11 research outputs found
Toxic and Adverse Effects of Chemotherapy with 5-Fluoropyrimidine Drugs. Could Dihydropyrimidine Dehydrogenase Enzyme Screening Serve as a Prerequisite to Successful Chemotherapy?
No full textThe article presents a detailed survey of recent publications in the literature concerning clinical expertise, existing guidelines, and differing opinions on Fluoropyrimidine chemotherapy-related toxicity and the implication of Dihydropyrimidine dehydrogenase (DPD) screening aiming to prevent severe 5-Fluorouracil-induced adverse drug reactions. The first section provides information on the mechanism of action, clinical application, pharmacokinetics and pharmacodynamics, and toxicity and adverse reactions of 5-Fluorouracil, Capecitabine, Floxuridine, and Flucytosine.The second section summarizes DPD phenol- and genotype data and provides reasons for determining a DPD life-threatening complete or partial enzyme deficiency. The pros and cons of the methodological approaches for DPD screening are analysed, and recommendations are made to introduce them into clinical practice.The third section includes a brief economic analysis of expenses for DPD screening of patients scheduled for 5-Fluorouracil chemotherapy. The costs are compared to those related to the treatment of patients suffering from 5-Fluorouracil-induced toxicity and unwanted adverse effects
The level of dihydropyrmidine dehydrogenase and antioxidant capacity in blood plasma of patients with colorectal cancer treated with fluoropyrimidine chemotherapy
No full textЦЕЛ И ЗАДАЧИ
ЦЕЛИ:
1. Да бъде направен качествен и количествен анализ на някои неблагоприятни и благоприятни ефекти на химиотерапията с флуоропиримидинови лекарствени продукти.
2. На тази основа да бъде изследвана корелацията на тези ефекти с плазмените нива на ензима дихидропиримидин дехидрогеназа (DPD) и окислително-редукционния капацитет на пациенти с колоректален карцином, третирани в клинични условия с комплексна химиотерапия, включваща 5-флуороурацил (5-FU).
3. Да бъде разгледана икономическата целесъобразност при препоръчване за прилагане в клиниката на изследване на нивото на дихидропиримидин дехидрогеназа в кръвната плазма преди започване на химиотерапия с флуоропиримидини.
4. В този аспект да бъде обсъден алгоритъм, който би могъл да бъде приложен в онкологичната практика.
ЗАДАЧИ:
1. Да бъде подбран достатъчен брой пациенти с колоректален карцином, които са в стадий на комплексна химиотерапия съдържаща флуорпиримидини и те бъдат рекрутирани в изследванията след дадено информирано съгласие.
2. Да бъде направен пълен демографски и нозологичен анализ на създадената кохорта от рекругирани пациенти.
3. Да бъдат изследвани плазмените нива на DPD в проби от венозна кръв, взети преди започване на съответен цикъл на химиотерапия. Да бъде създадена провизорна работна скала градирана като ниско, средно и високо DPD ниво.
4. Да бъде изработен подход за разкриване на евентуална корелация между лимфоцитно / тромбоцитния статус на пациентите и установените при тях плазмени DPD нива.
5. Да бъде определен окислително-редукционния капацитет в плазмата на пациентите (тотален анти-оксидантен капацитет и фери-редукционен потенциал) чрез:
(i) спектрофотометричен анализ на ТБА-активни продукти;
(ii) хемилуминисцентен анализ на анти-радикални системи, съдържащи АФК.
6. Да бъдат верифицирани евентуално съществуващи зависимости между окислително- редукционния статус, нивото на дихидропиримидин дехидрогеназа и някои параклинични показатели при химиотерапия с 5-Fluorouracil на пациенти с колоректален карцином.
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SUMMARY. A total number of 74 male and female patients with colorectal cancer have been enrolled with informed consent in this investigation. In the first stage of this investigation a fraction of the common unwanted and therapeutic effects of fluoropyrimidine chemotherapy was precisely surveyed and qualitatively and quantitatively evaluated in in extenso analysis including thorough demography- and nosology-characterization of the whole cohort of recruited patients. In the next stage ELISA method was used to estimate the level of enzyme dihydropyrimidine dehydrogenase (DPD) in 71 samples of blood plasma collected from the recruited patients before receiving fluoropyrimidine chemotherapy. According to DPD concentrations quantified in the blood plasma four level ranges ware defined and the patients were allotted to four different DPD groups as (i) ≤ 0.15 ng / mL, (ii) 15 - 30 ng / mL, (iii) 30 ng / mL - 70 ng / mL, (iv) ≥ 70 ng /mL. In the third stage of present investigation the presence of correlation was examined between the intensity of the post-chemotherapy effects analyzed and the levels of DPD estimated in patients’ blood plasma. Data reviled that the increase of DPD concentration is inversely related to 5-Fluorouracil (5-FU) toxicity on leucocyte, lymphocyte and thrombocyte counts in peripheral blood. The results show that the higher is DPD level the less unwanted and more therapeutic effects are produced by 5-FU chemotherapy. In this series clinical and laboratory data from 70 of the recruited patients are processed. In the last stage of this investigation the plasma redox capacity was studied in blood plasma collected before and after fluoropyrimidine chemotherapy of 38 patients. Complex spectrophotometry was employed to study the total redox capacity (ABTS and FRAP methods) and lipid peroxidation (TBA-RS method). Chemiluminescence methods (generation of О 2● and ОCl-) were applied to study the changes of ROS generation induced by 5-FU chemotherapy at various plasma DPD levels. Data revealed that 5-FU treatment decreased plasma redox capacity which is inversely modulated by plasma DPD levels. Present investigation provides first data for quantification of plasma DPD concentration by ELISA assay and evaluation of plasma redox capacity in patients hospitalized for chemotherapy of colorectal cancer. The economic rationale is considered of implementing DPD evaluation as a routine test in patients recommended for fluoropyrimidine chemotherapy
Relation to social robotics from the perspective of the extended theory of planned behavior
Get PDFV okviru magistrskega dela sem proučevala odnos do socialne robotike v zvezi s pomočjo osebam v pozni odraslosti z vidika (a) razširjene teorije načrtovanega vedenja in (b) utemeljene teorije trenutno zaznanih problemov. V študiji je sodelovalo 238 udeležencev in udeleženk. Od tega je 158 udeležencev in udeleženk, ki jih lahko uvrstimo v razvojno obdobje prehoda v odraslost (študenti in študentke različnih študijskih smeri), izpolnjevalo vprašalnik v spletni obliki. Ostalih 82 udeležencev, ki jih lahko uvrstimo v razvojno obdobje pozne odraslosti (upokojenci in upokojenke), je izpolnjevalo vprašalnik v klasični, papir-svinčnik obliki. Uporabljen je bil izvorno konstruiran vprašalnik (Malovrh in Rus, 2019) z naslovom: Analiza modela razširjene teorije načrtovanega vedenja na področju socialne robotike (v zvezi s pomočjo osebam v pozni odraslosti). Pri tem je konstrukcija vprašalnika v glavnem sledila smernicam, ki jih je določil avtor teorije načrtovanega vedenja Icek Ajzen (2006 in 2013). Rezultati so pokazali, da se vsi posamično obravnavani napovedniki razširjenega modela pomembno pozitivno povezujejo z vedenjskimi ter implementacijskimi nameni. Poleg tega se je pokazala pomembna razlika v zaznanem vedenjskem nadzoru do socialne robotike glede na spol in izbrana starostna obdobja ter pomembna razlika v stališčih do socialne robotike glede na spol. Analiza odgovorov po postopku utemeljene teorije je pokazala, da udeleženci znotraj obravnavanega področja zaznavajo tehnične probleme, problem nedostopnosti robotske tehnologije, problem zavračanja tehnologije s strani starostnikov in problem \u27\u27(ne)etičnosti\u27\u27 odnosa robot-starostnik. Ugotovitve magistrske raziskave ponujajo predloge za nadaljnje praktično delo na področju socialne robotike, ki bo namenjeno uporabnikom iz obdobja pozne odraslosti.Within the framework of the master thesis, I studied the relations towards social robotics in the connection with the assistance to persons in the late adulthood from the perspective (a) of the extended theory of planned behavior and (b) the grounded theory of the problems sensed currently. In the study, there were 238 participants. There were 158 participants who could be classified in the developmental period of transition to adulthood (students of different fields of study) and who filled in the online questionnaire. The other 82 participants who could be classified in the developmental period of late adulthood (retirees) filled in the questionnaire in a classical paper-pencil form. An originally designed questionnaire was used (Malovrh and Rus, 2019). It was titled The Analysis of the Model of the Extended Theory of Planned Behavior in the Field of Social Robotics (in Connection with the Assistance to Persons in Late Adulthood). In the process, the construction of the questionnaire mainly followed the directives which were determined by the author of the theory of planned behavior Icek Ajzen (200 and 20013). The results showed that all the individually discussed predictors of the extended model connect with behavioral and implementation purposes positively and significantly. In addition, a significant difference in the sensed behavioral control towards social robotics with regards to the gender and the selected age brackets emerged, as well as a significant difference in the attitudes towards social robotics with regards to the gender. The analysis of the answers according to the procedure of the grounded theory showed that the participants within the selected field sense technical problems, the problem of inaccessibility of robotic technology, the problem of rejecting the technology by the elderly, and the problem of the “unethical” relationship a robot – the elderly. The ascertainments of the research for the master’s thesis offer the proposals for further practical work in the field of social robotics which will be intended to the users in the period of late adulthood
A new Macedonian novel about a young and growing
Get PDFIn this paper we refer to a new, in fact the latest novel by Macedonian author of children Velko Nedelkovski dedicated to young readers. What makes this book special is that it applies to young people who are at the exit from childhood and the threshold of adolescence, and the author attempted to help them on that rocky road through friendships, initial loves, nourishing love to animals, respect for elders, and all this in order to grow into healthy, strong young men, ready to face all difficulties in life
Мрачните ходници на адолесценцијата
Get PDFIn this scientific article we are talking about a contemporary adolescent novel "When the prince is late" by the Macedonian author Velko Nedelkovski. The novel is significant because it was published in 1999, at a time when Macedonian literature for adolescents began to treat some previously taboo topics more freely and openly, such as prostitution among young people, vices, murders, etc. In the article, we refer to the adolescent period and all the phenomena related to it and how the protagonists face them. All of this can help young adolescents identify with the protagonists and find the solution to their problems in books like this one
Does dihydropyrimidine dehydrogenase level modify plasma antioxidant capacity in colorectal cancer patients treated with fluoropyrimidines? 
No full textIntroduction: Colorectal cancer is the third most common cancer type worldwide. Fluoropyrimidines and their prodrug-based regimens are widely applied as primary medications. The main enzyme responsible for the rate-limiting step in pyrimidine and for the 5-fluorouracil catabolism is dihydropyrimidine dehydrogenase (DPD).Aim: We aimed to screen DPD level and the changes of plasma antioxidant capacity of colorectal cancer patients on 5-fluorouracil regimen. Materials and methods: Human DPD Elisa Kit based on sandwich enzyme-linked immune-sorbent assay and spectrophotometric methods (FRAP and ABTS) were used in the study.Results: No statistically significant changes in plasma scavenging activity according to the results obtained in the ABTS system have been observed after evaluating all patients and considering DPD concentration. A decrease of the ferric reducing ability of patients’ plasma taken after the administered treatment was found. The increase of DPD level is accompanied by a decrease in the p values and therefore the statistical significance of the differences increases.Conclusions: Based on the aforementioned observations, it could be concluded that some aspects of plasma antioxidant capacity and individuals’ antioxidant status might be involved in the pathogenesis of the disease and could be altered by the activity of some enzymes. The cancer therapy in question, by the specificity of its mechanism of action, can modify patient’s oxidative status
Gastrointestinal Cancers with Consideration of DPD and UGT1A1 Plasma Levels: Chemotherapy-Related Toxicity
No full textUnpredictable, dose-limiting toxicity remains a challenge in cancer treatment. We evaluated dihydropyrimidine dehydrogenase (DPD) and UDP-glucuronosyltransferase 1A1 (UGT1A1) plasma levels in the context of chemotherapy-induced toxicity and disease progression. Seventy gastrointestinal cancer patients (30 FOLFOX; 40 FOLFIRI) were enrolled. DPD and UGT1A1 plasma levels were determined using ELISA. Univariable and bivariable analyses and a general linear model (GLM) framework were used. Post-infusional reductions in white blood cell and granulocyte counts were observed. For FOLFOX, the granulocyte counts decreased by 17% (r = 0.54; p = 0.0030), while FOLFIRI caused a 41% reduction (r = 0.43; p = 0.0063). DPD levels were lower in FOLFOX than in FOLFIRI (2.543 vs. 3.579; p = 0.0363; Cohen’s d = 0.52). The multiple linear regression models associated DPD levels with cancer progression (b* = 0.258, p = 0.034). The bivariate analysis and multiple linear regression indicated some trends of association between UGT1A1 levels and reduction in white blood cell (b* = 0.359, p = 0.042) and granulocyte counts (b* = 0.383, p = 0.030) among FOLFIRI-treated patients. These preliminary observations suggest that DPD and UGT1A1 might contribute to evaluating response assessment
Bone health in breast cancer patients: a comprehensive statement by CECOG/SAKK Intergroup
No full textBone is the most common site of distant metastases in breast cancer that can cause severe and debilitating skeletal related events (SRE) including hypercalcemia of malignancy, pathologic fracture, spinal cord compression and the need for palliative radiation therapy or surgery to the bone. SRE are associated with substantial pain and morbidity leading to frequent hospitalization, impaired quality of life and poor prognosis. The past 25 years of research on the pathophysiology of bone metastases led to the development of highly effective treatment options to delay or prevent osseous metastases and SRE. Management of bone metastases has become an integral part of cancer treatment requiring expertise of multidisciplinary teams of medical and radiation oncologists, surgeons and radiologists in order to find an optimal treatment for each individual patient. A group of international breast cancer experts attended a Skeletal Care Academy Meeting in November 2012 in Istanbul and discussed current preventive measures and treatment options of SRE, which are summarized in this evidence-based consensus for qualified decision- making in clinical practice
RNA therapies and medicines – general overview and pharmacological challenges
Get PDFRecent advances in the science of RNA production, purification, and intracellular delivery have enabled the development of RNA therapeutics. RNA therapies represent a rapidly expanding category of medicinal products that will change the standard treatment of many diseases, redefining the concept of personalized medicine. They may have great therapeutic potential in hereditary, oncological, and neurological diseases, metabolic diseases, etc. RNA therapies may provide better opportunities to target the underlying pathophysiological mechanisms of diseases, which in turn may lead to better therapeutic results. These medications are cost-effective to develop, relatively easy to manufacture, and hold potential for many presently incurable conditions. They are rapidly gaining traction in clinical practice.In this comprehensive review, we discuss the general concepts of the different classes of RNA drugs and their pharmacological properties. Furthermore, we provide an overview of RNA drugs that have already received approval from regulatory bodies such as the FDA and EMA, shedding light on their pivotal role in modern medicine
Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study
No full textBackground Second-line treatment options for persistent, recurrent or metastatic (r/m) cervical cancer are limited. We investigated the safety, efficacy, and immunogenicity of the therapeutic DNA-based vaccine VB10.16 combined with the immune checkpoint inhibitor atezolizumab in patients with human papillomavirus (HPV)16-positive r/m cervical cancer.Patients and methods This multicenter, single-arm, phase 2a study (NCT04405349, registered 26 May 2020) enrolled adult patients with persistent, r/m HPV16-positive cervical cancer. Patients received 3 mg VB10.16 (every 3 weeks (Q3W) for 12 weeks, hereafter every 6 weeks) combined with 1,200 mg atezolizumab (Q3W) for 48 weeks in total with a 12-month follow-up. The primary endpoints were incidence and severity of adverse events (AEs) and objective response rate (ORR; Response Evaluation Criteria in Solid Tumor V.1.1). ORR was assessed in the efficacy population, being all response-evaluable patients who received any administration of VB10.16 and atezolizumab and had at least one post-baseline imaging assessment.Results Between June 16, 2020, and January 25, 2022, 52 patients received at least one administration of study treatment. Of these, 47 patients had a minimum of one post-baseline tumor assessment. The median follow-up time for survival was 11.7 months. AEs related to VB10.16 were non-serious and mainly mild injection site reactions (9 of 52 patients). There were no signs of new toxicities other than what was already described with atezolizumab. ORR was 19.1% (95% CI 9.1% to 33.3%). Median duration of response was not reached (n.r.) (95% CI 2.2 to n.r.), median progression-free survival was 4.1 months (95% CI 2.1 to 6.2), and median overall survival was 21.3 months (95% CI 8.5 to n.r.). In programmed death-ligand 1 (PD-L1)-positive patients (n=24), ORR was 29.2% (95% CI 12.6 to 51.1). HPV16-specific T-cell responses were analyzed in 36 of 47 patients with an increase observed in 22/36 (61%).Conclusions The therapeutic DNA-based vaccine VB10.16 combined with atezolizumab was safe and well tolerated showing a promising clinically meaningful efficacy with durable responses in patients with persistent, r/m HPV16-positive cervical cancer, especially if PD-L1-positive
