151 research outputs found

    Specific aspects of researching the oncogenesis and metastatasing potential of laringeal squamous cell carcinoma

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    Malignant tumor metastasizing, comprised of several consecutive steps beginning with local cancer cell invasion, is a key factor which compromises the prognosis of cancer patients and is responsible for 90% of the lethal outcome. 2/3 of our diagnosed patients show with locally advanced process and/or metastatic disease (stage III/IV).Researching key molecular and cellular mechanisms tied to development and metastasizing of laryngeal squamous cell carcinoma is of clinical importance to developing and using molecular target therapy.Based on popular literature studies the emphasize was put on the following genes: TP53, CDKN2A – accentuating on exons 1,2,3, and PIK3CA – exons 9, 20, as primarily connected to the higher mutation potential of laryngeal squamous cell carcinoma.Researching the genetic similarity between carcinoma and metastasis could potentially help understanding the genotype and mutation potential of Head and Neck squamous cell carcinomas. The practical potential use of this knowledge is the developing of predictive markers and better therapeutic algorithms for diagnosed patients.Β ----------------------------------------------------------------------Β Π’ΡƒΠΌΠΎΡ€Π½ΠΎΡ‚ΠΎ мСтастазиранС, Π²ΠΊΠ»ΡŽΡ‡Π²Π°Ρ‰ΠΎ няколко послСдоватСлни ΡΡ‚ΡŠΠΏΠΊΠΈ, Π·Π°ΠΏΠΎΡ‡Π²Π°ΠΉΠΊΠΈ ΠΎΡ‚ инвазия Π½Π° Ρ€Π°ΠΊΠΎΠ²ΠΈΡ‚Π΅ ΠΊΠ»Π΅Ρ‚ΠΊΠΈ Π² ΠΎΠΊΠΎΠ»Π½ΠΈΡ‚Π΅ Ρ‚ΡŠΠΊΠ°Π½ΠΈ, Π΅ ΠΊΠ»ΡŽΡ‡ΠΎΠ²ΠΈΡΡ‚ Ρ„Π°ΠΊΡ‚ΠΎΡ€, ΠΊΠΎΠΉΡ‚ΠΎ ΠΊΠΎΠΌΠΏΡ€ΠΎΠΌΠ΅Ρ‚ΠΈΡ€Π° ΠΏΡ€ΠΎΠ³Π½ΠΎΠ·Π°Ρ‚Π° Π½Π° Ρ€Π°ΠΊΠΎΠ²ΠΎ Π±ΠΎΠ»Π½ΠΈΡ‚Π΅ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΈ ΠΈ отговаря Π·Π° 90% ΠΎΡ‚ ΡΠΌΡŠΡ€Ρ‚Π½ΠΎΡΡ‚Ρ‚Π°. 2/3 ΠΎΡ‚ диагностициранитС ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΈ са с Π»ΠΎΠΊΠ°Π»Π½ΠΎ авансирал процСс ΠΈ/ ΠΈΠ»ΠΈ мСтастатична болСст (стадий III ΠΈΠ»ΠΈ IV).ΠŸΡ€ΠΎΡƒΡ‡Π²Π°Π½Π΅Ρ‚ΠΎ Π½Π° молСкулярни ΠΈ ΠΊΠ»Π΅Ρ‚ΡŠΡ‡Π½ΠΈ ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΠΈ, Π²ΠΎΠ΄Π΅Ρ‰ΠΈ Π΄ΠΎ Ρ„ΠΎΡ€ΠΌΠΈΡ€Π°Π½Π΅Ρ‚ΠΎ ΠΈ мСтастазиранСто Π½Π° ΠΏΠ»ΠΎΡΠΊΠΎΠΊΠ»Π΅Ρ‚ΡŠΡ‡Π½ΠΈΡ ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌ ΠΎΡ‚ Π»Π°Ρ€ΠΈΠ½Π³Π΅Π°Π»Π΅Π½ ΠΏΡ€ΠΎΠΈΠ·Ρ…ΠΎΠ΄, Π±ΠΈ Π±ΠΈΠ»ΠΎ ΠΎΡ‚ ΠΊΠ»ΠΈΠ½ΠΈΡ‡Π½Π° ΠΏΠΎΠ»Π·Π° Π·Π° Ρ€Π°Π·Ρ€Π°Π±ΠΎΡ‚Π²Π°Π½Π΅Ρ‚ΠΎ Π½Π° молСкулярна Ρ‚Π°Ρ€Π³Π΅Ρ‚Π½Π° тСрапия.На Π±Π°Π·Π°Ρ‚Π° Π½Π° ΠΎΠ±ΡˆΠΈΡ€Π΅Π½ Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Π΅Π½ ΠΎΠ±Π·ΠΎΡ€ Π°ΠΊΡ†Π΅Π½Ρ‚ΡŠΡ‚ Π΅ поставСн Π²ΡŠΡ€Ρ…Ρƒ слСднитС Π³Π΅Π½ΠΈ – TP53, CDKN2A – exons 1,2,3 and PIK3CA – exons 9, 20, ΠΊΠ°Ρ‚ΠΎ ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π»Π½ΠΈ ΠΎΡ‚Π³ΠΎΠ²ΠΎΡ€Π½ΠΈΡ†ΠΈ Π·Π° повишаванС мСтастатичния ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π» Π½Π° ΠΏΠ»ΠΎΡΠΊΠΎΠ»Π΅Ρ‚ΡŠΡ‡Π½ΠΈΡ ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌ ΠΎΡ‚ Π»Π°Ρ€ΠΈΠ½Π³Π΅Π°Π»Π΅Π½ ΠΏΡ€ΠΎΠΈΠ·Ρ…ΠΎΠ΄.Π˜Π·ΡΠ»Π΅Π΄Π²Π°Π½Π΅Ρ‚ΠΎ Π½Π° Π³Π΅Π½Π΅Ρ‚ΠΈΡ‡Π½ΠΎ сродство ΠΌΠ΅ΠΆΠ΄Ρƒ ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌ ΠΈ мСтастаза Π±ΠΈ ΠΈΠΌΠ°Π»ΠΎ Ρ‚Π΅ΠΎΡ€Π΅Ρ‚ΠΈΡ‡Π΅Π½ принос към ΠΎΠΏΠΎΠ·Π½Π°Π²Π°Π½Π΅Ρ‚ΠΎ Π½Π° Π³Π΅Π½ΠΎΡ‚ΠΈΠΏΠ° ΠΈ мутационния статус Π½Π° ΠΏΠ»ΠΎΡΠΊΠΎΠΊΠ»Π΅Ρ‚ΡŠΡ‡Π½ΠΈΡ‚Π΅ ΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌΠΈ Π½Π° Π³Π»Π°Π²Π° ΠΈ шия, Ρ‡ΠΈΠΉΡ‚ΠΎ практичСски ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π» сС изразява ΠΊΠ°Ρ‚ΠΎ прогностична стойност Π·Π° прСТивяСмостта Π½Π° ΠΎΠ½ΠΊΠΎΠ±ΠΎΠ»Π½ΠΈΡ‚Π΅ ΠΈ подобряванС Π½Π° тСрапСвтичния Π°Π»Π³ΠΎΡ€ΠΈΡ‚ΡŠΠΌ ΠΏΡ€ΠΈ диагностицирани ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΈ

    Evaluation of paralytic shellfish poisoning toxin profile of mussels from Bulgarian North Black Sea coast by HPLC-FlD with post and pre-column derivatization

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    Marine toxins are produced by certain toxic phytoplankton species. Harmful toxins may accumulate in the shellfish tissue, potentially impacting human health. Paralytic shellfish poisoning (PSP) is a syndrome caused by ingestion of shellfish contaminated with paralytic shellfish toxins (PST) that comprise saxitoxin and its variants (neosaxitoxin, gonyautoxins and their decarbamoyl and N-sulfocambamoyl analogs). The aim of this study was to evaluate the presence of paralytic shellfish toxins (PSTs) in plankton samples and in mussels intended for human consumption. Mussels collected in the main areas of production and recreational harvesting off the north coast of Bulgaria have been investigated for PSP toxins. Individual toxins were determined using two methods both involving fluorescence detection: ion pair-liquid chromatography with post-column derivatization (method 1) and high-performance liquid chromatographic procedure employing pre-column oxidation of the toxins (method 2). The results according method 1 demonstrated the presence of gonyautoxin 2 in 53% of the mussel samples and no toxins were detected in the plankton samples. The toxicity level - 1.6 ΞΌg STX.2HCl .kg-1 was far beneath the EU legislative limit of 800 ΞΌg STX.2HCl .kg-1 concluding in negligible risk for human health. Due to higher limits of detection no toxins were detected via method 2. Even though, considering method 2 is recognized by European Commission as official for regulatory purposes and the relative high value of the legislative threshold, thus obtained toxin levels are enough representative to conclude if mussels are safe for consumption or not. On the other hand, the more sensitive method 1 provides important data on extremely low toxin levels which would be useful for chronic exposure estimation and for completing the knowledge about occurrence of PSTs in certain locations

    Phosphorus consumption. From linear to circular flow

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    Wastewater and waste sludge are generated in all parts of the world during domestic and industrial activities. Conventional wastewater treatment methods generate a highly concentrated municipal sludge, which needs to be disposed of effectively without leading to secondary pollution. Animal manure and post generated manure wastewater are another environmental concern. Both of the above wastewater and sludge/manure are rich in organic/inorganic forms of carbon, nitrogen (N) and phosphorus (P). Anthropogenic and industrial activities in the global biogeochemical cycles have resulted in a drastic one-way mobilization of these resources into the atmosphere and the environment.The current intensive agriculture requires huge quantities of nitrogen (N) and Phosphorus (P) containing fertilizers. The industrial production of ammonia and nitrates is quite energy demanding; however, nitrogen is abundantly present in the nature and therefore it is a non-restricted resource for nitrogen derivate production. Unlike nitrogen, P can be obtained primarily from mineral deposits available only in few geographic locations. The phosphate rock reserves are finite and the current intensive fertilizer production based on economically mined rocks could last only another 50-100 years. Since phosphates are available only in limited geographic locations and the recognition that geologic phosphates are a non-renewable resource, Phosphorus recovery becomes a crucial for sustainable food production as EU depends for 90% on import of phosphate rocks (European Commission 2017). Within the EU only Finland has some phosphate rocks. The list of supplying countries is quite short; more than 70% of the present known global reserves of phosphate rock are located in Morocco as of all mined and processed phosphate rock (2009).Β  Phosphorus, being a finite resource with deficits starting approximately from the year 2070 due to increased demand might also result in high prices and reliance on single point sources, giving them monopoly over the market.The EU phosphorus flows show that the main losses of phosphorus in the food sector are through sewage sludge, other waste water and food waste. In general, phosphorus can be recycled, mainly from wastewater (e.g. sewage water), manure and organic waste (e.g. wasted food). Thus, wastewater can be considered as a renewable source of N and P. Instead of releasing the N and P rich wastewater into coastal and inland waters increasing eutrophication risk their utilization can be beneficial resulting in multiple benefits like nutrient recovery, water reclamation for reuse and maintenance of ecological balance in aquatic systems.Presently, the recovery and reuse of P is still far from being a main stream practice. Yet, the techniques already accepted and applied differ by the origin of the used matter (wastewater, sludge, ash) are mainly focused on the process of precipitation. One of these techniques is struvite precipitation, which can be implemented in wastewater treatment plants that use enhanced biological or semi biological/chemical phosphorus removal. Struvite (magnesium ammonium phosphate or MAP (MgNH4PO4Β·6H2O)) is formed by a basic precipitation reaction in different stages of the wastewater treatment process where magnesium (Mg2+), ammonium (NH4+) and orthophosphate (PO4βˆ’3).The article discusses the progress in extracting P from sewage sludge and animal manure, the conditions to create optimal conditions for struvite precipitation in such media and the way to overcome the problems associated with choosing the right Mg source, pH adjustment and the non-acceptable level of organic matter in the initial suspension

    Membrane filtration pretreatment preceding struvite precipitation

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    The ability of Microfiltration (MF) and Ultrafiltration (UF) technique for separation of organic matter in treatment of nutrient rich fluids is investigated in the study. Such separation is of great importance in case of performing magnesium-ammonium phosphate hexahydrate (struvite) precipitation as the struvite yield depends negatively on organic matter content.The advantage of cross-flow UF in separating the particulate organic matter and soluble phosphorus (P) was proved. Such a process allows COD removal rates over 99 %, while the P in permeate was kept high enough to perform a successful P precipitation as struvite

    Structure of the complete, membrane-assembled COPII coat reveals a complex interaction network

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    COPII mediates Endoplasmic Reticulum to Golgi trafficking of thousands of cargoes. Five essential proteins assemble into a two-layer architecture, with the inner layer thought to regulate coat assembly and cargo recruitment, and the outer coat forming cages assumed to scaffold membrane curvature. Here we visualise the complete, membrane-assembled COPII coat by cryo-electron tomography and subtomogram averaging, revealing the full network of interactions within and between coat layers. We demonstrate the physiological importance of these interactions using genetic and biochemical approaches. Mutagenesis reveals that the inner coat alone can provide membrane remodelling function, with organisational input from the outer coat. These functional roles for the inner and outer coats significantly move away from the current paradigm, which posits membrane curvature derives primarily from the outer coat. We suggest these interactions collectively contribute to coat organisation and membrane curvature, providing a structural framework to understand regulatory mechanisms of COPII trafficking and secretion

    Structure of the complete, membrane-assembled COPII coat reveals a complex interaction network

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    COPII mediates Endoplasmic Reticulum to Golgi trafficking of thousands of cargoes. Five essential proteins assemble into a two-layer architecture, with the inner layer thought to regulate coat assembly and cargo recruitment, and the outer coat forming cages assumed to scaffold membrane curvature. Here we visualise the complete, membrane-assembled COPII coat by cryo-electron tomography and subtomogram averaging, revealing the full network of interactions within and between coat layers. We demonstrate the physiological importance of these interactions using genetic and biochemical approaches. Mutagenesis reveals that the inner coat alone can provide membrane remodelling function, with organisational input from the outer coat. These functional roles for the inner and outer coats significantly move away from the current paradigm, which posits membrane curvature derives primarily from the outer coat. We suggest these interactions collectively contribute to coat organisation and membrane curvature, providing a structural framework to understand regulatory mechanisms of COPII trafficking and secretion

    Combinatorial multivalent interactions drive cooperative assembly of the COPII coat

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    Protein secretion is initiated at the endoplasmic reticulum by the COPII coat, which self-assembles to form vesicles. Here, we examine the mechanisms by which a cargo-bound inner coat layer recruits and is organized by an outer scaffolding layer to drive local assembly of a stable structure rigid enough to enforce membrane curvature. An intrinsically disordered region in the outer coat protein, Sec31, drives binding with an inner coat layer via multiple distinct interfaces, including a newly defined charge-based interaction. These interfaces combinatorially reinforce each other, suggesting coat oligomerization is driven by the cumulative effects of multivalent interactions. The Sec31 disordered region could be replaced by evolutionarily distant sequences, suggesting plasticity in the binding interfaces. Such a multimodal assembly platform provides an explanation for how cells build a powerful yet transient scaffold to direct vesicle traffic

    Combinatorial multivalent interactions drive cooperative assembly of the COPII coat

    Get PDF
    Protein secretion is initiated at the endoplasmic reticulum by the COPII coat, which self-assembles to form vesicles. Here, we examine the mechanisms by which a cargo-bound inner coat layer recruits and is organized by an outer scaffolding layer to drive local assembly of a stable structure rigid enough to enforce membrane curvature. An intrinsically disordered region in the outer coat protein, Sec31, drives binding with an inner coat layer via multiple distinct interfaces, including a newly defined charge-based interaction. These interfaces combinatorially reinforce each other, suggesting coat oligomerization is driven by the cumulative effects of multivalent interactions. The Sec31 disordered region could be replaced by evolutionarily distant sequences, suggesting plasticity in the binding interfaces. Such a multimodal assembly platform provides an explanation for how cells build a powerful yet transient scaffold to direct vesicle traffic.</p

    Infiltrazione macrofagica e densitΓ  capillare nel carcinoma della laringe. Studio su 52 casi

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    L’angiogenesi Γ¨ uno dei sei principali meccanismi alla base del cancro, ed Γ¨ stato studiato approfonditamente negli ultimi 20 anni. L’obiettivo del presente studio Γ¨ stato quello di determinare sia la densitΓ  capillare sia l’infiltrato macrofagico nei campioni di carcinoma laringeo e di determinarne la correlazione con gli aspetti clinici e patologici. Sia la densitΓ  capillare (CD34) sia l’infiltrato macrofagico (CD68) sono stati determinati con metodiche immunoistochimiche mediante microarray. Il nostro campione ha mostrato una densitΓ  capillare media di 14,27 Β± 12,92 vasi su campo ingrandito a 200Γ—, e l’infiltrato macrofagico medio Γ¨ stato di 5,19 Β± 4,32. La densitΓ  capillare si Γ¨ dimostrata superiore nei pazienti metastatici. Inoltre uno studio di regressione lineare ha mostrato che l’entitΓ  dell’infiltrato macrofagico poteva predire la densitΓ  capillare del campione di carcinoma laringeo preso in esame. Non abbiamo invece individuato una correlazione fra ambo i fattori studiati e l’incidenza delle recidive o gli altri fattori clinici presi in esame. Il nostro studio aggiunge dati ad un problema che per quanto studiato a fondo negli ultimi 20 anni resta nella sostanza controverso
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