Paul Langerhans: hodočasnik koji je "putovao" of funkcionalne histologije do biologije mora

The nineteenth century was the time of a real revolution in science and medicine. A lot of seminal discoveries in medicine and biology were done in this time, and many of them were coincident with the introduction of the compound microscope by Hermann van Deijl and the standard histological technique by Paul Ehrlich. The main tissue types and individual cells were characterized and originally classified more than hundred years ago, although less attention was paid to their basic functions. This was mainly due to the modality of tissue specimen processing that allowed particularly detailed descriptive studies. Even so, we can notice some attempts to correlate the structure with the function. The German scientist Paul Langerhans, well-known for the discovery of Langerhans islets of the pancreas and Langerhans cells from the epidermis, tried to change the conventional fate of morphological studies introducing in his works functional hypothesis based on traditional microscopic observations even from the beginning of his scientific career. Paul Langerhans was a complex personality of the second half of the nineteenth century, not only in medicine, but also in other fields of biology. In the present review, presented is the life and research activity of Paul Langerhans, not only because of the importance of his discoveries, but also for perspectives that were opened by these findings in unexpected fields of medicine and biology.Devetnaesto stoljeće bilo je vrijeme prave revolucije u znanosti i medicini. U tom je stoljeću došlo do mnogih otkrića u medicini i biologiji, a mnoga od njih su se podudarala s primjenom mikroskopa (Hermann van Deijl) i uvođenjem standardne histološke tehnike (Paul Ehrlich). Glavne vrste tkiva i pojedinačne stanice karakterizirane su i izvorno klasificirane prije više od stotinu godina, iako je manje pozornosti bilo posvećeno njihovim osnovnim funkcijama. To je uglavnom bilo zbog modaliteta obrade uzoraka tkiva koja je omogućavala posebno detaljne deskriptivne studije. Ipak, primjećuju se neki pokušaji povezivanja strukture s funkcijom. Njemački znanstvenik Paul Langerhans, poznat po otkriću Langerhansovih otočića gušterače i Langerhansovih stanica u epidermisu, pokušao je promijeniti konvencionalnu sudbinu morfoloških istraživanja uvodeći već od početka svoje znanstvene karijere u svoja istraživanja funkcionalnu hipotezu koja se temelji na tradicionalnim mikroskopskim promatranjima. Paul Langerhans bio je složena ličnost druge polovice XIX. stoljeća ne samo u medicini nego i u drugim područjima biologije. U ovom radu predstavljen je njegov život i njegova istraživačka djelatnost ne samo zbog važnosti njegovih otkrića već i zbog gledišta koja su ta otkrića potaknula u neočekivanim područjima medicine i biologije

B-cell lymphoma-2 receptor in human primary breast and its lymph node metastases: more than a surrogate marker

Background: Due to its anti-apoptotic and anti-proliferative contradictory functions, BCL2 role in breast carcinoma progression is not clearly understood. The purpose of this study was to highlight BCL2 expression during metastatic progression of invasive breast carcinoma of no special type (NST). Materials and methods: The specimens, primary tumors and corresponding lymph node metastases (LNM) from 84 patients were immunostained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER)-2, basal cytokeratin CK5, nuclear protein Ki67 and B-cell lymphoma (Bcl)-2 receptor. Results: BCL2 expression was higher at primary site than in axillary metastases. Its score correlates positively with hormone receptors’ level and negatively with HER2, CK5 and Ki67 at both sites. Switch of molecular profile was determined in 22.62% of cases. BCL2 expression was not influenced by subtypes switch. Changes of BCL2 expression were found in 25% of cases with stable molecular subtype. The Luminal A and Luminal B/Ki67 were encountered in the majority of BCL2 transitions, mainly from positive to negative state. Conclusions: Molecular subtypes and BCL2 expression are not stable during tumor progression and metastatic development. In the present study we established immunohistochemically that BCL2 is not influenced by subtypes’ transitions. BCL2 switches were encountered only in cases with a stable HER2, Luminal A or B phenotypes. We expect a further confirmation of our results by other research groups. Key words: BCL2, breast carcinoma, immunohistochemistry, molecular subtypes, metastases

Oddziaływanie kwaśnego białka włókienkowego gleju i białka S100 w gruczolakach przysadki mózgowej: dwóch czy więcej graczy?

Introduction: S100 protein and GFAP expression in pituitary adenomas tumour cells is not well known; few correlations with other prognostic or therapeutic factors have previously been reported in pituitary adenomas. We aim to elucidate their involvement in the pathogenesis of pituitary adenomas and to establish the correlation of their expression with different growth factors and growth factor receptors known to have a prognostic and/or therapeutic role. Material and methods: Sixty-one cases of pituitary adenomas were immunohistochemically assessed for the expression of GFAP and S100 protein in both tumour cells and FS cells, in close relationship with hormone profile, and correlated with vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression, previously studied by our team. Results: GFAP and S100 protein were expressed both in tumour cells and FS cells. Differences between morphology, distribution, and density of GFAP+ FS cells and S100+ FS cells were observed according to the hormone profile of pituitary adenomas. GFAP and S100 protein expression in tumour cells was significantly related to hormone profile of pituitary adenomas and also with VEGF and EGFR expression. Conclusions: GFAP and S100 protein expressions in tumour cells from pituitary adenomas are influenced by hormone profile. Our re­sults support the presence of two molecular subtypes of FS cells GFAP+/VEGF+/S100 respectively and another one that is GFAP-/S100+/EGFR+ simultaneously with the classical variant GFAP+/S100+. It is possible that S100+/EGFR+ pituitary adenomas represent a group of pituitary adenomas with an aggressive behaviour and a high ability of invasion and recurrence.Wstęp: Ekspresja białka S100 i kwaśnego białka włókienkowego gleju (GFAP, glial fibrillary acid protein) w gruczolakach przysadki mózgowej nie została dobrze poznana. Dostępne są nieliczne publikacje dotyczące korelacji tych cząsteczek z innymi czynnikami prognostycznymi lub terapeutycznymi w gruczolakach przysadki. Celem niniejszej pracy jest wyjaśnienie udziału tych białek w patogenezie gruczolaków przysadki i ustalenie korelacji między ich ekspresją a różnymi czynnikami wzrostu lub receptorami czynników wzrostu o znanej wartości prognostycznej i/lub terapeutycznej. Materiał i metody: Sześćdziesiąt sześć przypadków gruczolaka przysadki zbadano metodami immunohistochemicznymi w celu oceny ekspresji białek GFAP i S100 zarówno w komórkach guza, jak i w komórkach pęcherzykowo-gwiaździstych (FS, folliculo-stellate cells) oraz przeanalizowania uzyskanych wyników w ścisłej zależności z profilami hormonalnymi gruczolaków i w korelacji z ekspresją czynnika wzrostu śródbłonka naczyniowego (VEGF, vascular endothelial growth factor) i receptora naskórkowego czynnika wzrostu (EGFR, epidermal growth factor receptor), ocenianych w badaniu przeprowadzonym wcześniej przez nasz zespół. Wyniki: Ekspresję białek GFAP i S100 stwierdzono zarówno w komórkach guza, jak i w komórkach FS. Zaobserwowano różnice pod względem morfologii, rozkładu i gęstości komórek FS z dodatnią ekspresją białek GFAP i S100 (GFAP+FS i S100+FS) odpowiadające profilowi hormonalnemu gruczolaków przysadki. Ekspresja białek GFAP i S100 w komórkach guza była istotnie związana z profilem hormonalnym gruczolaków przysadki, a także z ekspresją VEGF i EGFR. Wnioski: Ekspresja białek GFAP i S100 w komórkach gruczolaka przysadki zależy od profilu hormonalnego guza. Uzyskane w badaniu wyniki potwierdzają obecność dwóch podtypów molekularnych komórek FS GFAP+/VEGF+/S100 oraz jednego typu GFAP–/S100+/EGFR+ występujących jednocześnie z klasycznym wariantem GFAP+/S100+. Możliwe, że gruczolaki przysadki z ekspresją S100+/EGFR+ należą do grupy tych nowotworów cechujących się agresywnością i dużą zdolnością do naciekania i nawrotów

Toward a Molecular Classification of the Head and Neck Squamous Cell Carcinoma

The frequency of the squamous cell carcinoma of the head and neck is constantly increasing, with over 550.000 new cases registered globally each year. The conventional histopathological diagnosis most commonly indicates the squamous cell carcinoma as tumor type and G2 as differentiation grade. Despite of this relative morphological uniformity, there is a great heterogeneity in the molecular profile, the therapeutic response and prognosis. Most probably, this entity includes many diseases, similar in basic morphologic features, but different in the biological behavior. Trying to answer this question and to show discrepancies when they exist, we have evaluated in this book chapter, our own results and data from the literature in terms of molecular profile at the protein level, including the spectrum of proliferation markers, growth factors and their receptors, stromal proliferation, angiogenesis and lymphangiogenesis. These data will allow to identify some major criteria for a better stratification of cases, selected for gene analysis and personalized therapy as a future perspective and direction

Graphene nanoplatelets-sericin surface-modified Gum alloy for improved biological response

In this study a “Gum Metal” titanium-based alloy, Ti-31.7Nb-6.21Zr-1.4Fe-0.16O, was synthesized by melting and characterized in order to evaluate its potential for biomedical applications. The results showed that the newly developed alloy presents a very high strength, high plasticity and a low Young\u27s modulus relative to titanium alloys currently used in medicine. For further bone implant applications, the newly synthesized alloy was surface modified with graphene nanoplatelets (GNP), sericin (SS) and graphene nanoplatelets/sericine (GNP–SS) composite films via Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The characterization of each specimen was monitored by scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle (CA) measurements, and Fourier Transform Infrared Spectroscopy (FTIR). The materials\u27 surface analyses suggested the successful coating of GNP, SS and GNP–SS onto the alloy surface. Additionally, the activities of pre-osteoblasts such as cell adhesion, cytoskeleton organization, cell proliferation and differentiation potentials exhibited on these substrates were investigated. Results showed that the GNP–SS-coated substrate significantly enhanced the growth and osteogenic differentiation of MC3T3-E1 cells when compared to bare and GNP-coated alloy. Collectively, the results show that GNP–SS surface-modified Gum alloy can modulate the bioactivity of the pre-osteoblasts holding promise for improved biological response in vivo

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference