Detection of Apoptosis in Cancer Cells Using Heat Shock Protein 70 and p53 Antibody Conjugated Quantum Dot Nanoparticles

Clinical experience indicates that enhanced level of heat shock protein 70 (Hsp70) and p53 correlates with poor prognosis due to malignant cell overexpression of these proteins in tumor progression. Cadmium selenide quantum dots (QDs) were synthesized in aqueous solution using mercaptopropionic acid and L-cysteine (L-Cys) as ligands. They were conjugated with a monoclonal antibody (Ab) to p53 and cmHp70.1 to Hsp70 for detection of cancer cell apoptosis that was demonstrated in the experiment by fluorescent confocal microscopy both for breast carcinoma cells and for thyroid tissue. It is shown that in comparison with organic dyes, quantum dots have superior photostability of tracking apoptosis in cancer cells for longer time

A Comparison of the Sensititre MycoTB Plate, the Bactec MGIT 960, and a Microarray-Based Molecular Assay for the Detection of Drug Resistance in Clinical <i>Mycobacterium tuberculosis</i> Isolates in Moscow, Russia

<div><p>Background</p><p>The goal of this study was to compare the consistency of three assays for the determination of the drug resistance of <i>Mycobacterium tuberculosis</i> (MTB) strains with various resistance profiles isolated from the Moscow region.</p><p>Methods</p><p>A total of 144 MTB clinical isolates with a strong bias toward drug resistance were examined using Bactec MGIT 960, Sensititre MycoTB, and a microarray-based molecular assay TB-TEST to detect substitutions in the <i>rpoB</i>, <i>katG</i>, <i>inhA</i>, <i>ahpC</i>, <i>gyrA</i>, <i>gyrB</i>, <i>rrs</i>, <i>eis</i>, and <i>embB</i> genes that are associated with resistance to rifampin, isoniazid, fluoroquinolones, second-line injectable drugs and ethambutol.</p><p>Results</p><p>The average correlation for the identification of resistant and susceptible isolates using the three methods was approximately 94%. An association of mutations detected with variable resistance levels was shown. We propose a change in the breakpoint minimal inhibitory concentration for kanamycin to less than 5 μg/ml in the Sensititre MycoTB system. A pairwise comparison of the minimal inhibitory concentrations (MICs) of two different drugs revealed an increased correlation in the first-line drug group and a partial correlation in the second-line drug group, reflecting the history of the preferential simultaneous use of drugs from these groups. An increased correlation with the MICs was also observed for drugs sharing common resistance mechanisms.</p><p>Conclusions</p><p>The quantitative measures of phenotypic drug resistance produced by the Sensititre MycoTB and the timely detection of mutations using the TB-TEST assay provide guidance for clinicians for the choice of the appropriate drug regimen.</p></div

MICs based on the comparison of the MycoTB plate and MGIT 960 results.

<p>MICs based on the comparison of the MycoTB plate and MGIT 960 results.</p

MIC distributions of the clinical isolates characterized using the MGIT and TB-TEST assays.

<p>Resistant and susceptible isolates based on the MGIT results are indicated by the red and green lines, respectively. The light-red and light-green bars represent the numbers of resistant and susceptible isolates with mutations detected by the TB-TEST. The MGIT was not performed for rifabutin (RFB); therefore, only the distributions of all isolates and the isolates with mutations are shown.</p

Consortium high level timelines/activities.

<p>1. Siberian State Medical University, Tomsk, Russian Federation, 2. Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands, 3. Department of Parasitology and Leiden Parasite Immunology Group, Leiden University Medical Center, Leiden, the Netherlands, 4. George Washington University Medical Center, United States, 5. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation, 6. Institute of Tropical Medicine, University of Tübingen, Germany, 7. Khon Kaen University, Khon Kaen, Thailand, 8. Pfizer LLC, Moscow, Russian Federation, 9. ReMedys Foundation, Geneva, Switzerland, 10. Royal Brompton Hospital, United Kingdom; Research Institute for Medical Genetics, Tomsk, Russian Federation, 11. Swiss Tropical and Public Health Institute, Basel, Switzerland.</p