The effectiveness of treatment for patients in the stage IIIA nonsmall cell lung cancer who were operated after neoadjuvant therapy

Karcinom bronha najčešći uzrok smrti među malignim bolesti u svetu. U XX veku je registrovan značajan porast kako incidence, tako i mortaliteta karcinoma bronha u većini zemalja. Medijana preživljavanja u svim stadijumima bolesti se značajno poboljšala poslednjih godina XX veka, ali nedovoljno u odnosu na očekivano. U najvećem broju slučajeva, bolest se otkriva u uznapredovalom stadijumu, kada je radikalno hirurško lečenje kao optimalan vid lečenja nemoguće. Neodjuvantna terapija kod bolesnika sa lokalno uznapredovalim karcinomom pluća i zahvaćenim N2 limfnim čvorovima jedan je od modusa multimodalnog lečenja bolesnika sa nemikrocelularnim karcinomima pluća (NSCLC) u cilju poboljšanja ishoda njihovog lečenja. Ovakav pristup podrazumeva prevođenje pacijenta iz višeg u niži stadijum bolesti - „downstaging”. Na taj način pacijent postaje potencijalno resektabilan u smislu daljeg hirurškog lečenja koji bi mogao da obezebedi sveukupni onkološki benefit. Osnovni ciljevi ove doktorske disertacije su bili: procena odgovora na neoadjuvantnu terapiju kod bolenika sa IIIA stadijumom nemikrocelularnog karcinoma bronha u odnosu na T faktor i N faktor, procena TNM klasifikacije pre i posle primenjene neoadjuvantne terapije kod bolesnika sa IIIA stadijumom nemikrocelularnog karcinoma bronha, određivanje stepena tumorske regresije patohistološkom analizom hirurškog resekata nemikrocelularnog karcinoma bronha operisanih bolesnika nakon primenjene neoadjuvantne terapije, kao prognostički faktor za period bez bolesti i ukupnog preživljavanja i određivanje stepena regresije tumora u maligno izmenjenim limfnim čvorovima nakon primenjene neoadjuvantne terapije kod bolesnka sa IIIA stadijumom nemikrocelularnog karcinoma bronha, kao prognostički faktor za period bez bolesti i ukupnog preživljavanja.Rezultati su pokazali da neoadjuvantna terapija prema RECIST kriterijumima dovodi značajnog smanjenja veličine tumora, T faktora, kao i do znčajnog downstaging“-a nodalnog statusa, N faktora, u terapiji bolesnika sa IIIA stadijumom nemikrocelularnog karcinoma bronha. Neoadjuvantna terapija prema RECIST kriterijumima dovodi značajnog smanjenja klinikog stadijuma bolesti, u terapiji bolesnika sa IIIA stadijumom nemikrocelularnog karcinoma bronha Nakon primenjene neoadjuvantne terapije nema značajne razlike u T faktoru koji je određen radiološki prema RECIST kriterijumima (ycT) i patohistološki (ypT) na hirurškom materijalu. Nakon primenjene neoadjuvantne terapije prisutna je značajna razlika u N faktoru koji je određen radiološki prema RECIST kriterijumima (ycN) i patohitološki (ypN) na hirurškom materijalu. Nakon primenjene neoadjuvantne terapije prisutna je značajna razlika u kliničkom stadijumu bolesti koji je određen radiološki prema RECIST kriterijumima (yc) i patohitološki (yp) na hirurškom materijalu. Gradusi tumorske regresije su usko povezani sa procentom očuvanog tumorskog tkiva. Stepen tumorske regresije u resekatu primarnog tumora nije u korelaciji sa ukupnim preživljavanjem i procenom perioda bez bolesti kod pacijenata sa IIIA stadijumom nemikrocelularnog karcinoma bronha.Lung cancer is the most common cause of death among malignant diseases in the world. In the twentieth century was a significant increase in both incidence and mortality of lung cancer in most countries. Median survival in all stages of the disease has improved significantly in recent years of the twentieth century, but not as we expected. In most cases, the disease is detected at an advanced stage, when the radical surgical treatment is considered impossible. Neoadjuvant therapy, in patients with locally advanced carcinoma of the lung, and with affected the lymph nodes N2, is one of the modes of multimodal treatment of patients with non-small cell lung cancer (NSCLC) in order to improve the outcome of their treatment. This involves translating the patient from a higher to a lower stage of the disease - "downstaging". In this way the patient is considered for further surgical treatment that could provide him overall oncology benefit. Main objectives of this PhD dissertation are: evaluation of response to neoadjuvant therapy in stage IIIA NSCLC patients in relation to T factor and N factor; evaluation of TNM classification before and after use of neoadjuvant therapy in stage IIIA NSCLC patients; determination of degree of tumor regression with pathohistologic analysis of resection specimen of NSCLC obtained from patients after application of neoadjuvant therapy, as a prognostic factor for disease-free period and overall survival rate; and determination of degree of tumor regression in malignant lymph nodes after application of neoadjuvant therapy in stage IIIA NSCLC patients, as a prognostic factor for disease-free period and overall survival rate. Results have shown that neoadjuvant therapy according to RECIST criteria leads to significant reduction of tumor size, T factors, as well as significant downstaging of nodal status, N factor, in treatment of stage IIIA NSCLC patients. Furthermore, neoadjuvant therapy according to RECIST criteria leads to significant reduction of clinical stage of the disease in treatment of stage IIIA NSCLC patients. However, after neoadjuvant therapy is applied there is no significant difference in T factor determined radiologically according to RECIST criteria (ycT) and by pathohistologic analysis (ypT) of resected specimen. Neoadjuvant therapy leads to significant difference in N factor which is determined radiologically according to RECIST criteria (ycN) and by pathohistologic analysis (ypN) of resection specimen. After neoadjuvant therapy is applied there is significant difference in clinical stage of the disease determined radiologically according to RECIST criteria (yc) and by pathohistologic analysis (yp) of resection specimen. Tumor regression grading is closely linked to the percentage of preserved tumor tissue. Degree of tumor regression in surgical resection of primary tumor does not correlate to the overall survival rate and estimation of disease-free period in stage IIIA NSCLC patients

Group form reconsidered : physicality and humanity of collective spaces

In 1964, Japanese architect Fumihiko Maki presented the need for investigation in housing collective form. The need was explained through his sensitivity towards the dynamic change of society and simultaneous inadequacy of architectural static and fragmented respond. This paper presents the contemporary view on the theory of collective form and its investigation into why and how the group of buildings stands together. It brings forward the need for renewed architectural focus on group form, one of Maki's collective form types, and the social and human reasoning of design decisions. The theory of linkages in group form is related to more recent socio-spatial analytical theories and interpreted as an analytical tool for understanding housing morphologies, configurations, and its social capacity of group form. It is proposed that the morphological and configurational approach can be used in combination for reading and understanding the historical and contemporary housing ensembles and their relation to an urban whole. The aim of the theoretical research is the identification of the analytical framework and design principles of group form based on architectural and configurational elements and their relations, as socially and culturally relevant

Similarity of cultivars of wheat (triticum durum) on the basis of composition of gliadin alleles

Djukic N., D. Knezevic, D. Horvat, D. Zivancev and A. Torbica (2011): Similarity of cultivars of wheat (Triticum durum) on the basis of composition of gliadin alleles. - Genetika, Vol 43, No. 3, 527- 536. Twenty one durum wheat cultivars originating from different world countries were investigated. Composition of gliadins was analyzed by acid polyacrylamide gel electrophoresis. Allele composition of gliadins was determined on the basis of identified gliadin blocks. Polymorphisms of Gli-loci was established and 27 different gliadin alleles were identified, namely, 5 at Gli-A1, 4 at Gli-B1, 9 at Gli-A2 and 9 alleles at Gli-B2 locus. The catalogue of determined alleles was presented. Frequency of alleles ranged from 4.76% to 42.86%. Heterozygous Gli- loci were identified at two durum cultivars. Similarity among cultivars was studied on composition of Gli-alleles and presented by UPGMA dendogram. On the base of Gli-allele composition, similarity varied from 0% to 100%

Minute pulmonary meningothelial-like nodules simulating a metastatic lung adenocarcinoma: A case report

Minute pulmonary meningothelial-like nodules (MPMNs) are relatively rare lesions that located at the pleura or parenchyma of the lung. They are usually found incidentally at autopsy or in surgical specimens. We presented a case of asymptomatic 47-year-old woman with an abnormal shadow in the right upper lung field found by a routine chest X ray. A computed tomography (CT) scan of the thorax revealed a hyperdense subpleural mass, which histologically conformed to adenocarcinoma. A resection of the right upper lobe discovered preponderance of small multiple lesions under the pleura. Microscopically, they were an interstitial nodular proliferation of oval or spindle-shape cells arranged in a zellenballen nesting pattern near small veins. Immunohistochemical and cytological analyses confirmed the diagnosis of MPMNs. Coexistence of multiple MPMNs and lung adenocarcinoma can be a differential diagnostic problem due to suspected metastasis of the primary carcinoma. To obtain an accurate diagnosis, the clinical findings should completely conform to histological, immunohistochemical, and cytological ones

Lab-on-a-Chip method uncertainties in determination of high-molecular- weight glutenin subunits

Polymeric wheat endosperm proteins, especially the high-molecular-weight glutenin subunits (HMW-GS), are probably the most interesting protein fraction giving the essential information about the bread-making quality of wheat flour. A relatively new method that shows great potential for a fast, reliable and automatable analysis of protein purity, sizing and quantification is microfluidic or Lab-on-a-Chip (LoaC) capillary electrophoresis. This aim of this work was to explore the possibilities of implementation of LoaC method to analysis of protein samples isolated from a Serbian common wheat variety, emphasizing the steps that might bring uncertainties and affect reproducibility of obtained glutenin subunits quantitation results. A good resolution of protein bands in a molecular weight range of 14.0 to 220.0 kDa was achieved. The reproducibility of HMW-GS sizing and quantitation were good, with the average coefficient of variation values of 1.2 and 12.2%. The ratio of HMW-GS to low-molecular-weight glutenin subunits (LMW-GS) was about 20%. The investigation ruled out influences of the extract solution addition and the buffer addition steps of the applied method, as well as the individual chip influence on GS quantitation results. However, there was statistically significant difference between HMW-GS quantitation results of multi-step and one-step extraction procedures applied prior to glutenin subunits extraction step

Variability of malondialdehyde content and yield elements in Triticum aestivum L. under heat stress conditions

Heat stress has a significant effect on the growth and development of cereals and affects cereals production by reducing the total yield. High temperatures in plants lead to oxidative stress, which creates reactive oxygen species that are specific to cause damage to the cell membrane. Due to the action of reactive oxygen species, lipid peroxidation can occur. For that reason, it is important to find cultivars that are more resistant to the harmful effects of heat stress and thus enable higher productivity. The aim of this study was to determine the effect of heat stress on the degree of lipid peroxidation and yield elements in leaves of 10 wheat cultivars, in order to select cultivars more resistant to heat stress. The degree of lipid peroxidation was determined spectrophotometrically by measuring the concentration of reactive substances of thiobarbiturate acid (mainly malondialdehyde - MDA). The cultivar Renesansa with the largest increase in MDA in conditions of high air temperature (2.848 µmol/g fw) was also characterized by the lowest yield (2870 kg/ha). On the other hand, the cultivar Talas with the smallest increase in MDA content (1800 µmol/g fw) in conditions of high air temperature showed significantly higher yield (3830 kg/ha). In this paper was shown that lipid peroxidation has a significant effect on yield reduction in the investigated wheat cultivars. Cultivars Talas, Apač, Hyfi, Mila and Salasar were characterized as cultivars more resistant to heat stress with higher yields. These results suggest that wheat cultivars were significantly different in their ability to respond to heat stress, which could be useful for the development of tolerant wheat cultivars in the breeding programs.Publishe

The trends in maize and wheat production in the Republic of Serbia

The total area under cereals during 2018 remained at a long-term stable level of about 1.7 million hectares. Maize and wheat are the most important crops grown in the Republic of Serbia. In the structure of harvested areas under cereals, maize dominates (53%), followed by wheat (38%). The objective of this paper was to determine if there was a recognisable trend line for the production of these crops in the 2007-2018 period. The yield data (Area harvested (ha), Production (tonnes), Production (t/ha)) were collected from the Statistical Office of the Republic of Serbia. Calculations of relevant and valid trends using central tendency measures, dispersion measures, relative ratios and percentage growth were used for statistical data processing. During the observation period, the average annual growth in maize yield was 6.38%, while the average annual growth in wheat yield was slightly lower, 2.00%. However, it is not possible to create an appropriate trend line for any of the variables in order to predict a future time period, since the coefficient of determination is low.Ukupna poljoprivredna površina pod strnim žitima u 2018. godini nije puno varirala u odnosu na prethodne godine i iznosila je oko 1.7 miliona hektara. Kukuruz i pšenica predstavljaju najznačajnije biljne kulture koje se gaje u Republici Srbiji. U strukturi požnjevenih površina pod žitaricama kukuruz je dominirao sa čak 53% i bio je praćen od strane pšenice sa 38%. Cilj ovog rada bio je utvrditi postoji li prepoznatljiva linija trenda proizvodnje ovih kultura za period od 2007. do 2018. godine. Podaci o prinosu (požnjevena površina (ha), proizvodnja (u tonama), prinos (t/ha)) prikupljeni su od Republičkog zavoda za statistiku. Za statističku obradu podataka korišćeni su proračuni relevantnih i validnih kretanja primenom mera centralne tendencije, mera disperzije, relativnih pokazatelja i procentualnog rasta. Prosečni godišnji rast prinosa kukuruza u posmatranom periodu iznosi 6,38%, dok je za pšenicu prosečan godišnji rast u posmatranom periodu nešto manji i iznosi 2,00%. Međutim, ni za jednu od promenljivih nije moguće napraviti odgovarajuću liniju trenda, u cilju predviđanja za budući vremenski period, jer je koeficijent determinacije mali

Benefits and Limitations of Lab-on-a-Chip Method over Reversed-Phase High-Performance Liquid Chromatography Method in Gluten Proteins Evaluation

RP-HPLC (reversed-phase high-performance liquid chromatography) is widely used to determine the amounts of the different gluten protein types. However, this method is time-consuming, especially at early stages of wheat breeding, when large number of samples needs to be analyzed. On the other hand, LoaC (Lab-on-a-Chip) technique has the potential for a fast, reliable, and automatable analysis of proteins. In the present study, benefits and limitations of Lab-on-a-Chip method over RP-HPLC method in gluten proteins evaluation were explored in order to determine in which way LoaC method should be improved in order to make its results more compliant with the results of RP-HPLC method. Strong correlation (P lt = 0.001) was found between numbers of HMW glutenin peaks determined by LoaC and RP-HPLC methods. Significant correlations (P lt = 0.05) were obtained between percentages of HMW and LMW glutenin subunits calculated with regard to total HMW + LMW area. Even more significant correlation (P lt = 0.001) was found when percentages of individual HMW areas were calculated with regard to total HMW. RP-HPLC method showed superiority in determination of gliadins since larger number and better resolution of gliadin peaks were obtained by this method

Characterization of bread wheat cultivars (Triticum aestivum L.) by glutenin proteins

Glutenin polymers composed of HMW and LMW subunits are important contributors to the wheat end-use properties. Twenty-six winter wheat cultivars differing in bread processing quality were collected at the experimental fields of the Agricultural Institute Osijek, Croatia and Institute of the Field and Vegetable Crops Novi Sad, Serbia, in 2008/2009 season. The HMW glutenins composition and glutenin proteins content were determined by SDS-PAGE and RP-HPLC, respectively, with aim to determine the relationship between glutenin protein fractions and wheat quality properties. Significant differences were found between Croatian and Serbian cultivars in several quality attributes (GI, WA, DDT, DS and R/EXT) as well as in the content of total glutenins and LMW glutenins and GLI/GLU ratio. The dominant HMW subunits in analyzed cultivars were 2*, 7 + 9/7 + 8 and 5 + 10. Principal component analysis (PCA) confirmed the presence of association between HMW glutenins composition and GI, dough E, R and R/EXT, while the glutenins quantitative data showed pronounced relation with P, DDT, DS, E, R and R/EXT. GLI/GLU ratio had the opposite effect on these parameters

Prediction of the genetic similarity of wheat and wheat quality by reversed-phase high-performance liquid chromatography and lab-on-chip methods

The aim of this study was to compare efficiency of RP-HPLC (Reversed-Phase High-Performance Liquid Chromatography) and LOC (Lab-on-Chip) methods for wheat gluten protein quantification regarding clustering of wheat cultivars according to the genetic similarity (HMW-GS combinations), as well as to explore relations of these two methods to wheat quality parameters. For that purpose, wheat quality parameters (protein content, falling number, wet gluten content, gluten index, Farinograph, Extensograph, and Amylograph), as well as amounts of gliadin and glutenin fractions by RP-HPLC and LOC methods were determined in two different sets of wheat cultivars (Croatian and Serbian). The percentages of gluten proteins and the values of quality parameters were used to characterize the samples by principal component analysis (PCA). Gluten protein quantification performed by method based on the protein fraction separation by molecular weights (LOC) was better for grouping of genetically similar wheat cultivars than quantification of proteins separated by their different solubility in specified solvent gradient (RP-HPLC). LOC method showed higher potential in wheat quality prediction