The effects of the essential oil of Mentha pulegium L. (EOMP), a plant commonly known as &amp... more The effects of the essential oil of Mentha pulegium L. (EOMP), a plant commonly known as "pennyroyal" or "poejo" that is used in folk medicine as an abortifaceant, were assessed on the isolated rat myometrium. Myometrial strips were stimulated with 10 nM oxytocin or 10 microM PGF (2alpha). EOMP (10 - 300 microg/mL) concentration-dependently and reversibly inhibited the amplitude of oscillatory contractions, being approximately 3-fold more active against contractions stimulated by oxytocin than those by PGF (2alpha) (IC (50) values of 45.7 +/- 5.6 microg/mL and 160.9 +/- 5.9 microg/mL , respectively), although the maximal inhibitory effect occurred at the same concentration (300 microg/mL ) in both cases. This action was shared by pulegone (30 - 300 microM), the principal component of the essential oil (IC (50) values of 21.8 +/- 2.1 microg/mL and 12.7 +/- 4.6 microg/mL , respectively). Nifedipine (30 nM - 30 microM) also abolished agonist-stimulated contractions, and was approximately twice and 12 times as potent as EOMP in inhibiting oxytocin- and prostaglandin F (2alpha) (PGF (2alpha))-stimulated contractions, respectively. In conclusion, our results show that the essential oil of the abortifaceant plant Mentha pulegium exerts an inhibitory effect on the contractile activity of the isolated rat myometrium. This oil shares a common effect with the voltage-dependent calcium channel (VDCC) blocker nifedipine, although ostensibly acting via a different mechanism. It thus appears that EOMP and pulegone do not exert direct toxic effects on the myometrium per se that would cause abortion, and other possibilities such as systemic metabolism of plant constituents may rather underlie the abusive use of Mentha pulegium in popular medicine.
Regular exercise is an exogenous factor of gene regulation with numerous health benefits. The stu... more Regular exercise is an exogenous factor of gene regulation with numerous health benefits. The study aimed to evaluate human genes linked to physical exercise in an 'omic scale, addressing biological questions to the generated database. Three literature databases were searched with the terms 'exercise', 'fitness', 'physical activity', 'genetics' and 'gene expression'. For additional references, papers were scrutinized and a text-mining tool was used. Papers linking genes to exercise in humans through microarray, RNA-Seq, RT-PCR and genotyping studies were included. Genes were extracted from the collected literature, together with information on exercise protocol, experimental design, gender, age, number of individuals, analytical method, fold change and statistical data. The 'omic scale dataset was characterized and evaluated with bioinformatics tools searching for gene expression patterns, functional meaning and gene clusters. As a res...
Resumo O objetivo deste estudo foi analisar os fatores de risco para o desenvolvimento de doenças... more Resumo O objetivo deste estudo foi analisar os fatores de risco para o desenvolvimento de doenças cardiovasculares (DCV) de homens que freqüentam o calçadão da Avenida Beira Mar da cidade de Fortaleza. A amostra foi composta de 144 homens com idades entre 16 ...
This study analyzed the sensorial, structural and functional response of rats subjected to paw im... more This study analyzed the sensorial, structural and functional response of rats subjected to paw immobilization. Animal pelvis, hip, knee and ankle were immobilized using waterproof tape during two weeks for assessment of sensorial response to thermal (hot plate test) and mechanical stimuli (Von Frey test), motor system structure (histology and radiography) and muscle function (soleus contractility). Disuse animals became more responsive to thermal stimuli (49%), although less responsive to mechanical challenge (58%). Disuse animals showed local injuries such as reduction in muscle fiber diameter (16.7% in gastrocnemius, 5.7% in soleus), contractile activity (55% of the control maximal tonic contraction) and tibia cortical thickness (9.3%), besides increased nitrite:protein ratio, suggestive of protein degradation. Disuse also evoked systemic adaptations that include increase in serum lactate dehydrogenase (36.1%) and alkaline phosphatase (400%), but reduction in calcium (8.4%) and total serum protein (5.5%), especially albumin (34.2%). Two weeks of functional paw disuse leads to local and systemic harmful adaptive changes in sensorial and structural systems. This study brings new insights into nervous and motor system mechanism associated with therapeutic limb immobilization in muscle and skeletal pathological conditions.
International journal of cancer. Journal international du cancer, Jan 23, 2016
Human hotspot TERT promoter (TERTp) mutations have been reported in a wide range of tumours. Seve... more Human hotspot TERT promoter (TERTp) mutations have been reported in a wide range of tumours. Several studies have shown that TERTp mutations are associated with clinico-pathological features; in some instances, TERTp mutations were considered as biomarkers of poor prognosis. The rs2853669 SNP, located in the TERT promoter region, was reported to modulate the increased TERT expression levels induced by the recurrent somatic mutations. In this study we aimed to determine the frequency and prognostic value of TERTp mutations and TERT rs2853669 SNP in 504 gliomas from Portuguese and Brazilian patients. TERTp mutations were detected in 47.8% of gliomas (216/452). Glioblastomas (GBM) exhibited the highest frequency of TERTp mutations (66.9%); in this glioma subtype, we found a significant association between TERTp mutations and poor prognosis, regardless of the population. Moreover, in a multivariate analysis, TERTp mutations were the only independent prognostic factor. Our data also show...
In the review some of the molecular alterations that can relate to the neoplastic development of ... more In the review some of the molecular alterations that can relate to the neoplastic development of well differentiated thyroid carcinomas (follicular and papillary carcinoma) and of the so-called Hürthle cell carcinomas are described. Diagnostic and/or prognostic significance of the most recent findings is discussed.
The growing incidence in thyroid cancer results mainly from the detection of small or very small ... more The growing incidence in thyroid cancer results mainly from the detection of small or very small papillary thyroid carcinomas. The management of patients with such small tumors represents a major clinical challenge. Could evaluation of the BRAF status of such tumors aid risk stratification and patient management?
The Journal of Clinical Endocrinology & Metabolism, 2015
Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is... more Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is conceivably a useful treatment strategy for PTC, which awaits comprehensive data demonstrating differential risks of PTC variants to support. To establish the differential clinicopathological risk of major PTC variants-conventional PTC (CPTC), follicular-variant PTC (FVPTC), and tall-cell PTC (TCPTC). Retrospective study of clinicopathological outcomes of 6,282 PTC patients (4,799 females and 1,483 males) from 26 centers and The Cancer Genome Atlas in 14 countries with a median age of 44 years (interquartile range [IQR], 33-56) and median follow-up time of 37 months (IQR 15-82). The cohort consisted of 4,702 (74.8%) CPTC, 1,126 (17.9%) FVPTC, and 239 (3.8%) TCPTC. The prevalence of high-risk parameters was significantly different among the three variants, including extrathyroidal invasion, lymph node metastasis, stages III/IV, disease recurrence, mortality and the use (need) of radioiodine treatment (all P < 0.001), being highest in TCPTC, lowest in FVPTC, and intermediate in CPTC, following an order of TCPTC>CPTC≫FVPTC. Recurrence and mortality in TCPTC, CPTC, and FVPTC were 27.3% and 6.7%, 16.1% and 2.5%, and 9.1% and 0.6%, corresponding to events per 1000 person-years (95% confidence interval-CI) of 92.47 (64.66-132.26) and 24.61 (12.31-49.21), 34.46 (30.71-38.66) and 5.87 (4.37-7.88), and 24.73 (18.34-33.35) and 1.68 (0.54-5.21), respectively. Mortality hazard ratios of CPTC and TCPTC over FVPTC were 3.44 (95% CI 1.07-11.11) and 14.96 (95% CI 3.93-56.89), respectively. Kaplan-Meier survival analyses showed the best prognosis in FVPTC, worst in TCPTC, and intermediate in CPTC in disease recurrence-free probability and disease-specific patient survival. This was particularly the case in patients ≥ 45 years old. This large multicenter study demonstrates differential prognostic risks of the three major PTC variants and establishes a unique risk order of TCPTC…
The abnormal activation of telomerase, codified by the telomerase reverse transcriptase (TERT) ge... more The abnormal activation of telomerase, codified by the telomerase reverse transcriptase (TERT) gene, is related to one of cancer hallmarks. Hotspot somatic mutations in the promoter region of TERT, specifically the c.-124:C>T and c.-146:C>T, were recently identified in a range of human cancers and have been associated with a more aggressive behavior. Testicular germ cell tumors frequently exhibit a good prognosis; however, the development of refractory disease is still a clinical challenge. In this study, we aim to evaluate for the first time the presence of the hotspot telomerase reverse transcriptase gene promoter mutations in testicular germ cell tumors. A series of 150 testicular germ cell tumor cases and four germ cell tumor cell lines were evaluated by PCR followed by direct Sanger sequencing and correlated with…
Genetic predictors of outcome are reviewed in the context of a disease - cancer - that can be (to... more Genetic predictors of outcome are reviewed in the context of a disease - cancer - that can be (too) simplistically described as a "Successful, invasive clone of our own tissues". Context has many faces that determine thyroid cancer patient's outcome beyond the influence of genetic markers. There is also plenty evidence on the prognostic meaning of the interplay between genetics and context/microenvironment factors (encapsulation, degree of invasion, staging,…). This review addresses only genetic alterations detected by molecular methods in surgically resected specimens, thus ruling out immunohistochemistry and (F)ISH, despite their crucial relevance as topographically oriented methods. For the sake of the discussion, well differentiated carcinomas were divided in two main morphologic types: papillary carcinoma (classic and most variants) displaying BRAF V600E mutations and RET/PTC rearrangements, and the group of follicular patterned carcinomas that encompasses follicular carcinoma and the encapsulated form of follicular variant of papillary carcinoma, displaying RAS mutations and PAX8/PPAR rearrangement. TERT promoter mutations have been recently described (and associated with distant metastases and reduced survival) in papillary and follicular carcinomas, as well as in poorly differentiated and undifferentiated carcinoma. TP53 mutations, previously thought to be restricted to less differentiated carcinomas, were also detected in papillary and follicular carcinoma and found to carry a guarded prognosis. Besides their putative importance for targeted therapies, the prognostic meaning of such mutations is discussed per se and in the setting of concurrent BRAF mutation.
The International Journal of Biological Markers, 2015
Oncogenic hotspot mutations in the promoter region of the TERT gene have been identified in sever... more Oncogenic hotspot mutations in the promoter region of the TERT gene have been identified in several cancer types as being associated with a worse outcome. Additionally, a polymorphism (rs2853669) in the TERT promoter region was reported to modify the survival of TERT-mutated patients. Our aim is to determine the frequency of c.-124 Cgt;T and c.-146 Cgt;T TERT mutations and to genotype the rs2853669 polymorphism in a series of 68 soft tissue sarcomas (STS) comprising 22 histological subtypes. PCR was performed, followed by direct sequencing of a fragment of TERT containing the hotspots and the rs2853669. We found TERT mutations in 4/68 (5.9%) STSs including 1 pleomorphic liposarcoma (1/1), 1 dedifferentiated liposarcoma (1/1) and 2 myxoid liposarcomas (2/9). The variant C allele of rs2853669 was found in 54.8% (34/62) of all STSs and in 75% (3/4) of TERT-mutated cases. TERT mutations were associated with younger age, and the C allele of the rs2853669 was associated with high histological grade (2 and 3). No association was found between TERT mutation status or rs2853669 genotype and patient prognosis. We showed that TERT promoter mutation is not a recurrent event in STS and is present in particular histological subtypes.
The effects of the essential oil of Mentha pulegium L. (EOMP), a plant commonly known as &amp... more The effects of the essential oil of Mentha pulegium L. (EOMP), a plant commonly known as "pennyroyal" or "poejo" that is used in folk medicine as an abortifaceant, were assessed on the isolated rat myometrium. Myometrial strips were stimulated with 10 nM oxytocin or 10 microM PGF (2alpha). EOMP (10 - 300 microg/mL) concentration-dependently and reversibly inhibited the amplitude of oscillatory contractions, being approximately 3-fold more active against contractions stimulated by oxytocin than those by PGF (2alpha) (IC (50) values of 45.7 +/- 5.6 microg/mL and 160.9 +/- 5.9 microg/mL , respectively), although the maximal inhibitory effect occurred at the same concentration (300 microg/mL ) in both cases. This action was shared by pulegone (30 - 300 microM), the principal component of the essential oil (IC (50) values of 21.8 +/- 2.1 microg/mL and 12.7 +/- 4.6 microg/mL , respectively). Nifedipine (30 nM - 30 microM) also abolished agonist-stimulated contractions, and was approximately twice and 12 times as potent as EOMP in inhibiting oxytocin- and prostaglandin F (2alpha) (PGF (2alpha))-stimulated contractions, respectively. In conclusion, our results show that the essential oil of the abortifaceant plant Mentha pulegium exerts an inhibitory effect on the contractile activity of the isolated rat myometrium. This oil shares a common effect with the voltage-dependent calcium channel (VDCC) blocker nifedipine, although ostensibly acting via a different mechanism. It thus appears that EOMP and pulegone do not exert direct toxic effects on the myometrium per se that would cause abortion, and other possibilities such as systemic metabolism of plant constituents may rather underlie the abusive use of Mentha pulegium in popular medicine.
Regular exercise is an exogenous factor of gene regulation with numerous health benefits. The stu... more Regular exercise is an exogenous factor of gene regulation with numerous health benefits. The study aimed to evaluate human genes linked to physical exercise in an 'omic scale, addressing biological questions to the generated database. Three literature databases were searched with the terms 'exercise', 'fitness', 'physical activity', 'genetics' and 'gene expression'. For additional references, papers were scrutinized and a text-mining tool was used. Papers linking genes to exercise in humans through microarray, RNA-Seq, RT-PCR and genotyping studies were included. Genes were extracted from the collected literature, together with information on exercise protocol, experimental design, gender, age, number of individuals, analytical method, fold change and statistical data. The 'omic scale dataset was characterized and evaluated with bioinformatics tools searching for gene expression patterns, functional meaning and gene clusters. As a res...
Resumo O objetivo deste estudo foi analisar os fatores de risco para o desenvolvimento de doenças... more Resumo O objetivo deste estudo foi analisar os fatores de risco para o desenvolvimento de doenças cardiovasculares (DCV) de homens que freqüentam o calçadão da Avenida Beira Mar da cidade de Fortaleza. A amostra foi composta de 144 homens com idades entre 16 ...
This study analyzed the sensorial, structural and functional response of rats subjected to paw im... more This study analyzed the sensorial, structural and functional response of rats subjected to paw immobilization. Animal pelvis, hip, knee and ankle were immobilized using waterproof tape during two weeks for assessment of sensorial response to thermal (hot plate test) and mechanical stimuli (Von Frey test), motor system structure (histology and radiography) and muscle function (soleus contractility). Disuse animals became more responsive to thermal stimuli (49%), although less responsive to mechanical challenge (58%). Disuse animals showed local injuries such as reduction in muscle fiber diameter (16.7% in gastrocnemius, 5.7% in soleus), contractile activity (55% of the control maximal tonic contraction) and tibia cortical thickness (9.3%), besides increased nitrite:protein ratio, suggestive of protein degradation. Disuse also evoked systemic adaptations that include increase in serum lactate dehydrogenase (36.1%) and alkaline phosphatase (400%), but reduction in calcium (8.4%) and total serum protein (5.5%), especially albumin (34.2%). Two weeks of functional paw disuse leads to local and systemic harmful adaptive changes in sensorial and structural systems. This study brings new insights into nervous and motor system mechanism associated with therapeutic limb immobilization in muscle and skeletal pathological conditions.
International journal of cancer. Journal international du cancer, Jan 23, 2016
Human hotspot TERT promoter (TERTp) mutations have been reported in a wide range of tumours. Seve... more Human hotspot TERT promoter (TERTp) mutations have been reported in a wide range of tumours. Several studies have shown that TERTp mutations are associated with clinico-pathological features; in some instances, TERTp mutations were considered as biomarkers of poor prognosis. The rs2853669 SNP, located in the TERT promoter region, was reported to modulate the increased TERT expression levels induced by the recurrent somatic mutations. In this study we aimed to determine the frequency and prognostic value of TERTp mutations and TERT rs2853669 SNP in 504 gliomas from Portuguese and Brazilian patients. TERTp mutations were detected in 47.8% of gliomas (216/452). Glioblastomas (GBM) exhibited the highest frequency of TERTp mutations (66.9%); in this glioma subtype, we found a significant association between TERTp mutations and poor prognosis, regardless of the population. Moreover, in a multivariate analysis, TERTp mutations were the only independent prognostic factor. Our data also show...
In the review some of the molecular alterations that can relate to the neoplastic development of ... more In the review some of the molecular alterations that can relate to the neoplastic development of well differentiated thyroid carcinomas (follicular and papillary carcinoma) and of the so-called Hürthle cell carcinomas are described. Diagnostic and/or prognostic significance of the most recent findings is discussed.
The growing incidence in thyroid cancer results mainly from the detection of small or very small ... more The growing incidence in thyroid cancer results mainly from the detection of small or very small papillary thyroid carcinomas. The management of patients with such small tumors represents a major clinical challenge. Could evaluation of the BRAF status of such tumors aid risk stratification and patient management?
The Journal of Clinical Endocrinology & Metabolism, 2015
Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is... more Individualized management, incorporating papillary thyroid cancer (PTC) variant-specific risk, is conceivably a useful treatment strategy for PTC, which awaits comprehensive data demonstrating differential risks of PTC variants to support. To establish the differential clinicopathological risk of major PTC variants-conventional PTC (CPTC), follicular-variant PTC (FVPTC), and tall-cell PTC (TCPTC). Retrospective study of clinicopathological outcomes of 6,282 PTC patients (4,799 females and 1,483 males) from 26 centers and The Cancer Genome Atlas in 14 countries with a median age of 44 years (interquartile range [IQR], 33-56) and median follow-up time of 37 months (IQR 15-82). The cohort consisted of 4,702 (74.8%) CPTC, 1,126 (17.9%) FVPTC, and 239 (3.8%) TCPTC. The prevalence of high-risk parameters was significantly different among the three variants, including extrathyroidal invasion, lymph node metastasis, stages III/IV, disease recurrence, mortality and the use (need) of radioiodine treatment (all P < 0.001), being highest in TCPTC, lowest in FVPTC, and intermediate in CPTC, following an order of TCPTC>CPTC≫FVPTC. Recurrence and mortality in TCPTC, CPTC, and FVPTC were 27.3% and 6.7%, 16.1% and 2.5%, and 9.1% and 0.6%, corresponding to events per 1000 person-years (95% confidence interval-CI) of 92.47 (64.66-132.26) and 24.61 (12.31-49.21), 34.46 (30.71-38.66) and 5.87 (4.37-7.88), and 24.73 (18.34-33.35) and 1.68 (0.54-5.21), respectively. Mortality hazard ratios of CPTC and TCPTC over FVPTC were 3.44 (95% CI 1.07-11.11) and 14.96 (95% CI 3.93-56.89), respectively. Kaplan-Meier survival analyses showed the best prognosis in FVPTC, worst in TCPTC, and intermediate in CPTC in disease recurrence-free probability and disease-specific patient survival. This was particularly the case in patients ≥ 45 years old. This large multicenter study demonstrates differential prognostic risks of the three major PTC variants and establishes a unique risk order of TCPTC…
The abnormal activation of telomerase, codified by the telomerase reverse transcriptase (TERT) ge... more The abnormal activation of telomerase, codified by the telomerase reverse transcriptase (TERT) gene, is related to one of cancer hallmarks. Hotspot somatic mutations in the promoter region of TERT, specifically the c.-124:C>T and c.-146:C>T, were recently identified in a range of human cancers and have been associated with a more aggressive behavior. Testicular germ cell tumors frequently exhibit a good prognosis; however, the development of refractory disease is still a clinical challenge. In this study, we aim to evaluate for the first time the presence of the hotspot telomerase reverse transcriptase gene promoter mutations in testicular germ cell tumors. A series of 150 testicular germ cell tumor cases and four germ cell tumor cell lines were evaluated by PCR followed by direct Sanger sequencing and correlated with…
Genetic predictors of outcome are reviewed in the context of a disease - cancer - that can be (to... more Genetic predictors of outcome are reviewed in the context of a disease - cancer - that can be (too) simplistically described as a "Successful, invasive clone of our own tissues". Context has many faces that determine thyroid cancer patient's outcome beyond the influence of genetic markers. There is also plenty evidence on the prognostic meaning of the interplay between genetics and context/microenvironment factors (encapsulation, degree of invasion, staging,…). This review addresses only genetic alterations detected by molecular methods in surgically resected specimens, thus ruling out immunohistochemistry and (F)ISH, despite their crucial relevance as topographically oriented methods. For the sake of the discussion, well differentiated carcinomas were divided in two main morphologic types: papillary carcinoma (classic and most variants) displaying BRAF V600E mutations and RET/PTC rearrangements, and the group of follicular patterned carcinomas that encompasses follicular carcinoma and the encapsulated form of follicular variant of papillary carcinoma, displaying RAS mutations and PAX8/PPAR rearrangement. TERT promoter mutations have been recently described (and associated with distant metastases and reduced survival) in papillary and follicular carcinomas, as well as in poorly differentiated and undifferentiated carcinoma. TP53 mutations, previously thought to be restricted to less differentiated carcinomas, were also detected in papillary and follicular carcinoma and found to carry a guarded prognosis. Besides their putative importance for targeted therapies, the prognostic meaning of such mutations is discussed per se and in the setting of concurrent BRAF mutation.
The International Journal of Biological Markers, 2015
Oncogenic hotspot mutations in the promoter region of the TERT gene have been identified in sever... more Oncogenic hotspot mutations in the promoter region of the TERT gene have been identified in several cancer types as being associated with a worse outcome. Additionally, a polymorphism (rs2853669) in the TERT promoter region was reported to modify the survival of TERT-mutated patients. Our aim is to determine the frequency of c.-124 Cgt;T and c.-146 Cgt;T TERT mutations and to genotype the rs2853669 polymorphism in a series of 68 soft tissue sarcomas (STS) comprising 22 histological subtypes. PCR was performed, followed by direct sequencing of a fragment of TERT containing the hotspots and the rs2853669. We found TERT mutations in 4/68 (5.9%) STSs including 1 pleomorphic liposarcoma (1/1), 1 dedifferentiated liposarcoma (1/1) and 2 myxoid liposarcomas (2/9). The variant C allele of rs2853669 was found in 54.8% (34/62) of all STSs and in 75% (3/4) of TERT-mutated cases. TERT mutations were associated with younger age, and the C allele of the rs2853669 was associated with high histological grade (2 and 3). No association was found between TERT mutation status or rs2853669 genotype and patient prognosis. We showed that TERT promoter mutation is not a recurrent event in STS and is present in particular histological subtypes.
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