MYC, FBXW7 and TP53 copy number variation and expression in Gastric Cancer

Abstract Background MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation. Methods We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines. Results MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. In vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells. Conclusion In conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.

APPLICABILITY OF kDNA-PCR FOR ROUTINE DIAGNOSIS OF AMERICAN TEGUMENTARY LEISHMANIASIS IN A TERTIARY REFERENCE HOSPITAL.

This study evaluated the applicability of kDNA-PCR as a prospective routine diagnosis method for American tegumentary leishmaniasis (ATL) in patients from the Instituto de Infectologia Emílio Ribas (IIER), a reference center for infectious diseases in São Paulo - SP, Brazil. The kDNA-PCR method detected Leishmania DNA in 87.5% (112/128) of the clinically suspected ATL patients, while the traditional methods demonstrated the following percentages of positivity: 62.8% (49/78) for the Montenegro skin test, 61.8% (47/76) for direct investigation, and 19.3% (22/114) for in vitro culture. The molecular method was able to confirm the disease in samples considered negative or inconclusive by traditional laboratory methods, contributing to the final clinical diagnosis and therapy of ATL in this hospital. Thus, we strongly recommend the inclusion of kDNA-PCR amplification as an alternative diagnostic method for ATL, suggesting a new algorithm routine to be followed to help the diagnosis and treatment of ATL in IIER.

MYC, FBXW7 and TP53 copy number variation and expression in gastric cancer

BACKGROUND: MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation. METHODS: We evaluated MYC, FBXW7, and TP53 copy number, mRNA levels, and protein expression in gastric cancer and paired non-neoplastic specimens from 33 patients and also in gastric adenocarcinoma cell lines. We also determined the invasion potential of the gastric cancer cell lines. RESULTS: MYC amplification was observed in 51.5% of gastric tumor samples. Deletion of one copy of FBXW7 and TP53 was observed in 45.5% and 21.2% of gastric tumors, respectively. MYC mRNA expression was significantly higher in tumors than in non-neoplastic samples. FBXW7 and TP53 mRNA expression was markedly lower in tumors than in paired non-neoplastic specimens. Moreover, deregulated MYC and FBXW7 mRNA expression was associated with the presence of lymph node metastasis and tumor stage III-IV. Additionally, MYC immunostaining was more frequently observed in intestinal-type than diffuse-type gastric cancers and was associated with MYC mRNA expression. In vitro studies showed that increased MYC and reduced FBXW7 expression is associated with a more invasive phenotype in gastric cancer cell lines. This result encouraged us to investigate the activity of the gelatinases MMP-2 and MMP-9 in both cell lines. Both gelatinases are synthesized predominantly by stromal cells rather than cancer cells, and it has been proposed that both contribute to cancer progression. We observed a significant increase in MMP-9 activity in ACP02 compared with ACP03 cells. These results confirmed that ACP02 cells have greater invasion capability than ACP03 cells. CONCLUSION: In conclusion, FBXW7 and MYC mRNA may play a role in aggressive biologic behavior of gastric cancer cells and may be a useful indicator of poor prognosis. Furthermore, MYC is a candidate target for new therapies against gastric cancer.

"Även om jag bor här i 100 år så blir det inte samma" : En kvalitativ studie av fem ensamkommande ungdomar och deras personliga identitetsutveckling i mottagarlandet.

SAMMANFATTNING: Människor tvingas fly ifrån sina hemländer på grund av våld för att söka säkerhet någon annanstans. Att människor lämnar ett land eller tvingas fly har skett under alla tider. Människor flyr från förföljelse, fattigdom, svält eller krig. Uppskattningsvis finns 19,2 miljoner människor på flykt runt om i världen och nära hälften av dessa är barn. Av de barn som befinner sig på flykt är de ensamkommande ungdomarna en viktig grupp att urskilja. Då de ensamkommande asylsökande ungdomarna är i behov av särskilt skydd. Under 2003 var de flesta ensamkommande ungdomar i Sverige från Somalia, Irak, Serbien och Montenegro. Vårt syfte är att få ökad förståelse för ensamkommande ungdomars upplevelser av hur deras identitet formats i hemlandet och senare i mottagarlandet i samspel med människor i sin omgivning. Samt vilken betydelse asylprocessen och tidigare trauman har haft för ungdomarnas personliga identitetsutveckling. De faktorer som berörts som viktiga för ungdomens personliga identitetsutveckling är förluster, boende, ovisshet, familjeåterförening och nätverk samt språket.Vi har valt att göra en explorativ studie som innefattar kvalitativa halvstrukturerade intervjuer med fem ensamkommande ungdomar. Resultatet i form av empiri och analys har utförts utifrån tidigare forskning och från Cullbergs kristeori samt relevanta begrepp som etnicitet och identitet utifrån symbolisk interaktionism. Studien har visat att samtliga ungdomar upplevt att den ovisshet de levt i under asylprocessen samt tidigare trauman har påverkat dem mycket både psykiskt och fysiskt. De ungdomar vi har intervjuat upplever alla att de idag har en ny personlighet efter att ha fått uppehållstillstånd. Den nya identiteten har enligt ungdomarna påverkats bland annat av föräldrarnas uppfostran och de nya människor de möter i mottagarlandet samt av de nya miljöerna ungdomarna befinner sig i.

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