Analysis of quality of life and functional capacity in cancer patients receiving chemotherapy in Paraná Southwest, Brazil

Understanding psychosocial responses in cancer patients is fundamental for prognosis and maintenance of the quality of life (QoL). Chemotherapy is the primary and essential treatment for cancer. However, patients submitted to chemotherapy frequently show emotional and cognitive disruptions, which negatively influence the overall QoL. Here we evaluated the relationship between the functional capacity (FC) and QoL of cancer patients submitted to chemotherapy in a public health hospital in southern Brazil. A total of 101 patients with cancer receiving chemotherapy were enrolled from June to December 2017. Karnofsky Performance Status Scale (KPS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) were used to evaluate FC and QoL, respectively. Patients presented a mean age of 59.6±13 years and were predominantly female. Breast cancer was the most common neoplasia (43.56%), and most patients exhibited advanced disease (73%) and distant metastasis (66.33%) at diagnosis. The global health score evaluated by EORTC QLQ-30 was 67.5%, and about 63% of patients presented a KPS of 80%. The working function was the most positive influence on the FC (R=0.515; p<0.05). Emotional and social functions were strongly associated with patients' global health status (R=0.960; p<0.05). Our data showed that the KPS is an excellent tool for evaluating the QoL in patients undergoing chemotherapy, which correlates positively with their global health and is affected by the emotional and social functions of patients.Comprender las respuestas psicosociales en pacientes con cáncer es fundamental para el pronóstico y el mantenimiento de la calidad de vida (CdV). La quimioterapia, es el tratamiento primario y esencial para el cáncer. Sin embargo, los pacientes sometidos a quimioterapia con frecuencia muestran trastornos emocionales y cognitivos, que influyen negativamente en la CV general. Aquí evaluamos la relación entre la capacidad funcional (CF) y la CV de pacientes con cáncer sometidos a quimioterapia en un hospital de salud pública del sur de Brasil. Un total de 101 pacientes con cáncer que recibieron quimioterapia se inscribieron de junio a diciembre de 2017. Se utilizaron Karnofsky Performance Status Scale (KPS) y European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) para evaluar la CF y la CdV, respectivamente. Los pacientes presentaron una edad promedio de 59,6±13 años y fueron predominantemente del sexo femenino. El cáncer de mama fue la neoplasia más frecuente (43,56%), y la mayoría de las pacientes presentaron enfermedad avanzada (73%) y metástasis a distancia (66,33%) en el momento del diagnóstico. El puntaje de salud global evaluado por EORTC QLQ-30 fue de 67,5%, y cerca de 63% de los pacientes presentaron un KPS de 80%. La función de trabajo fue la influencia más positiva en el CF (R=0,515; p<0,05). Las funciones emocionales y sociales se asociaron fuertemente con el estado de salud global de los pacientes (R=0,960; p<0,05). Nuestros datos mostraron que el KPS es una excelente herramienta para evaluar la CV en pacientes sometidos a quimioterapia, lo que se correlaciona positivamente con su salud global y se ve afectado por las funciones emocionales y sociales de los pacientes.Understanding psychosocial responses in cancer patients is fundamental for prognosis and quality of life (QoL). Chemotherapy is the primary and essential treatment for cancer. However, patients submitted to chemotherapy frequently show emotional and cognitive disruptions, which negatively influence the overall QoL. Here we evaluated the relationship between the functional capacity (FC) and QoL of cancer patients submitted to chemotherapy in a public health hospital in Paraná southwest, Brazil. We included 101 patients with cancer receiving chemotherapy who were enrolled from June to December 2017. Karnofsky Performance Status Scale (KPS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) were used to evaluate FC and QoL, respectively. Patients presented a mean age of 59.6±13 years and were predominantly female. Breast cancer was the most common neoplasia (43.56%), and most patients exhibited advanced disease (73%) and distant metastasis (66.33%) at diagnosis. The global health score evaluated by EORTC QLQ-30 was 67.5%, and about 63% of patients presented a KPS of 80%. The working function was the one most affected FC (R=0.515; p<0.05). Emotional and social functions were strongly associated with patients' global health status (R=0.960; p<0.05). Our data showed that the KPS is an excellent tool for evaluating the QoL in patients undergoing chemotherapy, which correlates positively with their global health and is affected by the emotional and social functions of patients

MECANISMOS DE CARCINOGÊNESE INDUZIDOS POR AGROTÓXICOS: REVISÃO SISTEMÁTICA: AGROCHEMICAL-INDUCED CARCINOGENESIS MECHANISMS: SYSTEMATIC REVIEW

A exposição crônica a pesticidas e desreguladores endócrinos causam alterações na expressão gênica em tecido mamário, o que torna mulheres submetidas a essa condição mais propicias a desenvolverem o câncer de mama. Este estudo teve como objetivo investigar e revisar sistematicamente a correlação entre exposição aos agrotóxicos e a carcinogênese mamária, apontando mecanismos observados in vivo e in situ. Foi utilizado o protocolo Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA), a busca foi realizada no PubMed, resultando em 58 artigos, incluídos no presente estudo. Diante do exposto pode-se observar genotoxicidade celular mediado pela exposição a pesticidas de diferentes classes químicas e desreguladores endócrinos, o que em tese desencadeiam o estresse genotóxico em tecido mamário normal promovendo a carcinogênese, e naquelas já diagnosticadas com câncer de mama levam a maior probabilidade de desenvolverem metástases. A presente revisão destaca a necessidade de estudos que explorem e identifiquem os mecanismos envolvidos em tal condição, sendo que evidências inequívocas relacionam a carcinogênese mamária com exposição a compostos químicos e desreguladores endócrinos

Avaliação diagnóstica da presença de resíduos de agrotóxicos em amostras de urina de moradores de uma “vila rural” do município de Francisco Beltrão/PR

Pesticide contamination in rural communities is a well-known problem worldwide, but it is often hidden or underestimated. The development of research projects that identify this type of contamination is essential to advance the debate on the deleterious effects of pesticides. This article presents the results of a research that investigated the levels of pesticide residues in urine samples from residents of a “vila rural” located in the municipality of Francisco Beltrão, state of Paraná, Brazil. According to residents’ reports, the main form of exposure has been due the drift of pesticides resulting from spraying carried out on crops neighboring Vila Rural. Through the application of questionnaires, residents stated that spraying is related to symptoms such as nausea, headaches, and dizziness, among others, in addition to problems in the development of food grown in their plots (of 5,000 m2), mostly without the use of pesticides. After the collection of urine samples, laboratory analyzes were performed to identify pesticide residues, such as glyphosate, 2,4D (the most used), and other active ingredients. Samples were collected immediately after the occurrence of spraying onto crops surrounding the site. In the collected samples (n=35), laboratory analyzes were performed to identify possible pesticide residues. To identify possible contaminating pesticides in the samples, multi-residue analysis was performed by gas chromatography coupled with mass spectrometry (GC-MS/MS). To identify 2.4D residues, an active widely used in the region and not detectable by the technique used for other pesticides, the analyzes were performed by Unioeste using the enzyme immunoassay technique. The results indicate that all urine samples collected showed the presence of 2,4D residues and that 33 samples (90% of them) presented the presence of glyphosate-AMPA residues, without the detection of the other investigated residues. The analysis of data obtained from interviews with residents shows an association between living in the place for longer and having cases of abortion (p<0.05, R=0.43) or feeling unwell after the application of the poison by the neighboring crop (p<0.05, R=0.47). In addition, residents who reported being poisoned with poison also reported having cancer (p<0.05, R=0.42). Assuming that it is unacceptable that urine samples have pesticide residues, it is concluded that the residents of this community are widely exposed and contaminated by pesticides sprayed by third parties, and that may be impacting the health of these people in the long term. It indicate a process of environmental injustice, given that the residents are being contaminated through pesticide use in the crops bordering the “vila rural”. Keywords: Pesticides; Contamination; Rural community; Urine; Environmental injustice.La contaminación por pesticidas en comunidades rurales es un problema mundialmente conocido, pero generalmente oculto. El desarrollo de investigaciones que identifiquen este tipo de contaminación es fundamental para avanzar en el debate sobre los efectos deletéreos de los plaguicidas. Este artículo presenta los resultados de una investigación acerca de los niveles de residuos de pesticidas en muestras de orina de residentes de una “vila rural”, ubicada en el municipio de Francisco Beltrão, Paraná, Brasil. Según los informes de personas de la comunidad, la principal forma de exposición se relaciona con la deriva de pesticidas resultante de las fumigaciones realizadas en los cultivos vecinos a la “vila rural”. Mediante la aplicación de cuestionarios, los residentes manifestaron que las fumigaciones se relacionan con síntomas como náuseas, dolores de cabeza, mareos, entre otros, además de problemas en el desarrollo de los alimentos que cultivan en sus parcelas (de 5.000 m2), en su mayoría sin el uso de pesticidas. A través de la recolección de muestras de orina, se realizaron análisis de laboratorio para identificar residuos de plaguicidas, como glifosato, 2,4D (los más utilizados) y otros principios activos. Para la identificación de los residuos de 2,4D, los análisis fueron realizados por la Unioeste, utilizando la técnica de inmunoensayo enzimático. Para la identificación de otros residuos, las muestras fueron enviadas para un laboratorio comercial especializado en análisis multiresiduos. Los resultados del análisis indican que las 35 muestras de orina recolectadas mostraron la presencia de residuos 2,4D, y que 33 muestras (90%) mostraron la presencia de residuos de glifosato-AMPA, sin que se detectaran residuos de los otros plaguicidas investigados. El análisis de los datos obtenidos a través de los cuestionarios indica una asociación entre vivir muchos años en el lugar y la existencia de casos de aborto (p<0,05, R=0,47). Además, los residentes que reportaron haber sido intoxicados por pesticidas también reportaron tener algún tipo de cáncer (p<0.05, R=0.42). Asumiendo que es inaceptable que las muestras de orina contengan residuos de pesticidas, se concluye que los habitantes de Vila Rural están ampliamente expuestos y contaminados por pesticidas rociados por terceros, y que esto debe impactar su salud a largo plazo. Esto indica un proceso de injusticia ambiental, dado que los residentes están siendo contaminados por el uso de pesticidas en los cultivos aledaños a la “vila rural”. Palabras clave: Pesticidas; Contaminación; Comunidad rural; Orina; Injusticia ambiental.A contaminação por agrotóxicos em comunidades rurais é um problema mundialmente conhecido, mas, geralmente, ocultado. O desenvolvimento de pesquisas que identifiquem este tipo de contaminação é fundamental para se avançar no debate sobre os efeitos deletérios dos agrotóxicos. Este artigo, apresenta os resultados de uma pesquisa que investigou os níveis de resíduos de agrotóxicos em amostras de urina de moradores de uma vila rural localizada no município de Francisco Beltrão/PR. Segundo relato dos moradores, a principal forma de exposição tem se dado em virtude da deriva de agrotóxicos decorrente da pulverização realizada em lavouras vizinhas à vila rural. Através da aplicação de questionários, os moradores afirmaram que as pulverizações estão relacionadas a sintomas como náuseas, dores de cabeça, tonturas, entre outros, além de problemas no desenvolvimento de alimentos plantados em seus lotes (de 5.000 m2), majoritariamente sem uso de agrotóxicos. Através da coleta de amostras de urina, foram realizadas análises laboratoriais para identificação de multiresíduos de agrotóxicos. Para identificação de resíduos de 2,4D, as análises foram feitas pela Unioeste, por meio da utilização da técnica de enzimaimunoensaio. Para os demais resíduos, as amostras foram avaliadas por cromatografia de alta resolução acoplada à espectrometria de massas para análises de multiresíduos de agrotóxicos. Os resultados das análises indicam que todas as 35 amostras de urina coletadas apresentaram presença de resíduos de 2,4D, e que 33 amostras (90%) apresentaram presença de resíduos de glifosato-AMPA, sem a detecção de resíduos dos outros agrotóxicos investigados. A análise dos dados obtidos através dos questionários indica uma associação entre residir no local por muitos anos e a existência de casos de aborto (p<0.05, R=0.47). Além disso, moradores que reportaram ter sido intoxicados por agrotóxicos também reportaram ter tido algum tipo de câncer (p<0.05, R=0.42). Partindo do pressuposto de que é inaceitável que amostras de urina possuam resíduos de agrotóxicos, conclui-se que os moradores da área estudada estão amplamente expostos e contaminados por agrotóxicos pulverizados por terceiros, e que isso deve impactar sua saúde em longo prazo. Isso indica um processo de injustiça ambiental, haja vista que os moradores estão sendo contaminados através da utilização de agrotóxicos nas lavouras limítrofes. Palavras-chave: Agrotóxicos; Contaminação; Comunidade rural; Urina; Injustiça ambiental.   Diagnostic evaluation of the presence of pesticide residues in urine samples from residents of a “vila rural” in the Francisco Beltrão municipality, state of Paraná, Brazil   Abstract Pesticide contamination in rural communities is a well-known problem worldwide, but it is often hidden or underestimated. The development of research projects that identify this type of contamination is essential to advance the debate on the deleterious effects of pesticides. This article presents the results of a research that investigated the levels of pesticide residues in urine samples from residents of a “vila rural” located in the municipality of Francisco Beltrão, state of Paraná, Brazil. According to residents’ reports, the main form of exposure has been due the drift of pesticides resulting from spraying carried out on crops neighboring Vila Rural. Through the application of questionnaires, residents stated that spraying is related to symptoms such as nausea, headaches, and dizziness, among others, in addition to problems in the development of food grown in their plots (of 5,000 m2), mostly without the use of pesticides. After the collection of urine samples, laboratory analyzes were performed to identify pesticide residues, such as glyphosate, 2,4D (the most used), and other active ingredients. Samples were collected immediately after the occurrence of spraying onto crops surrounding the site. In the collected samples (n=35), laboratory analyzes were performed to identify possible pesticide residues. To identify possible contaminating pesticides in the samples, multi-residue analysis was performed by gas chromatography coupled with mass spectrometry (GC-MS/MS). To identify 2.4D residues, an active widely used in the region and not detectable by the technique used for other pesticides, the analyzes were performed by Unioeste using the enzyme immunoassay technique. The results indicate that all urine samples collected showed the presence of 2,4D residues and that 33 samples (90% of them) presented the presence of glyphosate-AMPA residues, without the detection of the other investigated residues. The analysis of data obtained from interviews with residents shows an association between living in the place for longer and having cases of abortion (p<0.05, R=0.43) or feeling unwell after the application of the poison by the neighboring crop (p<0.05, R=0.47). In addition, residents who reported being poisoned with poison also reported having cancer (p<0.05, R=0.42). Assuming that it is unacceptable that urine samples have pesticide residues, it is concluded that the residents of this community are widely exposed and contaminated by pesticides sprayed by third parties, and that may be impacting the health of these people in the long term. It indicate a process of environmental injustice, given that the residents are being contaminated through pesticide use in the crops bordering the “vila rural”. Keywords: Pesticides; Contamination; Rural community; Urine; Environmental injustice.   Evaluación diagnóstica de la presencia de residuos de pesticidas en orina de residentes de una “vila rural” en el município de Francisco Beltrão, Paraná, Brasil   Resumen La contaminación por pesticidas en comunidades rurales es un problema mundialmente conocido, pero generalmente oculto. El desarrollo de investigaciones que identifiquen este tipo de contaminación es fundamental para avanzar en el debate sobre los efectos deletéreos de los plaguicidas. Este artículo presenta los resultados de una investigación acerca de los niveles de residuos de pesticidas en muestras de orina de residentes de una “vila rural”, ubicada en el municipio de Francisco Beltrão, Paraná, Brasil. Según los informes de personas de la comunidad, la principal forma de exposición se relaciona con la deriva de pesticidas resultante de las fumigaciones realizadas en los cultivos vecinos a la “vila rural”. Mediante la aplicación de cuestionarios, los residentes manifestaron que las fumigaciones se relacionan con síntomas como náuseas, dolores de cabeza, mareos, entre otros, además de problemas en el desarrollo de los alimentos que cultivan en sus parcelas (de 5.000 m2), en su mayoría sin el uso de pesticidas. A través de la recolección de muestras de orina, se realizaron análisis de laboratorio para identificar residuos de plaguicidas, como glifosato, 2,4D (los más utilizados) y otros principios activos. Para la identificación de los residuos de 2,4D, los análisis fueron realizados por la Unioeste, utilizando la técnica de inmunoensayo enzimático. Para la identificación de otros residuos, las muestras fueron enviadas para un laboratorio comercial especializado en análisis multiresiduos. Los resultados del análisis indican que las 35 muestras de orina recolectadas mostraron la presencia de residuos 2,4D, y que 33 muestras (90%) mostraron la presencia de residuos de glifosato-AMPA, sin que se detectaran residuos de los otros plaguicidas investigados. El análisis de los datos obtenidos a través de los cuestionarios indica una asociación entre vivir muchos años en el lugar y la existencia de casos de aborto (p<0,05, R=0,47). Además, los residentes que reportaron haber sido intoxicados por pesticidas también reportaron tener algún tipo de cáncer (p<0.05, R=0.42). Asumiendo que es inaceptable que las muestras de orina contengan residuos de pesticidas, se concluye que los habitantes de Vila Rural están ampliamente expuestos y contaminados por pesticidas rociados por terceros, y que esto debe impactar su salud a largo plazo. Esto indica un proceso de injusticia ambiental, dado que los residentes están siendo contaminados por el uso de pesticidas en los cultivos aledaños a la “vila rural”. Palabras clave: Pesticidas; Contaminación; Comunidad rural; Orina; Injusticia ambiental

Níveis De Estresse Oxidativo Ao Diagnóstico E Sua Associação Com O Perfil De Sobrevida Em Pacientes Portadoras De Câncer De Mama Operáveis Em Estadios Iniciais: Um Estudo Piloto

AAltos níveis de estresse oxidativo têm sido associados pior prognóstico do câncer de mama, mas não se sabe sua relação como possível preditor de sobrevida. Neste estudo investigamos a associação entre os níveis circulantes de estresse oxidativo no momento do diagnóstico e o perfil de sobrevida de pacientes portadoras de tumores de mama operáveis. Foi realizado um estudo prospectivo em uma população de 606 pacientes do sexo feminino com tumores de mama em estadios iniciais entre os anos de 2015-2020. Dentre essas pacientes, 18 vieram a óbito no seguimento do estudo, sendo pareadas com 36 pacientes que permaneceram vivas no período do estudo. Amostras de sangue foram coletadas ao diagnóstico, e os níveis de estresse quantificados por meio da dosagem dos metabólitos do óxido nítrico (NO) e perfil de peroxidação lipídicaplasmática. No grupo óbito, observou-se perfil de lipoperoxidação plasmática e níveis de NO elevados ao diagnóstico, quando comparado ao grupo de pacientes vivas. Altos níveis de lipoperoxidação plasmática foram diretamente relacionados com o desenvolvimento de metástases no grupo de pacientes vivas. Os resultados sugerem que o perfil oxidativo sistêmico aumentado ao diagnóstico observado em portadoras de câncer de mama está diretamente relacionado ao desfecho óbito em 5 anos.

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Brief research report pesticide occupational exposure leads to significant inflammatory changes in normal mammary breast tissue

Studies have documented the high occurrence of several tumors, including female breast cancer, in populations occupationally exposed to pesticides worldwide. It is believed that in addition to direct DNA damage, other molecular alterations that indicate genomic instability are associated, such as epigenetic modifications and the production of inflammation mediators. The present study characterized the profile of inflammatory changes in the breast tissue of women without cancer occupationally exposed to pesticides. In samples of normal breast tissue collected during biopsy and evaluated as negative for cancer by a pathologist, oxidative stress levels were assessed as inflammatory markers through measurements of lipoperoxides and total antioxidant capacity of the sample (TRAP) by high-sensitivity chemiluminescence, as well as levels of nitric oxide (NOx) metabolites. The levels of inflammation-modulating transcription factors PPAR-γ (peroxisome proliferator-activated receptor gamma) and NF-κB (nuclear factor kappa B) were also quantified, in addition to the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin 12 (IL-12). The levels of lipoperoxides, TRAP, and NOx were significantly lower in the exposed group. On the other hand, PPAR-γ levels were increased in the breast tissue of exposed women, with no variation in NF-κB. There was also a rise of TNF-α in exposed women samples without significant variations in IL-12 levels. These findings suggest an inflammatory signature of the breast tissue associated with pesticide exposure, which may trigger mechanisms related to mutations and breast carcinogenesis