Kersti Oselin - Academia.edu (original) (raw)
Papers by Kersti Oselin
PubMed, Jan 17, 2024
Lung cancer remains the leading cause of cancer-related deaths in Europe, with non-small cell lun... more Lung cancer remains the leading cause of cancer-related deaths in Europe, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. NSCLC is a heterogeneous disease encompassing various oncogenic alterations. Among them, EGFR exon 20 insertion mutations, constituting 0.3-2.2% of NSCLC cases, rank as the third most common EGFR alteration after exon 19 deletions and the L858R point mutation in exon 21, also known as "typical" EGFR alterations. Recent advancements in understanding the molecular pathogenesis of NSCLC have led to significant breakthroughs in targeted therapies, revolutionizing treatment options for patients with specific genetic alterations.This article presents the outcomes of a Virtual Meeting conducted on the online platform (provided Within3©) from September 19 to October 30, 2022. The meeting focused on addressing the challenges in the diagnosis and treatment of NSCLC patients with EGFR exon 20 insertion mutations. The participants consisted of healthcare professionals from ten Central and Eastern European countries who shared their experiences and opinions on various aspects, including epidemiology, treatment options, and diagnostic approaches employed in their respective healthcare institutions. The discussions were facilitated through open-ended and multiple-choice questions.The primary objective of this article is to provide an overview of the identified challenges associated with the diagnosis and treatment of this heterogeneous disease, based on the assessments of the meeting participants. Among the major emerging challenges discussed, the reimbursement issues concerning next-generation sequencing (NGS), a recommended method in NSCLC molecular diagnosis, and the availability of approved targeted treatments to enhance patient outcomes were of paramount importance. Furthermore, fostering community awareness of lung cancer and promoting harmonized lung cancer care were identified as areas deserving greater attention. Notably, the rapidly evolving treatment landscape, particularly with NGS for NSCLC patients with genomic alterations like EGFR, ALK, RET, MET, NTRK, and ROS1, necessitates prioritizing the development of new drugs, even for the relatively smaller subgroup with exon 20 insertion mutations.
![Research paper thumbnail of Comment on: Generic and therapeutic substitution: a viewpoint on achieving best practice in Europe by Johnston et al.[1]](https://attachments.academia-assets.com/115634424/thumbnails/1.jpg)
](British Journal of Clinical Pharmacology, Oct 11, 2011
![Research paper thumbnail of Comment on: Generic and therapeutic substitution: a viewpoint on achieving best practice in Europe by Johnston et al.[1]](https://attachments.academia-assets.com/115634454/thumbnails/1.jpg)
](British Journal of Clinical Pharmacology, 2011
Antimicrobial Agents and Chemotherapy, 2018
European Journal of Clinical Pharmacology, Aug 1, 2003
The aim of the present study was to determine the frequency of the G816A, T825C, T1684C, and G400... more The aim of the present study was to determine the frequency of the G816A, T825C, T1684C, and G4002A genetic polymorphisms of the human MRP1 gene in 230 healthy Caucasians. The functional assessment of these mutations was performed in fluorescence-activated cell sorting (FACS)-sorted peripheral blood CD4 + cells in a further 61 healthy volunteers by determining MRP1 mRNA expression. Methods: Genotyping of the MRP1 was carried out using real-time polymerase chain reaction (PCR) assays. Quantitative determination of the MRP1 mRNA expression was performed with real-time reverse-transcription-PCR. Results: A novel silent mutation G816A in exon 8 was found in this study. Allele frequencies of the 816A, 825C, 1684C, and 4002A were 4.1, 30.0, 80.0, and 28.3%, respectively. The frequency of the T825C polymorphism was comparable with that found in a previous Japanese study. In contrast, the frequency of the T1684C (OR 0.06, 95% CI 0.03-0.11, P<0.0001, vs Japanese) and the G4002A (OR 0.47, 95% CI 0.24-0.86, P=0.01, vs Japanese) was significantly rarer. The mean MRP1 mRNA expression in peripheral blood CD4 + cells was 1.03•10 4 ±3.8•10 3 molecules/ng of total RNA with an eightfold variation among individuals. However, MRP1 mRNA expression in CD4 + cells was not found to correlate with genetic polymorphisms investigated in this study. Conclusions: The genotypic results observed show an ethnic difference in the frequencies of the MRP1 genetic polymorphisms between Japanese and Caucasians. Further studies are required to better understand the clinical consequences of the MRP1 genetic variants.
Research Square (Research Square), Apr 1, 2020
Background: We aimed to study the mortality and intensity of health care in patients with advance... more Background: We aimed to study the mortality and intensity of health care in patients with advanced lung cancer assigned to systemic anti-cancer treatment (SACT) compared with patients who were not eligible for SACT (no-SACT). Methods: A retrospective cohort of lung cancer patients, who were treated at the North Estonia Medical Centre from 2015-2017, was linked to population-based health care data from the Estonian Health Insurance Fund. We calculated 14-and 30-day mortality after SACT and used a composite measure of intensity of care, comprised from the following: emergency department visit, admission to hospital, admission to intensive care unit, receipt of radiotherapy or systemic treatment. Results: The median overall survival (OS) of patients who received at least one cycle of SACT (n = 489) was 9.1 months and in patients with no-SACT (n = 289) 1.3 months (hazard ratio [HR]=4.23, 95% CI=3.60-5.00). In the SACT group 6.7% and 14.7% of patients died within 14 days and 30 days after the last cycle, respectively. During the final 30 days of life, intensive EOL care was received by 69.9% of the SACT patients and 43.7% of the no-SACT patients (p < 0.001). Among SACT patients, sepsis, bacterial infection and/or neutropenia had a significant adverse effect on survival (HR=1.7, 95% CI=1.3-2.21, p < 0.001), whereas the use of the granulocyte colony stimulating growth factor reduced the risk of death (HR= 0.71, 95% CI=0.55-0.93, p = 0.013). Conclusions: Significant proportions of patients with advanced lung cancer continue to receive intensive care near death. Our results highlight that neutropenia and infectious complications are still the primary cause of early SACT-related death.
Acta Oncologica, Jul 9, 2019
Background: Lung cancer (LC) remains the most frequent cause of cancer death worldwide. We aimed ... more Background: Lung cancer (LC) remains the most frequent cause of cancer death worldwide. We aimed to examine long-term trends in LC survival in Estonia by age, gender, histologic type and stage, with specific focus on surgical treatment. Material and methods: Data on all incident cases of LC diagnosed from 1996 to 2016 were obtained from the Estonian Cancer Registry. Logistic regression was used to examine receipt of surgical treatment in localized LC. Relative survival ratios (RSR) were calculated, and excess hazard ratios (EHR) of death were estimated by stage with gender, age, histology and period of diagnosis as independent variables. Results: Among the total of 16,423 cases, squamous cell carcinoma remained the most common histologic type. The odds of receiving surgical treatment in localized LC increased significantly over time and were associated with age, gender and histologic type. Overall, the age-standardized 5-year RSR improved significantly from 10% in 1996-2002 to 16% in 2010-2016 (from 8% to 15% in men and from 15% to 20% in women). Larger survival gain was seen in younger patients, for non-small cell LC subtypes, and for surgically treated patients. For localized disease, the 5-year RSR increased by more than 20 percentage units, reaching 50% in men and 69% in women. For all stages, the adjusted EHR of death was significantly associated with age, histologic type and period of diagnosis. Conclusions: We observed a substantial improvement of relative survival, with considerable variations across patient groups. After adjustment for age, gender and histology, a significant survival increase over time was seen for all stages. The considerable survival gain observed for localized LC can largely be attributed to rapidly growing proportion of surgically treated patients. Further investigation of LC management practices, particularly the use of non-surgical treatment options is warranted.
Journal of Clinical Oncology, Jun 1, 2023
8520 Background: In the randomized, triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372),... more 8520 Background: In the randomized, triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372), at the second interim analysis, pembrolizumab (pembro) significantly prolonged DFS vs placebo (pbo) in the overall population of patients (pts) with completely resected stage IB–IIIA NSCLC per AJCC v7 who may or may not have received adjuvant chemotherapy (chemo; up to 4 cycles) as recommended per local guidelines (n = 1177; HR, 0.76 [95% CI, 0.63–0.91]; P = 0.0014). Here we present outcomes for those pts who received 1–4 cycles of prior adjuvant chemo, per protocol. Methods: Eligible adults had pathologically confirmed, completely resected stage IB (T ≥4 cm), II, or IIIA NSCLC (AJCC v7) of any PD-L1 expression, ECOG performance status of 0 or 1, and had not received neoadjuvant radiotherapy or chemo. Pts were randomized 1:1 to pembro 200 mg or pbo Q3W for 18 doses (~1 year); receipt of adjuvant chemo (yes vs no) was one of the stratification factors. Dual primary endpoints were DFS in the ITT and PD-L1 TPS ≥50% populations. No alpha was assigned to this subgroup analysis of pts who received adjuvant chemo for 1–4 cycles per local guidelines. Results: Of 1177 pts in the ITT population, 1010 (85.8%) received adjuvant chemo and were included in this analysis (pembro, n = 506; pbo, n = 504). Pts received a median of 17 and 18 study doses, respectively. As of data cutoff (Sep 20, 2021), 52.6% in the pembro arm vs 64.9% in the pbo arm had completed treatment. Median time from randomization to data cutoff was 37.4 mo. Median (95% CI) DFS was 58.7 mo (39.2 mo–not reached [NR]) in the pembro arm vs 34.9 mo (28.6 mo–NR) in the pbo arm (HR, 0.73 [95% CI, 0.60–0.89]). Estimated 18-mo DFS rates were 73.8% and 63.1%, respectively. In pts with PD-L1 TPS ≥50% (pembro, n = 143; pbo, n = 141), median DFS was NR in both treatment arms (HR, 0.80 [95% CI, 0.54–1.20]). Grade 3–5 adverse events (AEs) occurred in 170 pts (34.3%) in the pembro arm and 128 (25.7%) in the pbo arm (grade 5, 2.2% vs 1.0%). Immune-mediated AEs and infusion reactions occurred in 195 pts (39.3%) in the pembro arm and 69 (13.8%) in the pbo arm. Conclusions: Consistent with the ITT population, pembro substantially improved DFS vs pbo in the subgroup of pts with stage IB (T2a ≥4 cm), II, or IIIA NSCLC who received adjuvant platinum-based chemo following complete resection. Based on these results, pembro was approved for adjuvant treatment in this pt population by the US FDA. Clinical trial information: NCT02504372 .
Journal of Chromatography B, Apr 1, 2006
Thiopurine S-methyltransferase (TPMT; EC 2.1.1.67) is the key enzyme in the metabolism of thiopur... more Thiopurine S-methyltransferase (TPMT; EC 2.1.1.67) is the key enzyme in the metabolism of thiopurine drugs. Determination of TPMT activity has been used for the individualization of thiopurine dose. We developed HPLC-UV assay for the determination of TPMT activity in human erythrocytes using 6-mercaptopurine as a substrate. Various extraction and chromatographic conditions were compared. In-house developed extraction with acetonitrile provided the
Applied sciences, Oct 7, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
European Journal of Haematology, Jul 22, 2003
ATP-binding cassette (ABC) transporters play an important role in the transport of various endoge... more ATP-binding cassette (ABC) transporters play an important role in the transport of various endogenous and exogenous compounds across biologic membranes (1). In cancer cells, they are known to confer multidrug resistance through enhanced efflux of chemotherapeutics. The human multidrug resistance-associated protein 1 (MRP1) and 2 (MRP2) belong to subfamily C of the ABC transporters, and were first identified by Cole et al. (1992) (2) in human small cell lung cancer cells, and by Taniguchi et al. (1996) (3) in cisplatin-resistant human head and neck cancer cell line, respectively. Within hematopoietic cells it has been found that CD3 + cells exhibited the highest and CD19 + cells the lowest MRP1 mRNA levels (4). Protein analysis determined that CD4 + cells exhibited higher MRP1 expression than other cells. In another study, Abbaszadegan et al. (5) showed that regardless of the cell lineage, normal peripheral blood and bone marrow hematopoietic cells express similar basal levels of the MRP1 mRNA. Laupe`ze et al. (6) investigated MRP activity in normal mature leukocytes using the Oselin K, Mrozikiewicz PM, Pa¨hkla R, Roots I. Quantitative determination of the human MRP1 and MRP2 mRNA expression in FACS-sorted peripheral blood CD4 + , CD8 + , CD19 + , and CD56 + cells.
GBM Annual Fall meeting Halle 2002, Sep 1, 2002
Journal of Clinical Pharmacy and Therapeutics, Oct 1, 1999
In comparison with neighbouring Scandinavian countries, the use of digoxin in Estonia is high. Th... more In comparison with neighbouring Scandinavian countries, the use of digoxin in Estonia is high. The present study was carried out to determine the use pattern of digoxin in Estonia and bioavailability of the local market leader preparation in comparison with Lanoxin. Drug use data were evaluated from the annual reports of wholesale companies. For the bioequivalence study, a single-blind cross-over randomised two-way single-dose comparative bioavailability study was performed using 14 healthy volunteers. Digoxin concentrations in serum samples and urine were measured by chemiluminescent competitive immunoassay. The use of digoxin in Estonia has increased by 35% during the period 1994-97. The steady market leader was the local generic drug. No statistically significant differences were found in any pharmacokinetic parameter between the generic preparation and Lanoxin. All parameters showed considerable variability. The total amount of drug excreted was the parameter with lowest inter- individual variation. The present study indicates that the generic digoxin preparation studied is bioequivalent to Lanoxin. The increasing use of digoxin in Estonia is not caused by low bioavailability of the local market leader but by therapeutic traditions.
Journal of Thoracic Oncology, Mar 1, 2021
PubMed, Jan 17, 2024
Lung cancer remains the leading cause of cancer-related deaths in Europe, with non-small cell lun... more Lung cancer remains the leading cause of cancer-related deaths in Europe, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. NSCLC is a heterogeneous disease encompassing various oncogenic alterations. Among them, EGFR exon 20 insertion mutations, constituting 0.3-2.2% of NSCLC cases, rank as the third most common EGFR alteration after exon 19 deletions and the L858R point mutation in exon 21, also known as "typical" EGFR alterations. Recent advancements in understanding the molecular pathogenesis of NSCLC have led to significant breakthroughs in targeted therapies, revolutionizing treatment options for patients with specific genetic alterations.This article presents the outcomes of a Virtual Meeting conducted on the online platform (provided Within3©) from September 19 to October 30, 2022. The meeting focused on addressing the challenges in the diagnosis and treatment of NSCLC patients with EGFR exon 20 insertion mutations. The participants consisted of healthcare professionals from ten Central and Eastern European countries who shared their experiences and opinions on various aspects, including epidemiology, treatment options, and diagnostic approaches employed in their respective healthcare institutions. The discussions were facilitated through open-ended and multiple-choice questions.The primary objective of this article is to provide an overview of the identified challenges associated with the diagnosis and treatment of this heterogeneous disease, based on the assessments of the meeting participants. Among the major emerging challenges discussed, the reimbursement issues concerning next-generation sequencing (NGS), a recommended method in NSCLC molecular diagnosis, and the availability of approved targeted treatments to enhance patient outcomes were of paramount importance. Furthermore, fostering community awareness of lung cancer and promoting harmonized lung cancer care were identified as areas deserving greater attention. Notably, the rapidly evolving treatment landscape, particularly with NGS for NSCLC patients with genomic alterations like EGFR, ALK, RET, MET, NTRK, and ROS1, necessitates prioritizing the development of new drugs, even for the relatively smaller subgroup with exon 20 insertion mutations.
British Journal of Clinical Pharmacology, Oct 11, 2011
British Journal of Clinical Pharmacology, 2011
Antimicrobial Agents and Chemotherapy, 2018
European Journal of Clinical Pharmacology, Aug 1, 2003
The aim of the present study was to determine the frequency of the G816A, T825C, T1684C, and G400... more The aim of the present study was to determine the frequency of the G816A, T825C, T1684C, and G4002A genetic polymorphisms of the human MRP1 gene in 230 healthy Caucasians. The functional assessment of these mutations was performed in fluorescence-activated cell sorting (FACS)-sorted peripheral blood CD4 + cells in a further 61 healthy volunteers by determining MRP1 mRNA expression. Methods: Genotyping of the MRP1 was carried out using real-time polymerase chain reaction (PCR) assays. Quantitative determination of the MRP1 mRNA expression was performed with real-time reverse-transcription-PCR. Results: A novel silent mutation G816A in exon 8 was found in this study. Allele frequencies of the 816A, 825C, 1684C, and 4002A were 4.1, 30.0, 80.0, and 28.3%, respectively. The frequency of the T825C polymorphism was comparable with that found in a previous Japanese study. In contrast, the frequency of the T1684C (OR 0.06, 95% CI 0.03-0.11, P<0.0001, vs Japanese) and the G4002A (OR 0.47, 95% CI 0.24-0.86, P=0.01, vs Japanese) was significantly rarer. The mean MRP1 mRNA expression in peripheral blood CD4 + cells was 1.03•10 4 ±3.8•10 3 molecules/ng of total RNA with an eightfold variation among individuals. However, MRP1 mRNA expression in CD4 + cells was not found to correlate with genetic polymorphisms investigated in this study. Conclusions: The genotypic results observed show an ethnic difference in the frequencies of the MRP1 genetic polymorphisms between Japanese and Caucasians. Further studies are required to better understand the clinical consequences of the MRP1 genetic variants.
Research Square (Research Square), Apr 1, 2020
Background: We aimed to study the mortality and intensity of health care in patients with advance... more Background: We aimed to study the mortality and intensity of health care in patients with advanced lung cancer assigned to systemic anti-cancer treatment (SACT) compared with patients who were not eligible for SACT (no-SACT). Methods: A retrospective cohort of lung cancer patients, who were treated at the North Estonia Medical Centre from 2015-2017, was linked to population-based health care data from the Estonian Health Insurance Fund. We calculated 14-and 30-day mortality after SACT and used a composite measure of intensity of care, comprised from the following: emergency department visit, admission to hospital, admission to intensive care unit, receipt of radiotherapy or systemic treatment. Results: The median overall survival (OS) of patients who received at least one cycle of SACT (n = 489) was 9.1 months and in patients with no-SACT (n = 289) 1.3 months (hazard ratio [HR]=4.23, 95% CI=3.60-5.00). In the SACT group 6.7% and 14.7% of patients died within 14 days and 30 days after the last cycle, respectively. During the final 30 days of life, intensive EOL care was received by 69.9% of the SACT patients and 43.7% of the no-SACT patients (p < 0.001). Among SACT patients, sepsis, bacterial infection and/or neutropenia had a significant adverse effect on survival (HR=1.7, 95% CI=1.3-2.21, p < 0.001), whereas the use of the granulocyte colony stimulating growth factor reduced the risk of death (HR= 0.71, 95% CI=0.55-0.93, p = 0.013). Conclusions: Significant proportions of patients with advanced lung cancer continue to receive intensive care near death. Our results highlight that neutropenia and infectious complications are still the primary cause of early SACT-related death.
Acta Oncologica, Jul 9, 2019
Background: Lung cancer (LC) remains the most frequent cause of cancer death worldwide. We aimed ... more Background: Lung cancer (LC) remains the most frequent cause of cancer death worldwide. We aimed to examine long-term trends in LC survival in Estonia by age, gender, histologic type and stage, with specific focus on surgical treatment. Material and methods: Data on all incident cases of LC diagnosed from 1996 to 2016 were obtained from the Estonian Cancer Registry. Logistic regression was used to examine receipt of surgical treatment in localized LC. Relative survival ratios (RSR) were calculated, and excess hazard ratios (EHR) of death were estimated by stage with gender, age, histology and period of diagnosis as independent variables. Results: Among the total of 16,423 cases, squamous cell carcinoma remained the most common histologic type. The odds of receiving surgical treatment in localized LC increased significantly over time and were associated with age, gender and histologic type. Overall, the age-standardized 5-year RSR improved significantly from 10% in 1996-2002 to 16% in 2010-2016 (from 8% to 15% in men and from 15% to 20% in women). Larger survival gain was seen in younger patients, for non-small cell LC subtypes, and for surgically treated patients. For localized disease, the 5-year RSR increased by more than 20 percentage units, reaching 50% in men and 69% in women. For all stages, the adjusted EHR of death was significantly associated with age, histologic type and period of diagnosis. Conclusions: We observed a substantial improvement of relative survival, with considerable variations across patient groups. After adjustment for age, gender and histology, a significant survival increase over time was seen for all stages. The considerable survival gain observed for localized LC can largely be attributed to rapidly growing proportion of surgically treated patients. Further investigation of LC management practices, particularly the use of non-surgical treatment options is warranted.
Journal of Clinical Oncology, Jun 1, 2023
8520 Background: In the randomized, triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372),... more 8520 Background: In the randomized, triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372), at the second interim analysis, pembrolizumab (pembro) significantly prolonged DFS vs placebo (pbo) in the overall population of patients (pts) with completely resected stage IB–IIIA NSCLC per AJCC v7 who may or may not have received adjuvant chemotherapy (chemo; up to 4 cycles) as recommended per local guidelines (n = 1177; HR, 0.76 [95% CI, 0.63–0.91]; P = 0.0014). Here we present outcomes for those pts who received 1–4 cycles of prior adjuvant chemo, per protocol. Methods: Eligible adults had pathologically confirmed, completely resected stage IB (T ≥4 cm), II, or IIIA NSCLC (AJCC v7) of any PD-L1 expression, ECOG performance status of 0 or 1, and had not received neoadjuvant radiotherapy or chemo. Pts were randomized 1:1 to pembro 200 mg or pbo Q3W for 18 doses (~1 year); receipt of adjuvant chemo (yes vs no) was one of the stratification factors. Dual primary endpoints were DFS in the ITT and PD-L1 TPS ≥50% populations. No alpha was assigned to this subgroup analysis of pts who received adjuvant chemo for 1–4 cycles per local guidelines. Results: Of 1177 pts in the ITT population, 1010 (85.8%) received adjuvant chemo and were included in this analysis (pembro, n = 506; pbo, n = 504). Pts received a median of 17 and 18 study doses, respectively. As of data cutoff (Sep 20, 2021), 52.6% in the pembro arm vs 64.9% in the pbo arm had completed treatment. Median time from randomization to data cutoff was 37.4 mo. Median (95% CI) DFS was 58.7 mo (39.2 mo–not reached [NR]) in the pembro arm vs 34.9 mo (28.6 mo–NR) in the pbo arm (HR, 0.73 [95% CI, 0.60–0.89]). Estimated 18-mo DFS rates were 73.8% and 63.1%, respectively. In pts with PD-L1 TPS ≥50% (pembro, n = 143; pbo, n = 141), median DFS was NR in both treatment arms (HR, 0.80 [95% CI, 0.54–1.20]). Grade 3–5 adverse events (AEs) occurred in 170 pts (34.3%) in the pembro arm and 128 (25.7%) in the pbo arm (grade 5, 2.2% vs 1.0%). Immune-mediated AEs and infusion reactions occurred in 195 pts (39.3%) in the pembro arm and 69 (13.8%) in the pbo arm. Conclusions: Consistent with the ITT population, pembro substantially improved DFS vs pbo in the subgroup of pts with stage IB (T2a ≥4 cm), II, or IIIA NSCLC who received adjuvant platinum-based chemo following complete resection. Based on these results, pembro was approved for adjuvant treatment in this pt population by the US FDA. Clinical trial information: NCT02504372 .
Journal of Chromatography B, Apr 1, 2006
Thiopurine S-methyltransferase (TPMT; EC 2.1.1.67) is the key enzyme in the metabolism of thiopur... more Thiopurine S-methyltransferase (TPMT; EC 2.1.1.67) is the key enzyme in the metabolism of thiopurine drugs. Determination of TPMT activity has been used for the individualization of thiopurine dose. We developed HPLC-UV assay for the determination of TPMT activity in human erythrocytes using 6-mercaptopurine as a substrate. Various extraction and chromatographic conditions were compared. In-house developed extraction with acetonitrile provided the
Applied sciences, Oct 7, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
European Journal of Haematology, Jul 22, 2003
ATP-binding cassette (ABC) transporters play an important role in the transport of various endoge... more ATP-binding cassette (ABC) transporters play an important role in the transport of various endogenous and exogenous compounds across biologic membranes (1). In cancer cells, they are known to confer multidrug resistance through enhanced efflux of chemotherapeutics. The human multidrug resistance-associated protein 1 (MRP1) and 2 (MRP2) belong to subfamily C of the ABC transporters, and were first identified by Cole et al. (1992) (2) in human small cell lung cancer cells, and by Taniguchi et al. (1996) (3) in cisplatin-resistant human head and neck cancer cell line, respectively. Within hematopoietic cells it has been found that CD3 + cells exhibited the highest and CD19 + cells the lowest MRP1 mRNA levels (4). Protein analysis determined that CD4 + cells exhibited higher MRP1 expression than other cells. In another study, Abbaszadegan et al. (5) showed that regardless of the cell lineage, normal peripheral blood and bone marrow hematopoietic cells express similar basal levels of the MRP1 mRNA. Laupe`ze et al. (6) investigated MRP activity in normal mature leukocytes using the Oselin K, Mrozikiewicz PM, Pa¨hkla R, Roots I. Quantitative determination of the human MRP1 and MRP2 mRNA expression in FACS-sorted peripheral blood CD4 + , CD8 + , CD19 + , and CD56 + cells.
GBM Annual Fall meeting Halle 2002, Sep 1, 2002
Journal of Clinical Pharmacy and Therapeutics, Oct 1, 1999
In comparison with neighbouring Scandinavian countries, the use of digoxin in Estonia is high. Th... more In comparison with neighbouring Scandinavian countries, the use of digoxin in Estonia is high. The present study was carried out to determine the use pattern of digoxin in Estonia and bioavailability of the local market leader preparation in comparison with Lanoxin. Drug use data were evaluated from the annual reports of wholesale companies. For the bioequivalence study, a single-blind cross-over randomised two-way single-dose comparative bioavailability study was performed using 14 healthy volunteers. Digoxin concentrations in serum samples and urine were measured by chemiluminescent competitive immunoassay. The use of digoxin in Estonia has increased by 35% during the period 1994-97. The steady market leader was the local generic drug. No statistically significant differences were found in any pharmacokinetic parameter between the generic preparation and Lanoxin. All parameters showed considerable variability. The total amount of drug excreted was the parameter with lowest inter- individual variation. The present study indicates that the generic digoxin preparation studied is bioequivalent to Lanoxin. The increasing use of digoxin in Estonia is not caused by low bioavailability of the local market leader but by therapeutic traditions.
Journal of Thoracic Oncology, Mar 1, 2021