Browsing by Author "Botelho, MF"
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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
- Cancer inhibition by normal differentiated cellsPublication . Martins, FC; Botelho, MF; Cabrita, AM; Oliveira, CF
- 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.
- 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.
- Evaluation of the impact of diabetes mellitus on the biology of prostate cancerPublication . Antunes, H; Teixo, R; Carvalho, J; Eliseu, M; Marques, I; Mamede, A; Neves, R; Oliveira, R; Tavares da Silva, E; Abrantes, M; Parada, B; Botelho, MF; Figueiredo, A
- 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 normal mammary epithelium on breast cancer progression: the protective role of early pregnancyPublication . Martins, FC; Botelho, MF; Cabrita, AM; Oliveira, CFAIMS AND BACKGROUND: The microenvironment has a well recognized role in breast cancer progression. Despite different theories, the mechanism of early pregnancy protection in mammary carcinogenesis is unknown. Since pregnancy is responsible for mammary gland differentiation, we tested the hypothesis that differentiated mammary epithelial cells may inhibit breast cancer progression. In other words, the protective role of early pregnancy could be due to the inhibitory influences of the more differentiated mammary tissue. METHODS: In order to test our hypothesis, we used 30 female Balb/c nude mice and MCF-7 cells of breast adenocarcinoma. The female mice were divided into two test groups, group I (GI) and group II (GII), and a control group. In GII, the animals were submitted to epithelial removal in the left fourth inguinal mammary gland at 3 weeks of age. Both groups were given continuous hormonal treatment to simulate the pregnancy development of the mammary gland. Two million MCF-7 cells were then injected into the fourth inguinal mammary gland (GI) or in the respective cleared mammary fat pad (GII). Five weeks later the mice were sacrificed and their tumors removed. Tumor development rates and tumor volumes were determined and proliferation and apoptosis were evaluated by immunohistochemistry. RESULTS: Tumors of GII mice had a larger mean volume than those of GI mice (P = 0.001, Mann-Whitney U-test) and an apparent increase in proliferation, demonstrated by a higher staining intensity for proliferating cell nuclear antigen (PCNA). As tumors presented caspase 8 staining, there may be apoptotic activation involved in cell death, mainly through an extrinsic pathway. CONCLUSIONS: These results suggest that a differentiated intact mammary gland may have an inhibitory influence on mammary tumor growth in mice.
- 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.
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