Prenylation Inhibition-Induced Cell Death in Melanoma: Reduced Sensitivity in BRAF Mutant/PTEN Wild-Type Melanoma Cells.

While targeted therapy brought a new era in the treatment of BRAF mutant melanoma, therapeutic options for non-BRAF mutant cases are still limited. In order to explore the antitumor activity of prenylation inhibition we investigated the response to zoledronic acid treatment in thirteen human melanoma cell lines with known BRAF, NRAS and PTEN mutational status. Effect of zoledronic acid on proliferation, clonogenic potential, apoptosis and migration of melanoma cells as well as the activation of downstream elements of the RAS/RAF pathway were investigated in vitro with SRB, TUNEL and PARP cleavage assays and videomicroscopy and immunoblot measurements, respectively. Subcutaneous and spleen-to-liver colonization xenograft mouse models were used to evaluate the influence of zoledronic acid treatment on primary and disseminated tumor growth of melanoma cells in vivo. Zoledronic acid more efficiently decreased short-term in vitro viability in NRAS mutant cells when compared to BRAF mutant and BRAF/NRAS wild-type cells. In line with this finding, following treatment decreased activation of ribosomal protein S6 was found in NRAS mutant cells. Zoledronic acid demonstrated no significant synergism in cell viability inhibition or apoptosis induction with cisplatin or DTIC treatment in vitro. Importantly, zoledronic acid could inhibit clonogenic growth in the majority of melanoma cell lines except in the three BRAF mutant but PTEN wild-type melanoma lines. A similar pattern was observed in apoptosis induction experiments. In vivo zoledronic acid did not inhibit the subcutaneous growth or spleen-to-liver colonization of melanoma cells. Altogether our data demonstrates that prenylation inhibition may be a novel therapeutic approach in NRAS mutant melanoma. Nevertheless, we also demonstrated that therapeutic sensitivity might be influenced by the PTEN status of BRAF mutant melanoma cells. However, further investigations are needed to identify drugs that have appropriate pharmacological properties to efficiently target prenylation in melanoma cells

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

EFFECT OF GENOTYPE, AGE, BODY WEIGHT AND SEX ON THE BODY COMPOSITION OF GROWING RABBITS

[EN] Body composition of 503 growing rabbits of both sexes was examined at the age of 6, 8, 1 O, 12, 14 and 16 weeks. The animals were of four genotypes: purebred Pannon White (PP) and Danish White (DD) and their reciproca! crossings: DP and PD. Between the ages of 6 and 16 weeks, dry matter of the empty body increased from 27.6% to 34.2%, fat from 5.4% to 10.1 % and protein from 18.4% to 20.9%, whereas ash content decreased from 3.5% to 3.0%. The effect of body weight was greater than that of the age. The two groups containing the highest numbers of animals (PP and DP) had similar protein and ash content, but the DP genotype had a higher fa! content than PP. Sex affected fa! content only: the female rabbits contained significantly (P < 0.01) more body fa! than !he male rabbits but only a! 12weeks.[FR] La composition corporelle de 503 lapins en croissance, des deux sexes, a été étudié a 6, 8, 1 O, 12, 14 et 16 semaines d'íige. Les animaux appartenaient a 4 génotypes : Pannon White pur (PP), Danish White (DD) et leurs croisements réciproques : DP et PD. Entre l'íige de 6 semaines et celui de 16 semaines, la matiére séche du corps entier augmente de 27,6 a 34,2%, le matiére grasse de 5,4 a 10,1% et les protéines de 18,4 a 20,9%, tandis que les matiéres minérales diminuent de 3,5 a 3,0%. L'effet du poids vif est plus important que celui de l'íige. Les deux groupes comprenant le plus grands nombres d'animaux (PP et DP) ont des taux de protéines et de maniéres minérales comparables, mais le génotype DP a un taux de matiére grasse supérieur a celui du génotype PP. Le sexe n'affecte que le taux de matiéres grasses : les femelles sont significativement plus grasses que les males mais seulement a 12 semaines d'íige (P<0,01 ).This work was supported by the EU (Copernicus) as part of project CIPA-CT93-0206. the authors gratefully ackowledge the expert technical assistance of E. Biró-Németh and I. Radnai.Szendrö, Z.; Kenessey, A.; Jensen, J.; Jensen, N.; Csapó, J.; Romvári, R.; Milisits, G. (1998). EFFECT OF GENOTYPE, AGE, BODY WEIGHT AND SEX ON THE BODY COMPOSITION OF GROWING RABBITS. World Rabbit Science. 6(3-4). doi:10.4995/wrs.1998.357SWORD63-

Glukozszenzitív insulinoma mérsékelten emelkedett széruminzulinszinttel, eltávolítása után is fennmaradó epilepsziás rohamokkal [A case of glucose-sensitive insulinoma accompanied by slightly elevated serum insulin levels and persisting convulsions after the surgically removed neuroendocrine tumor]

Insul(in)oma is a usually solitary or, in some cases, multifocal tumor of pancreatic beta cells. It may be a component of multiple endocrine neoplasia type 1. or von Hippel-Lindau syndrome. In typical forms the diagnosis - based on the Whipple triad - is simple, however, it may be difficult to recognize in cases with near normal or only slightly elevated serum insulin levels, as well as in patients with known convulsive episodes. With the case presentation of an 81-year-old woman the authors draw attention to the pitfalls of the correct diagnosis. A special feature of the presented case is that convulsions persisted after surgical removal of the pancreatic neuroendocrine tumor verified with functional and imaging methods. Recurrant or residual tumor was not found, and morphological damage of the brain was absent. In the background of the continuing convulsions cerebrovascular alterations as well as the cytotoxic effect of the hypoglycemia-induced excessive glutamate production can be postulated

In breast cancer patients sentinel lymph node metastasis characteristics predict further axillary involvement.

The aim of the study was to correlate various primary tumor characteristics with lymph node status, to examine sentinel lymph node (SLN) metastasis size and non-SLN axillary involvement, to look for a cut-off size/number value possibly predicting additional axillary involvement with more accuracy and to examine the relationship of SLN metastasis size to overall survival. Of 301 patients who underwent SLN biopsy, 75 had positive SLNs. The size of the metastases was measured. For different size categories, association with the prevalence of non-SLN metastases was assessed. Associations between metastasis size and tumor characteristics and overall survival (OS) were studied. The prevalence of axillary lymph node (ALN) involvement was not significantly different between cases with micrometastasis or macrometastasis in SLNs (p = 0.124). However, for metastases larger than 6, 7, and 8 mm, the prevalence of ALN involvement was significantly higher (p = 0.046, 0.022, and 0.025). OS was significantly lower in SLN-positive than in SLN-negative cases (p = 0.0375). Primary tumor size larger than 20 mm was associated with a significantly higher incidence of SLN metastasis (p /=7) in primary tumors was significantly (p < 0.001) associated with ALN involvement in SLN-positive cases, whereas higher Ki67 labeling index was not significantly correlated with SLN or ALN involvement. Lymphovascular invasion (LVI) in primary tumors was significantly correlated with SLN positivity (p < 0.001) but not with further ALN involvement or OS. Tumor size and LVI are predictive for SLN metastasis. Mitotic index, primary tumor size, and larger volume SLN involvement are determinants of further ALN involvement. SLN metastasis size over 6 mm is a strong predictor of further axillary involvement. OS is shorter in the presence of positive SLN