Prognostic impact of CD73 expression and its relationship to PD-L1 in patients with radically treated pancreatic cancer

Immune suppressing molecule CD73 is overexpressed in various cancers and associated with poor survival. Little is so far known about the predictive value of CD73 in pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to investigate the prognostic significance of CD73 in PDAC. The study material consisted of 110 radically treated patients for PDAC. Tissue microarray blocks were constructed and stained immunohistochemically using CD73 antibody. Staining intensity and numbers of stained tumour cells, inflammatory cells, stroma, and blood vessels were assessed. High-level CD73 expression in tumour cells was positively associated with PD-L1 expression, perineural invasion, and histopathological grade. CD73 positivity in tumour-infiltrating lymphocytes was significantly associated with lymph node metastasis. Lymphocytic CD73 positivity was also associated with staining positivity in both stroma and vascular structures. In addition, CD73 positivity in vascular structures and stroma were associated with each other. There were no significant associations between CD73 positive tumour cells and CD73 positivity in any other cell types. PD-L1 expression was associated with CD73 staining positivity in stroma (p = 0.007) and also with histopathological grade (p = 0.033) and T class (p = 0.016) of the primary tumour. CD73 positivity in tumour cells was significantly associated with poor disease-specific (p = 0.021) and overall survival (p = 0.016). In multivariate analysis, CD73 positivity in tumour cells was an independent negative prognostic factor together with histopathological grade, TNM stage, and low immune cell score. In conclusion, high CD73 expression in tumour cells is associated with poor survival in PDAC independently of the number of tumour-infiltrating lymphocytes or TNM stage

Mammalian Target of Rapamycin (mTOR) Activity Dependent Phospho-Protein Expression in Childhood Acute Lymphoblastic Leukemia (ALL)

Modern treatment strategies have improved the prognosis of childhood ALL; however, treatment still fails in 25–30% of patients. Further improvement of treatment may depend on the development of targeted therapies. mTOR kinase, a central mediator of several signaling pathways, has recently attracted remarkable attention as a potential target in pediatric ALL. However, limited data exists about the activity of mTOR. In the present study, the amount of mTOR activity dependent phospho-proteins was characterized by ELISA in human leukemia cell lines and in lymphoblasts from childhood ALL patients (n = 49). Expression was measured before and during chemotherapy and at relapses. Leukemia cell lines exhibited increased mTOR activity, indicated by phospho-S6 ribosomal protein (p-S6) and phosphorylated eukaryotic initiation factor 4E binding protein (p-4EBP1). Elevated p-4EBP1 protein levels were detected in ALL samples at diagnosis; efficacy of chemotherapy was followed by the decrease of mTOR activity dependent protein phosphorylation. Optical density (OD) for p-4EBP1 (ELISA) was significantly higher in patients with poor prognosis at diagnosis, and in the samples of relapsed patients. Our results suggest that measuring mTOR activity related phospho-proteins such as p-4EBP1 by ELISA may help to identify patients with poor prognosis before treatment, and to detect early relapses. Determining mTOR activity in leukemic cells may also be a useful tool for selecting patients who may benefit from future mTOR inhibitor treatments

Demographic shift disproportionately increases cancer burden in an aging nation: current and expected incidence and mortality in Hungary up to 2030

István KenesseyNational Cancer Registry of Hungary, National Institute of Oncology, Budapest, HungaryI would like to thank Menyhárt et al1 for their recent publication, but I have a number of issues I would like to raise regarding the data collection and analysis.Authors’ replyOtília Menyhárt,1,2 János T Fekete,2 Balázs Győrffy1,21MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Hungarian Academy of Sciences, Budapest,Hungary; 22nd Department of Pediatrics, Semmelweis University, Budapest, HungaryWe wish to thank Dr Kenessey for his queries and offer the following responses to help clarify the issues raised. View the original paper by Menyhárt and colleagues

THE EFFECT OF LIVE WEIGHT ON THE CARCASS TRAITS AND THE CHEMICAL COMPOSITION OF MEAT OF PANNON WHITE RABBITS BETWEEN 2.2 AND 3.5 KGS

[EN] For 267 Pannon White growing rabbits of both sexes slaughtered at a body weight of 2.2-2.4, 2.4-2.6, 2.6-2.8, 2.8-3.0, 3.0- 3.2, 3.2-3.4 and 3.4-3.5 kg, the average dressing percentage was 59.5, 60.7, 61.9, 62.2, 61.4, 62.4 and 62.1 % respectively. While the weight of live animals increased by about 50 % between 2.29 and 3.42 kg the change in the weight of blood (23 %), full gastrointestinal tract (26 %) and head (35 %) were the lowest, whereas the intermediate part (65 %), liver (82 %), skin (73 %), meat on hind legs (74 %), meat on the intermediate part (85 %) and perirenal fat (326 %) gained weight the most rapidly. 129 Pannon White rabbits were slaughtered between 2.2 and 3.5 kg live weight. The water, protein, fat and ash content of their meat was analyzed in the M. longissimus dorsi (LD), hind leg (HL) and M. /ongíssimus dorsi + belly (LD + B). Water content averaged 74.8, 73.8 and 71.0 % in LO, HL and LD + B respectively, whereas protein, fat and ash content averaged 23.1, 22.1 and 21.7 %, 1.08, 3.24 and 6.39 %, 1.15, 1.09 and 1.04 % respectively, in the arder of the meat parts Usted above. Water content decreased and fat content increased with increasing weight (r = -0.47, -0.33 and -0.51, r = 0.38, 0.31 and 0.45 for water and fat contents of LD, HL and LD + B respectively). Protein and ash content did not change significantly with weight.[FR] Pour 267 /apins en croissance de génotype Pannon White, des deux sexes, abattus au poids vif de 2,2-2,4; 2,4-2,6; 2,6-2,8; 2,8-3,0; 3,0- 3,2 ; 3,2-3,4 ; 3,4-3,5 kg, le rendement moyen a /'abattage a été de 59,5 - 60, 7 - 61,9 - 62,2 - 61,4 - 62,4 et 62, 1% respectivement. A/ors que le poids vif des animaux augmente d'environ 50% entre 2,29 et 3,42 kg, les augmentations de poids du sang (23%), du tractus gastrointestinal plein (26%), et de la téte (35%) ont été inférieures a cene du poids vif. A /'inverse, les augmentations de poids du rSble (65%), du foie (72%), de la peau (73%), des muse/es des pattes arriares ou du rSble (7 4% et 85%) et surtout du gras périrénal (326%) ont été plus rapides que ce/le du poids vif. Par ailleurs, 129 lapins Pannon White ont été abattus entre 2,2 et 3,5 kg de poids vif. Les teneurs en eau, protéines, lipides et matiares minéra/es ont été déterminées pour le muse/e longissimus dorsi (LO), /es muse/es d'une patte arriare (HL) et /'ensemble muscu/aire longissimus dorsi + paroi abdominale (LO + B). La teneur moyenne en eau est de 74,8- 73,8 et 71,0% pour LO, HL et LO+ B, tandis que les teneurs moyennes en protéines, lipides et minéraux des mémes ensemb/es muscu/aires sont de 23, 1 - 22, 1 et 21, 7 % ; 1,08 - 3,24 et 6,39% ; 1, 15 - 1,09 et 1,04 respectivement. Quand le poids vif augmente, la teneur en eau diminue et la teneur en lipides augmente (r = -0,47, -0,33 et -0,51 ; r = +0,38 ; +0,31 et +0,45 pour /'eau et les lipides de LO, HL et LO + B, respectivement). Les teneurs en protéines et en matiares minérales ne varient pes significativement avec le poíds vif.Szendrö, Z.; Randai, I.; Biro-Nemeth, E.; Romvari, R.; Milisits, G.; Kenessey, A. (1998). THE EFFECT OF LIVE WEIGHT ON THE CARCASS TRAITS AND THE CHEMICAL COMPOSITION OF MEAT OF PANNON WHITE RABBITS BETWEEN 2.2 AND 3.5 KGS. World Rabbit Science. 06(2). doi:10.4995/wrs.1998.351SWORD06