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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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

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

Escherichia coli Frameshift Mutation Rate Depends on the Chromosomal Context but Not on the GATC Content Near the Mutation Site

Different studies have suggested that mutation rate varies at different positions in the genome. In this work we analyzed if the chromosomal context and/or the presence of GATC sites can affect the frameshift mutation rate in the Escherichia coli genome. We show that in a mismatch repair deficient background, a condition where the mutation rate reflects the fidelity of the DNA polymerization process, the frameshift mutation rate could vary up to four times among different chromosomal contexts. Furthermore, the mismatch repair efficiency could vary up to eight times when compared at different chromosomal locations, indicating that detection and/or repair of frameshift events also depends on the chromosomal context. Also, GATC sequences have been proved to be essential for the correct functioning of the E. coli mismatch repair system. Using bacteriophage heteroduplexes molecules it has been shown that GATC influence the mismatch repair efficiency in a distance- and number-dependent manner, being almost nonfunctional when GATC sequences are located at 1 kb or more from the mutation site. Interestingly, we found that in E. coli genomic DNA the mismatch repair system can efficiently function even if the nearest GATC sequence is located more than 2 kb away from the mutation site. The results presented in this work show that even though frameshift mutations can be efficiently generated and/or repaired anywhere in the genome, these processes can be modulated by the chromosomal context that surrounds the mutation site

The Methyl-CpG Binding Proteins Mecp2, Mbd2 and Kaiso Are Dispensable for Mouse Embryogenesis, but Play a Redundant Function in Neural Differentiation

The precise molecular changes that occur when a neural stem (NS) cell switches from a programme of self-renewal to commit towards a specific lineage are not currently well understood. However it is clear that control of gene expression plays an important role in this process. DNA methylation, a mark of transcriptionally silent chromatin, has similarly been shown to play important roles in neural cell fate commitment in vivo. While DNA methylation is known to play important roles in neural specification during embryonic development, no such role has been shown for any of the methyl-CpG binding proteins (Mecps) in mice.. No evidence for functional redundancy between these genes in embryonic development or in the derivation or maintenance of neural stem cells in culture was detectable. However evidence for a defect in neuronal commitment of triple knockout NS cells was found.Although DNA methylation is indispensable for mammalian embryonic development, we show that simultaneous deficiency of three methyl-CpG binding proteins genes is compatible with apparently normal mouse embryogenesis. Nevertheless, we provide genetic evidence for redundancy of function between methyl-CpG binding proteins in postnatal mice

DNA methylation and methyl-CpG binding proteins: developmental requirements and function

DNA methylation is a major epigenetic modification in the genomes of higher eukaryotes. In vertebrates, DNA methylation occurs predominantly on the CpG dinucleotide, and approximately 60% to 90% of these dinucleotides are modified. Distinct DNA methylation patterns, which can vary between different tissues and developmental stages, exist on specific loci. Sites of DNA methylation are occupied by various proteins, including methyl-CpG binding domain (MBD) proteins which recruit the enzymatic machinery to establish silent chromatin. Mutations in the MBD family member MeCP2 are the cause of Rett syndrome, a severe neurodevelopmental disorder, whereas other MBDs are known to bind sites of hypermethylation in human cancer cell lines. Here, we review the advances in our understanding of the function of DNA methylation, DNA methyltransferases, and methyl-CpG binding proteins in vertebrate embryonic development. MBDs function in transcriptional repression and long-range interactions in chromatin and also appear to play a role in genomic stability, neural signaling, and transcriptional activation. DNA methylation makes an essential and versatile epigenetic contribution to genome integrity and function