Browsing by Author "Abrantes, AM"
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- Array-comparative genomic hybridization as a novel high-throughput approach in bladder cancer treatmentPublication . Neves, AR; Abrantes, AM; Ribeiro, IP; Marques, IA; Marques, V; Tavares da Silva, E; Carreira, IM; Figueiredo, A; Botelho, MF
- Cholangiocarcinoma: from molecular biology to treatmentPublication . Brito, AF; Abrantes, AM; Encarnação, JC; Tralhão, JG; Botelho, MFCholangiocarcinoma is a rare tumor originating in the bile ducts, which, according to their anatomical location, is classified as intrahepatic, extrahepatic and hilar. Nevertheless, incidence rates have increased markedly in recent decades. With respect to tumor biology, several genetic alterations correlated with resistance to chemotherapy and radiotherapy have been identified. Here, we highlight changes in KRAS and TP53 genes that are normally associated with a more aggressive phenotype. Also IL-6 and some proteins of the BCL-2 family appear to be involved in the resistance that the cholangiocarcinoma presents toward conventional therapies. With regard to diagnosis, tumor markers most commonly used are CEA and CA 19-9, and although its use isolated appears controversial, their combined value has been increasingly advocated. In imaging terms, various methods are needed, such as abdominal ultrasound, computed tomography and cholangiopancreatography. Regarding therapy, surgical modalities are the only ones that offer chance of cure; however, due to late diagnosis, most patients cannot take advantage of them. Thus, the majority of patients are directed to other therapeutic modalities like chemotherapy, which, in this context, assumes a purely palliative role. Thus, it becomes urgent to investigate new therapeutic options for this highly aggressive type of tumor.
- Endometrial Cancer Spheres Show Cancer Stem Cells Phenotype and Preference for Oxidative MetabolismPublication . Carvalho, MJ; Laranjo, M; Abrantes, AM; Casalta-Lopes, J; Sarmento-Santos, D; Costa, T; Serambeque, B; Almeida, N; Gonçalves, T; Mamede, C; Encarnação, J; Oliveira, R; Paiva, A; de Carvalho, R; Botelho, F; Oliveira, CThis study aimed to characterize endometrial cancer regarding cancer stem cells (CSC) markers, regulatory and differentiation pathways, tumorigenicity and glucose metabolism. Endometrial cancer cell line ECC1 was submitted to sphere forming protocols. The first spheres generation (ES1) was cultured in adherent conditions (G1). This procedure was repeated and was obtained generations of spheres (ES1, ES2 and ES3) and spheres-derived cells in adherent conditions (G1, G2 and G3). Populations were characterized regarding CD133, CD24, CD44, aldehyde dehydrogenase (ALDH), hormonal receptors, HER2, P53 and β-catenin, fluorine-18 fluorodeoxyglucose ([18F]FDG) uptake and metabolism by NMR spectroscopy. An heterotopic model evaluated differential tumor growth. The spheres self-renewal was higher in ES3. The putative CSC markers CD133, CD44 and ALDH expression were higher in spheres. The expression of estrogen receptor (ER)α and P53 decreased in spheres, ERβ and progesterone receptor had no significant changes and β-catenin showed a tendency to increase. There was a higher 18F-FDG uptake in spheres, which also showed a lower lactate production and an oxidative cytosol status. The tumorigenesis in vivo showed an earlier growth of tumours derived from ES3. Endometrial spheres presented self-renewal and differentiation capacity, expressed CSC markers and an undifferentiated phenotype, showing preference for oxidative metabolism.
- Estudo experimental do impacto da clampagem selectiva da veia porta na função hepatocelularPublication . Tralhão, JG; Abrantes, AM; Gonçalves, C; Carvalho, C; Portela, I; Laranjo, M; Oliveiros, B; Cardoso, D; Ribeiro, AB; Botelho, MF; Castro e Sousa, FThe influence of selective clamping of the elements of hepatic pedicle in the hepatocellular function and viability were evaluated in our department. AIM: Study the effect of selective clamping of the portal vein (CPV) in hepatocellular function in an animal model with normal liver. METHOD: Three groups of Wistar rats (males, 2 months) were subjected a CPV for 60 min: group A (n=21) submitted to a continuous inflow occlusion; group B (n=12) underwent to a CPV for 30 min with 5 min of reperfusion; group C (n=10) underwent a CPV for 15 min with 5 min of reperfusion. The group D (n=9) was not subjected to a CPV. A hepatic biopsy was done at the end of surgery. The degree of tissue injury was evaluated using: 1) blood markers: AST, ALT, total bilirubin (TB), GGT alkaline-phosphatase, LDH and hepatic extraction fraction (HEF) by radioisotopic methods three days before laparotomy (BS) and after surgery (AS); 2) apoptosis, necrosis were investigated after collagenase cell isolation from hepatectomy pieces by flow-cytometry using the followed probes: propidium-iodide and annexin-V. Statistical analysis: variance analysis, post-hoc comparisons by Turkey-test (p<0.05). RESULTS: 1) Mortality: Group A - 62%, Group B - 17%, Group C - 30%, Group D - 0% (p<0.03). 2) We observed statistical differences in these parameters: ALT (p<0,025) and LDH (p<0,002) preferentially in groups A but without differences between the A,B,C and D Groups (ns). 3) We also verified a significant decrease in HEF values (p<0,0001) preferentially in group A without differences between the groups. 4) No difference were observed when analysed apoptosis and necrosis and cell viability between the groups. CONCLUSIONS: Postoperative liver failure is the leading cause of mortality after hepatectomy, however selective clamping of the portal vein, is reflected in an increase in cell viability and a decrease in the type of cell death (necrosis ou apoptosis) compared to studies carried out previously by us and thus may be regarded as an alternative to the Pringle maneuver. However, selective clamping of the portal vein for periods above 30' should be avoided, given the high mortality verified.
- Evaluation of the efficacy of dentin hypersensitivity treatments - a systematic review and follow-up analysisPublication . Marto, CM; Baptista Paula, A; Nunes, T; Pimenta, M; Abrantes, AM; Pires, AS; Laranjo, M; Coelho, A; Donato, H; Botelho, MF; Marques Ferreira, M; Carrilho, EOBJECTIVES: To compare the treatments used to treat dentin hypersensitivity (DH), based on its efficacy and effect duration. METHODS: Medline/PubMed, Cochrane Library, EMBASE, and ClinicalTrials were searched for articles published between January 1st , 2008 and November 14th , 2018, in English, Portuguese or Spanish, reporting clinical trials, completed and with results. This systematic review protocol was registered in PROSPERO, number CRD42019121986. RESULTS: 74 randomized clinical trials were included in the systematic review, reporting patients from 16 to 65 years old, with a clinical diagnosis of DH, that evaluate the efficacy of a desensitizing product, compared to pre-treatment, used the evaporative method stimulation and the visual analogue scale. These studies evaluated 5366 patients and at least 9167 teeth. Seven follow-up periods were considered corresponding to an immediate, medium or long-time effect. 66 studies were included in the quantitative synthesis. Glutaraldehyde with HEMA, glass ionomer cements and Laser present significant immediate (until 7 days) DH reduction. Medium term (until 1 month) reduction was observed in stannous fluoride, glutaraldehyde with HEMA, hydroxyapatite, glass ionomer cements and Laser groups. Finally, long term significant reduction was seen at potassium nitrate, arginine, glutaraldehyde with HEMA, hydroxyapatite, adhesive systems, glass ionomer cements, and LASER. CONCLUSIONS: All active ingredients show efficacy in DH reduction in different follow-up times. Only in-office treatments are effective in immediate DH reduction, maintaining its efficacy over time. For long time effects, at home treatments can also be used. More standardized evaluation protocols should be implemented to increase the robustly of the results.
- Hepatectomy and liver regeneration: from experimental research to clinical applicationPublication . Tralhão, JG; Abrantes, AM; Hoti, E; Oliveiros, B; Cardoso, D; Faitot, F; Carvalho, C; Botelho, MF; Castro e Sousa, FBACKGROUND: The mechanisms and kinetics of hepatic growth have continuously been investigated. This study concerns liver regeneration in animal and patients who underwent partial hepatectomy evaluated by the hepatic extraction fraction (HEF) calculated through radioisotopic methods. METHODS: Thirty normal Wistar rats were submitted to an 85% hepatectomy, and 95 patients with primary and secondary liver tumours were included. In animal study, the liver regeneration kinetics was assessed by HEF using 99mTc-mebrofenin, the ratio liver/bodyweight and by using bromodeoxyuridine deoxyribonucleic acid incorporation. In patient study, the liver regeneration was evaluated by calculation of HEF before surgery, 5 and 30 days after hepatectomy. RESULTS: In animal, we verified a positive correlation between HEF kinetics and liver/bodyweight ratio or hepatocyte proliferation evaluated by bromodeoxyuridine deoxyribonucleic acid staining after 85% hepatectomy. In the clinical arm, no statistical differences of the HEF before hepatectomy, 5 and 30 days after hepatectomy, were observed. CONCLUSIONS: Our results support the view that human liver regeneration commences early, is fast, non-anatomical and functionally complete 5 days after hepatectomy. The fast functional liver regeneration may have a high clinical impact particularly concerning the post-operative oncological therapeutic approaches.
- Impact of splenic artery ligation after major hepatectomy on liver function, regeneration and viabilityPublication . Carrapita, J; Abrantes, AM; Campelos, S; Gonçalves, AC; Cardoso, D; Sarmento-Ribeiro, AB; Rocha, C; Santos, JN; Botelho, MF; Tralhão, JG; Farges, O; Barbosa, JMIt was reported that prevention of acute portal overpressure in small-for-size livers by inflow modulation results in a better postoperative outcome. The aim is to investigate the impact of portal blood flow reduction by splenic artery ligation after major hepatectomy in a murine model. Forty-eight rats were subjected to an 85% hepatectomy or 85% hepatectomy and splenic artery ligation. Both groups were evaluated at 24, 48, 72 and 120 post-operative hours: liver function, regeneration and viability. All methods and experiments were carried out in accordance with Coimbra University guidelines. Splenic artery ligation produces viability increase after 24 h, induces a relative decrease in oxidative stress during the first 48 hours, allows antioxidant capacity increment after 24 h, which is reflected in a decrease of half-time normalized liver curve at 48 h and at 72 h and in an increase of mitotic index between 48 h and 72 h. Splenic artery ligation combined with 85% hepatectomy in a murine model, allows portal inflow modulation, promoting an increase in hepatocellular viability and regeneration, without impairing the function, probably by inducing a less marked elevation of oxidative stress at first 48 hours.
- Influence of P53 on the radiotherapy response of hepatocellular carcinomaPublication . Gomes, AR; Abrantes, AM; Brito, AF; Laranjo, M; Casalta-Lopes, JE; Gonçalves, AC; Sarmento-Ribeiro, AB; Botelho, MF; Tralhão, JGHepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines.
- Intermittent Pringle Maneuver and Hepatic Function: Perioperative Monitoring by Noninvasive ICG-ClearancePublication . Tralhão, JG; Hoti, E; Oliveiros, B; Abrantes, AM; Botelho, MF; Castro e Sousa, FBACKGROUND: Intermittent Pringle maneuver or selective portal clamping often are used to control inflow during parenchymal liver transection. This study was designed to determinate whether these maneuvers are associated with adverse hepatic function. METHODS: Resection was performed without portal clamping in 17 patients (group 1). Selective continuous portal clamping was performed in 11 patients (group 2) and the remaining 33 patients (group 3) had intermittent nonselective portal clamping (occlusion of the main portal trunk). The centers' protocol for total portal occlusion is 15-min occlusion alternated with 5-min reperfusion in patients with normal liver parenchyma or 10 min alternated with 5 min in patients with abnormal parenchyma. ICG elimination tests were conducted concurrently using a noninvasive monitor that tracks the plasma disappearance rate (PDR-ICG-%/min) and 15-min retention rate after administration (ICG-R15-%). RESULTS: There was no statistically difference between the three studied groups in terms of sequential changes of ICG-PDR (p < 0.625) or ICG-R15 (p < 0.398). CONCLUSIONS: Our study indicates that 15 min of intermittent Pringle maneuver or selective hemihepatic continuous portal clamping are safe methods of vascular control during liver resection, with no adverse effects on hepatocellular function.
- Oxidative Stress, DNA, Cell Cycle/Cell Cycle Associated Proteins and Multidrug Resistance Proteins: Targets of Human Amniotic Membrane in Hepatocellular CarcinomaPublication . Mamede, AC; Guerra, S; Laranjo, M; Santos, K; Carvalho, MJ; Carvalheiro, T; Moura, P; Paiva, A; Abrantes, AM; Maia, CJ; Botelho, MFThe anticancer effects of human amniotic membrane (hAM) have been studied over the last decade. However, the action mechanisms responsible for these effects are not fully understood until now. Previously results reported by our team proved that hAM is able to induce cytotoxicity and cell death in hepatocellular carcinoma (HCC), a worldwide high incident and mortal cancer. Therefore, this experimental study aimed to investigate the cellular targets of hAM protein extracts (hAMPE) in HCC through in vitro studies. Our results showed that hAMPE is able to modify oxidative stress environment in all HCC cell lines, as well as its cell cycle. hAMPE differently targets deoxyribonucleic acid (DNA), P21, P53, β-catenin and multidrug resistance (MDR) proteins in HCC cell lines. In conclusion, hAMPE has several targets in HCC, being clear that the success of this treatment depends of a personalized therapy based on the biological and genetic characteristics of the tumor.