Prognostic significance of angiogenesis and tumor microenvironment on treatment outcome of Hodgkin lymphoma patients

Uvod: I pored značajnog napretka u lečenju bolesnika sa Hočkinovim limfomom (HL) poslednjih nekoliko decenija i dalje značajan broj bolesnika ima loš klinički tok i kratko preživljavanje. U poslednje vreme su vrlo atraktivna istraživanja angioegeneze i mikrosredine tumora u limfomima i njihov prognostički značaj. Cilj istraživanja: Cilj ovog istraživanja je ispitivanje prognostičkog značaja karakteristika mikrosredine tumora (broj makrofaga (TAM), FOXP3 limfocita, gustine krvnih sudova i nivo ekspresije faktora rasta vaskularnog endotela (VEGF)), rutinskih kliničkih i biohemijskih parametara, i određivanje profila bolesnika sa rizikom za loš ishod lečenja. Materijal i metode: Ova retrospektivna studija je obavljena na 84 bolesnika sa novodijagnostikovanim Hočkinovim limfomom. Demografski, patohistološki, klinički i biohemijski podaci su dobijeni iz medicinske dokumentacije. Karakteristike angiogeneze i mikrosredine tumora određivane su na preparatima tkiva dobijenih iz parafinskih kalupa limfnih žlezda iz kojih je postavljena dijagnoza. Rezultati: U univarijantnoj analizi pacijenti sa VEGF pozitivnošću, velikim brojem TAM, malim brojem FOXP3, bulky bolešću, B simptomima, SE>50 mm/h i visokim IPS skorom imali su značajno kraće ukupno preživljavanje (OS) (p=0.046, p=0.017, p=0.003, p=0.006, p=0.022, p=0.013, p=0.024, po redosledu). Multivarijantna analiza kao nezavisne faktore rizika za OS identifikovala je veliki broj TAM i mali broj FOXP3 u grupi biomarkera (p=0.034, p=0.006, po redosledu), dok među kliničkim i laboratorijskim parametrima bulky bolest (p=0.002) i visok IPS (p=0.004) su identifikovani. Na osnovu kumultivnog skora nepovoljnih prognoznih faktora za OS, dizajnirali smo prognozni model za identifikovanje pacijenata sa malim (0-1 faktor), srednjim (2 faktora) i visokim rizikom (3-4 faktora) za loš ishod (p=0.000), sa 5-godišnjim OS 100%, 75% i 50%. Zaključak: Kombinovanje bioloških sa poznatim kliničkim i laboratorijskim prognoznim faktorima može rezultirati boljom stratifikacijom rizika pacijenata sa HL.Introduction: In spite of great progress in treatment of Hodgkin’s lymphoma (HL) in recent few decades, still there is a portion of patients who have bad clinical course of the disease and short survival. In the past few years, the researches regarding prognostic role of angiogenesis and the tumor microenvironment in lymphomas are very attractive. Aim: The aim of this research is to investigate prognostic significance of the characteristics of tumor microenvironment (number of macrophages (TAM), FOXP3 lymphocytes, the density of blood vessels and, the level of expression of vascular endothel growth factor (VEGF)), routine clinical and laboratory findings and, to determinate profile of patients with risk for poor outcome. Patients and methods: A retrospective study was performed on 84 newly diagnosed Hodgkin lymphoma patients. Demographic, pathohistological, clinical and laboratory findings were collected from medical records. The characteristics of angiogenesis and microenvironment were determined on tissue samples taken from paraffin embeded tissue blocks of lymph nodes from which the diagnosis was established. Results: In univariate analysis patients with VEGF positivity, high number of TAM, low number of FOXP3, bulky disease, B symptoms, ESR>50 mm/h and high IPS score had significantly shorter overall survival (OS) (p=0.046, p=0.017, p=0.003, p=0.006, p=0.022, p=0.013, p=0.024, respectively). Multivariate analysis as the independent risk factors for poor OS identified high number of TAM and low number of FOXP3 in the group of biomarkers (p=0.034, p=0.006, respectively), while between clinical and laboratory parameters bulky disease (p=0.002) and high IPS (p=0.004) were identified. Utilizing the cumulative score of unfavorable prognostic factors for OS, we developed prognostic model for identifying patients at low (0-1 factors), intermediate (2 factors) and high risk (3-4 factors) for poor outcome (p=0.000), with 5-years OS of 100%, 75% and 50%. Conclusion: Combining of biological with established clinical and laboratory prognostic factors could result in better risk stratification of patients with HL

Modeling of the buckstay system of membrane walls in watertube boiler construction

Membrane walls are very important structural parts of water-tube boiler construction. Based on their specific geometry, one special type of finite element was defined to help model the global boiler construction. That is the element of reduced orthotropic plate with two thicknesses and two elasticity matrixes, for membrane and bending load separately. A global model of the boiler construction showed that the high value of stress is concentrated in plates of the buckstay system in boiler corners. Validation of the new finite element was done on the local model of the part of membrane wall and buckstay. A very precise model of tubes and flanges was compared to the model formed on the element of a reduced orthotropic plate. Pressure and thermal loads were discussed. Obtained results indicated that the defined finite element was quite favorable in the design and reconstruction of the boiler substructures such as a buckstay system

Modeling of the buckstay system of membrane walls in watertube boiler construction

Membrane walls are very important structural parts of water-tube boiler construction. Based on their specific geometry, one special type of finite element was defined to help model the global boiler construction. That is the element of reduced orthotropic plate with two thicknesses and two elasticity matrixes, for membrane and bending load separately. A global model of the boiler construction showed that the high value of stress is concentrated in plates of the buckstay system in boiler corners. Validation of the new finite element was done on the local model of the part of membrane wall and buckstay. A very precise model of tubes and flanges was compared to the model formed on the element of a reduced orthotropic plate. Pressure and thermal loads were discussed. Obtained results indicated that the defined finite element was quite favorable in the design and reconstruction of the boiler substructures such as a buckstay system

Spectral characterization of families of split graphs

An upper bound for the sum of the squares of the entries of the principal eigenvector corresponding to a vertex subset inducing a k-regular subgraph is introduced and applied to the determination of an upper bound on the order of such induced subgraphs. Furthermore, for some connected graphs we establish a lower bound for the sum of squares of the entries of the principal eigenvector corresponding to the vertices of an independent set. Moreover, a spectral characterization of families of split graphs, involving its index and the entries of the principal eigenvector corresponding to the vertices of the maximum independent set is given. In particular, the complete split graph case is highlighted

Metastasis of hepatocellular carcinoma presented as a tumor of the maxillary sinus and retrobulbar tumor

Introduction. Hepatocellular carcinoma (HCC) is the most frequent primary malignant tumor of the liver. It is usually seen in the 6th and 7th decades of life and chronic hepatitis B is the most frequent cause. Extrahepatic metastasis of HCC is an indicator of a poor prognosis and the most common sites are lungs, bones, lymph nodes, kidneys and adrenal glands. We reported a case of isolated metastasis in the right maxilla, which had been found initially, before the tumor in the liver was diagnosed. Case report. A 70-year-old man underwent dental surgery of the upper right molar. Prolonged bleeding control was difficult for up to two weeks, so the biopsy was performed. Histopathological analysis revealed a metastatic hepatocellular carcinoma. Computerized tomography (CT) of the abdomen revealed a diffusely heterogeneous liver parenchyma with irregular borders and two foci of mass lesions. There were metastasis in the spleen and also two pathological retroperitoneal lymph nodes were detected, but no ascit, liver cirrhosis, cholestasis or portal vein thrombosis were seen. CT of the orbital and maxillary regions revealed a tumor mass in the right maxillary sinus, spreading to the alveolar sinus, nasal cavity and partially infratemporal space. A tumor mass was in the right orbit as well, infiltrating the surrounding bones and muscles. Clinically, there was proptosis of the right eye accompanied by amaurosis. The treatment started with chemotherapy based on 5-fluorouracil (sorafenib was not available). After three cycles, control CTs showed a stable disease in the liver, but progression in the right maxillary sinus and orbit. Enucleation of the right eye was performed and postoperative radiotherapy was planed. The patient deteriorated rapidly and died, about 6 months after the disease had been diagnosed. Conclusion. Extrahepatic metastasis of HCC represents a progressive phase of the disease with poor prognosis, so the main aim of the treatment should be palliation and care of symptoms

Basic research for coincidence method of Cs-134 measurement

Odnosom 134Cs/137Cs u nekom uzorku utvrđuje se porijeklo 137Cs, globalni fallout ili reaktorski akcident. Njihova detekcija i razdvajanje NaI(Tl) detektorom otežana je bliskim energijama zraka (605 keV i 662 keV), kao i zracima bliskih energija iz prirodnih radionuklida, zbog čega se nameće potreba razvoja koincidentnog metoda mjerenja. Koristeći 2 detektora spektrometra PRIPJAT (∼180°) izvor 134Cs razmatran je u integralnom, nekoincidentnom i režimu dvostrukih koincidencija.The origin of 137Cs, whether it was generated as a global fallout or reactor (Chernobyl) accident, is determined with assessment its relationship with 134Cs. 134Cs is artificial radionuclide, produced in nuclear power reactors, with a half-life of 2.1 years. Since the data on 134Cs activity in Montenegro weren’t publish after the Chernobyl disaster in 1986, there is no information about relation between these two radionuclides and therefore its detection in the Montenegro’s environment is not possible nowadays. Their detection (134Cs and 137Cs) and separation with NaI (Tl) detector is aggravated with close energies of gamma rays (605 keV and 662 keV), as well as with rays of close energies from natural radionuclides, causing a need for the development of coincidence measurement method. Using 2 detectors of spectrometer Pripyat (∼180°), 134Cs source is analyzed in an integrated, non-coincidence and the mode of double coincidences. This paper presents the results of the initial research for the establishment of coincident detection methods and determination of artificial radionuclide 134Cs activity in samples from the environment.Article is part of: [http://vinar.vin.bg.ac.rs/handle/123456789/8230

Basic research for coincidence method of Cs-134 measurement

Odnosom 134Cs/137Cs u nekom uzorku utvrđuje se porijeklo 137Cs, globalni fallout ili reaktorski akcident. Njihova detekcija i razdvajanje NaI(Tl) detektorom otežana je bliskim energijama zraka (605 keV i 662 keV), kao i zracima bliskih energija iz prirodnih radionuklida, zbog čega se nameće potreba razvoja koincidentnog metoda mjerenja. Koristeći 2 detektora spektrometra PRIPJAT (∼180°) izvor 134Cs razmatran je u integralnom, nekoincidentnom i režimu dvostrukih koincidencija.The origin of 137Cs, whether it was generated as a global fallout or reactor (Chernobyl) accident, is determined with assessment its relationship with 134Cs. 134Cs is artificial radionuclide, produced in nuclear power reactors, with a half-life of 2.1 years. Since the data on 134Cs activity in Montenegro weren’t publish after the Chernobyl disaster in 1986, there is no information about relation between these two radionuclides and therefore its detection in the Montenegro’s environment is not possible nowadays. Their detection (134Cs and 137Cs) and separation with NaI (Tl) detector is aggravated with close energies of gamma rays (605 keV and 662 keV), as well as with rays of close energies from natural radionuclides, causing a need for the development of coincidence measurement method. Using 2 detectors of spectrometer Pripyat (∼180°), 134Cs source is analyzed in an integrated, non-coincidence and the mode of double coincidences. This paper presents the results of the initial research for the establishment of coincident detection methods and determination of artificial radionuclide 134Cs activity in samples from the environment.Article is part of: [http://vinar.vin.bg.ac.rs/handle/123456789/8230

Some new considerations about double nested graphs

In the set of all connected graphs with fixed order and size, the graphs with maximal index are nested split graphs, also called threshold graphs. It was recently (and independently) observed in [F.K.Bell, D. Cvetkovi´c, P. Rowlinson, S.K. Simi´c, Graphs for which the largest eigenvalue is minimal, II, Linear Algebra Appl. 429 (2008)] and [A. Bhattacharya, S. Friedland, U.N. Peled, On the first eigenvalue of bipartite graphs, Electron. J. Combin. 15 (2008), #144] that double nested graphs, also called bipartite chain graphs, play the same role within class of bipartite graphs. In this paper we study some structural and spectral features of double nested graphs. In studying the spectrum of double nested graphs we rather consider some weighted nonnegative matrices (of significantly less order) which preserve all positive eigenvalues of former ones. Moreover, their inverse matrices appear to be tridiagonal. Using this fact we provide several new bounds on the index (largest eigenvalue) of double nested graphs, and also deduce some bounds on eigenvector components for the index. We conclude the paper by examining the questions related to main versus non-main eigenvalues