Rui Medeiros | IPO-Porto - Academia.edu (original) (raw)
Papers by Rui Medeiros
Veterinary world/Veterinary World, May 1, 2024
Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E... more Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs.
![Research paper thumbnail of Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei](https://attachments.academia-assets.com/119033005/thumbnails/1.jpg)
](International journal of molecular sciences, May 10, 2024
Disclosing the Antifungal Mechanisms of the Cyclam Salt H 4 [H 2 (4-CF3 PhCH 2) 2 Cyclam]Cl 4
Genes
Gene variation linked to physiological functions is recognised to affect elite athletic performan... more Gene variation linked to physiological functions is recognised to affect elite athletic performance by modulating training and competition-enabling behaviour. The fatty acid amide hydrolase (FAAH) has been investigated as a good candidate for drug targeting, and recently, its single-nucleotide polymorphism (SNP) rs324420 was reported to be associated with athletic performance. Given the implications, the biological pathways of this genetic polymorphism linked to elite athletic performance, considering sport type, psychological traits and sports injuries, need to be dissected. Thus, a narrative review of the literature concerning the biological mechanisms of this SNP was undertaken. In addition to its role in athletic performance, FAAH rs324420 is also involved in important mechanisms underlying human psychopathologies, including substance abuse and neural dysfunctions. However, cumulative evidence concerning the C385A variant is inconsistent. Therefore, validation studies considerin...
Discover Oncology, Jan 8, 2023
Viruses are pathogenic agents responsible for approximately 10% of all human cancers and signific... more Viruses are pathogenic agents responsible for approximately 10% of all human cancers and significantly contribute to the global cancer burden. Until now, eight viruses have been associated with the development of a broad range of malignancies, including solid and haematological tumours. Besides triggering and promoting oncogenesis, viral infections often go hand-in-hand with haemostatic changes, representing a potential risk factor for venous thromboembolism (VTE). Conversely, VTE is a cardiovascular condition that is particularly common among oncological patients, with a detrimental impact on patient prognosis. Despite an association between viral infections and coagulopathies, it is unclear whether viral-driven tumours have a different incidence and prognosis pattern of thromboembolism compared to non-viralinduced tumours. Thus, this review aims to analyse the existing evidence concerning the association of viruses and viral tumours with the occurrence of VTE. Except for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection, which are associated with a high risk of VTE, little evidence exists concerning the thrombogenic potential associated with oncoviruses. As for tumours that can be induced by oncoviruses, four levels of VTE risk are observed, with hepatocellular carcinoma (HCC) and gastric carcinoma (GC) associated with the highest risk and nasopharyngeal carcinoma (NPC) associated with the lowest risk. Unfortunately, the incidence of cancer-related VTE according to tumour aetiology is unknown. Given the negative impact of VTE in oncological patients, research is required to better understand the mechanisms underlying blood hypercoagulability in viral-driven tumours to improve VTE management and prognosis assessment in patients diagnosed with these tumours.
Ovarian Cancer - From Pathogenesis to Treatment, Oct 24, 2018
Over the previous two decades, there has been a shift in the ovarian cancer paradigm to consider ... more Over the previous two decades, there has been a shift in the ovarian cancer paradigm to consider it as a multiplicity of disease types rather than a single disease, requiring specialized medical management from molecular diagnosis through to treatment. Despite the achieved improvements in diagnosis, surgery, and systemic treatment, ovarian cancer remains the leading cause of death from gynecological tumors in western countries. The study of ovarian cancer at a molecular level could reveal potential biomarkers of disease diagnosis and progression, as well as possible therapeutic targets in areas such as angiogenesis and homologous recombination deficiencies. Although this area of research is proving invaluable concerning newer therapeutic approaches, platinum-based chemotherapy continues to be the core of the first-line treatment. Genomic screening focusing on the identification of prognostic and predictive markers is considered one of the leading areas for future ovarian cancer research.
Pharmacogenomics, Feb 1, 2018
Renal cell carcinoma (RCC) is the most commonly occurring solid cancer of the adult kidney with t... more Renal cell carcinoma (RCC) is the most commonly occurring solid cancer of the adult kidney with the majority of RCC cases being detected accidentally. The most aggressive subtype is clear cell RCC (ccRCC). miRNAs, a family of small noncoding RNAs regulating gene expression have been identified as key biological modulators. The von Hippel-Lindau pathway is one of the signaling pathways involved in the pathophysiology of ccRCC. Another oncogenic mechanism involves the activation of PI3K/AKT/mTOR signaling and serves as a central regulator of cell metabolism, proliferation and survival. Several studies have described the involvement of miRNA dysregulation in the pathogenesis and progression of ccRCC. These molecules can be considered as potential diagnostic and prognostic biomarkers, allowing response to therapy to be monitored.
Oncotarget, Jan 28, 2017
Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achiev... more Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. The ability to predict tumor response before treatment may significantly have impact the selection of patients for nCRT in rectal cancer. The aim is to identify potential predictive pretreatment factors for Mandard response and build a clinical predictive model design. 167 patients with locally advanced rectal cancer were treated with nCRT and curative surgery. Blood cell counts in peripheral blood were analyzed. Pretreatment biopsies expression of cyclin D1, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and protein 21 were assessed. A total of 61 single nucleotide polymorphisms were characterized using the Sequenom platform through multiplex amplification followed by mass-spectometric product separation. Surgical specime...
The International journal of biological markers, Jan 8, 2017
Several studies have suggested that there are single nucleotide polymorphisms (SNPs) that can be ... more Several studies have suggested that there are single nucleotide polymorphisms (SNPs) that can be considered potential biomarkers in the prognosis and therapeutic response of cancer patients. The present study investigated the association between ERCC1 rs3212986 and XRCC3 rs861539 polymorphisms and clinical toxicities induced by chemoradiotherapy (CRT) in cervical cancer. This hospital-based retrospective cohort study included 260 patients with cervical cancer, FIGO stages Ib2-IVa, who underwent CRT (cisplatin). Genetic polymorphisms analysis was performed by allelic discrimination with real-time polymerase chain reaction (RT-PCR). Our results indicated a link between ERCC1 rs3212986 and the onset of late gastrointestinal toxicity (p = 0.038). Furthermore, using a recessive model (AA vs. CC/CA), we found that patients carrying AA homozygous genotype presented a fourfold increased risk of developing late gastrointestinal toxicity when compared with patients with the C allele (odds rat...
Urologic oncology, Aug 2, 2017
Hypoxia-inducible factor (HIF-1) is a key regulator of the genes involved in the cellular respons... more Hypoxia-inducible factor (HIF-1) is a key regulator of the genes involved in the cellular response to hypoxia. Overexpression of HIF-1 has been implicated in the pathogenesis of renal cell carcinoma (RCC), and functional polymorphisms of the HIF1A gene may confer susceptibility to RCC. Our purpose was to assess the influence of HIF1A+1772C/T (rs11549465) polymorphism on RCC prognosis. This study evaluated the associations of the HIF1A+1772C/T (rs11549465) polymorphism with clinicopathologic prognostic factors, recurrence/progression, and survival in a cohort of 179 patients with RCC treated at Portuguese Oncology Institute of Porto. Genotyping analysis, using DNA extracted from peripheral blood, was performed by real-time polymerase chain reaction allelic discrimination. The genotype associations with clinicopathologic parameters and recurrence/progression were analyzed by the chi-square or Fisher tests. Genotypes influencing cancer-specific survival were compared using Cox proporti...
Virus research, May 3, 2017
For decades, research on the pathogenesis of papillomavirus-induced lesions, particularly of huma... more For decades, research on the pathogenesis of papillomavirus-induced lesions, particularly of human papillomavirus (HPV) has relied on the use of animal models. Among these, HPV-transgenic mice are some of the most frequently employed. After some initial unsuccessful attempts, researchers have succeeded in targeting the expression of one or more HPV-16 oncogenes to squamous epithelia, closely mimicking the lesions observed in cancer patients. The present review describes the relevance and usefulness of these animal models in understanding the tumour-associated immune response and developing new preventive and therapeutic strategies for HPV-associated cancers. In particular, this review details the importance of transgenic mice for dissecting and modulating relevant aspects of the tumour-associated immune response. Other animal models for studying papillomaviral diseases are briefly mentioned, along with their respective advantages and limitations. HPV-transgenic mouse strains remain ...
Molecular and Clinical Oncology, 2017
Acute myeloid leukemia (AML) is a clonal hematological malignant condition and the implications o... more Acute myeloid leukemia (AML) is a clonal hematological malignant condition and the implications of pretreatment risk criteria as predictive or prognostic factors are constantly under evaluation. With this study, the authors' intent was to characterize AML patients and to evaluate the clinical outcome associated with Southwestern Oncology Group (SWOG) coding pretreatment risk criteria/cytogenetic score. Between 2002 and 2010, 225 patients were diagnosed with AML at the Portuguese Institute of Oncology (Porto, Portugal). From this patient group, 128 patients aged <65 years were selected. The patients were treated using a combination of cytarabine and anthracycline, with the addition of cyclosporine when bone marrow dysplasia was observed. A median survival of 24 months was observed in this group. The patients were divided in subgroups according to the SWOG pretreatment risk criteria. We observed a statistically significant association of non-favorable SWOG coding with female gender [P=0.025; risk ratio (RR)=3.632, 95% confidence interval (CI): 1.113-11.852], indication for allogeneic bone marrow transplantation (P=0.023,
Anticancer research, 2016
Papillomaviruses induce a range of benign and malignant lesions in their hosts, including cervica... more Papillomaviruses induce a range of benign and malignant lesions in their hosts, including cervical cancer, that is associated with high-risk human papillomavirus (HPV) types. The nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) plays a pivotal role in HPV-infected cells, and its expression and activity are modulated by several viral oncoproteins. NFκB modulation seems to first facilitate viral persistence and immune evasion, and later to drive tumour progression, but the many conflicting results and the complexity of its signaling networks require great prudence while interpreting the role of NFκB in papillomaviral lesions. Accordingly, the pharmacological targeting of the NFκB pathway in HPV-induced lesions is a complex and currently unmet challenge. This review deals with recent findings concerning NFκB activation in HPV-infected cells, its role in viral persistence, cell transformation and tumour progression, and with current efforts to target this pathway fo...
International Braz J Urol, 2011
Purpose: Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in the world. A... more Purpose: Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in the world. Although PSA utilization as a serum marker has improved prostate cancer detection it still presents some limitations, mainly regarding its specificity. The expression of this marker, along with the detection of PCA3 mRNA in urine samples, has been suggested as a new approach for PCa detection. The goal of this work was to evaluate the efficacy of the urinary detection of PCA3 mRNA and PSA mRNA without performing the somewhat embarrassing prostate massage. It was also intended to optimize and implement a methodological protocol for this kind of sampling. Materials and Methods: Urine samples from 57 patients with suspected prostate disease were collected, without undergoing prostate massage. Increased serum PSA levels were confirmed by medical records review. RNA was extracted by different methods and a preamplification step was included in order to improve gene detection by Real-Time PCR. Results: An increase in RNA concentration with the use of TriPure Isolation Reagent. Despite this optimization, only 15.8% of the cases showed expression of PSA mRNA and only 3.8% of prostate cancer patients presented detectable levels of PCA3 mRNA. The use of a preamplification step revealed no improvement in the results obtained. Conclusion: This work confirms that prostate massage is important before urine collection for gene expression analysis. Since PSA and PCA3 are prostate specific, it is necessary to promote the passage of cells from prostate to urinary tract, in order to detect these genetic markers in urine samples.
Human Reproduction, 2003
BACKGROUND: Catechol-O-methyltransferase (COMT) is the principal enzyme in the conjugation pathwa... more BACKGROUND: Catechol-O-methyltransferase (COMT) is the principal enzyme in the conjugation pathway for hydroxylated estrogens. We hypothesize that blood 17b-estradiol (E 2) and estrone (E 1) levels in postmenopausal women receiving an oral E 2 preparation are dependent on the enzyme activity of COMT. METHODS: To determine the in¯uence of this enzyme on E 2 serum levels three groups of 12 selected from 159 healthy normotensive postmenopausal women were selected according to their codon 158 COMT genotype (COMT HH , COMT HL , COMT LL) which is known to be associated with enzyme activity. All selected women received one 2 mg tablet estradiol valerate and blood samples were taken before treatment and after 1, 3 and 48 h. RESULTS: After 3 h the serum levels of E 2 were signi®cantly higher in women with the COMT LL genotype (median 69 pg/ml, range 58±91) and the COMT HL genotype (median 69 pg/ml, range 43±84) compared with women with the COMT HH genotype (median 45 pg/ml, range 15±68, P < 0.005). In a univariate analysis of variance, considering age, body weight, and COMT genotype, body weight (P = 0.034) and COMT genotype (P < 0.001) were independently related to the increase of serum E 2 levels, whereas age was not. CONCLUSIONS: Our data demonstrate that serum E 2 levels signi®cantly correlate with the COMT genotype. Differences in COMT genotype might be involved in causing variable effects of estrogens on diseases such as hormone-dependent cancers, coronary heart disease and on ef®cacy of hormone replacement therapy.
Cancer, 1998
Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV). Detection of... more Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV). Detection of EBV in biopsy specimens may serve as a tumor marker. To assess the sensitivity and specificity of the polymerase chain reaction (PCR) and in situ hybridization in the diagnosis of NPC, formalin fixed, paraffin embedded nasopharyngeal biopsies from patients in Taiwan suspected of having NPC were studied. In specimens from 107 patients with NPC, EBV was detected by PCR in 97 cases (90.7%) and by EBER in situ hybridization in 105 cases (98.1%). In specimens from 61 patients without neoplasia, EBV was detected by PCR in 7 cases (11.5%) and by EBER in situ hybridization in 0 cases. These results suggest that although EBV DNA may occasionally be detected in nonneoplastic nasopharyngeal tissues, cells expressing EBER are not. EBER in situ hybridization may therefore prove to be a useful adjunct in the diagnosis of NPC.
BMC Gastroenterology, 2013
Background: Earlier, we reported a highly statistically significant association between T-helper ... more Background: Earlier, we reported a highly statistically significant association between T-helper 1 (Th1) and Th2 cytokine genotypes and hepatocellular carcinoma (HCC) risk among natives of southern Guangxi, China, a hyperendemic region for HCC. Epidermal growth factor (EGF) plays a critical role in malignant transformation of hepatocytes and tumor progression. A polymorphism in the EGF gene (61A > G) results in elevation of EGF in liver tissues and blood. Epidemiological data are sparse on the possible association between EGF genetic polymorphism and HCC risk. Methods: The EGF 61A > G polymorphism, multiple Th1 and Th2 genotypes, and environmental risk factors for HCC were determined on 117 HCC cases and 225 healthy control subjects among non-Asians of Los Angeles County, California, a low-risk population for HCC, and 250 HCC cases and 245 controls of southern Guangxi, China. Results: Following adjustment for all known or suspected HCC risk factors, non-Asians in Los Angeles who possessed at least one copy of the high activity 61*G allele of the EGF gene showed a statistically non-significant, 78% increased risk of HCC compared with those possessing the EGF A/A genotype. This EGF-HCC risk association significantly strengthened among heavy users of alcohol [odds ratio (OR) = 3.44, 95% confidence interval (CI) = 0.93-12.76, P = 0.065)], and among individuals carrying the high-risk Th1/Th2 genotypes for HCC (OR = 3.34, 95% CI = 1.24-9.03, P = 0.017). No association between EGF genotype and HCC risk was observed among Chinese in southern Guangxi, China. Conclusion: Genetic polymorphism in the EGF gene resulting in elevated level of EGF, may contribute to HCC risk among low-risk non-Asians in Los Angeles.
CSAC 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Clinical Oncology, May 20, 2015
255 Background: In a prior study, we found that 8 single nucleotide polymorphisms (SNPs) from 4 c... more 255 Background: In a prior study, we found that 8 single nucleotide polymorphisms (SNPs) from 4 candidate hormone-related genes (JAK2, TRMT11, NKX3-1 and HSD17B12) were associated with overall survival (OS) in CRPC stage in a North American cohort of 519 subjects. We attempt to replicate these findings in an independent cohort of Portuguese patients. Methods: A hundred and forty CRPC stage patients in the new cohort were genotyped fort he candidate SNPs. The primary endpoint was overall survival (OS), defined as time from development of CRPC to death. For SNP level results we estimated hazard ratios (HR) and 95% confidence intervals (CI) under the dominant allele model using Cox regression and adjusted for age and Gleason score (GS). Results: The median age of the Portuguese cohort was 69 years (range 53-84). The GS distribution was 48% subjects with GS≥8; 35% with GS=7 and 17% with GS&amp;lt;7. Median time from castration resistance to death for the cohort was 2.2 years (IQ range: 0.8-3.4, 93 deaths). One of the 3 SNPs (rs2295005; C&amp;gt;G; MAF = 0.16) in the TRMT11gene was associated with OS after adjustment for age and GS: (dominant model p=0.05, HR=0.56; 95 CI=0.31-1.00). No other SNP was observed to have statistical significance with OS (Table 1). Conclusions: Variation in the TRMT11 gene is significantly associated with overall survival in patients with CRPC and warrants further validation as a potential prognostic biomarker. [Table: see text]
Otolaryngology-Head and Neck Surgery, Aug 1, 2007
OBJECTIVES: A polymorphism in the TP53 gene, corresponding to codon 72, has been suggested as a s... more OBJECTIVES: A polymorphism in the TP53 gene, corresponding to codon 72, has been suggested as a susceptibility and prognostic factor for several cancers. Aim of this study: Evaluation of the association between the polymorphic variants on p53 codon 72 and the ...
Veterinary world/Veterinary World, May 1, 2024
Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E... more Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs.
International journal of molecular sciences, May 10, 2024
Disclosing the Antifungal Mechanisms of the Cyclam Salt H 4 [H 2 (4-CF3 PhCH 2) 2 Cyclam]Cl 4
Genes
Gene variation linked to physiological functions is recognised to affect elite athletic performan... more Gene variation linked to physiological functions is recognised to affect elite athletic performance by modulating training and competition-enabling behaviour. The fatty acid amide hydrolase (FAAH) has been investigated as a good candidate for drug targeting, and recently, its single-nucleotide polymorphism (SNP) rs324420 was reported to be associated with athletic performance. Given the implications, the biological pathways of this genetic polymorphism linked to elite athletic performance, considering sport type, psychological traits and sports injuries, need to be dissected. Thus, a narrative review of the literature concerning the biological mechanisms of this SNP was undertaken. In addition to its role in athletic performance, FAAH rs324420 is also involved in important mechanisms underlying human psychopathologies, including substance abuse and neural dysfunctions. However, cumulative evidence concerning the C385A variant is inconsistent. Therefore, validation studies considerin...
Discover Oncology, Jan 8, 2023
Viruses are pathogenic agents responsible for approximately 10% of all human cancers and signific... more Viruses are pathogenic agents responsible for approximately 10% of all human cancers and significantly contribute to the global cancer burden. Until now, eight viruses have been associated with the development of a broad range of malignancies, including solid and haematological tumours. Besides triggering and promoting oncogenesis, viral infections often go hand-in-hand with haemostatic changes, representing a potential risk factor for venous thromboembolism (VTE). Conversely, VTE is a cardiovascular condition that is particularly common among oncological patients, with a detrimental impact on patient prognosis. Despite an association between viral infections and coagulopathies, it is unclear whether viral-driven tumours have a different incidence and prognosis pattern of thromboembolism compared to non-viralinduced tumours. Thus, this review aims to analyse the existing evidence concerning the association of viruses and viral tumours with the occurrence of VTE. Except for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection, which are associated with a high risk of VTE, little evidence exists concerning the thrombogenic potential associated with oncoviruses. As for tumours that can be induced by oncoviruses, four levels of VTE risk are observed, with hepatocellular carcinoma (HCC) and gastric carcinoma (GC) associated with the highest risk and nasopharyngeal carcinoma (NPC) associated with the lowest risk. Unfortunately, the incidence of cancer-related VTE according to tumour aetiology is unknown. Given the negative impact of VTE in oncological patients, research is required to better understand the mechanisms underlying blood hypercoagulability in viral-driven tumours to improve VTE management and prognosis assessment in patients diagnosed with these tumours.
Ovarian Cancer - From Pathogenesis to Treatment, Oct 24, 2018
Over the previous two decades, there has been a shift in the ovarian cancer paradigm to consider ... more Over the previous two decades, there has been a shift in the ovarian cancer paradigm to consider it as a multiplicity of disease types rather than a single disease, requiring specialized medical management from molecular diagnosis through to treatment. Despite the achieved improvements in diagnosis, surgery, and systemic treatment, ovarian cancer remains the leading cause of death from gynecological tumors in western countries. The study of ovarian cancer at a molecular level could reveal potential biomarkers of disease diagnosis and progression, as well as possible therapeutic targets in areas such as angiogenesis and homologous recombination deficiencies. Although this area of research is proving invaluable concerning newer therapeutic approaches, platinum-based chemotherapy continues to be the core of the first-line treatment. Genomic screening focusing on the identification of prognostic and predictive markers is considered one of the leading areas for future ovarian cancer research.
Pharmacogenomics, Feb 1, 2018
Renal cell carcinoma (RCC) is the most commonly occurring solid cancer of the adult kidney with t... more Renal cell carcinoma (RCC) is the most commonly occurring solid cancer of the adult kidney with the majority of RCC cases being detected accidentally. The most aggressive subtype is clear cell RCC (ccRCC). miRNAs, a family of small noncoding RNAs regulating gene expression have been identified as key biological modulators. The von Hippel-Lindau pathway is one of the signaling pathways involved in the pathophysiology of ccRCC. Another oncogenic mechanism involves the activation of PI3K/AKT/mTOR signaling and serves as a central regulator of cell metabolism, proliferation and survival. Several studies have described the involvement of miRNA dysregulation in the pathogenesis and progression of ccRCC. These molecules can be considered as potential diagnostic and prognostic biomarkers, allowing response to therapy to be monitored.
Oncotarget, Jan 28, 2017
Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achiev... more Survival improvement in rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. The ability to predict tumor response before treatment may significantly have impact the selection of patients for nCRT in rectal cancer. The aim is to identify potential predictive pretreatment factors for Mandard response and build a clinical predictive model design. 167 patients with locally advanced rectal cancer were treated with nCRT and curative surgery. Blood cell counts in peripheral blood were analyzed. Pretreatment biopsies expression of cyclin D1, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and protein 21 were assessed. A total of 61 single nucleotide polymorphisms were characterized using the Sequenom platform through multiplex amplification followed by mass-spectometric product separation. Surgical specime...
The International journal of biological markers, Jan 8, 2017
Several studies have suggested that there are single nucleotide polymorphisms (SNPs) that can be ... more Several studies have suggested that there are single nucleotide polymorphisms (SNPs) that can be considered potential biomarkers in the prognosis and therapeutic response of cancer patients. The present study investigated the association between ERCC1 rs3212986 and XRCC3 rs861539 polymorphisms and clinical toxicities induced by chemoradiotherapy (CRT) in cervical cancer. This hospital-based retrospective cohort study included 260 patients with cervical cancer, FIGO stages Ib2-IVa, who underwent CRT (cisplatin). Genetic polymorphisms analysis was performed by allelic discrimination with real-time polymerase chain reaction (RT-PCR). Our results indicated a link between ERCC1 rs3212986 and the onset of late gastrointestinal toxicity (p = 0.038). Furthermore, using a recessive model (AA vs. CC/CA), we found that patients carrying AA homozygous genotype presented a fourfold increased risk of developing late gastrointestinal toxicity when compared with patients with the C allele (odds rat...
Urologic oncology, Aug 2, 2017
Hypoxia-inducible factor (HIF-1) is a key regulator of the genes involved in the cellular respons... more Hypoxia-inducible factor (HIF-1) is a key regulator of the genes involved in the cellular response to hypoxia. Overexpression of HIF-1 has been implicated in the pathogenesis of renal cell carcinoma (RCC), and functional polymorphisms of the HIF1A gene may confer susceptibility to RCC. Our purpose was to assess the influence of HIF1A+1772C/T (rs11549465) polymorphism on RCC prognosis. This study evaluated the associations of the HIF1A+1772C/T (rs11549465) polymorphism with clinicopathologic prognostic factors, recurrence/progression, and survival in a cohort of 179 patients with RCC treated at Portuguese Oncology Institute of Porto. Genotyping analysis, using DNA extracted from peripheral blood, was performed by real-time polymerase chain reaction allelic discrimination. The genotype associations with clinicopathologic parameters and recurrence/progression were analyzed by the chi-square or Fisher tests. Genotypes influencing cancer-specific survival were compared using Cox proporti...
Virus research, May 3, 2017
For decades, research on the pathogenesis of papillomavirus-induced lesions, particularly of huma... more For decades, research on the pathogenesis of papillomavirus-induced lesions, particularly of human papillomavirus (HPV) has relied on the use of animal models. Among these, HPV-transgenic mice are some of the most frequently employed. After some initial unsuccessful attempts, researchers have succeeded in targeting the expression of one or more HPV-16 oncogenes to squamous epithelia, closely mimicking the lesions observed in cancer patients. The present review describes the relevance and usefulness of these animal models in understanding the tumour-associated immune response and developing new preventive and therapeutic strategies for HPV-associated cancers. In particular, this review details the importance of transgenic mice for dissecting and modulating relevant aspects of the tumour-associated immune response. Other animal models for studying papillomaviral diseases are briefly mentioned, along with their respective advantages and limitations. HPV-transgenic mouse strains remain ...
Molecular and Clinical Oncology, 2017
Acute myeloid leukemia (AML) is a clonal hematological malignant condition and the implications o... more Acute myeloid leukemia (AML) is a clonal hematological malignant condition and the implications of pretreatment risk criteria as predictive or prognostic factors are constantly under evaluation. With this study, the authors' intent was to characterize AML patients and to evaluate the clinical outcome associated with Southwestern Oncology Group (SWOG) coding pretreatment risk criteria/cytogenetic score. Between 2002 and 2010, 225 patients were diagnosed with AML at the Portuguese Institute of Oncology (Porto, Portugal). From this patient group, 128 patients aged <65 years were selected. The patients were treated using a combination of cytarabine and anthracycline, with the addition of cyclosporine when bone marrow dysplasia was observed. A median survival of 24 months was observed in this group. The patients were divided in subgroups according to the SWOG pretreatment risk criteria. We observed a statistically significant association of non-favorable SWOG coding with female gender [P=0.025; risk ratio (RR)=3.632, 95% confidence interval (CI): 1.113-11.852], indication for allogeneic bone marrow transplantation (P=0.023,
Anticancer research, 2016
Papillomaviruses induce a range of benign and malignant lesions in their hosts, including cervica... more Papillomaviruses induce a range of benign and malignant lesions in their hosts, including cervical cancer, that is associated with high-risk human papillomavirus (HPV) types. The nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) plays a pivotal role in HPV-infected cells, and its expression and activity are modulated by several viral oncoproteins. NFκB modulation seems to first facilitate viral persistence and immune evasion, and later to drive tumour progression, but the many conflicting results and the complexity of its signaling networks require great prudence while interpreting the role of NFκB in papillomaviral lesions. Accordingly, the pharmacological targeting of the NFκB pathway in HPV-induced lesions is a complex and currently unmet challenge. This review deals with recent findings concerning NFκB activation in HPV-infected cells, its role in viral persistence, cell transformation and tumour progression, and with current efforts to target this pathway fo...
International Braz J Urol, 2011
Purpose: Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in the world. A... more Purpose: Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in the world. Although PSA utilization as a serum marker has improved prostate cancer detection it still presents some limitations, mainly regarding its specificity. The expression of this marker, along with the detection of PCA3 mRNA in urine samples, has been suggested as a new approach for PCa detection. The goal of this work was to evaluate the efficacy of the urinary detection of PCA3 mRNA and PSA mRNA without performing the somewhat embarrassing prostate massage. It was also intended to optimize and implement a methodological protocol for this kind of sampling. Materials and Methods: Urine samples from 57 patients with suspected prostate disease were collected, without undergoing prostate massage. Increased serum PSA levels were confirmed by medical records review. RNA was extracted by different methods and a preamplification step was included in order to improve gene detection by Real-Time PCR. Results: An increase in RNA concentration with the use of TriPure Isolation Reagent. Despite this optimization, only 15.8% of the cases showed expression of PSA mRNA and only 3.8% of prostate cancer patients presented detectable levels of PCA3 mRNA. The use of a preamplification step revealed no improvement in the results obtained. Conclusion: This work confirms that prostate massage is important before urine collection for gene expression analysis. Since PSA and PCA3 are prostate specific, it is necessary to promote the passage of cells from prostate to urinary tract, in order to detect these genetic markers in urine samples.
Human Reproduction, 2003
BACKGROUND: Catechol-O-methyltransferase (COMT) is the principal enzyme in the conjugation pathwa... more BACKGROUND: Catechol-O-methyltransferase (COMT) is the principal enzyme in the conjugation pathway for hydroxylated estrogens. We hypothesize that blood 17b-estradiol (E 2) and estrone (E 1) levels in postmenopausal women receiving an oral E 2 preparation are dependent on the enzyme activity of COMT. METHODS: To determine the in¯uence of this enzyme on E 2 serum levels three groups of 12 selected from 159 healthy normotensive postmenopausal women were selected according to their codon 158 COMT genotype (COMT HH , COMT HL , COMT LL) which is known to be associated with enzyme activity. All selected women received one 2 mg tablet estradiol valerate and blood samples were taken before treatment and after 1, 3 and 48 h. RESULTS: After 3 h the serum levels of E 2 were signi®cantly higher in women with the COMT LL genotype (median 69 pg/ml, range 58±91) and the COMT HL genotype (median 69 pg/ml, range 43±84) compared with women with the COMT HH genotype (median 45 pg/ml, range 15±68, P < 0.005). In a univariate analysis of variance, considering age, body weight, and COMT genotype, body weight (P = 0.034) and COMT genotype (P < 0.001) were independently related to the increase of serum E 2 levels, whereas age was not. CONCLUSIONS: Our data demonstrate that serum E 2 levels signi®cantly correlate with the COMT genotype. Differences in COMT genotype might be involved in causing variable effects of estrogens on diseases such as hormone-dependent cancers, coronary heart disease and on ef®cacy of hormone replacement therapy.
Cancer, 1998
Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV). Detection of... more Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV). Detection of EBV in biopsy specimens may serve as a tumor marker. To assess the sensitivity and specificity of the polymerase chain reaction (PCR) and in situ hybridization in the diagnosis of NPC, formalin fixed, paraffin embedded nasopharyngeal biopsies from patients in Taiwan suspected of having NPC were studied. In specimens from 107 patients with NPC, EBV was detected by PCR in 97 cases (90.7%) and by EBER in situ hybridization in 105 cases (98.1%). In specimens from 61 patients without neoplasia, EBV was detected by PCR in 7 cases (11.5%) and by EBER in situ hybridization in 0 cases. These results suggest that although EBV DNA may occasionally be detected in nonneoplastic nasopharyngeal tissues, cells expressing EBER are not. EBER in situ hybridization may therefore prove to be a useful adjunct in the diagnosis of NPC.
BMC Gastroenterology, 2013
Background: Earlier, we reported a highly statistically significant association between T-helper ... more Background: Earlier, we reported a highly statistically significant association between T-helper 1 (Th1) and Th2 cytokine genotypes and hepatocellular carcinoma (HCC) risk among natives of southern Guangxi, China, a hyperendemic region for HCC. Epidermal growth factor (EGF) plays a critical role in malignant transformation of hepatocytes and tumor progression. A polymorphism in the EGF gene (61A > G) results in elevation of EGF in liver tissues and blood. Epidemiological data are sparse on the possible association between EGF genetic polymorphism and HCC risk. Methods: The EGF 61A > G polymorphism, multiple Th1 and Th2 genotypes, and environmental risk factors for HCC were determined on 117 HCC cases and 225 healthy control subjects among non-Asians of Los Angeles County, California, a low-risk population for HCC, and 250 HCC cases and 245 controls of southern Guangxi, China. Results: Following adjustment for all known or suspected HCC risk factors, non-Asians in Los Angeles who possessed at least one copy of the high activity 61*G allele of the EGF gene showed a statistically non-significant, 78% increased risk of HCC compared with those possessing the EGF A/A genotype. This EGF-HCC risk association significantly strengthened among heavy users of alcohol [odds ratio (OR) = 3.44, 95% confidence interval (CI) = 0.93-12.76, P = 0.065)], and among individuals carrying the high-risk Th1/Th2 genotypes for HCC (OR = 3.34, 95% CI = 1.24-9.03, P = 0.017). No association between EGF genotype and HCC risk was observed among Chinese in southern Guangxi, China. Conclusion: Genetic polymorphism in the EGF gene resulting in elevated level of EGF, may contribute to HCC risk among low-risk non-Asians in Los Angeles.
CSAC 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Clinical Oncology, May 20, 2015
255 Background: In a prior study, we found that 8 single nucleotide polymorphisms (SNPs) from 4 c... more 255 Background: In a prior study, we found that 8 single nucleotide polymorphisms (SNPs) from 4 candidate hormone-related genes (JAK2, TRMT11, NKX3-1 and HSD17B12) were associated with overall survival (OS) in CRPC stage in a North American cohort of 519 subjects. We attempt to replicate these findings in an independent cohort of Portuguese patients. Methods: A hundred and forty CRPC stage patients in the new cohort were genotyped fort he candidate SNPs. The primary endpoint was overall survival (OS), defined as time from development of CRPC to death. For SNP level results we estimated hazard ratios (HR) and 95% confidence intervals (CI) under the dominant allele model using Cox regression and adjusted for age and Gleason score (GS). Results: The median age of the Portuguese cohort was 69 years (range 53-84). The GS distribution was 48% subjects with GS≥8; 35% with GS=7 and 17% with GS&amp;lt;7. Median time from castration resistance to death for the cohort was 2.2 years (IQ range: 0.8-3.4, 93 deaths). One of the 3 SNPs (rs2295005; C&amp;gt;G; MAF = 0.16) in the TRMT11gene was associated with OS after adjustment for age and GS: (dominant model p=0.05, HR=0.56; 95 CI=0.31-1.00). No other SNP was observed to have statistical significance with OS (Table 1). Conclusions: Variation in the TRMT11 gene is significantly associated with overall survival in patients with CRPC and warrants further validation as a potential prognostic biomarker. [Table: see text]
Otolaryngology-Head and Neck Surgery, Aug 1, 2007
OBJECTIVES: A polymorphism in the TP53 gene, corresponding to codon 72, has been suggested as a s... more OBJECTIVES: A polymorphism in the TP53 gene, corresponding to codon 72, has been suggested as a susceptibility and prognostic factor for several cancers. Aim of this study: Evaluation of the association between the polymorphic variants on p53 codon 72 and the ...
Otolaryngology - Head and Neck Surgery, 2007
OBJECTIVES: A polymorphism in the TP53 gene, corresponding to codon 72, has been suggested as a s... more OBJECTIVES: A polymorphism in the TP53 gene, corresponding to codon 72, has been suggested as a susceptibility and prognostic factor for several cancers. Aim of this study: Evaluation of the association between the polymorphic variants on p53 codon 72 and the ...
of 0.54 (p < 0.001) between predicted and measured treatment response, while extracted DCEMRI par... more of 0.54 (p < 0.001) between predicted and measured treatment response, while extracted DCEMRI parameters together with volumes and PSA gave a correlation coefficient of 0.66 (p < 0.001). The approach where all parameters (DWMRI, DCEMRI, volumes, PSA) were combined was superior to all other BPNN simulations and successfully predicted ultimate treatment response with a correlation coefficient of 0.85 (p < 0.001).