Anastrozole as aromatase inhibitor – new approaches to breast cancer treatment in postmenopausal women

Introduction. Anastrozole is a chemotherapeutic drug used to treat breast cancer in postmenopausal women. The condition for success of this type of treatment is the presence of estrogen receptors in cancer cells. Anastrozole belongs to strong-acting, nonsteroidal inhibitors of aromatase, which is responsible for androgen-estrogen conversion process. The metabolism of this drug is based on biotransformation both in phase I and II. Initially it metabolizes in the liver with cytochrome P450 isoenzymes, followed by a glucuronidation reaction catalyzed by the UGT1A4 enzyme.Material and method. In order to minimize the side effects, new therapeutic approaches are sought to increase the success of the therapy.Conclusions. Biodegradable nano-tools that deliver anastrozole to the target site with an increase in its half-life to 144 hours are a promising method. A similar effect can be achieved by using a transdermal anastrozole administration system, which is a completely non-invasive method of treatment

Anastrozol jako inhibitor aromatazy – nowe podejścia w terapii raka piersi u kobiet w wieku pomenopauzalnym

Wstęp. Anastrozol jest chemoterapeutykiem stosowanym w leczeniu nowotworów piersi u kobiet po menopauzie. Warunkiem powodzenia tego typu leczenia jest obecność receptorów estrogenowych w komórkach nowotworowych. Anastrozol należy do silnych, niesteroidowych inhibitorów aromatazy, która jest odpowiedzialna za proces konwersji androgenów w estrogeny. Metabolizm tego leku oparty jest na biotransformacji zarówno w fazie I, jak i II. Początkowo ulega metabolizmowi w wątrobie z udziałem izoenzymów cytochromu P450, po czym następuje reakcja glukuronidacji katalizowana przez enzym UGT1A4.Materiał i metoda. Aby zminimalizować występujące skutki uboczne, poszukuje się nowych podejść terapeutycznych zwiększających powodzenie terapii.Wnioski. Obiecującą metodę stanowią biodegradowalne nanonarzędzia, dostarczające anastrozol do miejsca docelowego, ze zwiększeniem jego okresu półtrwania do 144 godzin. Podobny efekt można uzyskać, stosując transdermalny system podawania anastrozolu, który stanowi całkowicie bezinwazyjną metodę leczenia

Polyphenon E enhances the antitumor immune response in neuroblastoma by inactivating myeloid suppressor cells

This is the author's accepted manuscript. The final published article is available from the link below. Note: In this manuscript as well as in the original published version of this article the word "Polyphenon" was incorrectly spelled in the title as "Polyphenol."Purpose: Neuroblastoma is a rare childhood cancer whose high risk, metastatic form has a dismal outcome in spite of aggressive therapeutic interventions. The toxicity of drug treatments is a major problem in this pediatric setting. In this study, we investigated whether Polyphenon E, a clinical grade mixture of green tea catechins under evaluation in multiple clinical cancer trials run by the National Cancer Institute (Bethesda, MD), has anticancer activity in mouse models of neuroblastoma. Experimental Design: We used three neuroblastoma models: (i) transgenic TH-MYCN mouse developing spontaneous neuroblastomas; (ii) nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenotransplanted with human SHSY5Y cells; and (iii) A/J mice transplanted with syngeneic Neuro 2A cells. Mice were randomized in control and Polyphenon E–drinking groups. Blood from patients with neuroblastoma and normal controls was used to assess the phenotype and function of myeloid cells. Results: Polyphenon E reduced the number of tumor-infiltrating myeloid cells, and inhibited the development of spontaneous neuroblastomas in TH-MYCN transgenic mice. In therapeutic models of neuroblastoma in A/J, but not in immunodeficient NOD/SCID mice, Polyphenon E inhibited tumor growth by acting on myeloid-derived suppressor cells (MDSC) and CD8 T cells. In vitro, Polyphenon E impaired the development and motility of MDSCs and promoted differentiation to more neutrophilic forms through the 67 kDa laminin receptor signaling and induction of granulocyte colony-stimulating factor. The proliferation of T cells infiltrating a patient metastasis was reactivated by Polyphenon E. Conclusions: These findings suggest that the neuroblastoma-promoting activity of MDSCs can be manipulated pharmacologically in vivo and that green tea catechins operate, at least in part, through this mechanism.SPARKS, Research in Childhood Cancer, the CGD Research Trust, and the Wellcome Trust

Evaluation of the oral cavity state and Candida occurence in generally healthy Polish and foreign dental students

Aim of the study. This study aimed at comparing the oral cavity condition and Candida prevalence in generally healthy Polish and foreign dentistry students and evaluating the relationship between Candida occurrence and the oral cavity condition. Material and methods. 79 dentistry students with no systemic diseases, aged 20–25 (mean 23.5), were examined in the present study. Two groups of examined subjects were specified: 43 Polish students (group I) and 36 foreign students (group II). Group II has been divided into subgroups: IIa – students from Taiwan and IIb – students from Europe and USA. Occurence of oral mucosa lesions, periodontal treatment needs (CPITN), caries prevalence (DMFT) and oral hygiene (OHIs) were investigated. Evaluation of Candida occurrence on the oral mucosa was included in the study. Results. Comparison of the oral cavity condition in Polish and foreign students showed no significant difference, with the exception of the number of teeth with active caries, that was significantly higher in foreign students (D 1,2) than in Polish students (D 0.4). Mean indices rates in the group I were: CPITN 0.9; PUWz 8.7; OHI-s 0.4 in the group II 1.0; 7.0; 0,5, respectively. The most commonly observed oral mucosa lesions, in both groups, were white coated tongue and buccal white line. Candida was found in 38,0% of the subjects, its prevalence was similar in both groups (I – 34.9%, II – 41.7%). No correlation between Candida occurence and oral cavity state was detected. Higher frequency of active caries in Candida carriers was the exception

A study on the spatial and temporal variability in airborne Betula pollen concentration in five cities in Poland using multivariate analyses

During the spring period, Betula pollen is the main cause of inhalant allergies in Poland and therefore it is impor- tant to monitor and forecast airborne pollen concentrations of this taxon. This study conducted a comparative analysis of the basic characteristics of Betula pollen seasons at the regional scale. The study was carried out from 2001 to 2016 in fi ve cities in Poland: Lublin, Warsaw, Cracow, Sosnowiec, and Szczecin. To fi nd the attri- butes of birch pollen seasons that mostly differentiated the individual cities, a general discriminant analysis (GDA) was performed, while a principal component analysis (PCA) allowed us to reduce the data space and pres- ent a scatterplot of PCA scores in order to compare pollen seasons in the individual cities. The contingency table was also analyzed to check whether there was a signi fi cant relationship between pollen counts in the studied years and cities. At most of the sites, biennial cycles of low and high pollen concentrations can be observed. Due to the high variation in seasons in each of these cities, two data groups were distinguished: Group 1 was composed of seasons with high pollen deposition (2001, 2003, 2006, 2008, 2010, 2012, 2014, 2016), and Group 2 comprising the other seasons. Multivariate analyses were performed on both these groups as well as in the entire dataset. End98, Peak Value, and Annual Total had the highest discriminant power. In Group 1, Warsaw and Sosnowiec differed the most in the investigated parameters, while Cracow and Szczecin differed the least. In both groups, most seasons with the highest pollen birch concentration were observed in Lublin, followed by Warsaw, while in Cracow, the number of such seasons was the smallest

The analysis of hazel pollen count in selected Polish cities in 2008

Praca przedstawia przebieg sezonu pylenia leszczyny w wybranych punktach pomiarowych w Polsce w 2008 r. Pomiary wykonywano we Wrocławiu, w Krakowie, Warszawie, Sosnowcu, Szczecinie, Lublinie, Olsztynie i Bydgoszczy. Badania prowadzono metodą objętościową z wykorzystaniem aparatów firmy Burkard i Lanzoni. Sezon pyłkowy wyznaczono jako okres, w którym w powietrzu występuje 95% rocznej sumy ziaren pyłku leszczyny. Pylenie leszczyny w 2008 roku rozpoczęło się około 10 dni później niż w 2007 roku. Najwcześniej pyłek leszczyny zarejestrowano we Wrocławiu i Szczecinie (21 i 22 stycznia), a najpóźniej w Lublinie (4 lutego). Najwyższe wartości średniodobowych stężeń pyłku leszczyny odnotowano w Sosnowcu, gdzie 23 lutego zanotowano stężenie 115 z/m3 powietrza.This paper presents the course of hazel pollination season in selected cities of Poland in 2008. The measurements were performed in Wrocław, Kraków, Lublin, Warszawa, Sosnowiec, Szczecin, Olsztyn and Bydgoszcz. Volumetric method with the use of Volumetric Spore Trap (Burkard, Lanzoni) was implemented. Pollen season was defined as the period in which 95% of the total annual catch occurred. Pollen season of hazel in 2008 started about 10 days later in comparison to 2007. The season started first in Wrocław and Szczecin (21, 22 January). The highest 24-hour average pollen count was recorded in Sosnowiec on 23 February (115 hazel pollen grains/1m3)

The analysis of birch pollen count in selected Polish cities in 2009

W pracy porównano przebieg sezonu pyłkowego brzozy w Polsce w 2009 roku. Pomiary koncentracji pyłku w powietrzu wykonano w Białymstoku, Bydgoszczy, Krakowie, Lublinie, Olsztynie, Sosnowcu, Szczecinie, Warszawie i we Wrocławiu. Badania wykonano przy zastosowaniu metody objętościowej i aparatów firmy Burkard i Lanzoni. Długość sezonu pyłkowego wyznaczono metodą 98%. Wykazano, że sezon pyłkowy brzozy rozpoczął się w 2009 roku w pierwszej dekadzie kwietnia, podobnie jak w latach 2007 i 2008. Stwierdzono duże różnice w długości sezonu pyłkowego między miastami oraz w dobowych stężeniach ziaren pyłku. Najwyższe dobowe stężenia ziaren pyłku brzozy zanotowano we Wrocławiu (1317 z/m3) i w Szczecinie (1166 z/m3). We wszystkich miastach zarejestrowano dużą liczbę dni ze stężeniem przekraczającym stężenie progowe dla brzozy (17–29 dni).In the present study, birch pollen season patterns in Poland in 2009 have been compared. Airborne pollen counts were made in Białystok, Bydgoszcz, Kraków, Lublin, Olsztyn, Sosnowiec, Szczecin, Warsaw and Wrocław. The investigations were performed using the volumetric method as well as the Burkard and Lanzoni traps. The pollen season duration was determined using the method of 98%. It has been shown that the birch pollen season started in 2009 in the first decade of April, similarly to the years 2007 and 2008. Significant differences were found in pollen season duration between particular cities and in diurnal pollen grain counts. The highest diurnal birch pollen count was recorded in Wrocław (1317 grains/m3) and Szczecin (1166 grains/m3). In all the cities, a large number of days was recorded with a concentration exceeding the threshold concentration for birch (17–29 days)