Stosowanie leków biopodobnych w hematoonkologii – stanowisko Polskiego Towarzystwa Hematologów i Transfuzjologów

Leki biopodobne odgrywają coraz większą rolę w terapii wielu chorób wraz z wygaśnięciem ochrony patentowej dla kolejnych leków biologicznych. Celem niniejszego opracowania jest przybliżenie terminologii i zasad wprowadzania na rynek leków biopodobnych, zagadnień dotyczących ich etykietowania, ekstrapolacji, wymienialności i automatycznej substytucji. Opracowanie to przedstawia stanowisko Polskiego Towarzystwa Hematologów i Transfuzjologów dotyczące leków biopodobnych, oparte na wytycznych EMA (European Medicine Agency) i stanowisku ESMO (European Society of Medical Oncology)

Kemampuan Siswa Dalam Menyelesaikan Soal-soal Uraian Terstruktur Pokok Bahasan Teori Kinetik Gas

"> Penelitian ini bertujuan untuk mengetahui (1) kemampuan kognitif yang dilihat dari hasil belajar peserta didik yang kelas XI MAN Model Palangka Raya dalam mengerjakan soal-soal uraian terstruktur pada pokok bahasan Teori Kinetik Gas; dan (2) kesulitan peserta didik dalam mengerjakan soal-soal uraian terstruktur. Penelitian ini menggunakan metode penelitian kuantitatif dalam mengumpulkan datanya. Penelitian ini menggunakan instrumen dalam bentuk soal uraian terstruktur. Hasil uji coba soal uraian terstruktur pada kelas XI IA-1 MAN Model Palangka Raya mendapatkan tingkat validitas rata-rata 0,536 dan tingkat reliabilitas soal 0,539 dengan kategori cukup. Hasil penelitian menunjukkan bahwa: (1) peserta didik yang mampu dan tidak mengalami masalah dalam mengerjakan soal-soal uraian terstruktur berjumlah 18 peserta didik dan 12 peserta didik tidak mampu dan mengalami masalah dalam mengerjakan soal-soal uraian terstruktur. Peserta didik yang mampu mengerjakan soal-soal uraian terstruktur memiliki ketuntasan belajar ≥ batas KKM, yaitu 60% (2) kesulitan peserta didik dalam mengerjakan soal-soal uraian terstruktur terdapat pada penyebutan dan penulisan satuan besaran pada jawaban dengan persentase kesulitan 36,7%, penguasaan operasi hitungan denganpersentase kesulitan 31,4% dan penulisan besaran yang ditanya dalam soal dengan persentase kesulitan 28,6%

Secondary malignancy in patients with essential thrombocythemia – case reports

Nadpłytkowość samoistna (ET; essential thrombocythemia) należy do przewlekłych chorób mieloproliferacyjnych i ma na ogół mało agresywny przebieg, jednak czas przeżycia chorych jest krótszy w porównaniu z ogólną populacją. Do niedawna za główne przyczyny skrócenia czasu życia chorych uznawano zaawansowany wiek i przebyte epizody zakrzepowe. Obecnie coraz więcej uwagi zwraca się na inny powód, jakim jest rozwój u tych chorych wtórnych nowotworów niehematologicznych.ET is a relatively indolent disease, but a shorter survival of patients has been observed. Previously the main risk factors for reduced survival time were advanced age and the history of thrombotic complications. Recently the other cause of reduced survival is put on – secondary nonhematological neoplasms

The Role of Complement Activating Collectins and Associated Serine Proteases in Patients With Hematological Malignancies, Receiving High-Dose Chemotherapy, and Autologous Hematopoietic Stem Cell Transplantations (Auto-HSCT)

We conducted a prospective study of 312 patients (194 with multiple myeloma, 118 with lymphomas) receiving high-dose conditioning chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Polymorphisms of MBL2 and MASP2 genes were investigated and serial measurements of serum concentrations of mannose-binding lectin (MBL), CL-LK collectin and MASP-2 as well as activities of MBL-MASP-1 and MBL-MASP-2 complex were made. Serum samples were taken before conditioning chemotherapy, before HSCT and once weekly after (totally 4-5 samples); in minority of subjects also 1 and/or 3 months post transplantation. The results were compared with data from 267 healthy controls and analyzed in relation to clinical data to explore possible associations with cancer and with chemotherapy-induced medical complications. We found a higher frequency of MBL deficiency-associated genotypes (LXA/O or O/O) among multiple myeloma patients compared with controls. It was however not associated with hospital infections or post-HSCT recovery of leukocytes, but seemed to be associated with the most severe infections during follow-up. Paradoxically, high MBL serum levels were a risk factor for prolonged fever and some infections. The first possible association of MBL2 gene 3′-untranslated region polymorphism with cancer (lymphoma) in Caucasians was noted. Heterozygosity for MASP2 gene +359 A>G mutation was relatively frequent in lymphoma patients who experienced bacteremia during hospital stay. The median concentration of CL-LK was higher in myeloma patients compared with healthy subjects. Chemotherapy induced marked increases in serum MBL and MASP-2 concentrations, prolonged for several weeks and relatively slighter decline in CL-LK level within 1 week. Conflicting findings on the influence of MBL on infections following chemotherapy of myeloma and lymphoma have been reported. Here we found no evidence for an association between MBL deficiency and infection during the short period of neutropenia following conditioning treatment before HSCT. However, we noted a possible protective effect of MBL during follow-up, and suspected that to be fully effective when able to act in combination with phagocytic cells after their recovery

High efficacy and safety of VTD as an induction protocol in patients with newly diagnosed multiple myeloma eligible for high dose therapy and autologous stem cell transplantation : a report of the Polish Myeloma Study Group

The present retrospective analysis evaluated the efficacy and safety of the VTD (bortezomib, thalidomide, dexamethasone) regimen in 205 newly‑diagnosed patients with multiple myeloma (MM) eligible for high dose therapy and autologous stem cell transplantation (HDT/ASCT) in routine clinical practice. With a median of 6 cycles (range, 1‑8), at least partial response was achieved in 94.6% and at least very good partial response (VGPR) was achieved in 67.8% of patients. Peripheral neuropathy (PN) grade 2‑4 was observed in 28.7% of patients. In 72% of patients undergoing stem cell mobilization one apheresis allowed the number of stem cells sufficient for transplantation to be obtained. Following HDT/ASCT the sCR rate increased from 4.9 to 14.4% and CR from 27.8 to 35.6%. The results demonstrated that VTD as an induction regimen was highly efficient in transplant eligible patients with MM with increased at least VGPR rate following prolonged treatment (≥6 cycles). Therapy exhibited no negative impact on stem cell collection, neutrophils and platelets engraftment following ASCT. Therapy was generally well tolerated and PN was the most common reason of dose reduction or treatment discontinuation

Current status and achievements of Polish haemato-oncology

The number of newly diagnosed haematological malignancies in Polish adults and children is about 9,000 a year, which constitutes about 5.5% of all malignancies in the country. Adult patients with haematological malignancies are diagnosed and treated in 42 institutions in Poland. The scientific and educational support for this activity is provided under the umbrella of the Polish Society of Haematologists and Transfusiologists (PTHiT, Polskie Towarzystwo Hematologów i Transfuzjologów), the Polish Adult Leukemia Group (PALG), the Polish Lymphoma Research Group (PLRG), the Polish Myeloma Study Group (PMSG), the Polish Myeloma Consortium (PMC), and consultants in haematology. The aim of this position paper is to present the current status and progress in therapy of haematological malignancies in Polish haematology adult centres, focusing on the activity of PALG, PLRG, and PMSG. The achievements of Polish haemato-oncology at the beginning of the third decade of the 21st century are set out in this paper. Polish haemato-oncology today has an important international position based on contributions to the development of knowledge, international cooperation, and a high quality of patient care. In many instances, clinical trials run by Polish collaborative groups have influenced international standards. Polish haematologists have been the authors of treatment recommendations, and their research has indicated areas for further research

Hydrophobicity of protein determinants influences the recognition of substrates by EDEM1 and EDEM2 in human cells

Background EDEM1 and EDEM2 are crucial regulators of the endoplasmic reticulum (ER)-associated degradation (ERAD) that extracts misfolded glycoproteins from the calnexin chaperone system. The degradation of ERAD substrates involves mannose trimming of N-linked glycans; however the precise mechanism of substrate recognition and sorting to the ERAD pathway is still poorly understood. It has previously been demonstrated that EDEM1 and EDEM2 binding does not require the trimming of substrate glycans or even ERAD substrate glycosylation, thus suggesting that both chaperones probably recognize misfolded regions of aberrant proteins. Results In this work, we focused on the substrate recognition by EDEM1 and EDEM2, asking whether hydrophobicity of protein determinants might be important for these interactions in human cells. In the study we used ricin, a protein toxin that utilizes the ERAD pathway in its retrotranslocation from the ER to the cytosol, and a model misfolded protein, the pancreatic isoform of human β-secretase, BACE457. Mutations in the hydrophobic regions of these proteins allowed us to obtain mutated forms with increased and decreased hydrophobicity. Conclusions Our data provide the first evidence that recognition of ERAD substrates by EDEM1 and EDEM2 might be determined by a sufficiently high hydrophobicity of protein determinants. Moreover, EDEM proteins can bind hydrophobic transmembrane regions of misfolded ERAD substrates. These data contribute to the general understanding of the regulation of ERAD in mammalian cells

The imaginary community: writers from Central Europe in the face of literary, social and political problems between 1914 and 1945

Tytuł tomu redaktorki zapożyczyły od inicjatorów konferencji, która odbyła się w Warszawie 21 i 22 kwietnia 2016 roku. A zarówno konferencja, jak i książka stanowią część składową projektu badawczego Polska i ukraińska proza kobieca - perspektywa modernizmu (środkowo)europejskiego, zrealizowanego w Instytucie Badań Literackich PAN z udziałem międzynarodowej grupy historyków literatury i tłumaczy […] Redaktorki i współautorki przyjęły, że czas od początku pierwszej wojny światowej po koniec drugiej stanowi odrębną epokę w dziejach Europy, naznaczoną narastającą falą autorytaryzmów, zmaganiami militarnymi, zmianami politycznymi i społecznymi, które między innymi wiązały się z nowym statusem kobiet, ich samodzielnością, aktywnością zawodową i stricte artystyczna, a przede wszystkim z tragedią wojen, przesiedleń i okupacji. W dwudziestoleciu międzywojennym idee modernistyczne, wcześniej elitarne i podejmowane głównie w środowiskach artystycznych, weszły w fazę działań społecznych, związanych z nowoczesnością, zmianami technologicznymi, demokratyzacją życia społecznego. Choć - rzecz jasna - procesy te realizowały się różnie w różnych krajach, a w wielu miejscach nie realizowały się wcale. Tym bardziej warto przyjrzeć się porównawczo literackim reprezentacjom sytuacji kobiet, biorąc pod uwagę nie jeden lub dwa kraje, ale cały region nazywany Europą Środkową

GPAT Gene Silencing in Muscle Reduces Diacylglycerols Content and Improves Insulin Action in Diet-Induced Insulin Resistance

Skeletal muscle is an important tissue responsible for glucose and lipid metabolism. High-fat diet (HFD) consumption is associated with the accumulation of bioactive lipids: long chain acyl-CoA, diacylglycerols (DAG) and ceramides. This leads to impaired insulin signaling in skeletal muscle. There is little data on the involvement of DAG in the development of these disorders. Therefore, to clarify this enigma, the gene encoding glycerol-3-phosphate acyltransferase enzyme (GPAT, responsible for DAG synthesis) was silenced through shRNA interference in the gastrocnemius muscle of animals with diet-induced insulin resistance. This work shows that HFD induces insulin resistance, which is accompanied by an increase in the concentration of plasma fatty acids and the level of bioactive lipids in muscle. The increase in these lipids inhibits the insulin pathway and reduces muscle glucose uptake. GPAT silencing through electroporation with shRNA plasmid leads to a reduction in DAG and triacylglycerol (TAG) content, an increase in the activity of the insulin pathway and glucose uptake without a significant effect on ceramide content. This work clearly shows that DAG accumulation has a significant effect on the induction of muscle insulin resistance and that inhibition of DAG synthesis through GPAT modulation may be a potential target in the treatment of insulin resistance

Cellulite, overweight and obesity in female patients with hypothyroidism

Introduction. A bad diet and lack of physical activity are the most commonly reported causes of overweight and cellulite. Unfortunately, problems with slimming and "orange peel" may not only result from dietary mistakes but also hormonal imbalance. Aim of the paper. The aim of the study was to assess the impact of hypothyroidism on overweight, the degree of obesity and the prevalence of cellulite in patients with hypothyroidism in the course of Hashimoto's disease. Material and methods. The study was carried out in March 2018 in Opole Lubelskie. The study group consisted of 35 women over 18 years of age. The research tool was the standardised Contour Drawing Rating Scale (Thompson and Gray) and the author's questionnaire. Results. The calculated BMI values of the subjects showed the presence of overweight in every fifth woman, class I obesity in 11.43%, class II obesity in 28.57% and class III obesity in 40% of the respondents. According to 94.28% of the respondents, physical activity affects the appearance of the body, but only 5.72% of the study subjects do sports. Among the respondents, over half (68.57%) indicated the presence of third-degree cellulite. Conclusions. Cellulite is most common in overweight and obese women. The occurrence of overweight and obesity may be associated with a poor diet and low physical activity, but also with hormonal disorders resulting from thyroid dysfunction