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

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. ---------------------------------------------------------------------- Туморното метастазиране, включващо няколко последователни стъпки, започвайки от инвазия на раковите клетки в околните тъкани, е ключовият фактор, който компрометира прогнозата на раково болните пациенти и отговаря за 90% от смъртността. 2/3 от диагностицираните пациенти са с локално авансирал процес и/ или метастатична болест (стадий III или IV).Проучването на молекулярни и клетъчни механизми, водещи до формирането и метастазирането на плоскоклетъчния карцином от ларингеален произход, би било от клинична полза за разработването на молекулярна таргетна терапия.На базата на обширен литературен обзор акцентът е поставен върху следните гени – TP53, CDKN2A – exons 1,2,3 and PIK3CA – exons 9, 20, като потенциални отговорници за повишаване метастатичния потенциал на плосколетъчния карцином от ларингеален произход.Изследването на генетично сродство между карцином и метастаза би имало теоретичен принос към опознаването на генотипа и мутационния статус на плоскоклетъчните карциноми на глава и шия, чийто практически потенциал се изразява като прогностична стойност за преживяемостта на онкоболните и подобряване на терапевтичния алгоритъм при диагностицирани пациенти

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

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 μg STX.2HCl .kg-1 was far beneath the EU legislative limit of 800 μg 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

Changes in gene expression of EGFR and LAD1 in patients with metastatic squamous cell laryngeal carcinoma

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

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

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

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

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 densità capillare nel carcinoma della laringe. Studio su 52 casi

L’angiogenesi è uno dei sei principali meccanismi alla base del cancro, ed è stato studiato approfonditamente negli ultimi 20 anni. L’obiettivo del presente studio è stato quello di determinare sia la densità capillare sia l’infiltrato macrofagico nei campioni di carcinoma laringeo e di determinarne la correlazione con gli aspetti clinici e patologici. Sia la densità capillare (CD34) sia l’infiltrato macrofagico (CD68) sono stati determinati con metodiche immunoistochimiche mediante microarray. Il nostro campione ha mostrato una densità capillare media di 14,27 ± 12,92 vasi su campo ingrandito a 200×, e l’infiltrato macrofagico medio è stato di 5,19 ± 4,32. La densità capillare si è dimostrata superiore nei pazienti metastatici. Inoltre uno studio di regressione lineare ha mostrato che l’entità dell’infiltrato macrofagico poteva predire la densità 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