Browsing by Author "Medeiros, R"
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- Detection of the Epstein-Barr virus in blood and bone marrow mononuclear cells of patients with aggressive B-cell non-Hodgkin's lymphoma is not associated with prognosisPublication . Marques, H; Catarino, R; Domingues, N; Barros, E; Portela, C; Almeida, MI; Costa, S; Reis, RM; Medeiros, R; Longatto-Filho, AThe Epstein-Barr virus (EBV) is associated with a large spectrum of lymphoproliferative diseases. Traditional methods of EBV detection include the immunohistochemical identification of viral proteins and DNA probes to the viral genome in tumoral tissue. The present study explored the detection of the EBV genome, using the BALF5 gene, in the bone marrow or blood mononuclear cells of patients with diffuse large B-cell lymphomas (DLBCL) and related its presence to the clinical variables and risk factors. The results show that EBV detection in 21.5% of patients is not associated with age, gender, staging, B symptoms, international prognostic index scores or any analytical parameters, including lactate dehydrogenase (LDH) or β-2 microglobulin (B2M). The majority of patients were treated with R-CHOP-like (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone or an equivalent combination) and some with CHOP-like chemotherapy. Response rates [complete response (CR) + partial response (PR)] were not significantly different between EBV-negative and -positive cases, with 93.2 and 88.9%, respectively. The survival rate was also similar in the two groups, with 5-year overall survival (OS) rates of 64.3 and 76.7%, respectively. However, when analyzing the treatment groups separately there was a trend in EBV-positive patients for a worse prognosis in patients treated with CHOP-like regimens that was not identified in patients treated with R-CHOP-like regimens. We conclude that EBV detection in the bone marrow and blood mononuclear cells of DLBC patients has the same frequency of EBV detection on tumoral lymphoma tissue but is not associated with the risk factors, response rate and survival in patients treated mainly with immunochemotherapy plus rituximab. These results also suggest that the addition of rituximab to chemotherapy improves the prognosis associated with EBV detection in DLBCL.
- Emotional, inflammatory, and genetic factors of resilience and vulnerability to depression in patients with premenopausal breast cancer: A longitudinal study protocolPublication . Almeida, SS; Oliveira, MA; Medeiros, R; Guerra, MP; Pariante, CM; Fernandes, LBackground: Psychosocial stress and depressive disorder have been associated with cancer as putative contributors to worse prognosis. On the other hand, cancer diagnosis is a recognised life event that can contribute to distress and depressive states. Humoral and cellular inflammation can promote depressive disorder by means of decreased monoamine synthesis, glutamate neurotoxicity, neurogenesis and neuroplasticity, dysregulated hypothalamic-pituitary-adrenal axis, and glucocorticoid resistance. This protocol objectives are to observe the interactions between psychosocial variables and biochemical and immunological biomarkers in a longitudinal, prospective design; to identify inflammation-related depression endophenotypes in breast cancer patients and to understand if early diagnosed and treated depression in this population will translate in better inflammation status and better global prognosis. Methods: Prospective observational cohort, composed by 100 consecutive premenopausal patients, diagnosed with non-distant metastatic breast carcinoma and with no history of major psychopathology or other organic illness. The participants will have an in-person assessment in three different moments, along illness treatment and follow-up, with respect to cytometric, immunologic, and psychosocial parameters and will be tested for depression vulnerability and resilience inflammation-related functional genetic polymorphisms. Additionally, at years 5 and 10 post enrollment, patients`medical records will be assessed. As a control cohort, all patients excluded due to psychiatric history or past psychiatric treatments will have their clinical records assessed at years 5 and 10 after admission. All the data will be managed with the SPSS® software. Discussion and conclusion: This study is an original longitudinal cohort of breast cancer premenopausal patients, with a comprehensive approach to psychosocial, clinical, inflammatory, and genetic variables. It expects to provide evidence regarding the links between genetic, cytometric, immunologic, and psychosocial factors, their potential contribution to the pathophysiology of depressive disorder, breast cancer course, progression, and prognosis. It may further contribute with data to better efficacy of the psycho-oncological interventions. Trial registration: National Commission of Data Protection (CNPD) 13413/2017; Ethics Committee of IPOP project code CI-IPOP81/2017.
- Role of the RAD51 G172T polymorphism in the clinical outcome of cervical cancer patients under concomitant chemoradiotherapyPublication . Nogueira, A; Catarino, R; Faustino, I; Nogueira-Silva, C; Figueiredo, T; Lombo, L; Hilário-Silva, I; Pereira, D; Medeiros, RINTRODUCTION: Cervical cancer is one of the most common cancers diagnosed in women worldwide. Mammalian cells are constantly exposed to a wide variety of genotoxic agents from both endogenous and exogenous sources. The RAD51 protein is required for meiotic and mitotic recombination and plays a central role in homology-dependent recombinational repair of double-strand breaks (DSBs). Given the functional relevance of the DNA repair system on carcinogenesis, potential associations between genetic polymorphisms of DNA repair genes, cancer risk and response to therapy have been intensively evaluated. This is the first study evaluating the role of the RAD51 G172T genetic variants in cancer prognosis and clinical outcome of cervical cancer patients. MATERIAL AND METHODS: We analyzed RAD51 G172T polymorphism genotypes in cervical cancer patients who underwent a platinum-based chemotherapy in combination with radiotherapy. Genotyping was performed by Taqman™ Allelic Discrimination methodology. RESULTS AND DISCUSSION: Concerning the overall survival rates found using Kaplan-Meier method and Log Rank Test, we observed that the mean survival rates were statistically different according to the patients RAD51 genotypes. The group of patients carrying the T allele present a higher mean survival rate than the other patients (102.3months vs. 86.4months, P=0.020). Using the Cox regression analysis, we found an increased overall survival time for T-carrier patients, when compared with GG genotype, with tumor stage, age and presence of lymph nodes as covariates [hazard ratio (HR), 0.373; 95% CI, 0.181-0.770; P=0.008]. Among patients (n=193), RAD51 genotype frequency distributions were not under the influence of clinicopathologic characteristics, namely, treatment response (P=0.508), recurrence (P=0.150) and tumor stage (P=0.250). CONCLUSIONS: This is the first study evaluating the role of the RAD51 G172T genetic variants in cancer prognosis and clinical outcome of cervical cancer patients. Our results indicate an influence of the RAD51 genetic variants in overall survival of cervical cancer. Thereby, RAD51 G172T genotypes may provide additional prognostic information in cervical cancer patients who underwent cisplatin-based chemotherapy in combination with radiotherapy.
- The impact of GGH -401C>T polymorphism on cisplatin-based chemoradiotherapy response and survival in cervical cancerPublication . Silva, IH; Nogueira-Silva, C; Figueiredo, T; Lombo, L; Faustino, I; Catarino, R; Nogueira, A; Pereira, D; Medeiros, RAIMS: Cervical cancer is the third most frequent cancer in women worldwide, mostly treated with cisplatin-based chemoradiotherapy. Since it is known that folate metabolism might interfere with cisplatin effectiveness, we intended to study the influence of the Gamma Glutamyl Hydrolase -401C>T polymorphism in treatment response in cervical cancer. METHODS: We retrospectively reviewed the clinical data of 167 patients with bulky cervical cancer submitted to cisplatin-based chemoradiotherapy. The genotypes of GGH -401C>T SNP were determined by real-time PCR and statistical analysis was performed by χ(2) test and survival analysis. RESULTS: The genotypes of GGH-401C>T were significantly associated with the response to platinum-based chemoradiotherapy. Treatment response was higher in patients carrying the CC genotype, who presented a significant increased chance of treatment response (survival time in months/genotype: 91 for CC Vs 72 for CT/TT; p=0.035, log rank test). A Cox regression analysis accordingly showed that the presence of the T allele was significantly linked to a worse treatment response (HR=3.036; CI 95% 1.032-8.934, p=0.044). CONCLUSIONS: The results of our study suggested the potential interest of GGH -401C>T as a predictive factor of the outcome of cervical carcinoma treated with cisplatin-based chemoradiotherapy.
- The impact of GGH -401C>T polymorphism on cisplatin-based chemoradiotherapy response and survival in cervical cancerPublication . Silva, IH; Nogueira-Silva, C; Figueiredo, T; Lombo, L; Faustino, I; Catarino, R; Nogueira, A; Nogueira, D; Medeiros, RAIMS: Cervical cancer is the third most frequent cancer in women worldwide, mostly treated with cisplatin-based chemoradiotherapy. Since it is known that folate metabolism might interfere with cisplatin effectiveness, we intended to study the influence of the Gamma Glutamyl Hydrolase -401C>T polymorphism in treatment response in cervical cancer. METHODS: We retrospectively reviewed the clinical data of 167 patients with bulky cervical cancer submitted to cisplatin-based chemoradiotherapy. The genotypes of GGH -401C>T SNP were determined by real-time PCR and statistical analysis was performed by χ(2) test and survival analysis. RESULTS: The genotypes of GGH-401C>T were significantly associated with the response to platinum-based chemoradiotherapy. Treatmentresponse was higher in patients carrying the CC genotype, who presented a significant increased chance of treatment response (survival time in months/genotype: 91 for CC Vs 72 for CT/TT; p=0.035, log rank test). A Cox regression analysis accordingly showed that the presence of the T allele was significantly linked to a worse treatment response (HR=3.036; CI 95% 1.032-8.934, p=0.044). CONCLUSIONS: The results of our study suggested the potential interest of GGH -401C>T as a predictive factor of the outcome of cervical carcinoma treated with cisplatin-based chemoradiotherapy.