Publications by authors named "Olena Kis"
Article Synopsis
- Multiple myeloma is a type of cancer affecting plasma cells, characterized by specific genetic changes that evolve as the disease progresses.
- The study introduces a new method called CapIG-seq, which efficiently detects important genetic rearrangements, oncogenic translocations, and mutations related to myeloma, addressing limitations of previous PCR-based techniques.
- The results show that CapIG-seq aligns well with existing sequencing methods and is effective in analyzing both cancer cell lines and patient samples, indicating its potential for better understanding and monitoring myeloma.
The tuberous sclerosis genes and MTOR are increasingly being found to have important roles in novel subtypes of renal cancer, particularly emerging entities eosinophilic solid and cystic renal cell carcinoma (RCC) and high-grade oncocytic renal tumor (HOT)/RCC with eosinophilic and vacuolated cytoplasm. We report a unique renal neoplasm in a 66-year-old woman that initially mimicked MITF family translocation RCC due to mixed clear and eosinophilic cells, extensive stromal hyalinization, and psammoma bodies, yet which was negative for TFE3 and TFEB fluorescence in situ hybridization and a next generation sequencing (NGS) gene fusion assay. Cytoplasmic stippling triggered consideration of TSC-associated neoplasms, and a targeted NGS assay revealed a variant in exon 21 of TSC1 resulting in c.
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- The use of liquid biopsies is becoming more popular for cancer detection and management, particularly through analyzing circulating tumor DNA in blood samples.
- Current methods have low sensitivity for early-stage cancer detection due to few recurring mutations, but large-scale epigenetic changes show promise in identifying cancers more effectively.
- This study introduces a new protocol to analyze DNA methylation in small amounts of circulating DNA, demonstrating strong performance in detecting and classifying various cancer types, paving the way for improved early-stage cancer diagnostics.
Article Synopsis
- The study addresses challenges in enrolling multiple myeloma patients in clinical trials due to the need for invasive bone-marrow aspirates for genomic profiling.
- Researchers developed a Liquid Biopsy Sequencing (LB-Seq) method to analyze cell-free DNA (cfDNA) from blood samples, achieving high sensitivity in detecting tumors.
- Findings show that LB-Seq can accurately identify most somatic mutations found in bone marrow samples, with high concordance and the ability to discover additional mutations, making it a valuable alternative to traditional methods.
Article Synopsis
- The study examined how HIV-1 infection and antiretroviral therapy (ART) affect the expression of intestinal drug transporters and metabolic enzymes in the human upper intestine.
- Researchers compared intestinal tissue from HIV-negative healthy individuals, ART-naive HIV-positive individuals, and those receiving ART, using methods like microarray and qPCR.
- Findings showed lower expression of certain enzymes and transporters in ART-naive subjects, which partially improved with ART, suggesting that HIV infection can alter drug metabolism and may affect the effectiveness of antiretroviral drugs.
Raltegravir permeability across blood-tissue barriers and the potential role of drug efflux transporters.
Antimicrob Agents Chemother
May 2015
The objectives of this study were to investigate raltegravir transport across several blood-tissue barrier models and the potential interactions with drug efflux transporters. Raltegravir uptake, accumulation, and permeability were evaluated in vitro in (i) P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 1 (MRP1), or MRP4-overexpressing MDA-MDR1 (P-gp), HEK-ABCG2, HeLa-MRP1, or HEK-MRP4 cells, respectively; (ii) cell culture systems of the human blood-brain (hCMEC/D3), mouse blood-testicular (TM4), and human blood-intestinal (Caco-2) barriers; and (iii) rat jejunum and ileum segments using an in situ single-pass intestinal perfusion model. [(3)H]Raltegravir accumulation by MDA-MDR1 (P-gp) and HEK-ABCG2-overexpressing cells was significantly enhanced in the presence of PSC833 {6-[(2S,4R,6E)-4-methyl-2-(methylamino)-3-oxo-6-octenoic acid]-7-L-valine-cyclosporine}, a P-gp inhibitor, or Ko143 [(3S,6S,12aS)-1,2,3,4,6,7,12,12a-octahydro-9-methoxy-6-(2-methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid 1,1-dimethylethyl ester], a BCRP inhibitor, suggesting the inhibition of a P-gp- or BCRP-mediated efflux process, respectively.
View Article and Find Full Text PDFPurpose: The objectives of this study were to evaluate the effects of intestinal lumen pH, food intake, and acid-reducing agents on the intestinal permeability of atazanavir, an HIV-1 protease inhibitor.
Methods: Atazanavir permeability across Caco-2 cell monolayers (P app) and in situ steady-state permeability across rat jejunum and ileum (P eff) were evaluated in buffers of varied pH (4.5-8.
Article Synopsis
- - Drug transport in the central nervous system is regulated by various transport proteins located at barriers like the blood-brain barrier, as well as within brain cells like astrocytes and neurons.
- - Key transporter families involved include the ATP-Binding Cassette and Solute Carrier families, which help manage the movement of both natural substances and drugs into and out of the brain.
- - These transport proteins are linked to several neurological conditions, such as HIV-encephalitis, Alzheimer's, and Parkinson's disease, highlighting their importance in understanding brain health.
Article Synopsis
- The study aimed to understand how membrane-associated drug transporters influence the absorption of the HIV-1 protease inhibitor, atazanavir, and its interactions with other drugs like protease inhibitors and tenofovir disoproxil fumarate (TDF).
- Research methods included in vitro experiments using Caco-2 cell lines and in situ tests on rat intestinal segments, assessing the effects of various transporter inhibitors and other antiretroviral drugs.
- Results showed that atazanavir's absorption was significantly affected by P-glycoprotein and OATP inhibitors, revealing a higher secretory flux compared to absorptive flux, and co-administration with TDF reduced atazanavir's intestinal permeability, indicating complex drug-drug interactions
Article Synopsis
- African traditional medicinal plants like Sutherlandia frutescens may affect the safety and efficacy of antiretroviral drugs, specifically the protease inhibitor atazanavir, through pharmacokinetic interactions.
- The study involved preparing and analyzing different extracts of Sutherlandia frutescens to observe their effects on the absorption and metabolism of atazanavir using Caco-2 cell monolayers and human liver microsomes.
- Results showed that certain extracts decreased atazanavir absorption while others enhanced its metabolism, indicating that these plant components could significantly influence the drug's effectiveness and safety.
Article Synopsis
- - The human intestinal epithelium has transporters that regulate drug absorption, notably the OATP2B1 transporter, which affects how various drugs, including HIV protease inhibitors (PIs), are taken up by cells.
- - This study used Caco-2 cells to investigate how PIs interact with the OATP2B1 transporter, finding that different PIs can inhibit OATP2B1-mediated transport, with specific concentration thresholds (IC50) for each drug.
- - Results indicate that while the uptake of certain PIs is influenced by extracellular pH, it does not depend on OATP2B1, suggesting that these interactions may lead to significant drug-drug interactions that could affect treatment outcomes in
The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters.
Trends Pharmacol Sci
January 2010
Article Synopsis
- - HIV treatment involves highly active antiretroviral therapy (HAART), which uses a mix of antiviral drugs from different classes to effectively suppress the virus.
- - Antiretroviral drugs have complicated absorption and metabolism, leading to potential drug-drug interactions that can affect the effectiveness and safety of treatment.
- - The review highlights the significance of transport proteins, specifically ATP-binding cassette (ABC) transporters and solute carriers (SLC), in how these drugs are processed and identifies key interactions that could impact therapy outcomes.