Signaling pathways in melanoma biology and new targeted therapeutic approaches

Despite the broad prevention programs and early detection and therapy progress, melanoma of skin is still responsible for 0.6% of deaths caused by tumour disease. Every year 300,000 patients are diagnosed and 60,000 die from the most malignant of skin cancer. Generally, melanoma is formed as a result of mutation of growth pathways responsible for proliferation and apoptosis. One of the most investigated pathway, mutated in 90% of melanomas, is RAS > RAF > MEK > ERK also known as mitogen-activated protein kinase (MAPK) pathway. The second one is phosphoinositide-3-OH kinase (PI3K) pathway. The better understanding of melanoma biology resulted in research of inhibitors, which can affect presented pathways and prevent uncontrolled proliferation of melanoma. The BRAF inhibitors vemurafenib and dabrafenib and MEK inhibitor trametinib seem to be the most successful ones. Recent advances in biology of melanoma provided new interesting therapeutic targets. One of the most inquiring is microphthalmia associated transcription factor (MITF), the principal regulator of melanocyte lineage. MITF perform the role of so-called ‘survival’ or ‘addiction’ oncogene. Moreover, the interleukin-1 receptor-associated kinases (IRAKs) might clarify the connection between the inflammatory environment and melanoma carcinogenesis. IRAKs play a key role as mediators of toll-like receptor (TLR) and interleukin-1 receptor (IL1R) in inflammation signalling processes. Moreover, it was observed that metformin cause cell cycle arrest in melanoma cells, secondly leading to activation of autophagy and apoptosis. Although due to targeted and immunotherapy the prognosis of patients with metastatic melanoma is incomparably better, melanoma in its advanced stadium is still predominantly lethal. Therefore, the most present research concentrates on acquired resistance against targeted therapy

Rak jelita grubego - charakterystyka i oporność na leczenie

Colorectal cancer is a neoplasm with the worst prognosis in Poland. The possibility of cure depends mainly on the stage of disease at diagnosis. The use of chemotherapy is essential in the management of colorectal cancer, but chemotherapy is effective in some patients only due to the resistance to cytotoxic agents. Chemotherapy constitutes usually only part of combined treatment that includes surgery and radiotherapy as well as multidrug resistance modulators and targeted agents. Modern anti-cancer targeted therapies aim at inhibition of molecular oncogenic pathways and selective introduction of active compounds into malignant cells. Novel agents include signal transduction pathways modulators, cell cycle regulators, agents controlling angiogenesis and multidrug resistance, and oncogenes. Anticancer antibodies used either as immunological response modifiers or as an alternative to deliver cytotoxic agents directly to cancer cells play an important role. This therapeutic strategy intends to improve the effectiveness of anticancer treatment with reducing its toxicity. The application of the combined therapies can contribute to the improvement of the treatment in patients.W Polsce rak jelita grubego należy do grupy nowotworów o najgorszym rokowaniu. Możliwość wyleczenia jest przede wszystkim uzależniona od stopnia zaawansowania choroby w chwili jej rozpoznania. Podstawową metodą jest chemioterapia, która jest skuteczna tylko u części chorych z powodu oporności na zastosowane leki cytotoksyczne. Chemioterapia jest zazwyczaj częścią skojarzonego postępowania, które składa się dodatkowo z chirurgicznego leczenia i radioterapii oraz wprowadzonych ostatnio modulatorów oporności wielolekowej i leków celowanych. Zadaniem nowoczesnych przeciwnowotworowych leków celowanych jest hamowanie molekularnych szlaków onkogenezy oraz selektywne wprowadzanie aktywnych substancji do komórek nowotworowych. Do nowoczesnych leków należą między innymi: modulatory aktywności cząsteczek biorących udział w przekazywaniu sygnałów, regulatory cyklu komórkowego, czynniki kontrolujące angiogenezę i aktywność procesów przerzutowania, mechanizmy warunkujące lekooporność oraz onkogeny. Ważną rolę w nowoczesnym leczeniu odgrywają przeciwciała, które mogą stymulować odpowiedź immunologiczną przeciw nowotworowi oraz doprowadzać lek do komórki nowotworowej. Wdrożenie łączonych terapii przyczyni się do poprawy wyników leczenia chorych na raka jelita grubego

A simple and established method of tissue culture of human gingival fibroblasts for gingival augmentation.

Recent advances in tissue engineering technology suggest its application in different medical fields, including periodontology. There are some reports of new non-enzymatic methods of isolating human gingival fibroblast for short-time cultivation in vitro to be used in autologous gingival augmentation. The aim of this study was to obtain a simple and established method of culturing human gingival fibroblasts. The authors developed a recurrent method that can be successfully used in autologous gingival augmentation

Evaluation of superoxide dismutase activity and its impact on semen quality parameters of infertile men.

The evaluation of superoxide dismutase (SOD) activity, as one of the most important antioxidative defence enzymes, in seminal plasma of patients consulting for male infertility was presented in the article. The study included also the determination of its influence on selected human semen quality parameters. The material represents semen samples obtained from 15 men, which were divided into two groups: Group I (n=10) including patients consulting for infertility and Group II (n=5) containing healthy sperm donors as a control. All of the semen samples were cryopreserved and stored in liquid nitrogen. The frozen samples were thawed at the same time and then SOD activity was determined spectrophotometrically. The analysis of the investigations results indicates a significantly lower semen SOD activity detected in oligoasthenozoospermic patients, comparing to the activity found in normospermic men. The study showed a positive correlation between SOD activity in seminal plasma and semen quality parameters--sperm concentration and overall motility, which are regarded as the most important for normal fertilizing ability of the spermatozoa. Significantly lower SOD activity in seminal plasma of infertile patients, comparing to healthy sperm donors, as well as positive correlation and beneficial impact of SOD activity on human semen quality parameters seem to confirm the observations, that decreased seminal plasma scavenger antioxidant capacity, particularly in form of low SOD activity, can be responsible for male infertility. This trial shows that SOD activity survey in seminal plasma could be a useful tool for determining sperm fertilization potential and could improve the diagnosis of male infertility

Pregnancy induced hypertension. Etiopathogenesis

Choroby przebiegające z podwyższonym ciśnieniem u kobiet w okresie ciąży to częsta przyczyna zgonów kobiet i porodów martwych płodów. W dużym stopniu są one przyczyną przedwczesnych porodów i powikłań u noworodków. Etiopatogeneza nadciśnienia indukowanego ciążą (PIH) pozostaje nieznana, a patomechanizm tego schorzenia nie jest do końca wyjaśniony. W nadciśnieniu chronicznym głównym objawem jest podwyższone ciśnienie tętnicze, podczas gdy w nadciśnieniu indukowanym ciążą wzrost ciśnienia jest syndromem specyficznych zaburzeń i potencjalną przyczyną komplikacji występujących u kobiet w ciąży. Badania ostatnich lat wskazują, że istotną rolę w wywoływaniu PIH odgrywa stres oksydacyjny powodowany niekontrolowanym wzrostem reaktywnych form tlenu (RFT).Hypertension-associated disorders in pregnant women are a frequent cause of death, premature births, stillbirths and complications in infants. Etiopathogenesis of most cases of hypertension in pregnant women remains unknown. Pathomechanism of pregnancy induced hypertension has not been fully elucidated. In chronic hypertension the main feature is elevated blood pressure, whereas in pregnancy induced hypertension (PIH) the increase blood pressure is a syndrome of specific disorders and potential cause of complications in pregnant women. The last studies suggest involvement of oxidative stress inducing uncontrolled increase of reactive oxygen species (ROS) in the PIH etiopathogenesis

A Worldwide Test of the Predictive Validity of Ideal Partner Preference-Matching

©American Psychological Association, [2024]. This paper is not the copy of record and may not exactly replicate the authoritative document published in the APA journal. The final article is available, upon publication, at: [ARTICLE DOI]”Ideal partner preferences (i.e., ratings of the desirability of attributes like attractiveness or intelligence) are the source of numerous foundational findings in the interdisciplinary literature on human mating. Recently, research on the predictive validity of ideal partner preference-matching (i.e., do people positively evaluate partners who match versus mismatch their ideals?) has become mired in several problems. First, articles exhibit discrepant analytic and reporting practices. Second, different findings emerge across laboratories worldwide, perhaps because they sample different relationship contexts and/or populations. This registered report—partnered with the Psychological Science Accelerator—uses a highly powered design (N=10,358) across 43 countries and 22 languages to estimate preference-matching effect sizes. The most rigorous tests revealed significant preference-matching effects in the whole sample and for partnered and single participants separately. The “corrected pattern metric” that collapses across 35 traits revealed a zero-order effect of β=.19 and an effect of β=.11 when included alongside a normative preference-matching metric. Specific traits in the “level metric” (interaction) tests revealed very small (average β=.04) effects. Effect sizes were similar for partnered participants who reported ideals before entering a relationship, and there was no consistent evidence that individual differences moderated any effects. Comparisons between stated and revealed preferences shed light on gender differences and similarities: For attractiveness, men’s and (especially) women’s stated preferences underestimated revealed preferences (i.e., they thought attractiveness was less important than it actually was). For earning potential, men’s stated preferences underestimated—and women’s stated preferences overestimated—revealed preferences. Implications for the literature on human mating are discussed.Unfunde

The content of cholesterol in arterial fragments – study of 34 cases

BACKGROUND Atherosclerosis is a multifactor disease. It is commonly believed that a high cholesterol level in blood plasma is the main factor which is responsible for the formation of atherosclerotic plaques in arteries. Lipid molecules form not only pathological arteries, but are also part of each blood vessel as an important element of cell mem-branes. The aim of this study is to investigate whether the amount of cholesterol in the arteries is correlated with the degree of atherosclerosis. MATERIAL AND METHODS The research material consists of 34 fragments of arteries originated from the bodies of people who died a sudden death. The samples were divided into four groups according to the severity of atherosclerosis. Cholesterol was determined using a colorimetric method with ferric chloride in concentrated phosphoric and sulfuric acid. RESULTS It was observed that the content of arterial cholesterol in the samples increased with the severity of atherosclerosis. The arteries from persons with severe and very high intensification of the disease were characterized by high levels of cholesterol. CONCLUSIONS There is a relationship between the content of cholesterol in the blood vessel wall and the severity of atherosclerosis, but it is not a directly proportional rectilinear relationship due to the fact that plaques with the progression of the disease are not only enriched in lipids but also in cellular and protein components, such as monocytes, macrophages, thrombocytes, necrotic cells, extracellular matrix proteins and others. Further studies are needed to better understand the pathogenesis of atherosclerosis and verify the thesis of the key role of cholesterol in the formation of atherosclerotic lesions.WSTĘP Miażdżyca jest chorobą wieloczynnikową. Powszechnie uważa się, że głównym czynnikiem odpowiedzialnym za powstawanie blaszek miażdżycowych w tętnicach jest wysoki poziom cholesterolu w osoczu krwi. Cząsteczki tego lipidu wchodzą w skład nie tylko tętnic objętych patologicznym stłuszczeniem, ale też każdego naczynia krwionośnego jako element budulcowy błon komórkowych. Celem pracy jest odpowiedź na pytanie, czy ilość cholesterolu całkowitego w tętnicach jest skorelowana z poziomem zaawansowania miażdżycy. MATERIAŁ I METODY Materiałem badawczym były 34 wycinki tętnic pochodzące ze zwłok ludzi zmarłych śmiercią nagłą. Próbki były podzielone na 4 grupy ze względu na stopień zaawansowania miażdżycy. Cholesterol oznaczano kolorymetryczną metodą z użyciem chlorku żelaza w stężonym kwasie siarkowym i fosforowym. WYNIKI Zaobserwowano, że średnia zawartość cholesterolu w próbkach tętnic wzrastała wraz ze stopniem zaawansowania miażdżycy. Tętnice pochodzące od osób ze znacznym i bardzo dużym nasileniem choroby charakteryzują się wysokim poziomem cholesterolu. WNIOSKI 1. Istnieje związek między zawartością cholesterolu w ścianie naczynia krwionośnego a zaawansowaniem miażdżycy; nie jest to jednak zależność wprost proporcjonalna, gdyż blaszki miażdżycowe wraz z postępem choroby wzbogacane są nie tylko w lipidy, ale także w komórkowe i białkowe składniki, takie jak monocyty, makrofagi, trombocyty, komórki nekrotyczne, białka macierzy zewnątrzkomórkowej i inne. 2. Konieczne są dalsze badania w celu pogłębienia wiedzy na temat patomechanizmu miażdżycy i weryfikacji tezy o nadrzędnej roli cholesterolu w powstawaniu zmian miażdżycowych

A simple and established method of tissue culture of human gingival fibroblasts for gingival augmentation.

Recent advances in tissue engineering technology suggest its application in different medical fields, including periodontology. There are some reports of new non-enzymatic methods of isolating human gingival fibroblast for short-time cultivation in vitro to be used in autologous gingival augmentation. The aim of this study was to obtain a simple and established method of culturing human gingival fibroblasts. The authors developed a recurrent method that can be successfully used in autologous gingival augmentation