Bisphosphonat kezelés hatása a csontok fibrosus dysplasiájára = The effect of bisphosphonate treatment on the fibrous dysplasia

A SE Ortopédiai Klinikán külföldi tapasztalatok alapján 2002-től 6 beteget kezeltünk 3 éves időtartamig iv. és per os, majd 2004 és 2006 között további 11 beteget 1 éves időtartamig per os adott BP-tal. Laboratóriumi, rtg és ODM vizsgálatokkal történt prospektív utánkövetés, majd 2006-tól indult meg 16 betegből kivett FD-s csontminta genetikai elemzése a SE I.sz. Belgyógyászati Klinika biológiai laborjával együtt végzett közös munkában. A kezelés hatására a korábban magas értékek csökkentek. A kezelés ideje alatt egyetlen betegnél sem észleltünk patológiás törést. ODM vizsgálattal a 3 éves kezelésbe bevont betegek teljes test csonttömege és az egészséges lumbalis csigolyák, ill. egészséges oldali combnyak densitása mérhetően emelkedett, ami a BP kezelés eredménye. A kizárólag a velőüregben, a fibrosus dysplasiás területeken mért densitások azonban nem változtak, nem emelkedtek a kezelés hatására. mRNS izolálás után cDNS készítéssel és real time PCR vizsgálattal mértük meg a fibrosus dysplasiás szövet fehérje eloszlását 120, a csontanyagcseréhez kapcsolt gén aktivitása szempontjából, ahol a kontroll csoportot egészséges, praemenopausás női csontszövet alkotta. Vizsgálataink alapján a FD-s szövet nem tartalmaz bone morfogenetikus fehérjét és D-vitamin receptort, ill. szignifikánsan kevesebb mennyiségben tartalmaz még több olyan fehérjét is, ami a normál csontszövet kiéréséhez szükséges. Folyamatban van a BP-tal kezelt és nem kezelt FD-s csontminták génexpessiós változásának összehasonlító elemzése is. | Based on foreign observations 6 patients have been treated with iv. and oral BP at the Orthopedic Clinic, Semmelweis University, Budapest for 3 years since 2002, and then between 2004 and 2006 a further 11 patients were treated with oral BP for one year. Prospective follow-up was performed with laboratory tests, x-ray and ODM tests, and starting in 2006 genetic analysis of 16 patients? FD bone sample was performed in collaboration with the Biology Laboratory of the 1st Department of Internal Medicine, Semmelweis Univ. Bp. As an effect of the treatment the formerly high levels reduced. During the treatment no pathologic fractures occurred. The ODM test of patients receiving 3 years of treatment showed a positive increase of the whole body bone weight and of the densities of healthy lumbar vertebrae and the healthy side femoral neck which is due to the BP treatment. However, densities measured solely within the marrow space, at the sites of fibrous dysplasia did not change, no increase was seen here after the treatment. Following mRNA isolation the protein distribution of fibrous dysplasia tissue was measured by cDNA production and real time PCR for the activity of 120 genes related to bone metabolism; the control group consisted of healthy premenopausal female bone tissues. According to our examinations the FD-affected tissue doesn?t contain bone morphogenetic protein and vitamin D receptors and contains a significantly lower level of several proteins that are needed for the maturation of normal bone tissue

A Ewing-sarcomás betegek tünetmentes túlélési esélyeinek értékelése a Gyermekonkológiai Szekció eredményei alapján

Correlation between different prognostic factors and the overall survival of Ewing's sarcoma patients has been investigted. In this study data have been selected from the databank of Hungarian Pediatric Oncologist Section (1988-1999) (n=65). Whenever it was possible statistical analysis has been performed. Results: In our patients time interval from the primary symptoms to the diagnosis was 2-16 months. The average event-free survival in patients suffering from Ewing's sarcoma without metastasis is 0.39. Meanwhile, this value in patients with pulmonary or other metatasis is 0.24 (Kaplan-Meier analysis). Conclusion: Our results show a moderate difference between the Hungarian and the international event-free survival. Late detection is one of the answers of this discrepancy

A gyermekkori Ewing szarkómával szerzett magyarországi tapasztalataink

Magyarországon évente kb. 7-9 új Ewing szarkómás gyermeket diagnosztizálunk. Jelen munkánk célja az volt, hogy az Országos Gyermektumor Regiszter adatait felhasználva megvizsgáljuk a magyarországi Ewing szarkómás gyermekek prezentációs tüneteit, a klinikai paramétereket, a prognosztikai faktorokat, a terápiás és a túlélési eredményeket 1992 és 2002 közötti 11 éves periódusban. A fenti időszakban 88 új beteg került diagnosztizálásra, a fiú – leány arány 1,05 : 1 volt, az átlagéletkor 11 év 7 hónapnak bizonyult. A két leggyakoribb prezentációs tünet a lokális fájdalom és duzzanat voltak. 38 betegünkben hosszú csöves csontra lokalizálódott a megbetegedés, 29 gyermekben a Ewing szarkóma a csípő tájékról indult ki és 21 esetben valamely egyéb testtájékról. A betegeink közel egyharmadánál (29/88) már a diagnózis felállításakor áttétek voltak kimutathatóak. A fent nevezett időszakban három kemoterápiás protokollt alkalmaztunk Magyarországon: a CWS, az EICESS/CESS és 1999. decembere óta az Euro-EWING 99 protokollt. A 88 beteg 37,5%-nál (33/88) észleltünk recidívát átlagosan 22,4 hónappal a primer diagnózis felállítása után. A 88 betegből 45 jelenleg is él, az átlag követési idő 28,6 hónap. Az összes beteg 5-éves kumulatív túlélési valószínűsége 48,06±5,9%, a 10 éves 42,91±6,3%. A metasztázissal rendelkező betegek 5 és 8 éves túlélése 19,91±9,4%, a metasztázis nélküliek 5 éves túlélése 60,23±6,9%, míg a 10 éves 52,82±7,8%. A hazai eredmények megközelítik a nemzetközi adatokat, azonban törekednünk kell a diagnózis korai felállítására és ezáltal a kimondottan rossz prognózisú primer metasztatikus esetek számának csökkentésére. The number of newly diagnosed children in a year with Ewing’s sarcoma is 7-9 in Hungary. The aim of our study was to evaluate the presenting symptoms, clinical features, prognostic risk factors and treatment results of children’s Ewing’s sarcoma in Hungary using data from the National Childhood Cancer Registry in a 11 years-long period between 1992 and 2002. In this period, 88 new patients were diagnosed, the male-female ratio was 1,05:1 and the mean age was 11 years 7 months. The two most common presenting symptoms were local pain and swallowing. Tumor was located in the pelvis area in 29 patients, in the extremities in 38 and other sites in 21 cases. Almost one third of our patients (29/88) had metastasis at the time of the diagnosis. In this time period, three different protocols were used for treatment: CWS, EICESS/CESS and since December 1999 Euro-EWING 99. 37,5% of our patients (33/88) had relapse with a mean of 22,4 months after the diagnosis. 45 children are still alive, the median follow-up time is 28,6 months. The overall survival (OS) of all patients (n=88) was 48,06±5,9% at 5 years and 42,91±6,3% at 10 years. Patients with metastasis had OS 19,91±9,4% at 5 and at 8 years. The 5-year OS of children without metastasis was 60,23±6,9%, and 52,82±7,8% at 10 years. The Hungarian data are similar to international results, but we have to try to decrease the number of the primary metastatic cases with early diagnosis

Opposite prognostic roles of HIF1alpha and HIF2alpha expressions in bone metastatic clear cell renal cell cancer

BACKGROUND: Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1alpha/HIF2alpha and their selected target genes in primary tumors and corresponding bone metastases. RESULTS: Expression of HIF2alpha was lower in mRCC both at mRNA and protein levels (p/mRNA/=0.011, p/protein/=0.001) while HIF1alpha was similar to nmRCC. At the protein level, CAIX, GAPDH and GLUT1 were increased in mRCC. In all primary RCCs, low HIF2alpha and high HIF1alpha as well as CAIX, GAPDH and GLUT1 expressions correlated with adverse prognosis, while VEGFR2 and EPOR gene expressions were associated with favorable prognosis. Multivariate analysis confirmed high HIF2alpha protein expression as an independent risk factor. Prognostic validation of HIFs, LDH, EPOR and VEGFR2 in RNA-Seq data confirmed higher HIF1alpha gene expression in primary RCC as an adverse (p=0.07), whereas higher HIF2alpha and VEGFR2 expressions as favorable prognostic factors. HIF1alpha/HIF2alpha-index (HIF-index) proved to be an independent prognostic factor in both the discovery and the TCGA cohort. PATIENTS AND METHODS: Expressions of HIF1alpha and HIF2alpha as well as their 7 target genes were analysed on the mRNA and protein level in 59 non-metastatic ccRCCs (nmRCC), 40 bone metastatic primary ccRCCs (mRCC) and 55 corresponding bone metastases. Results were validated in 399 ccRCCs from the TCGA project. CONCLUSIONS: We identified HIF2alpha protein as an independent marker of the metastatic potential of ccRCC, however, unlike HIF1alpha, increased HIF2alpha expression is a favorable prognostic factor. The HIF-index incorporated these two markers into a strong prognostic biomarker of ccRCC

Opposite prognostic roles of HIF1α and HIF2α expressions in bone metastatic clear cell renal cell cancer

BACKGROUND Prognostic markers of bone metastatic clear cell renal cell cancer (ccRCC) are poorly established. We tested prognostic value of HIF1α/HIF2α and their selected target genes in primary tumors and corresponding bone metastases. RESULTS Expression of HIF2α was lower in mRCC both at mRNA and protein levels (p/mRNA/=0.011, p/protein/=0.001) while HIF1α was similar to nmRCC. At the protein level, CAIX, GAPDH and GLUT1 were increased in mRCC. In all primary RCCs, low HIF2α and high HIF1α as well as CAIX, GAPDH and GLUT1 expressions correlated with adverse prognosis, while VEGFR2 and EPOR gene expressions were associated with favorable prognosis. Multivariate analysis confirmed high HIF2α protein expression as an independent risk factor. Prognostic validation of HIFs, LDH, EPOR and VEGFR2 in RNA-Seq data confirmed higher HIF1α gene expression in primary RCC as an adverse (p=0.07), whereas higher HIF2α and VEGFR2 expressions as favorable prognostic factors. HIF1α/HIF2α-index (HIF-index) proved to be an independent prognostic factor in both the discovery and the TCGA cohort. PATIENTS AND METHODS Expressions of HIF1α and HIF2α as well as their 7 target genes were analysed on the mRNA and protein level in 59 non-metastatic ccRCCs (nmRCC), 40 bone metastatic primary ccRCCs (mRCC) and 55 corresponding bone metastases. Results were validated in 399 ccRCCs from the TCGA project. CONCLUSIONS We identified HIF2α protein as an independent marker of the metastatic potential of ccRCC, however, unlike HIF1α, increased HIF2α expression is a favorable prognostic factor. The HIF-index incorporated these two markers into a strong prognostic biomarker of ccRCC