are also the commonest organisms causing acute otitis media (AOM). A similar pattern of serotypes was also demonstrated. In vitro sensitivity testing showed that most of the organisms isolated were sensitive to most commonly-used antibiotics. The main exception was resistance to penicillin amongst strains of H. influenzae and Staph. aureus. It is suggested that some cases of chronic secretory otitis media (SOM) may arise as a result of incomplete resolution of AOM and that the use of penicillin to treat AOM may be one factor in this process.

scholarly journals Efficacy of Variable Tetraconazole Rates Against Cercospora beticola Isolates with Differing In Vitro Sensitivities to DMI Fungicides

Plant Disease ◽  
2012 ◽  
Vol 96 (12) ◽  
pp. 1749-1756 ◽  
Author(s):  
Melvin D. Bolton ◽  
Viviana Rivera-Varas ◽  
Luis E. del Río Mendoza ◽  
Mohamed F. R. Khan ◽  
Gary A. Secor
Keyword(s):  
Sugar Beet ◽  
Disease Severity ◽  
Cercospora Beticola ◽  
In Planta ◽  
Sensitivity Testing ◽  
In Vitro Sensitivity ◽  
Wide Range ◽  
Fungicide Efficacy ◽  
Dmi Fungicides

Cercospora leaf spot (CLS) of sugar beet is caused by the fungus Cercospora beticola. CLS management practices include the application of the sterol demethylation inhibitor (DMI) fungicides tetraconazole, difenoconazole, and prothioconazole. Evaluating resistance to DMIs is a major focus for CLS fungicide resistance management. Isolates were collected in 1997 and 1998 (baseline sensitivity to tetraconazole, prothioconazole, or difenoconazole) and 2007 through 2010 from the major sugar-beet-growing regions of Minnesota and North Dakota and assessed for in vitro sensitivity to two or three DMI fungicides. Most (47%) isolates collected in 1997–98 exhibited 50% effective concentration (EC50) values for tetraconazole of <0.01 μg ml–1, whereas no isolates could be found in this EC50 range in 2010. Since 2007, annual median and mean tetraconazole EC50 values have generally been increasing, and the frequency of isolates with EC50 values >0.11 μg ml–1 increased from 2008 to 2010. In contrast, the frequency of isolates with EC50 values for prothioconazole of >1.0 μg ml–1 has been decreasing since 2007. Annual median difenoconazole EC50 values appears to be stable, although annual mean EC50 values generally have been increasing for this fungicide. Although EC50 values are important for gauging fungicide sensitivity trends, a rigorous comparison of the relationship between in vitro EC50 values and loss of fungicide efficacy in planta has not been conducted for C. beticola. To explore this, 12 isolates exhibiting a wide range of tetraconazole EC50 values were inoculated to sugar beet but no tetraconazole was applied. No relationship was found between isolate EC50 value and disease severity. To assess whether EC50 values are related to fungicide efficacy in planta, sugar beet plants were sprayed with various dilutions of Eminent, the commercial formulation of tetraconazole, and subsequently inoculated with isolates that exhibited very low, medium, or high tetraconazole EC50 values. The high EC50 isolate caused significantly more disease than isolates with medium or very low EC50 values at the field application rate and most reduced rates. Because in vitro sensitivity testing is typically carried out with the active ingredient of the commercial fungicide, we investigated whether loss of disease control was the same for tetraconazole as for the commercial product Eminent. The high EC50 isolate caused more disease on plants treated with tetraconazole than Eminent but disease severity was not different between plants inoculated with the very low EC50 isolate.

Diagnosis, treatment, and temporary remission of disseminated paecilomycosis in a vizsla

1996 ◽  
Vol 32 (6) ◽  
pp. 509-514 ◽  
Author(s):  
PA March ◽  
K Knowles ◽  
CL Dillavou ◽  
R Jakowski ◽  
G Freden
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Marked Improvement ◽  
Clinical Signs ◽  
Central Nervous System Involvement ◽  
Disease Course ◽  
Sensitivity Testing ◽  
In Vitro Sensitivity ◽  
Multisystemic Disease

A case of disseminated paecilomycosis in a three-year-old vizsla is described. Clinical signs of lethargy, weight loss, lymphadenopathy, diarrhea, and vestibulocochlear deficits were exhibited. Dense colonization of bone marrow by the fungus was found early in the disease course. Serial culture of bone-marrow aspirates and in vitro sensitivity testing helped monitor disease progression and guide antifungal therapy. Clinical and laboratory parameters demonstrated marked improvement for a period of 12 weeks. Multisystemic disease with central nervous system involvement was found at necropsy.

SLIDE CULTURE OF TUBERCLE BACILLI: II. IN VITRO SENSITIVITY TESTING

1954 ◽  
Vol 1 (1) ◽  
pp. 30-35 ◽  
Author(s):  
R. W. Reed
Keyword(s):  
Sensitivity Testing ◽  
Simple Method ◽  
Slide Culture ◽  
In Vitro Sensitivity ◽  
Sensitivity Tests ◽  
Conventional Methods ◽  
Technical Simplicity ◽  
Tuberculostatic Agents

A technically simple method of testing the sensitivity of tubercle bacilli to tuberculostatic agents is described which gives accurate results directly from positive sputum in one or two weeks. Parallel slide and tube sensitivity tests against streptomycin and isoniazid on 136 specimens show 49% and 68% agreement respectively. The number of cultures within the sensitive range of each drug was almost identical. The advantages of slide sensitivity testing over conventional methods are technical simplicity and rapid results.

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