Hana Študentová - Academia.edu (original) (raw)

Papers by Hana Študentová

Analytical and Bioanalytical Chemistry

Therapeutic Advances in Medical Oncology, 2021

Background: Perioperative chemotherapy is a recommended treatment approach for localised oesophag... more Background: Perioperative chemotherapy is a recommended treatment approach for localised oesophago-gastric junction adenocarcinoma, but not all patients respond to neoadjuvant chemotherapy. Early identification of non-responders and treatment adaptation in the preoperative period could improve outcomes. GastroPET is a national, multicentre phase II trial evaluating a 18FDG-PET/CT-guided preoperative treatment strategy with the R0 resection rate as a primary endpoint. Here, we report on the accuracy of the methodology, the feasibility of the study design and patient safety data after enrolment of the first 63 patients. Methods: Patients with locally advanced oesophago-gastric junction adenocarcinoma (Siewert I – III) stage Ib–IIIc underwent baseline 18FDG-PET/CT scanning and re-evaluation after 14 days of oxaliplatinum-5FU-(docetaxel) chemotherapy. Responders were defined by a ⩾ 35% decrease in tumour FDG standardised uptake value (SUV)average from baseline. Responders continued with...

Expert Review of Anticancer Therapy, 2021

ABSTRACT Introduction: The dominant paradigm of sequential therapy of metastatic renal cell carci... more ABSTRACT Introduction: The dominant paradigm of sequential therapy of metastatic renal cell carcinoma (mRCC) with single agents has recently been challenged by improved outcomes obtained with combined regimens with immune checkpoint inhibitors. These combined regimens include the combination of pembrolizumab plus axitinib. Areas covered: Here, we provide a brief overview of the current clinical data on the pembrolizumab plus axitinib combination including mechanism of action, pharmacokinetics, efficacy and safety profile. Expert opinion: Both agents targeting the vascular endothelial growth factor (VEGF) pathway and immune checkpoint inhibitors are active as single agents in mRCC. Improved outcomes have been demonstrated in phase 3 trials in comparison with sunitinib for the combinations of axitinib plus pembrolizumab, axitinib plus avelumab, bevacizumab plus atezolizumab, and ipilimumab plus nivolumab. Among these combinations, an OS benefit has, so far, demonstrated only for the combinations of axitinib with pembrolizumab and ipilimumab with nivolumab. Although there are currently no prospective data comparing the combination of ipilimumab and nivolumab with the combination of immune checkpoint inhibitors and VEGF inhibitors, currently available retrospective analyses indicate that these two approaches achieve comparable outcomes.

Casopis lekaru ceskych, 2018

The tumors of the peritoneal surface, both primary and secondary, are associated with a very poor... more The tumors of the peritoneal surface, both primary and secondary, are associated with a very poor prognosis and rapid progression through conventional oncology treatment including systemic chemotherapy, targeted treatment, radiotherapy, surgery, and symptomatic treatment. Until recently, most of them were considered incurable. In the 1980s, the first cytoreductive surgery ("CRS") combined with intraperitoneal hyperthermic chemotherapy ("HIPEC") became the standard of treatment for selected tumor peritoneal tumor (pseudomyxoma peritonei and primary peritoneal malignant mesothelioma). In some cases of other peritoneal carcinomatosis associated with colorectal cancer, gastric cancer and ovarian cancer in the subgroup of well selected patients, this treatment can lead to a significant prolongation of overall survival and good standard of quality of life. This method is safe in specialized centers with an acceptable rate of morbidity and mortality comparable to foreig...

Neoplasma, 2021

The presence of wild-type RAS alleles, as determined by genotyping codons 12, 13, 59, 61, 117, an... more The presence of wild-type RAS alleles, as determined by genotyping codons 12, 13, 59, 61, 117, and 146, is a prerequisite for personalized anti-EGFR treatment of metastatic colorectal cancer (mCRC) patients. Here we describe analytical validation of in-house developed massively parallel sequencing technology (MPS) in comparison to the in vitro diagnostics (IVD) certified qPCR method. DNA extracted from FFPE samples from CRC patients (n=703) and reference standards (n=33) were tested for KRAS and NRAS mutations in 6 codons of exons 2, 3, and 4 using deep amplicon sequencing (DAS) on a MiSeq benchtop sequencer (Illumina). Two different amplicon lengths and two different library preparation methods (long-RAS and short-RAS) were tested in order to evaluate their impact on DAS performance. In parallel, identical tumor DNA was tested by the following IVD assays: therascreen KRAS RGQ PCR Kit (Qiagen), cobas® KRAS Mutation Test (Roche Diagnostics), and SNaPshot assay (Thermo Fisher Scientific). Both DAS assays detected all the mutations present in reference standards and external quality control samples, except for the artificially generated KRAS codon 146 mutation. The DAS assays performed sufficient analytical specificity and sensitivity (≥0.95). The use of shorter amplicons prolonged the preparation steps but significantly improved the sequencing success rate of FFPE-derived DNA. RAS mutation frequencies in the Czech CRC patients were similar to previous reports, although rare mutations were also detected. DAS with short amplicons is a good strategy for routine assessment of somatic mutations in low-quality FFPE-derived DNA.

Talanta, 2021

The lipidomic research is currently devoting considerable effort to the harmonization that should... more The lipidomic research is currently devoting considerable effort to the harmonization that should enable the generation of comparable and accurate quantitative lipidomic data across different laboratories and regardless of the mass spectrometry-based platform used. In the present study, we systematically investigate the effects of the experimental setup on quantitative lipidomics data obtained by two lipid class separation approaches, hydrophilic interaction liquid chromatography (HILIC) and ultrahigh-performance supercritical fluid chromatography (UHPSFC), coupled to two different quadrupoletime of flight (QTOF) mass spectrometers from the same vendor. This approach is applied for measurements of 268 human plasma samples of healthy volunteers and renal cell carcinoma patients resulting in four data sets. We investigate and visualize differences among these data sets by multivariate data analysis methods, such as principal component analysis (PCA), orthogonal partial least square discriminant analysis (OPLS-DA), box plots, and logarithmic correlations of molar concentrations of individual lipid species. The results indicate that even measurements in the same laboratory for the same samples using different analytical platforms may yield slight variations in the molar concentrations determined. The normalization to a reference sample with defined lipid concentrations can further diminish these small differences, resulting in highly homogenous molar concentrations of individual lipid species. This strategy indicates a potential approach towards the reporting of comparable quantitative results independent from the quantitative approach and mass spectrometer used, which is important for a wider acceptance of lipidomics data in various biomarker inter-laboratory studies and ring trials.

Scientific Reports, 2021

Early detection of cancer is one of the unmet needs in clinical medicine. Peripheral blood analys... more Early detection of cancer is one of the unmet needs in clinical medicine. Peripheral blood analysis is a preferred method for efficient population screening, because blood collection is well embedded in clinical practice and minimally invasive for patients. Lipids are important biomolecules, and variations in lipid concentrations can reflect pathological disorders. Lipidomic profiling of human plasma by the coupling of ultrahigh-performance supercritical fluid chromatography and mass spectrometry is investigated with the aim to distinguish patients with breast, kidney, and prostate cancers from healthy controls. The mean sensitivity, specificity, and accuracy of the lipid profiling approach were 85%, 95%, and 92% for kidney cancer; 91%, 97%, and 94% for breast cancer; and 87%, 95%, and 92% for prostate cancer. No association of statistical models with tumor stage is observed. The statistically most significant lipid species for the differentiation of cancer types studied are CE 16:0...

Expert Review of Anticancer Therapy, 2018

Introduction: Sequential administration of single targeted agents has evolved as the dominant par... more Introduction: Sequential administration of single targeted agents has evolved as the dominant paradigm in advanced RCC treatment. Lenvatinib plus everolimus is the first combination therapy in advanced RCC to show improvement in efficacy compared to monotherapy in advanced RCC while maintaining manageable toxicity profile. Areas covered: This review gives a brief overview of the contemporary clinical data on lenvatinib including its mechanism of action, pharmacokinetics, efficacy and safety profile in combination with everolimus. The clinical applications of lenvatinib in combination with everolimus are addressed within the context of the current competitive therapeutic landscape of RCC. Expert commentary: Lenvatinib is a new VEGF receptor-targeted tyrosine kinase inhibitor approved in combination with everolimus for second-line therapy in patients with advanced renal cell carcinoma progressing on a first-line VEGF receptor-targeted tyrosine kinase inhibitor. The combination of lenvatinib with everolimus significantly improved progression-free survival compared with everolimus with a hazard ratio of 0.40 and increased objective response to 43%. Optimal sequence of therapy targeting the tumor and the immune system remains a challenge and further investigation is warranted.

Analytica Chimica Acta, 2020

h i g h l i g h t s g r a p h i c a l a b s t r a c t Quality control system is developed for the... more h i g h l i g h t s g r a p h i c a l a b s t r a c t Quality control system is developed for the quality assurance of lipidomic quantitation. Lipidomic profiles are less influenced by the type of blood collection tubes than by the effect of time and collection site. Method dependent measurement bias can be compensated by the reference value normalization.

Pteridines, 2017

The aim of the present study was to investigate the association of peripheral-blood cell count (P... more The aim of the present study was to investigate the association of peripheral-blood cell count (PBC)-derived ratios, other biomarkers of inflammation and biomarkers of tumor growth with outcome in a cohort of patients presenting for the next line of therapy after the failure of prior systemic treatment. The data of 51 patients with advanced/metastatic colorectal carcinoma treated with cetuximab in the second or higher line of therapy were retrospectively analyzed. The median duration of cetuximab therapy and the median survival were 5.1 and 12.1 months, respectively. C-reactive protein (CRP), but not urinary neopterin correlated significantly with PBC-derived ratios. Both CRP and urinary neopterin correlated positively with carcinoembryonic antigen (CEA) concentrations and biomarkers of liver dysfunction. Although a number of parameters predicted overall survival in univariate analysis, only hemoglobin, CEA change and serum bilirubin were independent predictors of survival. In concl...

Pteridines, 2017

We report a patient who presented with synchronous second primary human epidermal growth factor r... more We report a patient who presented with synchronous second primary human epidermal growth factor receptor (HER)-2-positive breast cancer and rectal cancer that both required simultaneous neoadjuvant therapy. A modified regimen combining anti-HER-2 monoclonal antibody trastuzumab with chemotherapy and external beam radiation was selected. An organ-preserving surgical procedure was possible both in the breast and the rectum. Citrulline decreased rapidly after the start of the treatment, and then gradually returned to pre-treatment levels after the completion of chemoradiation. Urinary neopterin concentrations exhibited a fluctuating course. Both serum neopterin and C-reactive protein concentrations were more or less stable during the initial administration of trastuzumab, paclitaxel and carboplatin and then increased steeply during chemoradiation and subsequently declined to pre-treatment levels during the weekly trastuzumab administration. Changes were observed in the serum retinol co...

BMC cancer, Dec 21, 2017

It is well known that patient characteristics and survival outcomes in randomized trials may not ... more It is well known that patient characteristics and survival outcomes in randomized trials may not necessarily be similar to those in real-life clinical practice. The aim of the present study was to analyse second line treatment strategies in the real-world practice and to estimate the outcomes of patients treated with second-line targeted therapy for metastatic renal cell carcinoma (mRCC). This is a retrospective, registry-based study using data from the national registry of targeted therapies for mRCC. The RENIS registry contains data on 3049 patients who started the therapy with at least one targeted agent before 31 December, 2014. Of these patients, 1029 had a record of at least two different targeted therapies and sufficient data for analysis. Survival analysis was carried out using the Kaplan-Meier method. Statistical significance of differences in survival between subgroups was assessed using the log-rank test. The median overall survival from the start of second-line treatment...

Anticancer research, 2018

Pazopanib is approved for the first-line treatment of patients with metastatic renal cell carcino... more Pazopanib is approved for the first-line treatment of patients with metastatic renal cell carcinoma (mRCC). The present study was a retrospective registry-based analysis of 426 patients with mRCC treated with pazopanib as first-line targeted therapy. The data were obtained from the Renal Cell Carcinoma Information system registry. Patient baseline parameters, treatment course and outcomes, and toxicity were analysed. Median progression-free and overall survival were 12.9 (95% confidence interval(CI)=11.0-14.8) months and 33.2 (95% CI=29.9-36.4) months, respectively. Overall response rate and disease control rate were 25.1% and 57.4%, respectively. Adverse events led to discontinuation of treatment in 37 (12.1%) patients. The results confirm that pazopanib is an effective and safe first-line targeted treatment in patients with mRCC. Both the International mRCC Database Consortium and the Memorial Sloan Kettering models were valid predictors of prognosis and nephrectomy was associated...

Clinical Genitourinary Cancer, 2017

Outcomes of patients with long-term treatment response to vascular endothelial growth factortarge... more Outcomes of patients with long-term treatment response to vascular endothelial growth factortargeted therapy for metastatic renal cell cancer

Pteridines, 2016

Peritoneal mesothelioma is a rare tumor typically presenting with ascites and associated with occ... more Peritoneal mesothelioma is a rare tumor typically presenting with ascites and associated with occupational asbestos exposure with a latency period of 20–40 years. Intensive multi-modality approach combining cytoreductive surgery, intraperitoneal chemotherapy and possibly radiotherapy can be considered, but otherwise the prognosis is rather poor. Palliative chemotherapy may be an option in these rare cases. However, no approved systemic treatment exists for peritoneal mesothelioma. We present here a patient with peritoneal mesothelioma who was treated with the combination of pemetrexed with cisplatin shortly after the failure of hyperthermic intraperitoneal chemotherapy. The patient experienced durable partial response to the treatment, resolution of ascites, and returned to his normal daily life activities. With the exception of palliative chemotherapy in case of patients in good condition, therapeutic options in patients with peritoneal mesothelioma are currently very limited. The ...

Oncology Letters, 2015

The aim of the present study was to examine the changes in intima-media thickness (IMT) and myoca... more The aim of the present study was to examine the changes in intima-media thickness (IMT) and myocardial perfusion in association with other laboratory risk factors for atherosclerosis in patients treated with therapy that targeted vascular endothelial growth factor (VEGF). IMT, myocardial perfusion and laboratory risk factors of atherosclerosis were studied in 58 patients with metastatic colorectal carcinoma or metastatic renal cell carcinoma prior to and at 3-monthly intervals during anti-VEGF treatment. Compared with the pretreatment IMT, the results indicated that the IMT was consistently increased during therapy in the two patient groups. Patient blood pressure and concentration of troponin T increased transiently. An increase in the concentration of high-density lipoprotein cholesterol and decrease in the concentrations of C-reactive protein and homocysteine were also observed. Novel myocardial ischemia was evident in individual patients. In conclusion, anti-VEGF therapy affects the laboratory risk factors of atherosclerosis and results in an acceleration of atherosclerosis, as demonstrated by increased IMT.

Pteridines, 2015

The aim of the present study was to evaluate the correlations of peripheral blood cell count (PBC... more The aim of the present study was to evaluate the correlations of peripheral blood cell count (PBC)-derived ratios with neopterin concentration and biomarkers of atherosclerosis risk in patients with history of breast cancer. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) were calculated in three cohorts of patients with a history of breast cancer and in controls. Significant differences were observed between PBC-derived ratios obtained from automated and manual counts. NLR and PLR were significantly higher and LMR was significantly lower in patients. NLR and PLR correlated positively with each other and negatively with LMR. NLR exhibited a significant correlation with age, glucose and C-reactive protein (CRP) concentrations, whereas LMR correlated negatively with CRP. With the exception of a correlation between LMR and urinary or serum neopterin concentrations in controls, no other correlation between neopterin concent...

Immunotherapy, 2014

Tumors in about 15% of patients with breast cancer overexpress HER2. Trastuzumab (Herceptin(®); F... more Tumors in about 15% of patients with breast cancer overexpress HER2. Trastuzumab (Herceptin(®); F. Hoffmann-La Roche, Basel, Switzerland) is a humanized monoclonal antibody against HER2. While the introduction of trastuzumab has changed the natural course of HER2-positive breast cancer, the need for repeated administration of the drug over a prolonged period of time represents a challenge. Similarly to other chronic disorders, subcutaneous administration of monoclonal antibodies may be of advantage in this setting. The results of a prospective randomized Phase III study have demonstrated that subcutaneous trastuzumab is noninferior compared with the intravenous administration of the drug in terms of efficacy (assessed as pathological complete response rate) as well as in pharmacokinetic parameters. Moreover, another prospective randomized study showed that an overwhelming majority of patients prefer subcutaneous over intravenous trastuzumab. The advent of subcutaneous trastuzumab re...

In vivo (Athens, Greece)

Increased concentrations of neopterin, a biomarker of systemic immune response, have been reporte... more Increased concentrations of neopterin, a biomarker of systemic immune response, have been reported after administration of cytokines, cytotoxic chemotherapy or external-beam radiation, but little is known about the effects of targeted-agents on neopterin. Urinary neopterin was studied in pre-treated patients with metastatic colorectal carcinoma during therapy with cetuximab, administered mostly in combination with irinotecan, 5-fluorouracil and leucovorin. Urinary neopterin was determined by high-performance liquid chromatography. High initial urinary neopterin concentrations predicted poor prognosis. A significant correlation was observed between urinary neopterin and peripheral blood leukocyte count, hemoglobin and carcinoembryonic antigen concentrations. Urinary neopterin concentrations significantly increased during therapy only in patients with initially low neopterin concentrations. Urinary neopterin concentrations predict prognosis in patients with metastatic colorectal carci...

Pteridines, 2009

Increased serum or urinary concentrations of neopterin have been described in patients with tumor... more Increased serum or urinary concentrations of neopterin have been described in patients with tumors of different primary locations, but reports on neopterin in patients with melanoma are scanty. We have studied serum neopterin and a melanoma marker, S-100-beta, in 41 patients with melanoma. Serum neopterin and S-100-beta were determined by immunoassay. Neopterin concentrations were significantly increased compared to controls only in patients with active disease, but not in patients without evidence of disease activity. Serum neopterin and S-100-beta in patients with active disease were higher than in patients without evidence of disease activity. In patients a significant correlation existed between neopterin and S-100-beta (rs = 0.33, p <0.05), and, in patients without active disease, there was also a correlation between neopterin and age (rs = 0.51, p <0.01). In conclusion, increased serum neopterin in patients reflects disease activity. A significant correlation was observe...

Analytical and Bioanalytical Chemistry

Therapeutic Advances in Medical Oncology, 2021

Background: Perioperative chemotherapy is a recommended treatment approach for localised oesophag... more Background: Perioperative chemotherapy is a recommended treatment approach for localised oesophago-gastric junction adenocarcinoma, but not all patients respond to neoadjuvant chemotherapy. Early identification of non-responders and treatment adaptation in the preoperative period could improve outcomes. GastroPET is a national, multicentre phase II trial evaluating a 18FDG-PET/CT-guided preoperative treatment strategy with the R0 resection rate as a primary endpoint. Here, we report on the accuracy of the methodology, the feasibility of the study design and patient safety data after enrolment of the first 63 patients. Methods: Patients with locally advanced oesophago-gastric junction adenocarcinoma (Siewert I – III) stage Ib–IIIc underwent baseline 18FDG-PET/CT scanning and re-evaluation after 14 days of oxaliplatinum-5FU-(docetaxel) chemotherapy. Responders were defined by a ⩾ 35% decrease in tumour FDG standardised uptake value (SUV)average from baseline. Responders continued with...

Expert Review of Anticancer Therapy, 2021

ABSTRACT Introduction: The dominant paradigm of sequential therapy of metastatic renal cell carci... more ABSTRACT Introduction: The dominant paradigm of sequential therapy of metastatic renal cell carcinoma (mRCC) with single agents has recently been challenged by improved outcomes obtained with combined regimens with immune checkpoint inhibitors. These combined regimens include the combination of pembrolizumab plus axitinib. Areas covered: Here, we provide a brief overview of the current clinical data on the pembrolizumab plus axitinib combination including mechanism of action, pharmacokinetics, efficacy and safety profile. Expert opinion: Both agents targeting the vascular endothelial growth factor (VEGF) pathway and immune checkpoint inhibitors are active as single agents in mRCC. Improved outcomes have been demonstrated in phase 3 trials in comparison with sunitinib for the combinations of axitinib plus pembrolizumab, axitinib plus avelumab, bevacizumab plus atezolizumab, and ipilimumab plus nivolumab. Among these combinations, an OS benefit has, so far, demonstrated only for the combinations of axitinib with pembrolizumab and ipilimumab with nivolumab. Although there are currently no prospective data comparing the combination of ipilimumab and nivolumab with the combination of immune checkpoint inhibitors and VEGF inhibitors, currently available retrospective analyses indicate that these two approaches achieve comparable outcomes.

Casopis lekaru ceskych, 2018

The tumors of the peritoneal surface, both primary and secondary, are associated with a very poor... more The tumors of the peritoneal surface, both primary and secondary, are associated with a very poor prognosis and rapid progression through conventional oncology treatment including systemic chemotherapy, targeted treatment, radiotherapy, surgery, and symptomatic treatment. Until recently, most of them were considered incurable. In the 1980s, the first cytoreductive surgery ("CRS") combined with intraperitoneal hyperthermic chemotherapy ("HIPEC") became the standard of treatment for selected tumor peritoneal tumor (pseudomyxoma peritonei and primary peritoneal malignant mesothelioma). In some cases of other peritoneal carcinomatosis associated with colorectal cancer, gastric cancer and ovarian cancer in the subgroup of well selected patients, this treatment can lead to a significant prolongation of overall survival and good standard of quality of life. This method is safe in specialized centers with an acceptable rate of morbidity and mortality comparable to foreig...

Neoplasma, 2021

The presence of wild-type RAS alleles, as determined by genotyping codons 12, 13, 59, 61, 117, an... more The presence of wild-type RAS alleles, as determined by genotyping codons 12, 13, 59, 61, 117, and 146, is a prerequisite for personalized anti-EGFR treatment of metastatic colorectal cancer (mCRC) patients. Here we describe analytical validation of in-house developed massively parallel sequencing technology (MPS) in comparison to the in vitro diagnostics (IVD) certified qPCR method. DNA extracted from FFPE samples from CRC patients (n=703) and reference standards (n=33) were tested for KRAS and NRAS mutations in 6 codons of exons 2, 3, and 4 using deep amplicon sequencing (DAS) on a MiSeq benchtop sequencer (Illumina). Two different amplicon lengths and two different library preparation methods (long-RAS and short-RAS) were tested in order to evaluate their impact on DAS performance. In parallel, identical tumor DNA was tested by the following IVD assays: therascreen KRAS RGQ PCR Kit (Qiagen), cobas® KRAS Mutation Test (Roche Diagnostics), and SNaPshot assay (Thermo Fisher Scientific). Both DAS assays detected all the mutations present in reference standards and external quality control samples, except for the artificially generated KRAS codon 146 mutation. The DAS assays performed sufficient analytical specificity and sensitivity (≥0.95). The use of shorter amplicons prolonged the preparation steps but significantly improved the sequencing success rate of FFPE-derived DNA. RAS mutation frequencies in the Czech CRC patients were similar to previous reports, although rare mutations were also detected. DAS with short amplicons is a good strategy for routine assessment of somatic mutations in low-quality FFPE-derived DNA.

Talanta, 2021

The lipidomic research is currently devoting considerable effort to the harmonization that should... more The lipidomic research is currently devoting considerable effort to the harmonization that should enable the generation of comparable and accurate quantitative lipidomic data across different laboratories and regardless of the mass spectrometry-based platform used. In the present study, we systematically investigate the effects of the experimental setup on quantitative lipidomics data obtained by two lipid class separation approaches, hydrophilic interaction liquid chromatography (HILIC) and ultrahigh-performance supercritical fluid chromatography (UHPSFC), coupled to two different quadrupoletime of flight (QTOF) mass spectrometers from the same vendor. This approach is applied for measurements of 268 human plasma samples of healthy volunteers and renal cell carcinoma patients resulting in four data sets. We investigate and visualize differences among these data sets by multivariate data analysis methods, such as principal component analysis (PCA), orthogonal partial least square discriminant analysis (OPLS-DA), box plots, and logarithmic correlations of molar concentrations of individual lipid species. The results indicate that even measurements in the same laboratory for the same samples using different analytical platforms may yield slight variations in the molar concentrations determined. The normalization to a reference sample with defined lipid concentrations can further diminish these small differences, resulting in highly homogenous molar concentrations of individual lipid species. This strategy indicates a potential approach towards the reporting of comparable quantitative results independent from the quantitative approach and mass spectrometer used, which is important for a wider acceptance of lipidomics data in various biomarker inter-laboratory studies and ring trials.

Scientific Reports, 2021

Early detection of cancer is one of the unmet needs in clinical medicine. Peripheral blood analys... more Early detection of cancer is one of the unmet needs in clinical medicine. Peripheral blood analysis is a preferred method for efficient population screening, because blood collection is well embedded in clinical practice and minimally invasive for patients. Lipids are important biomolecules, and variations in lipid concentrations can reflect pathological disorders. Lipidomic profiling of human plasma by the coupling of ultrahigh-performance supercritical fluid chromatography and mass spectrometry is investigated with the aim to distinguish patients with breast, kidney, and prostate cancers from healthy controls. The mean sensitivity, specificity, and accuracy of the lipid profiling approach were 85%, 95%, and 92% for kidney cancer; 91%, 97%, and 94% for breast cancer; and 87%, 95%, and 92% for prostate cancer. No association of statistical models with tumor stage is observed. The statistically most significant lipid species for the differentiation of cancer types studied are CE 16:0...

Expert Review of Anticancer Therapy, 2018

Introduction: Sequential administration of single targeted agents has evolved as the dominant par... more Introduction: Sequential administration of single targeted agents has evolved as the dominant paradigm in advanced RCC treatment. Lenvatinib plus everolimus is the first combination therapy in advanced RCC to show improvement in efficacy compared to monotherapy in advanced RCC while maintaining manageable toxicity profile. Areas covered: This review gives a brief overview of the contemporary clinical data on lenvatinib including its mechanism of action, pharmacokinetics, efficacy and safety profile in combination with everolimus. The clinical applications of lenvatinib in combination with everolimus are addressed within the context of the current competitive therapeutic landscape of RCC. Expert commentary: Lenvatinib is a new VEGF receptor-targeted tyrosine kinase inhibitor approved in combination with everolimus for second-line therapy in patients with advanced renal cell carcinoma progressing on a first-line VEGF receptor-targeted tyrosine kinase inhibitor. The combination of lenvatinib with everolimus significantly improved progression-free survival compared with everolimus with a hazard ratio of 0.40 and increased objective response to 43%. Optimal sequence of therapy targeting the tumor and the immune system remains a challenge and further investigation is warranted.

Analytica Chimica Acta, 2020

h i g h l i g h t s g r a p h i c a l a b s t r a c t Quality control system is developed for the... more h i g h l i g h t s g r a p h i c a l a b s t r a c t Quality control system is developed for the quality assurance of lipidomic quantitation. Lipidomic profiles are less influenced by the type of blood collection tubes than by the effect of time and collection site. Method dependent measurement bias can be compensated by the reference value normalization.

Pteridines, 2017

The aim of the present study was to investigate the association of peripheral-blood cell count (P... more The aim of the present study was to investigate the association of peripheral-blood cell count (PBC)-derived ratios, other biomarkers of inflammation and biomarkers of tumor growth with outcome in a cohort of patients presenting for the next line of therapy after the failure of prior systemic treatment. The data of 51 patients with advanced/metastatic colorectal carcinoma treated with cetuximab in the second or higher line of therapy were retrospectively analyzed. The median duration of cetuximab therapy and the median survival were 5.1 and 12.1 months, respectively. C-reactive protein (CRP), but not urinary neopterin correlated significantly with PBC-derived ratios. Both CRP and urinary neopterin correlated positively with carcinoembryonic antigen (CEA) concentrations and biomarkers of liver dysfunction. Although a number of parameters predicted overall survival in univariate analysis, only hemoglobin, CEA change and serum bilirubin were independent predictors of survival. In concl...

Pteridines, 2017

We report a patient who presented with synchronous second primary human epidermal growth factor r... more We report a patient who presented with synchronous second primary human epidermal growth factor receptor (HER)-2-positive breast cancer and rectal cancer that both required simultaneous neoadjuvant therapy. A modified regimen combining anti-HER-2 monoclonal antibody trastuzumab with chemotherapy and external beam radiation was selected. An organ-preserving surgical procedure was possible both in the breast and the rectum. Citrulline decreased rapidly after the start of the treatment, and then gradually returned to pre-treatment levels after the completion of chemoradiation. Urinary neopterin concentrations exhibited a fluctuating course. Both serum neopterin and C-reactive protein concentrations were more or less stable during the initial administration of trastuzumab, paclitaxel and carboplatin and then increased steeply during chemoradiation and subsequently declined to pre-treatment levels during the weekly trastuzumab administration. Changes were observed in the serum retinol co...

BMC cancer, Dec 21, 2017

It is well known that patient characteristics and survival outcomes in randomized trials may not ... more It is well known that patient characteristics and survival outcomes in randomized trials may not necessarily be similar to those in real-life clinical practice. The aim of the present study was to analyse second line treatment strategies in the real-world practice and to estimate the outcomes of patients treated with second-line targeted therapy for metastatic renal cell carcinoma (mRCC). This is a retrospective, registry-based study using data from the national registry of targeted therapies for mRCC. The RENIS registry contains data on 3049 patients who started the therapy with at least one targeted agent before 31 December, 2014. Of these patients, 1029 had a record of at least two different targeted therapies and sufficient data for analysis. Survival analysis was carried out using the Kaplan-Meier method. Statistical significance of differences in survival between subgroups was assessed using the log-rank test. The median overall survival from the start of second-line treatment...

Anticancer research, 2018

Pazopanib is approved for the first-line treatment of patients with metastatic renal cell carcino... more Pazopanib is approved for the first-line treatment of patients with metastatic renal cell carcinoma (mRCC). The present study was a retrospective registry-based analysis of 426 patients with mRCC treated with pazopanib as first-line targeted therapy. The data were obtained from the Renal Cell Carcinoma Information system registry. Patient baseline parameters, treatment course and outcomes, and toxicity were analysed. Median progression-free and overall survival were 12.9 (95% confidence interval(CI)=11.0-14.8) months and 33.2 (95% CI=29.9-36.4) months, respectively. Overall response rate and disease control rate were 25.1% and 57.4%, respectively. Adverse events led to discontinuation of treatment in 37 (12.1%) patients. The results confirm that pazopanib is an effective and safe first-line targeted treatment in patients with mRCC. Both the International mRCC Database Consortium and the Memorial Sloan Kettering models were valid predictors of prognosis and nephrectomy was associated...

Clinical Genitourinary Cancer, 2017

Outcomes of patients with long-term treatment response to vascular endothelial growth factortarge... more Outcomes of patients with long-term treatment response to vascular endothelial growth factortargeted therapy for metastatic renal cell cancer

Pteridines, 2016

Peritoneal mesothelioma is a rare tumor typically presenting with ascites and associated with occ... more Peritoneal mesothelioma is a rare tumor typically presenting with ascites and associated with occupational asbestos exposure with a latency period of 20–40 years. Intensive multi-modality approach combining cytoreductive surgery, intraperitoneal chemotherapy and possibly radiotherapy can be considered, but otherwise the prognosis is rather poor. Palliative chemotherapy may be an option in these rare cases. However, no approved systemic treatment exists for peritoneal mesothelioma. We present here a patient with peritoneal mesothelioma who was treated with the combination of pemetrexed with cisplatin shortly after the failure of hyperthermic intraperitoneal chemotherapy. The patient experienced durable partial response to the treatment, resolution of ascites, and returned to his normal daily life activities. With the exception of palliative chemotherapy in case of patients in good condition, therapeutic options in patients with peritoneal mesothelioma are currently very limited. The ...

Oncology Letters, 2015

The aim of the present study was to examine the changes in intima-media thickness (IMT) and myoca... more The aim of the present study was to examine the changes in intima-media thickness (IMT) and myocardial perfusion in association with other laboratory risk factors for atherosclerosis in patients treated with therapy that targeted vascular endothelial growth factor (VEGF). IMT, myocardial perfusion and laboratory risk factors of atherosclerosis were studied in 58 patients with metastatic colorectal carcinoma or metastatic renal cell carcinoma prior to and at 3-monthly intervals during anti-VEGF treatment. Compared with the pretreatment IMT, the results indicated that the IMT was consistently increased during therapy in the two patient groups. Patient blood pressure and concentration of troponin T increased transiently. An increase in the concentration of high-density lipoprotein cholesterol and decrease in the concentrations of C-reactive protein and homocysteine were also observed. Novel myocardial ischemia was evident in individual patients. In conclusion, anti-VEGF therapy affects the laboratory risk factors of atherosclerosis and results in an acceleration of atherosclerosis, as demonstrated by increased IMT.

Pteridines, 2015

The aim of the present study was to evaluate the correlations of peripheral blood cell count (PBC... more The aim of the present study was to evaluate the correlations of peripheral blood cell count (PBC)-derived ratios with neopterin concentration and biomarkers of atherosclerosis risk in patients with history of breast cancer. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) were calculated in three cohorts of patients with a history of breast cancer and in controls. Significant differences were observed between PBC-derived ratios obtained from automated and manual counts. NLR and PLR were significantly higher and LMR was significantly lower in patients. NLR and PLR correlated positively with each other and negatively with LMR. NLR exhibited a significant correlation with age, glucose and C-reactive protein (CRP) concentrations, whereas LMR correlated negatively with CRP. With the exception of a correlation between LMR and urinary or serum neopterin concentrations in controls, no other correlation between neopterin concent...

Immunotherapy, 2014

Tumors in about 15% of patients with breast cancer overexpress HER2. Trastuzumab (Herceptin(®); F... more Tumors in about 15% of patients with breast cancer overexpress HER2. Trastuzumab (Herceptin(®); F. Hoffmann-La Roche, Basel, Switzerland) is a humanized monoclonal antibody against HER2. While the introduction of trastuzumab has changed the natural course of HER2-positive breast cancer, the need for repeated administration of the drug over a prolonged period of time represents a challenge. Similarly to other chronic disorders, subcutaneous administration of monoclonal antibodies may be of advantage in this setting. The results of a prospective randomized Phase III study have demonstrated that subcutaneous trastuzumab is noninferior compared with the intravenous administration of the drug in terms of efficacy (assessed as pathological complete response rate) as well as in pharmacokinetic parameters. Moreover, another prospective randomized study showed that an overwhelming majority of patients prefer subcutaneous over intravenous trastuzumab. The advent of subcutaneous trastuzumab re...

In vivo (Athens, Greece)

Increased concentrations of neopterin, a biomarker of systemic immune response, have been reporte... more Increased concentrations of neopterin, a biomarker of systemic immune response, have been reported after administration of cytokines, cytotoxic chemotherapy or external-beam radiation, but little is known about the effects of targeted-agents on neopterin. Urinary neopterin was studied in pre-treated patients with metastatic colorectal carcinoma during therapy with cetuximab, administered mostly in combination with irinotecan, 5-fluorouracil and leucovorin. Urinary neopterin was determined by high-performance liquid chromatography. High initial urinary neopterin concentrations predicted poor prognosis. A significant correlation was observed between urinary neopterin and peripheral blood leukocyte count, hemoglobin and carcinoembryonic antigen concentrations. Urinary neopterin concentrations significantly increased during therapy only in patients with initially low neopterin concentrations. Urinary neopterin concentrations predict prognosis in patients with metastatic colorectal carci...

Pteridines, 2009

Increased serum or urinary concentrations of neopterin have been described in patients with tumor... more Increased serum or urinary concentrations of neopterin have been described in patients with tumors of different primary locations, but reports on neopterin in patients with melanoma are scanty. We have studied serum neopterin and a melanoma marker, S-100-beta, in 41 patients with melanoma. Serum neopterin and S-100-beta were determined by immunoassay. Neopterin concentrations were significantly increased compared to controls only in patients with active disease, but not in patients without evidence of disease activity. Serum neopterin and S-100-beta in patients with active disease were higher than in patients without evidence of disease activity. In patients a significant correlation existed between neopterin and S-100-beta (rs = 0.33, p <0.05), and, in patients without active disease, there was also a correlation between neopterin and age (rs = 0.51, p <0.01). In conclusion, increased serum neopterin in patients reflects disease activity. A significant correlation was observe...