Toxicogenetic profile of the monoterpene alpha-terpineol on normal and tumor eukaryotic cells.

Alpha-terpineol is a monoterpene alcohol found in essential oils from medicinal plants with some well-known pharmacological activities and widely used in cosmetics. However, the toxicological effects and additional pharmacological activities need to be clarified. Thus, the study evaluated the toxic, cytotoxic, genotoxic, hemolytic, and oxidative potential of alpha-terpineol in non-clinical bioassays. Different concentrations of alpha-terpineol were used in bioassays, including MTT (50, 100, 200, and 400 µg/mL), Artemia salina (6.25-400 µg/mL), Allium cepa (10, 50, and 100 µg/mL), comet assay (100, 200, and 500 µg/mL), cytokinesis-block micronucleus (100, 250, and 500 µg/mL), confocal microscopy for apoptosis quantification (100 and 500 µg/mL), hemolysis and Saccharomyces cerevisiae central disk test (10, 35, and 75 µg/mL). For the MTT test, alpha-terpineol was more cytotoxic on melanoma murine B16-F10 cells rather than macrophages. For A. salina test, alpha-terpineol showed LC50 of 68.29 and 76.36 µg/mL for 24 h and 48 h of exposure time, respectively. Meanwhile, alpha-terpineol was also cytotoxic to meristematic cells, which revealed inhibition of cellular division and mutagenic action by formation of bridges and delayed anaphases. The compound increased damage index and frequency of damage corroborated by the presence of micronuclei, bridges and nuclear buds at 500 µg/mL, but it caused neither hemolysis, oxidative damage on the S. cerevisiae nor cell death in normal fibroblasts. The findings indicate alpha-terpineol has cytotoxic potential by cytogenetic and molecular mechanisms associated with apoptosis and probable target effects against melanoma cells.

Association between matrix metalloproteinase-9 gene polymorphism and breast cancer in Brazilian women.

OBJECTIVE: This study aimed to determine the relationship between rs17576 (MMP-9) polymorphism and increased cancer risk in a Brazilian breast cancer cohort. METHODS: This study included 141 women (71 breast cancer patients and 70 controls without breast cancer) who donated 3 mL of their peripheral blood for genomic DNA extraction. This DNA was then genotyped using a real-time polymerase chain reaction. RESULTS: The AG (rs17576) genotype was identified in 26 (18.43%) participants in the case group and in 22 (15.60%) participants in the control group (p=0.274), while the GG genotype was identified in ten (7.09%) participants in the case group and in one (0.70%) participant in the control group (p<0.003 - OR (95% CI) 13.13 (1.73, 593.08). No significant difference in the incidence rates was observed for AG or GG rs17576 genotypes in premenopausal women, p=0.813 and p=0.556, respectively. However, in postmenopausal women, the AG genotype was shown to occur in 14 (22.5%) participants in the case group and in 4 (6.45%) participants in the control (p<0.043), while GG genotype occurred in eight (12.90%) of the individuals in the case group and in none of the individuals in the control group (p<0.006). CONCLUSION: In this study, the MMP-9 rs17576 GG polymorphic variant was shown to be significantly associated with breast cancer risk in premenopausal women, while the AG and GG genotypes were associated with increased cancer risk in postmenopausal women.

Association between matrix metalloproteinase-9 gene polymorphism and breast cancer in Brazilian women

OBJECTIVE: This study aimed to determine the relationship between rs17576 (MMP-9) polymorphism and increased cancer risk in a Brazilian breast cancer cohort. METHODS: This study included 141 women (71 breast cancer patients and 70 controls without breast cancer) who donated 3 mL of their peripheral blood for genomic DNA extraction. This DNA was then genotyped using a real-time polymerase chain reaction. RESULTS: The AG (rs17576) genotype was identified in 26 (18.43%) participants in the case group and in 22 (15.60%) participants in the control group (p=0.274), while the GG genotype was identified in ten (7.09%) participants in the case group and in one (0.70%) participant in the control group (p<0.003 - OR (95% CI) 13.13 (1.73, 593.08). No significant difference in the incidence rates was observed for AG or GG rs17576 genotypes in premenopausal women, p=0.813 and p=0.556, respectively. However, in postmenopausal women, the AG genotype was shown to occur in 14 (22.5%) participants in the case group and in 4 (6.45%) participants in the control (p<0.043), while GG genotype occurred in eight (12.90%) of the individuals in the case group and in none of the individuals in the control group (p<0.006). CONCLUSION: In this study, the MMP-9 rs17576 GG polymorphic variant was shown to be significantly associated with breast cancer risk in premenopausal women, while the AG and GG genotypes were associated with increased cancer risk in postmenopausal women.

The influence of heavy metals on toxicogenetic damage in a Brazilian tropical river.

Anthropogenic activities in tropical rivers favor the eutrophication process, which causes increased concentration of heavy metals. The presence and bioaccumulation of metals are directly related to the presence of genotoxic damage in aquatic organisms. Thus, we evaluated the presence of heavy metals (Fe, Zn, Cr, Cu and Al) and performed toxicogenetic tests in surface (S) and bottom (B) of water samples of the Poti river (Piaui/Brazil). Cytotoxicity and genotoxicity tests were performed in Allium cepa, and micronucleus (MN) and comet assay were performed in Oreochromis niloticus. The chemical analysis showed concentrations above the limit for Cu, Cr, Fe and Al according to Brazilian laws, characterizing anthropogenic disturbance in this aquatic environment. Toxicogenetic analysis presented significant cytotoxic, mutagenic and genotoxic effects in different exposure times and water layers (S and B), especially alterations in mitotic spindle defects, MN formations, nuclear bud and DNA strand breaks. Correlations between Fe and cytotoxicity, and Al and mutagenicity were statistically significant and point out to the participation of heavy metals in genotoxic damage. Therefore, Poti river water samples presented toxicogenetic effects on all bioindicators analyzed, which are most likely related to heavy metals pollution.

Immunonutrition effects in the treatment of cancer patients and itscomplications - a review / Efeitos da imunonutrição no tratamento de pacientes com câncer esuas complicações – uma revisão

The aim of this study was to review and summarize the data from the literature regarding the effects ofpre- and postoperative immunonutrition in the outcome of cancer patients. The review was conductedthrough literature searches in databases such as Medline/Pubmed, Scielo and Lilacs, from July toSeptember 2014, for articles investigating the effects of immunonutrition related to nutritional recoveryand pre- and post-operative procedures in cancer patients. We found 32 articles, 27 of which met theinclusion criteria, including review articles, case-control studies, epidemiological studies and crosssectionalstudies. From this literature review it was possible to see the benefits of using preoperativeimmunomodulating diet in cancer patients undergoing major abdominal surgery, including reduction ofseptic and inflammatory complications during postoperative period and hence the hospital length of stay.Thus, the use of immunonutrition has been shown to be capable to reverse organic and immunologicalchanges caused by both malnutrition and the tumor itself in cancer patients.

O objetivou deste trabalho foi revisar, de forma sucinta e objetiva, as evidências disponíveis nos bancos de dados digitais, sobre os efeitos da imunonutrição para a resposta ao tratamento de pacientes com câncer em pré e pós-operatório. Foi realizada uma revisão de literatura, por meio de buscas bibliográficas nos bancos de dados informatizados Medline/Pubmed, Scielo e Lilacs, no período de julho a setembro de 2014, de artigos que investigaram os efeitos da imunonutrição na recuperação do estado nutricional e em procedimentos pré e pós-operatório de pacientes com câncer. Foram encontrados 32 artigos, dos quais 27 atenderam aos critérios de inclusão do estudo, compreendendo artigos de revisão, caso-controle,epidemiológicos e transversais. A partir desta revisão de literatura foi possível verificar o benefício do uso da dieta imunomoduladora em pacientes oncológicos submetidos ao tratamento no pré-operatório de cirurgias de grande porte abdominal, diminuindo complicações sépticas e inflamatórias no período pós operatório e consequentemente o tempo de internação hospitalar. Dessa forma, o uso da imunonutrição mostra-se com capacidade de reverter alterações orgânicas e imunológicas causadas tanto pela desnutrição como pelo próprio tumor em pacientes com câncer.

Frequência de mutações nos genes MSH6, PMS1, PMS2, TP53 e CHEK2 em pacientes suspeitos de Síndrome de Lynch / Frequency of mutations in MSH6, PMS1, PMS2, TP53 and CHEK2 in patients with hereditary nonpolyposis colorectal cancer

Introdução: A síndrome de Lynch (SL) ou Câncer colorretal hereditário sem polipose (HNPCC) é uma doença autossômica dominante que predispõe ao câncer colorretal e risco aumentado para câncer de endométrio, estômago, intestino delgado, sistema hepatobiliar, rim, ureter, ovário, tumores de glândulas sebáceas, entre outros. Mutações germinativas nos genes de reparo de DNA (MMR) MLH1, MSH2, MSH6, PMS1 e PMS2, são conhecidos por causar síndrome de Lynch (SL). Além disso, mutações herdadas em CHEK2 e TP53 também influenciam o risco de câncer colorretal. Mutações, no primeiro, tem sido identificadas em pacientes com SL, incluindo 1100delC, I157T e IVS2 +1 G> A e, no segundo, tem sido associadas com o câncer gástrico e colorretal no contexto da síndrome de Li-Fraumeni. Objetivo- O objetivo deste estudo foi determinar a frequência de tumores extracolônicos em famílias com os critérios de Amsterdam e de mutações nos genes MSH6, PMS1, PMS2, TP53 e CHEK2 em pacientes suspeitos de SL. Material e Métodos- A fim de avaliar a frequência de tumores colorretais e extracolônicos na SL, foram incluídas 60 famílias não relacionadas que preenchiam, exclusivamente, os critérios de Amsterdam I e II. Para a análise da frequência de mutações nos genes MSH6, PMS1, PMS2, TP53 e CHEK2, 71 famílias não relacionadas, negativas para mutações em MLH1 e MSH2, foram incluídas. Resultados- Para a frequência de tumores avaliados, um total de 2095 indivíduos foram analisados e o câncer colorretal foi encontrado em 334 casos. Tumores extracolônicos foram encontrados em 200 indivíduos, dos quais o câncer de mama (32 casos) foi a manifestação extracolônica mais frequentemente encontrada. Da análise de mutações, observou-se seis novas mutações patogênicas. ...

Mismatch repair genes in Lynch syndrome: a review.

Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeiotic segregation increased 1 (PMS1). It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3), also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50%) and MSH2 (40%), while others account for 10%. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

Mismatch repair genes in Lynch syndrome: a review: [review] / Genes de reparo de DNA na síndrome de Lynch: uma revisão: [revisão]

Lynch syndrome represents 1-7 percent of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeiotic segregation increased 1 (PMS1). It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3), also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50 percent) and MSH2 (40 percent), while others account for 10 percent. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

A síndrome de Lynch representa de 1-7 por cento de todos os casos de câncer colorretal. É uma síndrome de herança autossômica dominante que predispõe ao câncer e é causada por mutações nos genes de reparo de ácido desoxirribonucléico (DNA). Desde a descoberta dos principais genes com função de reparo de DNA, mutações nos genes MSH2, MLH1, MSH6, PMS2 e PMS1 estão relacionadas com a susceptibilidade à síndrome de Lynch. Outro gene, MLH3, tem sido proposto como tendo papel na predisposição à síndrome de Lynch, porém mutações de significância clínica nesse gene não são claras. De acordo com o banco de dados InSiGHT (International Society for Gastrointestinal Hereditary Tumors), aproximadamente 500 diferentes mutações associadas à síndrome de Lynch são conhecidas, envolvendo primeiramente MLH1 (50 por cento), MSH2 (40 por cento) e outros (10 por cento). Grandes progressos têm ocorrido para nosso entendimento das bases moleculares da síndrome de Lynch. A caracterização molecular será a forma mais precisa para definirmos a síndrome de Lynch e irá fornecer informações preditivas mais precisas sobre o risco de câncer colorretal e extra-colônico, além de permitir regimes otimizados de manejo.

Recurrence Factors In Stage II Colon Cancer

Objective and Methods: For evaluating recurrence factors in Stage II colon adenocarcinoma a clinical, non-experimental, longitudinal and retrospective study was done in the Department of Abdomen of INEN from January 1, 1990 to December 31,2000. Results: In 200 eligible patients 20 (10%) recurrence cases were observed that appeared in an average 2.3 years after surgery. The main site of recurrence was local-regional (5.5%), pulmonary (2.5%), hepatic (1%), and peritoneal (1%). The following factors were considered: age, sex, CEA level, type of operation (elective or emergency), site of the primary injury,invasion (T3 or T4), lymphatic vessel invasion, histologic differentiation, and synchronous carcinoma. We found that patients more than 70 years old (p=0.0305) have a lesser disease-free time. Be more than 70 years old was the only recurrencerelated factor; this group has 2.56 times more risk of recurrence. No other studied variable was related to recurrence.