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

Antidiabetic Potential of Plants Used in Bulgarian Folk Medicine and Traditional Diet

The idea of this chapter is that currently available antidiabetic drugs specifically target several points of the T2D pathophysiology but they do not cover all aspects of the disease. In addition, many adverse effects of synthetic antidiabetic agents have been reported. The suggested manuscript is an overview of the available scientific literature focused on antiobesity and antidiabetic potential of selected 42 medicinal and edible plants of the Bulgarian flora. Most of the reports reveal the effect of extracts or their active components on specific biochemical mechanisms. Mechanistic data about hypoglycemic and hypolipidemic action are presented for some of the plants. An essential part of this review is dedicated to the target mechanisms behind the effects of the selected plant species. The authors hope that this review will serve as a starting point for future investigations with a contribution to the prevention and therapy of diabetes

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

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Preparation of nanocrystalline thin films of ZnO by sol-gel dip coating”,

Nanocrystalline ZnO thin films are deposited from sol-gel of zinc acetateand using dip coating onto two different substrates: glass and aluminium foil. (i) Films on glass substrates. Nanostructured ZnO thin films with different concentrations of Ni 2+ doping (0, 1, 5, 10 and 15 wt%) are prepared for the first time by the sol gel method. The film surface is with a ganglia-like structure as observed by Scanning Electron Microscopy (SEM). The films comprise of ZnO nanocrystallites with hexagonal crystal structure, as revealed by means of X-ray diffraction (XRD). (ii) Films on aluminium foil substrates. The ZnO films are annealed at different temperatures (100 °C, 300 °C and 500 °C) and characterized by means of SEM and XRD. The film surface is with the characteristic ganglia-like patterns. The crystalline structure is hexagonal with the crystallite sizes increasing with the annealing temperature

Plasma metabolic signatures of healthy overweight subjects challenged with an oral glucose tolerance test

Insulin secretion following ingestion of a carbohydrate load affects a multitude of metabolic pathways that simultaneously change direction and quantity of interorgan fluxes of sugars, lipids and amino acids. In the present study, we aimed at identifying markers associated with differential responses to an OGTT a population of healthy adults. By use of three metabolite profiling platforms, we assessed these postprandial responses of a total of 202 metabolites in plasma of 72 healthy volunteers undergoing comprehensive phenotyping and of which half enrolled into a weight-loss program over a three-month period. A standard oral glucose tolerance test (OGTT) served as dietary challenge test to identify changes in postprandial metabolite profiles. Despite classified as healthy according to WHO criteria, two discrete clusters (A and B) were identified based on the postprandial glucose profiles with a balanced distribution of volunteers based on gender and other measures. Cluster A individuals displayed 26% higher postprandial glucose levels, delayed glucose clearance and increased fasting plasma concentrations of more than 20 known biomarkers of insulin resistance and diabetes previously identified in large cohort studies. The volunteers identified by canonical postprandial responses that form cluster A may be called pre-pre-diabetics and defined as “at risk” for development of insulin resistance. Moreover, postprandial changes in selected fatty acids and complex lipids, bile acids, amino acids, acylcarnitines and sugars like mannose revealed marked differences in the responses seen in cluster A and cluster B individuals that sustained over the entire challenge test period of 240 min. Almost all metabolites, including glucose and insulin, returned to baseline values within this timeframe, except a variety of amino acids and here those that have been linked to diabetes development. Analysis of the corresponding metabolite profile in a fasting blood sample may therefore allow for early identification of these subjects at risk for insulin resistance without the need to undergo an OGTT

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

Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol-metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study-specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol-metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer-specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta-analysed using fixed-effect and random-effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed-effect meta-analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed  = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed  = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed  = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed  = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low-grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression

Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort

BACKGROUND: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach. METHODS: We derived a weighted genetic risk score for pubertal development, combining 13 SNPs associated with male Tanner stage. A higher score indicated a later puberty onset. We examined the association of this score with prostate cancer risk, stage and grade in the UK-based ProtecT case-control study (n = 2,927), and used the PRACTICAL consortium (n = 43,737) as a replication sample. RESULTS: In ProtecT, the puberty genetic score was inversely associated with prostate cancer grade (odds ratio (OR) of high- vs. low-grade cancer, per tertile of the score: 0.76; 95 % CI, 0.64-0.89). In an instrumental variable estimation of the causal OR, later physical development in adolescence (equivalent to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade. CONCLUSIONS: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease