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1.
Appl. cancer res ; 40: 1-13, Oct. 19, 2020. ilus
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1283485

RESUMO

Background: Cell culture (spheroid and 2D monolayer cultures) is an essential tool in drug discovery. Piperlongumine (PLN), a naturally occurring alkaloid present in the long pepper (Piper longum), has been implicated in the regulation of GSTP1 activity. In vitro treatment of cancer cells with PLN increases ROS (reactive oxygen species) levels and induces cell death, but its molecular mode of action has not been entirely elucidated. Methods: In this study, we correlated the antiproliferative effects (2D and 3D cultures) of PLN (CAS 20069­09-4, Sigma-Aldrich) with morphological and molecular analyses in HepG2/C3A cell line. We performed assays for cytotoxicity (MTT), comet assays for genotoxicity, induction of apoptosis, analysis of the cell cycle phase, and analysis of the membrane integrity by flow cytometry. Relative expression of mRNA of genes related to proliferation, apoptosis, cell cycle control, metabolism of xenobiotics, and reticulum endoplasmic stress. Results: PLN reduced the cell proliferation by the cell cycle arrest in G2/M. Changes in the mRNA expression for CDKN1A (4.9x) and CCNA2 (0.5x) of cell cycle control genes were observed. Cell death occurred due to apoptosis, which may have been induced by increased expression of proapoptotic mRNAs (BAK1, 3.1x; BBC3, 2.4x), and by an increase in 9 and 3/7 active caspases. PLN induced cellular injury by ROS generation and DNA damage. DNA damage induced MDM2 signaling (3.0x) associated with the appearance of the monastral spindle in mitosis. Genes associated with ROS degradation also showed increased mRNA expression (GSR, 2.0x; SOD1, 2.1x). PLN induce endoplasmic reticulum stress with the increase in the mRNA expression of ERN1 (4.5x) and HSPA14 (2.2x). The xenobiotic metabolism showed increased mRNA expression for CYP1A2 (2.2x) and CYP3A4 (3.4x). In addition to 2D culture, PLN treatment also inhibited the growth of 3D culture (spheroids). Conclusion: Thus, the findings of our study show that several gene expression biomarkers (mRNAs) and monastral spindle formation indicated the many pathways of damage induced by PLN treatment that contributes to its antiproliferative effects


Assuntos
Humanos , RNA Mensageiro/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Técnicas de Cultura de Células , Proliferação de Células/efeitos dos fármacos , Dioxolanos/farmacologia , Antineoplásicos/farmacologia , Biomarcadores/análise , Expressão Gênica/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Células Hep G2/efeitos dos fármacos
2.
Appl. cancer res ; 40: 1-5, Oct. 19, 2020. ilus
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1282478

RESUMO

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin's lymphoma. In oral cavity represents approximately 2% of all malignancies. Case presentation: This report describes a rare mandibular involvement of DLBCL. A 56 year-old man was referred for evaluation of left mandible pain. In the anamnesis, the patient informed to be treating tooth pain in lasting 6 months. On oral evaluation, an intense mobility of the left mandibular second molar and a swelling in posterior left mandible were observed. Computed tomography showed a large osteolytic lesion affecting both mandibular body and ramus. An incisional biopsy was performed and according to histopathological and imumnohistochemical features, DLBCL was diagnosed. The treatment consisted of 8 cycles of R-CHOP and adjuvant radiotherapy. He is asymptomatic after 6 years. Conclusion: This case showed a rare bone presentation of DLBCL and such tumor should be considered as differential diagnosis of osteolytic lesion of the mandible.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Mandibulares/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Diagnóstico Diferencial
3.
Appl. cancer res ; 40: 1-6, Oct. 19, 2020. ilus, tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1282611

RESUMO

Background: Oral squamous cell carcinoma (OSCC) is the most frequently occurring malignant tumor of the head and neck region. Chk2 (Checkpoint kinase 2) is considered a tumor suppressor gene that acts on the cellular response to DNA damage. However, the role of Chk2 in OSCC prognosis is not yet fully understood. The objective of this study was to evaluate Chk2 immunoexpression in OSCC and to elucidate the association between its expression and clinicopathological parameters of prognostic importance, including overall survival, disease-free survival, and metastasis-free survival. Methods: Chk2 expression was analyzed in 101 samples from patients with OSCC using immunohistochemistry. We stratified the patients into high expression (> 66% of cells positive for Chk2) and low expression (< 66%) groups. Results: Chk2 showed high expression in 57.43% of OSCC. In our study, the expression of Chk2 did not correlate with any of the prognostic parameters evaluated. There was no difference between overall survival, metastasis-free survival, and disease-free survival according to Chk2 expression. Conclusion: Despite the great importance of Chk2 in the development of different types of cancer, our findings do not favor Chk2 as a prognostic marker in oral squamous cell carcinoma.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Imuno-Histoquímica , Carcinoma de Células Escamosas/metabolismo , Quinase do Ponto de Checagem 2/metabolismo , Prognóstico , Análise de Sobrevida
4.
Appl. cancer res ; 40: 1-8, Oct. 19, 2020. ilus, tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1282417

RESUMO

Background: Randomized controlled trials (RCTs) play an integral role in childhood cancer research. Several efforts to improve the quality of reporting of clinical trials have been published in recent years, including the TIDieR checklist. Many reviews have since used TIDieR to evaluate how well RCTs are being reported, but no such study has yet been done in childhood cancer. The aim of this study is to evaluate adherence of RCTs involving acute lymphocytic leukemia (ALL) to the TIDieR checklist. Methods: The PubMed database was used to screen for RCTs involving ALL published since 2015. Of 1546 articles identified, 46 met study criteria and were then evaluated against the TIDieR 12-point checklist to measure the degree of adherence. Results: Of the 46 articles included, 9 (19.6%) met full TIDieR criteria. Seven of the 9 reported non-pharmacological interventions, and the remaining 2 reported pharmacological interventions. The average article properly reported 8.98/12 checklist items. Item 5 (intervention provider) was the most poorly reported item, properly reported in only 34.8% of articles. Conclusion: We conclude that overall TIDieR adherence is low and needs to be adhered to more fully in order to improve research in ALL as well as in all childhood cancers.


Assuntos
Humanos , Leucemia Linfoide , Ensaio Clínico Controlado Aleatório , Lista de Checagem , Doença Aguda
5.
Appl. cancer res ; 40: 1-9, Oct. 19, 2020. ilus
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1281364

RESUMO

A large number of cancer patients relapse after chemotherapeutic treatment. The immune system is capable of identifying and destroying cancer cells, so recent studies have highlighted the growing importance of using combinatorial chemotherapy and immunotherapy. However, many patients have innate or acquired resistance to immunotherapies. Long-term follow-up in a pooled meta-analysis exhibited long-term survival in approximately 20% of patients treated with immune checkpoint inhibitors or the adoptive transfer of chimeric T cells. It has been reported that high levels of immunoregulatory cells in cancer patients contribute to immunotherapy resistance via immunosuppression. Among the most important regulatory cell subtypes are the CD4+ T-regulatory cells (Tregs), identified by their expression of the well-characterized, lineage-specific transcription factor FOXP3. In addition to CD4+ Tregs, other regulatory cells present in the tumor microenvironment, namely CD8+ Tregs and IL10-producing B-regulatory cells (Bregs) that also modulate the immune response in solid and lymphoid tumors. These cells together have detrimental effects on tumor immune surveillance and anti-tumor immunity. Therefore, targeting these regulatory lymphocytes will be crucial in improving treatment outcomes for immunotherapy.


Assuntos
Linfócitos T Reguladores , Imunoterapia , Neoplasias , Imunossupressão
6.
Appl. cancer res ; 40: 1-7, Oct. 19, 2020. ilus, tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1255030

RESUMO

Background: Lymphoedema is a common side effect after treatment for head and neck cancer. Our treatment protocol involves staging the degree of lymphoedema and then offering treatment comprising skin care, manual lymphatic drainage, simple lymphatic drainage, compression and elastic therapeutic tape. The Glasgow Benefit Inventory is a validated post-interventional questionnaire applicable to otorhinolaryngology interventions which measures changes in health status. The aim of this study was to quantify the health benefits of lymphoedema treatment using the Glasgow Inventory Benefit questionnaire, in patients with a history of treated head and neck cancer. Methods: Any patient who had undergone treatment with curative intent of a primary head and neck malignancy who had been referred for lymphoedema treatment within a 6 month period was eligible for inclusion. Patients completed a questionnaire after finishing the course of lymphoedema treatment. Results: A total of 15 patients completed the questionnaire. Ten patients (67%) demonstrated some level of improvement in quality of life, while two (13%) reported no benefit and three (20%) reported negative improvements. The average score for the total Glasgow Benefit Inventory scale was + 7.2. The greatest benefit was demonstrated with the physical benefit subscale (+ 13.1). The average general benefit score was + 9.0. Conclusions: Lymphoedema treatment involves techniques which can fairly easily be taught to patients to complete at home. In this study, there were mild improvements in patient reported quality of life using the Glasgow Benefit Inventory in the majority of patients. Clinical interest has increased in lymphoedema recently, but there is still limited information about the effectiveness of treatments and future research should look to address these issues.


Assuntos
Qualidade de Vida , Neoplasias de Cabeça e Pescoço , Linfedema , Inquéritos e Questionários
7.
Appl. cancer res ; 40: 1-12, Oct. 19, 2020. tab, ilus
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1281498

RESUMO

Background: Next-generation sequencing (NGS) based assay for finding an actionable driver in non-small-cell lung cancer is a less used modality in clinical practice. With a long list of actionable targets, limited tissue, arduous single-gene assays, the alternative of NGS for broad testing in one experiment looks attractive. We report here our experience with NGS for biomarker testing in hundred advanced lung cancer patients. Methods: Predictive biomarker testing was performed using the Ion AmpliSeq™ Cancer Hotspot Panel V2 (30 tumors) and Oncomine™ Solid Tumor DNA and Oncomine™ Solid Tumor Fusion Transcript kit (70 tumors) on IonTorrent sequencing platform. Results: One-seventeen distinct aberrations were detected across 29 genes in eighty-six tumors. The most commonly mutated genes were TP53 (43% cases), EGFR (23% cases) and KRAS (17% cases). Thirty-four patients presented an actionable genetic variant for which targeted therapy is presently available, and fifty-two cases harbored non-actionable variants with the possibility of recruitment in clinical trials. NGS results were validated by individual tests for detecting EGFR mutation, ALK1 rearrangement, ROS1 fusion, and c-MET amplification. Compared to single test, NGS exhibited good agreement for detecting EGFR mutations and ALK1 fusion (sensitivity- 88.89%, specificity- 100%, Kappa-score 0.92 and sensitivity- 80%, specificity- 100%, Kappa-score 0.88; respectively). Further, the response of patients harboring tyrosine kinase inhibitor (TKI) sensitizing EGFR mutations was assessed. The progression-free-survival of EGFR positive patients on TKI therapy, harboring a concomitant mutation in PIK3CAmTOR and/or RAS-RAF-MAPK pathway gene and/or TP53 gene was inferior to those with sole-sensitizing EGFR mutation (2 months vs. 9.5 months, P = 0.015). Conclusions: This is the first study from South Asia looking into the analytical validity of NGS and describing the mutational landscape of lung cancer patients to study the impact of co-mutations on cancer biology and treatment outcome. Our study demonstrates the clinical utility of NGS testing for identifying actionable variants and making treatment decisions in advanced lung cancer


Assuntos
Humanos , Masculino , Feminino , Proto-Oncogenes/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares/genética , Mutação/genética , Reprodutibilidade dos Testes
8.
Appl. cancer res ; 40: 1-9, Oct. 19, 2020. ilus, tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1281398

RESUMO

Background: Ovarian cancer is the most common gynecological malignancy. In patients with advanced ovarian cancer, some biological parameters have prognostic implementations. P27kip1 is an inhibitor of a cycline-dependent kinase, its loss, can contribute to tumor progression. Objective: This study aimed to examine the importance of P27KIP1 protein in predicting the prognosis and response to neoadjuvant chemotherapy in patients with advanced ovarian epithelial cancer and to compare the outcomes of immunohistochemistry with Quantitative Real-time PCR. Patients and methods: We have studied P27KIP1expression by both immunohistochemistry and Quantitative Realtime PCR from 88 patients with advanced ovarian carcinomas undergone radical debulking surgery and received Paclitaxel followed by Cisplatin every 3 weeks for a total of 6 cycles. We also studied their association with both chemotherapy response and patient survival. Results: Nuclear expression of p27KIP1 protein was intense in 86 normal ovarian tissues and 42 of 88 carcinomas. The P27kip1mRNA expression level by qRT-PCR was very low in ovarian cancer tissues relative to its adjacent normal tissues. The results were statistically significant by both methods of determination. p27KIP1 expression was significantly related to good prognostic parameters as low stage tumors, differentiated tumors, absence of ascites, residual disease < 2 cm, and response to chemotherapy but not with histopathological type in case of determination by immunohistochemistry. Comparison of P27kip1 by both immunohistochemistry and qRTPCR with different prognostic parameters revealed no significant difference between both methods in the assessment of these parameters. In 4 years of follow-up, 20.5% of patients were alive without evidence of disease. 6.8% were alive with disease. The disease-related four -year survival rate for the whole group was 28.2%. In multivariate analysis, residual disease, histological type, tumor differentiation, ascites was of independent prognostic significance. Conclusion: In ovarian cancer, patients with loss of p27KIP1 expression are at a greater likelihood of disease progression, p27KIP1 may be used as a molecular marker to predict response to chemotherapy and prognosis. Both immunohistochemistry and qRT-PCR have equal reliability in the determination of p27 KIP1


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Neoplasias Ovarianas/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Carcinoma Epitelial do Ovário/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Prognóstico , Imuno-Histoquímica , Terapia Neoadjuvante , Reação em Cadeia da Polimerase em Tempo Real , Carcinoma Epitelial do Ovário/tratamento farmacológico , Estadiamento de Neoplasias
9.
Appl. cancer res ; 40: 1-3, Oct. 19, 2020. tab, graf
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1281353

RESUMO

Background: Cervical cancer is a prominently diagnosed form of cancer in several resource-constrained settings particularly within the sub-Saharan African region. Globally, Africa region has the highest incidence and mortality rates of cervical cancer. The high prevalence has been attributed to several factors including lack of awareness of the disease. The aim of this paper is to explore the prevalence and factors associated with awareness of cervical cancer among women of reproductive age in Republic of Benin and Zimbabwe, sub-Saharan Africa. Methods: We used population-based cross-sectional data from Benin Demographic and Health Survey (BDHS) and Zimbabwe Demographic and Health Survey (ZDHS) respectively. BDHS 2017­18 and ZDHS - 2015 are the 5th and 6th rounds of the surveys respectively. About 15,928 and 9955 women aged 15­49 years were included in this study respectively. The awareness of cervical cancer among women of reproductive age in Benin and Zimbabwe was measured dichotomously; yes (if a woman heard of cervical cancer) vs. no (if a woman has not heard of cervical cancer). All significant variables from the bivariate analysis were included in the multivariable logistic regression model to calculate the adjusted odds ratios (AOR) with corresponding 95% confidence interval. Results: While majority (79.2%) of women from Zimbabwe have heard about cervical cancer, only about one-tenth (10.2%) of their Beninese counterparts have heard about the disease. Advanced maternal age, having formal education, use of internet, having professional/technical/managerial occupation significantly increased the odds of awareness of cervical cancer after adjusting for other confounders. However, in Benin, women who resided in the rural area and those of Islamic belief had 20% (AOR = 0.80; 95%CI: 0.64, 0.99) and 35% (AOR = 0.65; 95%CI: 0.50, 0.86) reduction in the odds of awareness of cervical cancer respectively, when compared with women from urban residence and Christianity. Results from the predictive marginal effects showed that, assuming the distribution of all factors remained the same among women, but every woman is an urban dweller, we would expect 11.0 and 81.0% level of awareness of cervical cancer; If everywoman had higher education, we would expect 20.0 and 90% level of awareness of cervical cancer and if instead the distribution of other maternal factors were as observed and other covariates remained the same among women, but all women were in the richest household wealth quintile, we would expect about 11.0 and 83.0% level of awareness of cervical cancer, among women of reproductive age from Benin and Zimbabwe respectively. Conclusion: The study has revealed that socio-demographical factors including geographical location and selected economic factors explained the inequality in distribution of women's awareness on cervical cancer in both countries. Designing an effective population-based health education and promotion intervention programs on cervical cancer will be a great way forward to improving women's awareness level on cervical cancer.


Assuntos
Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Neoplasias do Colo do Útero , Conhecimentos, Atitudes e Prática em Saúde , Benin , Educação em Saúde , Prevalência , Estudos Transversais , África ao Sul do Saara
10.
Gastroenterol. latinoam ; 31(1): 9-20, mayo 2020. tab, ilus
Artigo em Espanhol | LILACS, PrevCan | ID: biblio-1103076

RESUMO

The outbreak of COVID-19 disease has recently spread from its original place in Wuhan, Hubei province, China, to the entire world, and has been declared to be a pandemic by the World Health Organization in March 2020. All countries in America, in particular Chile, show an important increase in COVID-19 cases and deaths. The clinical manifestations of COVID-19 are a broad spectrum, from asymptomatic mild disease, to severe respiratory failure, shock, multiorgan dysfunction and death. Thus, high clinical suspicion and appropriate structure risk stratification are needed. Health care teams in endoscopy units, are at an increased risk of infection by COVID-19 from inhalation of droplets, mucosae contact, probably contamination due to contact with stools. Endoscopic aerosolized associated infections have also been reported. Different societies' recommendations, have recently placed digestive endoscopy (especially upper) among the high risk aerosol generating procedures (AGPs). In addition, live virus has been found in patient stools. On top of this, the infected health professionals may transmit the infection to their patients. Health care infection prevention and control (HCIPC), has been shown to be effective in assuring the safety of both health care personnel and patients. This is not limited to the correct use of personal protective equipment (PPE), but is based on a clear, detailed and well communicated HCIPC strategy, risk stratification, use of PPE, and careful interventions in patients with moderate and high risk of COVID-19. A conscientious approach regarding limited resources is important, as the simultaneous outbreak in all countries heavily affects the availability of health supplies. The Chilean Gastroenterology Society (SChGE) and Digestive Endoscopy Association of Chile (ACHED) are joining to provide continued updated guidance in order to assure the highest level of protection against COVID-19, for both patients and health care workers. This guideline will be updated online as needed.


El brote de la enfermedad denominada COVID-19, se ha extendido desde su origen en Wuhan, provincia de Hubei, China, a todo el mundo. La Organización Mundial de la Salud lo declaró pandemia en marzo de 2020. Todos los países de América, en especial Chile, presentan incremento de casos y fallecidos. Las manifestaciones clínicas de COVID-19 van desde una enfermedad leve, hasta insuficiencia respiratoria severa, shock, disfunción orgánica y muerte. Se necesita una alta sospecha clínica y una adecuada estratificación del riesgo. El equipo de salud en las unidades de endoscopia, tiene un mayor riesgo de COVID-19 que otras unidades clínicas y de apoyo diagnóstico, dada la mayor exposición a inhalación de gotas, contacto posible con mucosas y contaminación por contacto con deposiciones. Recomendaciones de diferentes sociedades colocan la endoscopia digestiva (especialmente la esofagogastroscopia o endoscopia digestiva alta, EDA) entre los procedimientos generadores de aerosoles (PGA) de alto riesgo. Además, se han encontrado virus viables en las deposiciones de los pacientes. Potencialmente, los profesionales de la salud infectados podrían contagiar a los pacientes. Se ha demostrado que la prevención y control de infecciones asociadas a la atención de salud (IAAS), son efectivos para garantizar la seguridad tanto del personal de salud, como de los pacientes. Esto no es solamente el correcto uso del equipo de protección personal (EPP), sino que se basa en una clara estrategia de IAAS, bien comunicada, con estratificación de riesgo, uso de EPP e intervenciones correctas en pacientes con riesgo moderado y alto. Es relevante un enfoque sobre los limitados recursos, dado la simultaneidad del brote en todos los países, que afecta la disponibilidad de insumos. La Sociedad Chilena de Gastroenterología (SChGE) y la Asociación Chilena de Endoscopia Digestiva (ACHED) publican esta guía actualizada para apoyar las buenas prácticas contra COVID-19, tanto para pacientes como para el equipo de salud. Esta guía podrá tener actualizaciones según avance la información disponible.


Assuntos
Humanos , Pneumonia Viral/prevenção & controle , Endoscopia do Sistema Digestório/normas , Infecções por Coronavirus/prevenção & controle , Betacoronavirus , Pneumonia Viral/epidemiologia , Fatores de Risco , Controle de Infecções/métodos , Guias de Prática Clínica como Assunto , Infecções por Coronavirus/epidemiologia , Pandemias , Unidades Hospitalares/normas
11.
Rev. bras. cancerol ; 66(4): e-041053, 2020.
Artigo em Português | LILACS, PrevCan | ID: biblio-1123243

RESUMO

Introdução: O câncer acometerá cerca de 50% dos indivíduos com infecção pelo vírus da imunodeficiência adquirida (HIV), com importante carga daqueles do tipo não definidores da síndrome da imunodeficiência adquirida (aids). Objetivo: Analisar diferentes fatores de risco para câncer do tipo não definidor na população HIV positiva, por meio da seleção de estudos de coorte realizados em diferentes Regiões do mundo. Método: Trata-se de uma revisão de literatura realizada no período de março a abril de 2019, utilizando os descritores Cancer Risck, HIV e non-AIDS-defining Cancer. Resultados: Os cânceres não definidores, que representam maior incidência entre a população HIV positiva, são o de pulmão, colorretal, cervical, de vagina e útero, gástrico, linfoma de Hodgkin e de fígado. Conclusão: Os estudos demonstram risco aumentado para diversos tipos de câncer não definidores da aids, o que nos leva a um novo paradigma, voltado não somente para o controle do HIV, mas também para a detecção precoce e tratamento oportuno, a fim de minimizar as morbidades e aumentar a expectativa de vida desses indivíduos.


Introduction: Cancer will affect about 50% of HIV (human immunodeficiency virus) infected individuals with a significant burden of non-AIDS-defining cancers (acquired immunodeficiency syndrome). Objective: To analyse different risk factors for the non-defining type in the HIV positive population through selection of cohort studies conducted in several regions of the world. Method: Literature review conducted from March to April 2019 using the descriptors Cancer Risk, HIV and non-AIDS-defining Cancer. Results: Non-defining cancers representing the greatest incidence among HIV-positive population are lung, colorectal, cervical, vaginal and uterine, gastric, Hodgkin's lymphoma, and liver. Conclusion: Studies demonstrate that there are increased risks for several types of non-AIDS defining cancers, leading to a new paradigm, not only for HIV control but for early detection and timely treatment, in order to minimize the morbidities and increase life expectancy of these individuals.


Introducción: El cáncer afectará aproximadamente al 50% de las personas con infección por virus de inmunodeficiencia adquirida (VIH) con una carga significativa de cánceres que no definen el síndrome de inmunodeficiencia adquirida (sida). Objetivo: Analizar diferentes factores de riesgo para el cáncer no definitorio en la población VIH positivo en estudios de cohortes realizados en diferentes regiones del mundo. Método: Esta es una revisión de la literatura realizada de marzo a abril de 2019 utilizando los descriptores Cancer Risk, HIV non-AIDS-defining Cancer. Resultados: Los cánceres no definitorios que representan el mayor riesgo e incidencia entre la población VIH positivo son de pulmón, colorrectal, cervical, vaginal y uterino, gástrico, linfoma de Hodgkin y de hígado. Conclusión: Los estudios muestran riesgos para varios tipos de cáncer que no definen el sida, lo que nos lleva a un nuevo paradigma, que se centra no solo en el control del VIH sino también en la detección temprana y el tratamiento oportuno.


Assuntos
Humanos , Masculino , Feminino , Infecções por HIV/complicações , Neoplasias/epidemiologia , Incidência , Fatores de Risco , Expectativa de Vida , Síndrome de Imunodeficiência Adquirida/complicações , Neoplasias/complicações
12.
Rev. salud pública ; 21(2): 161-167, ene.-abr. 2019. tab, graf
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1101852

RESUMO

ABSTRACT Objective To describe cervical cancer mortality rates and their corresponding trends, and to analyze the spatial correlations of this type of cancer in Natal-RN, Brazil, between 2000 and 2012. Materials and Methods The simple linear regression model, the empirical Bayes method and the Global Moran's index were used for the statistical analysis. Results The mortality coefficient of cervical cancer in Natal, standardized by age range, was 5.5 per 100 000 women. All historical series for the coefficients studied were classified as stable. The Global Moran's index obtained was 0.048, with a p-value for the spatial test correlation between neighborhoods of 0.300. The average family income by neighborhood showed no significant correlation to cervical cancer mortality rates. Conclusion This study found a temporal stabilization and spatial independence trend of cervical cancer mortality rates in women from Natal, as well as the absence of correlation between these rates and the average family income of the of the participating women distributed by neighborhoods. In view of this, changes in the public policies should be made aimed at preventing the disease; adopting these measures could positively impact the screening program, improving the coverage of Pap smears and immunization campaigns against HPV, in order to reverse this trend and achieve a reduction of mortality rates.(AU)


RESUMEN Objetivo Describir las tasas de mortalidad por cáncer de cuello uterino y sus tendencias, así como analizar las correlaciones espaciales de este tipo de cáncer en Natal-RN, Brasil, entre 2000 y 2012. Materiales y Métodos Para el análisis estadístico se utilizaron el modelo de regresión lineal simple, la estimación empírica de Bayes y el índice Moran Global. Resultados La tasa de mortalidad por cáncer de cuello uterino en Natal, estandarizado por rango de edad, fue 5.5 por cada 100 000 mujeres. Todas las series históricas para los coeficientes estudiados se clasificaron como estables. El índice Moran Global obtenido fue 0.048, con un valor p de 0.300 para la correlación de prueba espacial entre vecindarios. El ingreso familiar promedio por vecindario no mostró correlación significativa con las tasas de mortalidad por cáncer de cuello uterino. Conclusión En este estudio se observó una tendencia temporal de estabilización e independencia espacial de la tasa de mortalidad por cáncer cervical en mujeres de Natal, así como la ausencia de correlación entre estas tasas y el ingreso familiar promedio de las mujeres participantes, distribuidas por vecindarios de la ciudad. En vista de esto, se sugiere que se adopten cambios en las políticas públicas dirigidas a la prevención de la enfermedad que apunten a medidas que puedan tener un impacto positivo en el programa de monitoreo, mejorando la cobertura de la prueba de Papanicolaou, así como de las campañas de vacunación contra el VPH, con el objetivo de revertir esta tendencia y lograr una reducción en las tasas de mortalidad de la enfermedad.(AU)


Assuntos
Humanos , Feminino , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/epidemiologia , Programas de Imunização/provisão & distribuição , Teste de Papanicolaou/instrumentação , Análise Estatística , Teorema de Bayes , Análise Espaço-Temporal
13.
Appl. cancer res ; 39: 1-6, 2019. tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-994750

RESUMO

Background: Colorectal cancer (CRC) is one of the most common cancers in Japan. Many factors influence this cancer, one of which is circadian rhythm disruption. Our research investigated the correlation between singlenucleotide polymorphisms (SNPs) in the Period 3 (PER3) (rs2640908), which is one of the circadian genes, and colorectal cancer in the Japanese population. Methods: The study participants consisted of 121 cases and 197 controls. DNA was extracted from participants' peripheral blood cells, and polymerase chain reaction­restriction fragment length polymorphism analysis (PCRRFLP) was performed to detect genotypes of PER3. Results: Participants with T/T genotype were at lower risk of developing colorectal cancer than participants with C/C genotype (adjusted ORs = 0.32 (95% CI: 0.15­0.63)). When stratified by gender and smoking status, T/T genotype were associated with a decreased susceptibility to cancer in males only (adjusted ORs: 0.23 (95% CI: 0.09­0.59)), T/T genotype were also associated with a decreased susceptibility to cancer among both smokers and non-smokers. Conclusions: A significant association was found between the T allele of PER3 polymorphism and a reduced risk of colorectal cancer, especially in males. Smoking status showed no association with the relationship between PER3 genotype and CRC carcinogenesis (AU)


Assuntos
Humanos , Masculino , Feminino , Polimorfismo Genético , Neoplasias Colorretais , Fatores de Risco , Grupo com Ancestrais do Continente Asiático , Genótipo
14.
Appl. cancer res ; 39: 1-6, 2019. ilus, tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-994774

RESUMO

Background: PTEN loss is observed in 20­30% of prostate cancers and is associated with a poor outcome, but clinical details of the impact of this biomarker are unclear for intermediate grade tumors. Methods: We investigated 43 radical prostatectomy-derived grade 7 prostate tumors from the Clinics Hospital of Ribeirão Preto. Tissue microarray (TMA) blocks were constructed and PTEN copy number status was determined for all patients through fluorescence in situ hybridization (FISH). To determine the presence of PTEN protein loss in our study cohort, we performed immunohistochemistry (IHC) in TMA sections. We then developed an automated algorithm in HALO™ to identify regions of PTEN protein loss in whole prostate scanned sections from ten patients with known PTEN deletion status by FISH. Clinical analyses were conducted to determine the associations between PTEN loss and patient outcome. All statistical analyses were conducted in R v3.4.3 with P-values below 0.05 being considered statistically significant. Results: In this study of 43 grade 7 tumors, we found PTEN deletions by FISH in 18.9% of tumors, and PTEN protein loss by IHC in 16.3% of tumors. Both techniques were highly concordant and complementary. Clinical analysis demonstrated that PTEN deletion by FISH was significantly associated with positive margin invasion (P = 0.04) and Gleason score upgrade (P = 0.001). Digital image analysis of ten representative tumors demonstrated distinct intratumoral heterogeneity for PTEN protein loss in four tumors. Conclusions: This study shows that PTEN loss in Gleason grade 7 tumors can be heterogeneous and that a systematic analysis of this biomarker using a combination of FISH, IHC, and digital imaging may identify patients with a greater risk of poor outcome (AU)


Assuntos
Humanos , Masculino , Neoplasias da Próstata/patologia , PTEN Fosfo-Hidrolase/metabolismo , Prognóstico , Prostatectomia , Neoplasias da Próstata/genética , Imuno-Histoquímica , Biomarcadores Tumorais , Estudos de Coortes , Hibridização in Situ Fluorescente , Heterogeneidade Genética , Gradação de Tumores
15.
Appl. cancer res ; 39: 1-8, 2019. ilus, tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-994785

RESUMO

Background: Epidermal growth factor receptor (EGFR) is potential prognostic biomarker expressed in many human cancers. Prognostic significance of EGFR immunohistochemical expression has not been established in prostatic acinar adenocarcinoma, therefore we aimed to evaluate the frequency of expression of EGFR in prostatic adenocarcinoma and its association with other prognostic parameters. Methods: The study included 123 cases of biopsy proven prostatic acinar adenocarcinoma treated at Liaquat National hospital, Karachi from January 2013 till December 2017. Paraffin blocks of all cases were retrieved; sections were cut and stained with haematoxylin and eosin. Pathologic characteristics including tumor quantification, WHO grade group, gleason score, perineural and lymphovascular invasion were evaluated. EGFR immunohistochemistry (IHC) was performed on all tissue blocks. Results: Mean age of the patients included in the study was 69.05±8.68years. High gleason scores i.e. 8 & 9 were noted in 22% (27 cases) and 22.8% (28 cases) respectively. Similarly, 22.8% (28 cases) showed WHO grade group 5. 52.8% (65 cases) had > 50% tissue involvement by carcinoma and perineural invasion was seen in 37.4% (46 cases). Positive EGFR expression was noted in 18.7% (23 cases), while 81.3% (100 cases) showed negative EGFR expression. Significant association of EGFR expression was noted with gleason score (p-value = < 0.001), WHO grade (p = < 0.001), tumor quantification (p =0.007) and perineural invasion (p = < 0.001). Moreover, significant association of EGFR expression was also seen with disease recurrence and Her2neu over expression. Patients with low gleason scores (score 6 and 7) and lower grade group (1, 2 & 3) were less likely to have positive EGFR expression as compared to patients with high gleason score (score 9) and higher grade group (5). Similarly, patients with perineural invasion were more likely to have positive EGFR expression. Conclusion: We found a relatively low EGFR expression in our patients with prostatic adenocarcinoma; however, its association with poor prognostic parameters like high gleason score, higher grade group, perineural invasion, higher tissue involvement by cancer and disease recurrence signifies its importance as a prognostic parameter in prostatic acinar adenocarcinoma (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Próstata/patologia , Carcinoma de Células Acinares/patologia , Receptores ErbB/análise , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Biomarcadores Tumorais , Carcinoma de Células Acinares/diagnóstico , Carcinoma de Células Acinares/genética , Intervalo Livre de Doença , Gradação de Tumores
16.
Appl. cancer res ; 39: 1-5, 2019. ilus, tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-997737

RESUMO

Purpose: We investigated the clinical outcome of sodium alginate treatment in radiation-induced pharyngeal mucositis (RIPM) after neck irradiation. Materials and methods: The study population included 32 patients (11 lung cancer, 10 breast cancer, 7 head and neck cancer, and 4 other primary lesions) who underwent neck external beam radiotherapy at the authors' institution between June 2006 and 2016. The patients received 5% sodium alginate solution orally for RIPM. Those who were followed up for less than 2 months or did not receive 5% sodium alginate were excluded from this retrospective study. RIPM was graded weekly as an acute toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4. The administration of 10-15 ml of sodium alginate before each meal was continued until the radiotherapy was completed and after resolution of odynophagia. The efficacy of sodium alginate was assessed by two radiation oncologists as follows: Grade I, ineffective; grade II, moderately effective; grade III, very effective. When sodium alginate was ineffective, other analgesics, such as nonsteroidal antiinflammatory drugs (NSAIDS) or opioids, were added. Relationships between the presence/absence of additional analgesics and the radiation dose were investigated. Results: The median duration from the start of irradiation to sodium alginate administration was 15 days (range, 5­36 days). RIPM improved in 29/32 patients (grade: II, n = 22; III, n = 7). Three patients showed no improvement. No sodium alginate-related toxicities occurred. Additional analgesics were required in 5/32 patients. The radiation dose in these 5 patients was significantly higher than that in the sodium alginate-alone group (63.6 ± 7.8 Gy vs 48.3 ± 14.8Gy, P = 0.02). Patients who received > 50 Gy tended to require additional analgesics more frequently than those who received ≤50Gy (P = 0.10). Conclusions: The concurrent administration of sodium alginate and neck irradiation was feasible and tolerable without obvious toxicities. Under certain conditions sodium alginate could be a promising alternative to NSAIDs and opioids in RIPM. The results justify further prospective evaluations with detailed treatment protocols to clarify whether sodium alginate can improve RIPM (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Faringe/efeitos da radiação , Alginatos/uso terapêutico , Mucosite/tratamento farmacológico , Radioterapia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Mucosite/etiologia , Analgésicos/uso terapêutico , Pescoço/efeitos da radiação
17.
Appl. cancer res ; 39: 1-8, 2019. ilus, tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-997743

RESUMO

Background: Squamous cell carcinoma (SCC) of head and neck is highly prevalent in South-asian countries, owing to high consumption of areca nut/gutka and chewing tobacco. p27kip1 is a tumor suppressor gene, thought to be downregulated in oral squamous cell carcinoma. Therefore, in the present study we used immunohistochemical analysis to investigate an association between low p27kip1 expression in SCC of the head and neck and adverse outcomes/risk factors. Methods: Total 105 cases of SCC of head and neck excision specimens were selected from records of pathology department archives that underwent surgeries at Liaquat National hospital, Karachi from January 2008 till December 2013. Clinical and pathologic characteristics of patients were evaluated and p27kip1 immunohistochemistry was applied on tumor blocks. Results: In our study, low expression of p27kip1 in SCC of head and neck was seen in 39(37.1%) cases while 66(62. 9%) of the cases showed high expression for p27kip1. Significant association of p27kip1 expression with pan/gutka usage (p = 0.004), and recurrence (p = 0.001) was noted; however, no significant association of p27kip1 expression with other clinicopathologic features was seen. Multivariate binary logistic regression showed cases with history of pan/gutka usage were more likely to show low p27kip1 expression. Similarly, we also found that recurrence was more likely to develop in patients with low expression of p27kip1 in comparison to cases showing high p27kip1 expression. Conclusion: Loss of p27kip1 expression is a significant event involved in the pathogenesis of SCC head and neck especially that of oral cavity. Significant association of gutka/areca nut with low p27kip1 expression in our study suggests that loss p27kip1 expression is a major event involved in areca nut induced SCC of head and neck in this part of the world; however, more large scale molecular based studies are required to validate this observation. Moreover, significant association of low p27kip1 expression with tumor recurrence suggests its importance as a prognostic biomarker in SCC of head and neck (AU)


Assuntos
Humanos , Masculino , Feminino , Tabaco/efeitos adversos , Neoplasias Bucais/complicações , Imuno-Histoquímica/métodos , Carcinoma de Células Escamosas , Biomarcadores , Inibidor de Quinase Dependente de Ciclina p27 , Neoplasias de Cabeça e Pescoço/genética
18.
Appl. cancer res ; 39: 1-8, 2019. tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-999247

RESUMO

Background: The population-based mammography screening program (MSP) is aimed to reduce breast cancer mortality, to detect breast cancer at an early stage, and to allow for less invasive treatment. However, it also has some potential harms, such as overdiagnosis and overtreatment. Therefore, it is necessary that women receive sufficient and balanced information to enable informed decision-making. We examined knowledge about benefits and harms of the MSP in Germany among first-time invitees of different socio-demographic backgrounds. Methods: This observational study assessed knowledge about benefits and harms of the MSP among women who were invited to the MSP for the first time by six multiple choice items, using a postal survey. We investigated (i) single items of knowledge, (ii) the distribution of sufficient knowledge stratified by education, migration status and invitation, and (iii) possible determinants of sufficient knowledge by analyzing Odds Ratios (ORs) using bivariate and multivariate logistic regression. Results: In total, 5397 women included in the analyses. 46.1% of the study population had sufficient knowledge about benefits and harms of the MSP. However, women with low educational level and migration background had higher proportions of insufficient knowledge and used most frequently the option "don't know". Women had the most difficulties answering the numeric question and the question about the target group correctly. Results from the logistic regression showed that the odds of having sufficient knowledge were higher among well-educated women (OR 3.84, 95%CI 3.24­4.55), among women who already received the MSP invitation (OR 1.38, 95%CI 1.20­1.59) and lowest among Turkish women (OR 0.14, 95%CI 0.07­0.25). Conclusions: Women with low education and migration background need adapted information regarding benefits and harms of the MSP and are important target groups for further developing the information material about mammography screening to reduce disparities in knowledge and enable informed decision-making (AU)


Assuntos
Humanos , Feminino , Migrantes , Mamografia , Programas de Rastreamento , Conhecimento , Dano ao Paciente , Estudo Observacional
19.
Appl. cancer res ; 39: 1-6, 2019. ilus, tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1006568

RESUMO

Background: Detection of somatic mutations is a mandatory practice for therapeutic definition in precision oncology. However, somatic mutation detection protocols use DNA from formalin-fixed and paraffin-embedded (FFPE) tumor tissues, which can result in detection of nonreproducible sequence artifacts, especially C:G > T:A transitions, in DNA. In recent studies, DNA pretreatment with uracil DNA glycosylase (UDG), an enzyme involved in base excision repair, significantly reduced the number of DNA artifacts after mutation detection by next-generation sequencing (NGS) and other methods, without affecting the capacity to detect real mutations. This study aimed to evaluate the effects of UDG enzymatic pretreatment in reducing the number of DNA sequencing artifacts from FFPE tumor samples, to improve the accuracy of genetic testing in the molecular diagnostic routine. Methods: We selected 12 FFPE tumor samples (10 melanoma, 1 lung, and 1 colorectal tumor sample) with different storage times. We compared sequencing results of a 16-hotspot gene panel of NGS libraries prepared with UDG-treated and untreated samples. Results: All UDG-treated samples showed large reductions in the total number of transitions (medium reduction of 80%) and the transition/transversion ratio (medium reduction of 75%). In addition, most sequence artifacts presented a low variant allele frequency (VAF < 10%) which are eliminated with UDG treatment. Conclusion: Including UDG enzymatic treatment before multiplex amplification in the NGS workflow significantly decreased the number of artifactual variants detected in FFPE samples. Thus, including this additional step in the current methodology should improve the rate of true mutation detection in the molecular diagnostic routine.


Assuntos
Humanos , Medição da Dor , Inclusão em Parafina , Testes Diagnósticos de Rotina , Uracila-DNA Glicosidase , Sequenciamento Completo do Genoma
20.
Appl. cancer res ; 39: 1-5, 2019. ilus, tab
Artigo em Inglês | LILACS, PrevCan | ID: biblio-1015230

RESUMO

Background: Human biological material has become an important resource for biomedical research. Tumor Biobanks are facilities that collect, store and distribute samples of tumor and normal tissue for further use in basic and translational cancer research. mRNA-translation has been demonstrated to modulate protein levels and is considered a fundamental post-transcriptional mechanism of gene expression regulation. Thus, determining translation efficiencies of individual mRNAs in human tumors may add another layer of information that contributes to the understanding of tumorigenic pathways. To analyze the RNAs actively engaged in translation, RNAs associated with ribosomes (polysomes) are isolated, identified and compared to total RNA. However, the application of this technique in human tumors depends on the stability of the polysomal structure under Biobank storage conditions that usually consists of ultra-low temperature. Since the effect of freezing on the stability of the polysomal structure in stored tumor samples is not known, it is essential to evaluate this factor in the frozen samples, validating the use of biobank samples in studies of translational efficiency. Methods: Xenograft tumors were divided in two parts, half was subject to immediate processing, and half was frozen for posterior analysis. Both parts were subject to polysomal separation, RNA extraction and identification through RNAseq. Results: It was possible to successfully extract and identify total and polysomal RNA from both fresh and frozen tumoral tissue. The quantification of the polysome profile indicated no difference in the translational efficiency estimated in fresh versus frozen tissue. Gene expression data from the fresh versus frozen tissues were compared and the correlation between the polysome associated fresh x frozen (R = 0,89) and total fresh x frozen (0,90) mRNAs was calculated. No difference was identified between the two conditions. Conclusions: We demonstrated that tissue freezing does not affect the polysomal structure, consequently validating the viability of the use of biobank stored tissue for polysome associated RNA analysis (AU)


Assuntos
Humanos , Polirribossomos , RNA , Expressão Gênica , Regulação da Expressão Gênica , Neoplasias
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