Bioinformatics and expression analysis of the Xeroderma Pigmentosum complementation group C (XPC) of Trypanosoma evansi in Trypanosoma cruzi cells / Análises de bioinformática e da expressão do gene Xeroderma Pigmentosum complementation group C (XPC) de Trypanosoma evansi em células de Trypanosoma cruzi

Nucleotide excision repair (NER) acts repairing damages in DNA, such as lesions caused by cisplatin. Xeroderma Pigmentosum complementation group C (XPC) protein is involved in recognition of global genome DNA damages during NER (GG-NER) and it has been studied in different organisms due to its importance in other cellular processes. In this work, we studied NER proteins in Trypanosoma cruzi and Trypanosoma evansi, parasites of humans and animals respectively. We performed three-dimensional models of XPC proteins from T. cruzi and T. evansi and observed few structural differences between these proteins. In our tests, insertion of XPC gene from T. evansi (TevXPC) in T. cruzi resulted in slower cell growth under normal conditions. After cisplatin treatment, T. cruzi overexpressing its own XPC gene (TcXPC) was able to recover cell division rates faster than T. cruzi expressing TevXPC gene. Based on these tests, it is suggested that TevXPC (being an exogenous protein in T. cruzi) interferes negatively in cellular processes where TcXPC (the endogenous protein) is involved. This probably occurred due interaction of TevXPC with some endogenous molecules or proteins from T. cruzi but incapacity of interaction with others. This reinforces the importance of correctly XPC functioning within the cell.

O reparo por excisão de nucleotídeos (NER) atua reparando danos no DNA, como lesões causadas por cisplatina. A proteína Xeroderma Pigmentosum complementation group C (XPC) está envolvida no reconhecimento de danos pela via de reparação global do genoma pelo NER (GG-NER) e tem sido estudada em diferentes organismos devido à sua importância em outros processos celulares. Neste trabalho, estudamos proteínas do NER em Trypanosoma cruzi e Trypanosoma evansi, parasitos de humanos e animais, respectivamente. Modelos tridimensionais das proteínas XPC de T. cruzi e T. evansi foram feitos e observou-se poucas diferenças estruturais entre estas proteínas. Durante testes, a inserção do gene XPC de T. evansi (TevXPC) em T. cruzi resultou em crescimento celular mais lento em condições normais. Após o tratamento com cisplatina, T. cruzi superexpressando seu próprio gene XPC (TcXPC) foi capaz de recuperar as taxas de divisão celular mais rapidamente do que T. cruzi expressando o gene TevXPC. Com base nesses testes, sugere-se que TevXPC (sendo uma proteína exógena em T. cruzi) interfere negativamente nos processos celulares em que TcXPC (a proteína endógena) está envolvida. Isso provavelmente ocorreu pois TevXPC é capaz de interagir com algumas moléculas ou proteínas endógenas de T. cruzi, mas é incapaz de interagir com outras. Isso reforça a importância do correto funcionamento de XPC dentro da célula.

Bioinformatics and expression analysis of the Xeroderma Pigmentosum complementation group C (XPC) of Trypanosoma evansi in Trypanosoma cruzi cells.

Nucleotide excision repair (NER) acts repairing damages in DNA, such as lesions caused by cisplatin. Xeroderma Pigmentosum complementation group C (XPC) protein is involved in recognition of global genome DNA damages during NER (GG-NER) and it has been studied in different organisms due to its importance in other cellular processes. In this work, we studied NER proteins in Trypanosoma cruzi and Trypanosoma evansi, parasites of humans and animals respectively. We performed three-dimensional models of XPC proteins from T. cruzi and T. evansi and observed few structural differences between these proteins. In our tests, insertion of XPC gene from T. evansi (TevXPC) in T. cruzi resulted in slower cell growth under normal conditions. After cisplatin treatment, T. cruzi overexpressing its own XPC gene (TcXPC) was able to recover cell division rates faster than T. cruzi expressing TevXPC gene. Based on these tests, it is suggested that TevXPC (being an exogenous protein in T. cruzi) interferes negatively in cellular processes where TcXPC (the endogenous protein) is involved. This probably occurred due interaction of TevXPC with some endogenous molecules or proteins from T.cruzi but incapacity of interaction with others. This reinforces the importance of correctly XPC functioning within the cell.

[Early stage liver cancer : Hepatocellular carcinoma]. / Frühkarzinom der Leber : Hepatozelluläres Karzinom.

Hepatocellular carcinoma (HCC) ranks among the most common primary cancers of the liver. The major risk factor for the formation of HCC is liver cirrhosis. The grade of cirrhosis as well as the extent of the tumor itself, can play an important role in the treatment options and patient prognosis. An operation aimed at an R0 resection is the treatment of choice for patients in an early stage of the disease and is associated with favorable long-term and recurrence-free survival. Liver transplantation offers an even better long-term survival rate after 5 years for selected patients with HCC meeting the Milan criteria as the underlying cirrhosis, the major risk factor for HCC recurrence, is simultaneously treated. Local tumor ablation is the least invasive curative surgical treatment, however, it is associated with an increased local recurrence rate; therefore, the early detection of tumors is of essential importance. As tumor-associated symptoms tend to arise only in advanced tumor stages, it is indispensable to identify patients with typical risk factors and to provide closely monitored screening examinations.

Randomized clinical trial of efficacy and costs of three dissection devices in liver resection.

BACKGROUND: In recent decades a variety of instruments for liver dissection has become available. This randomized controlled trial analysed the efficacy and costs of three different liver dissection devices. METHODS: Ninety-six patients without cirrhosis undergoing liver resection were randomized to either ultrasonic dissection, waterjet dissection or dissecting sealer (32 in each group). Patients were unaware of the device used. The primary endpoint was dissection speed. Secondary endpoints were intraoperative blood loss, morbidity and mortality, and costs of dissection devices, staplers and haemostatic agents. RESULTS: Dissection was slower with the dissecting sealer (P = 0.004 versus waterjet dissector). The difference was more pronounced for extended resections (mean(s.e.m.) 1.62(0.36) cm(2)/min versus 3.42(0.53) and 3.63(0.51) cm(2)/min for ultrasonic and water dissectors respectively; P = 0.037). Costs were significantly higher for the dissecting sealer when atypical or segmental resections were performed. Four patients died after extended resections; postoperative complications did not differ between groups. CONCLUSION: The dissecting sealer is slower than the ultrasonic dissector or water dissector. The three devices are equally safe in terms of blood loss, transfusions and postoperative complications. Ultrasonic and water dissectors might be more favourable economically than the dissecting sealer. REGISTRATION NUMBER: ISRCTN52294555 (http://www.controlled-trials.com).

[Anatomic and atypical resections of the gallbladder bed in patients with gallbladder carcinoma]. / Anatomische und atypische Resektionen des Gallenblasenbetts beim Gallenblasenkarzinom.

BACKGROUND: At present, atypical as well as anatomic liver resections are recommended as the surgical therapy for gallbladder cancer (GC) at stages > or = T 2. The aim of this study was to compare atypical with anatomic resections (mostly resections of segments IV b / V with selective vascular occlusion using the round ligament approach). PATIENTS AND METHODS: Between November 1994 and January 2007, n = 56 patients were treated for GC. The staging, operative and histological results and the postoperative course were recorded. In addition, the survivals at a mean follow-up of 13 (range: 3-54) months were estimated and compared between the two study groups. RESULTS: We performed 28 liver resections for GC (n = 14 atypical and n = 14 anatomic resections). In the anatomic resection group, there was one extended right hepatectomy as well as thirteen segment IV b / V resections. The volume of the resected liver specimen, the frequency of the Pringle manoeuvre, the transfusion requirements, and the duration of the operation did not differ between the two study groups. However, in only 64 % of the atypical resections, the recommended resection margin of at least 3 cm could be achieved. One patient died after extended hepatectomy. There were no other major complications. The mean follow-up was 16 +/- 5 months in the anatomic and 22 +/- 7 months in the atypical resection group. Survival was not statistically different between the two study groups. CONCLUSION: Segment IV b / V resections are attractive procedures to treat GC due to their lower invasiveness in spite oncological adequacy. However, we could not demonstrate any superiority in terms of survival for the segment IV b / V liver resections. Nevertheless, extended liver resections are rarely necessary in the operative treatment of GC.