The role of long non-coding RNA NORAD in digestive system tumors.

In recent years, it has been discovered that the expression of long non-coding RNAs is highly deregulated in several types of cancer and contributes to its progression and development. Recently, it has been described that in tumors of the digestive system, such as colorectal cancer, pancreatic cancer, and gastric cancer, DNA damage-activated lncRNA (NORAD) was frequently up-regulated. The purpose of this review is to elucidate the functions of NORAD in tumors of the digestive system, emphasizing its involvement in important cellular processes such as invasion, metastasis, proliferation, and apoptosis. NORAD acts as a ceRNA (competitive endogenous RNA) that sponges microRNAs and regulates the expression of target genes involved in tumorigenesis. Thus, the mechanisms underlying the effects of NORAD are complex and involve multiple signaling pathways. This review consolidates current knowledge on the role of NORAD in digestive cancers and highlights the need for further research to explore its potential as a therapeutic target. Understanding the intricate functions of NORAD could elucidate the way for innovative approaches to cancer treatment.

Prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros / Smoking prevalence and lung cancer morbimortality in Brazilian states / Prevalencia del tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños

Introdução: O câncer de pulmão é uma doença grave, sendo a segunda maior causa de morte em todo o mundo, entretanto, em alguns países desenvolvidos, tornou-se já a primeira causa de morte. Cerca de 90% dos casos de neoplasia pulmonares são causados pela inalação da fumaça do cigarro. Objetivo: Correlacionar a prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, além de demonstrar a associação destes com sexo e faixa etária. Métodos: Estudo de caráter ecológico acerca da prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, nos períodos de 2013 e 2019, dividida por sexo e faixa etária. Foram utilizados bancos de coleta de dados como o Tabnet e Pesquisa Nacional de Saúde. Resultados: As maiores taxas de mortalidade e internações hospitalares foram do público masculino, em 2013, com taxa de 2,7 e 10, respectivamente, e em 2019 com 3,3 e 11,9, respectivamente. Ademais, a maior prevalência de tabagismo foi encontrada nos homens; entretanto seu índice tem caído, enquanto a quantidade de mulheres tabagistas tem aumentado. A Região Sul demonstrou maiores números de mortalidade em ambos os períodos estudados, com taxas de 4,9 e 5,8 por 100 mil habitantes, e morbidade hospitalar com 19,9 e 23,5 por 100 mil habitantes. Já a Região Norte se configurou com as menores prevalências: em 2013 apresentou taxa de óbito por câncer de pulmão de 1,0 e morbidade hospitalar de 3,5/100 mil habitantes, em 2019 apresentou taxa de mortalidade de 4,6 e internações de 1,6/100 mil habitantes. Os coeficientes de correlação de morbidade hospitalar e prevalência de tabagismo foram R2=0,0628, r=0,251 e p=0,042, enquanto os de mortalidade e prevalência de tabagismo foram R2=0,0337, r=0,183 e p=0,140. Conclusões: Na presente pesquisa, pode-se inferir que houve associação positiva na comparação entre taxa de morbidade hospitalar e prevalência de tabagismo; em contrapartida, não foi possível observar associação positiva na correlação da taxa de mortalidade por câncer de pulmão e prevalência de tabagismo.

Introduction: Lung cancer is a serious disease, being the second leading cause of death worldwide. Moreover, in some developed countries, it has already become the leading cause of death. About 90% of lung cancer cases are caused by cigarette smoking. Objective: To correlate the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states, and to demonstrate their association with sex and age group as well. Methods: An ecological study on the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states between 2013 and 2019, divided by sex and age group. The data collection databases Tabnet and National Health Survey were used. Results: The highest rates of mortality and hospital admissions were among men, in 2013 with a rate of 2.7 and 10, respectively, and in 2019 with 3.3 and 11.9, respectively. In addition, the highest prevalence of smoking was found in men, but this rate has fallen, while the number of women smokers has increased. The South region showed higher mortality rates in both periods studied, with rates of 4.9 and 5.8 per 100,000 inhabitants, and hospital morbidity with 19.9 and 23.5 per 100,000 inhabitants. The North region had the lowest prevalence, where in 2013, it had a death rate from lung cancer of 1.0 and hospital morbidity of 3.5/100 thousand inhabitants, and where in 2019, it had a mortality rate of 4.6 and hospitalizations of 1.6/100 thousand inhabitants. The correlation coefficients for hospital morbidity and smoking prevalence were R2=0.0628, r=0.251 and p=0.042, while for mortality and smoking prevalence, these were R2=0.0337, r=0.183 and p=0.140. Conclusions: In the present study, it can be inferred that there was a positive association between hospital morbidity rate and prevalence of smoking, while it was not possible to observe a correlation between lung cancer mortality rate and prevalence of smoking.

Introducción: El cáncer de pulmón es una enfermedad grave, siendo la segunda causa de muerte en todo el mundo, sin embargo, en algunos países desarrollados, ya se ha convertido en la primera causa de muerte. Alrededor del 90% de los casos de neoplasias pulmonares están causados por la inhalación del humo del cigarrillo. Objetivo: Correlacionar la prevalencia de tabaquismo y la morbimortalidad por cáncer de pulmón en los estados brasileños, además de demostrar la asociación de estos con el género y el grupo de edad. Métodos: estudio ecológico sobre la prevalencia de tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños, dentro de los períodos 2013 y 2019, divididos por sexo y grupo de edad. Se utilizaron bancos de recogida de datos como Tabnet y la Encuesta Nacional de Salud. Resultados: las mayores tasas de mortalidad e ingresos hospitalarios se dieron en el público masculino, en 2013 con una tasa de 2,7 y 10, respectivamente, y en 2019 con 3,3 y 11,9, respectivamente. Además, la mayor prevalencia del tabaquismo se encontró en los hombres, sin embargo, su tasa ha disminuido, mientras que la cantidad de mujeres fumadoras ha aumentado. La región Sur presentó cifras más altas de mortalidad en ambos periodos estudiados, con tasas de 4,9 y 5,8 por 100.000 habitantes, y de morbilidad hospitalaria con 19,9 y 23,5 por 100.000 habitantes. Mientras que la región Norte se configuró con las prevalencias más bajas, en 2013 presentó una tasa de mortalidad por cáncer de pulmón de 1,0 y una morbilidad hospitalaria de 3,5/100.000 habitantes, en 2019 presentó una tasa de mortalidad de 4,6 y hospitalizaciones de 1,6/100.000 habitantes. Los coeficientes de correlación para la morbilidad hospitalaria y la prevalencia del tabaquismo fueron R2=0,0628, r=0,251 y p=0,042, mientras que para la mortalidad y la prevalencia del tabaquismo fueron R2=0,0337, r=0,183 y p=0,140. Conclusiones: En la presente investigación se puede inferir que existe una asociación positiva en la comparación entre la tasa de morbilidad hospitalaria y la prevalencia de tabagismo, en contrapartida, no fue posible observar una asociación positiva en la correlación de la tasa de mortalidad por cáncer de pulmón y la prevalencia de tabagismo.

Experiencias de la sexualidad de mujeres diagnosticadas con cáncer ginecológico: una aproximación desde la teoría de los holones / Experiences of sexuality of women diagnosed with gynecological cancer: a holon theory approach

Resumen La investigación tuvo como objetivo comprender las experiencias alrededor de la sexualidad desde la teoría de los holones en un grupo de mujeres diagnosticadas con cáncer ginecológico en la ciudad de Pereira, Colombia. Se implementó un diseño cualitativo y fenomenológico, con la participación de seis mujeres entre 30 y 60 años, a quienes se aplicaron entrevistas semiestructuradas explorando los holones de reproductividad, género, erotismo y vinculación afectiva interpersonal. Las entrevistas fueron transcritas y analizadas de forma manual, mediante codificación abierta y axial para identificar categorías emergentes. En los discursos de las mujeres se evidenciaron elementos relacionados a los holones de la sexualidad. En el holón de reproductividad, se encontró una resignificación del rol reproductivo como madres; en el holón de género, se presentaron actitudes positivas hacia el cuerpo y amenazas a la identidad de género por causa de los cambios provocados por la enfermedad; en el holón de erotismo, las mujeres relataron experiencias sexuales marcadas por el dolor y el apoyo erótico de la pareja; y en el holón de vinculación afectiva interpersonal, se evidenciaron situaciones de estabilidad conyugal, separación temporal con la pareja y sostenimiento de vínculos abusivos durante el proceso de tratamiento oncológico. Estos hallazgos muestran una amplia reconfiguración integral de la sexualidad femenina en cada uno de los holones y realizan un aporte significativo a la comprensión de las subjetividades de las mujeres en el proceso de afrontar el cáncer ginecológico. Se recomienda realizar nuevas investigaciones con mayor cantidad de participantes y en otras regiones de Colombia.

Abstract The research aimed to understand the experiences around sexuality, from the holon theory, in a group of women diagnosed with gynecological cancer from Pereira, Colombia. A qualitative and phenomenological design was carried out, with the participation of six women between 30 and 60 years of age, to whom semi-structured interviews were applied, exploring the holons of reproductivity, gender, eroticism and interpersonal affective bonding. The interviews were transcribed and analyzed manually, using open and axial coding to identify emerging categories. In the women's discourses, elements related to the holons of sexuality were evident. In the holon of reproductivity, a resignification of the reproductive role as mothers was found; in the holon of gender, positive attitudes towards their bodies and threats to gender identity due to the changes caused by the disease were presented; in the holon of eroticism, women reported sexual experiences characterized by pain and erotic support from their partners; and in the holon of affective interpersonal bonding, they reported situations of marital stability, temporary separation from their partners and abusive ties during the process of cancer treatment. These findings show a comprehensive reconfiguration of female sexuality in each of the holons and make a significant contribution to the understanding of women's subjectivities in the process of coping with gynecological cancer. Further research with a larger number of participants and in other regions of Colombia is recommended.

Pilot Study of the Effectiveness of Repetitive Transcranial Magnetic Stimulation on Pain and Quality of Life in Patients with Chemotherapy-Induced Peripheral Neuropathic Pain / Estudio piloto de la eficacia de la estimulación magnética transcraneal repetitiva sobre el dolor y la calidad de vida en pacientes con dolor neuropático periférico inducido por quimioterapia

Abstract Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that acts on the activity of the cerebral cortex employing electrical currents. Aim: The objective of this project is to evaluate the effectiveness of rTMS on pain and quality of life in patients with chemotherapy-induced peripheral neuropathic pain. Method: Ten patients with chemotherapy-induced peripheral neuropathic pain received 20 sessions of rTMS, consisting of 15 minutes of treatment repeated 5 times per week for four weeks (10 Hz, 20s, 30 trains with 81% intensity). Patients were evaluated using the Brief pain inventory (BPI) and the Functional Assessment of Cancer Therapy and neurotoxicity (FACT-GOG-NTX 13). Results: There were significant differences in BPI mean severity, interference score and FACT-GOG-NTX 13 (p<0,05). Conclusion: The pilot study results suggest that rTMS is potentially beneficial for the treatment of chemotherapy-induced peripheral neuropathy. rTMS over the M1 had an important reduction in pain severity, interference with daily activities, and quality of life scores. However, results should be taken with caution due to the small sample size, absence of a control group and short period of follow-up.

Resumen Antecedentes: La estimulación magnética transcraneal repetitiva (EMTr) es una técnica no invasiva que actúa sobre la actividad de la corteza cerebral, empleando corrientes eléctricas. Objetivo: El objetivo de este proyecto es evaluar la eficacia de la EMTr sobre el dolor y la calidad de vida en pacientes con dolor neuropático periférico inducido por quimioterapia. Métodos: Diez pacientes con dolor neuropático periférico inducido por quimioterapia recibieron 20 sesiones de EMTr que consistieron en un tratamiento de 15 minutos repetido 5 veces por semana durante cuatro semanas (10 Hz, 20 s, 30 trenes con 81 % de intensidad). Los pacientes fueron evaluados mediante el Inventario Breve de Dolor (BPI) y la Evaluación Funcional de la Terapia del Cáncer y la neurotoxicidad (FACT-GOG-NTX 13). Resultados: Hubo diferencias significativas en la severidad media del dolor del BPI, la puntuación de interferencia y el FACT-GOG-NTX 13 (p<0,05). Conclusión: Los resultados del estudio piloto sugieren que la rTMS es potencialmente beneficiosa para el tratamiento de la neuropatía periférica inducida por la quimioterapia. La rTMS sobre M1 tuvo una reducción importante de la severidad del dolor, la interferencia con las actividades diarias y las puntuaciones de calidad de vida. Sin embargo, los resultados deben tomarse con cautela debido al pequeño tamaño de la muestra, la ausencia de un grupo de control y el corto período de seguimiento.

A perspectiva do consumo de plantas medicinais porpacientes idosos em tratamento quimioterápico / The perspective of the consumption of medicinal plants byelderly patients undergoing chemotherapy treatment

O câncer, frequentemente relacionado ao envelhecimento, impulsiona pacientes a buscarem tratamento hospitalar ou métodos alternativos, como plantas medicinais. Este estudo visou avaliar os perfis sociodemográfico e clínico e o consumo de plantas para fins medicinais entre pacientes idosos em tratamento oncológico no Hospital Araújo Jorge (HAJ). Dados de 55 pacientes foram analisados, abrangendo informações sociodemográficas, tipos de câncer, tratamento, a utilização de plantas medicinais, o objetivo de uso, as fontes de informações sobre plantas e se notaram alguma reação adversa após o consumo. A faixa etária mais encontrada foi 61 a 70 anos (67,27%), a maioria dos pacientes eram homens (63,64%), com ensino fundamental incompleto (32,73%), casados (56,36%) e que moram no interior de Goiás (43,64%). Quanto ao tratamento, a maioria realizava quimioterapia (40,00%) e o câncer gástrico foi mais relatado (14,54%). Sobre o uso de plantas medicinais, a maioria relatou simpatizar com o consumo (58,18%), e acredita em sua segurança devido à origem natural (59,37%). Informações sobre o uso de plantas medicinais eram obtidas com amigos, vizinhos e familiares (21,81%). Ao relatar sobre o consumo de plantas medicinais durante a quimioterapia, a maioria não percebeu nenhum efeito (40,63%). Foram citadas 17 plantas, que eram utilizadas no tratamento anticâncer (29,00%) e preparadas como infusões (18,75%) pelo uso das folhas frescas (60,00%), principalmente para uso interno (46,87%). Diante disso, a atenção farmacêutica se mostra vital para guiar pacientes nas práticas seguras e eficazes de consumo. Isso inclui direcionar sobre doses adequadas, efeitos colaterais e interações, garantindo bem-estar e prevenindo riscos à saúde.

Cancer, which is often related to ageing, drives patients to seek hospital treatment or alternative methods such as medicinal plants. This study aimed to evaluate the sociodemographic and clinical profile and the consumption of plants for medicinal purposes among elderly patients undergoing cancer treatment at the Araújo Jorge Hospital (AJH). Data from 55 patients was analyzed, covering sociodemographic information, types of cancer, treatment, the use of medicinal plants, the purpose of use, the source of information about plants and whether they noticed any adverse reactions after consumption. The most common age group was 61 to 70 years (67.27%), the majority of patients were men (63.64%), had incomplete primary education (32.73%), were married (56.36%) and lived in the interior of Goiás (43.63%). With regard to treatment, the majority were undergoing chemotherapy (40,00%) and gastric cancer was the most frequently reported (14.54%). With regard to the use of medicinal plants, the majority were sympathetic to their consumption (58.18%) and believed them to be safe due to their natural origin (59.37%). Information on the use of medicinal plants was obtained from friends, neighbors and family members (21.81%). When reporting on the consumption of medicinal plants during chemotherapy, the majority did not notice any effect (40.63%). Seventeen plants were mentioned, which were used for anticancer treatment (29,00%) and prepared as infusions (18.75%) with fresh leaves (60,00%), mainly for internal use (46.87%). In view of this, pharmaceutical care is vital to guide patients in safe and effective consumption practices. This includes guidance on appropriate doses, side effects and interactions, ensuring well-being and preventing health risks.

Genes da instabilidade de microssatélites no câncer colorretal: papel na inflamação e estresse oxidativo / Microsatellite instability genes in colorectal cancer: role in inflammation and oxidative stress

A instabilidade de microssatélites é um fenômeno genético caracterizado pela alteração na repetição de sequências de nucleotídeos conhecidas como microssatélites. Esta instabilidade pode ocorrer devido a defeitos nos genes reparadores de DNA, como os genes MLH1, MSH2, MSH6 e PMS2. A inflamação crônica tem sido associada ao desenvolvimento do câncer colorretal. Os genes da instabilidade de microssatélites estão envolvidos na regulação da resposta inflamatória, podendo influenciar a progressão tumoral. Estudos demonstraram que a presença de instabilidade de microssatélites em tumores colorretais está relacionada a uma maior infiltração de células imunes, como linfócitos T, macrófagos e neutrófilos, que podem modular a resposta inflamatória no microambiente tumoral. O estresse oxidativo é caracterizado pelo desequilíbrio entre a produção de espécies reativas de oxigênio e a capacidade antioxidante do organismo e desempenha um papel importante na carcinogênese. Os genes da instabilidade de microssatélites podem influenciar a resposta ao estresse oxidativo, afetando a capacidade das células tumorais de lidar com o dano oxidativo e promovendo a sobrevivência celular. O objetivo deste trabalho consiste na compreensão dos genes envolvidos na instabilidade de microssatélites no câncer colorretal e como eles contribuem para o desenvolvimento da doença, relacionando com processos inflamatórios e estresse oxidativo nas células tumorais. Justifica-se pela necessidade de compreensão das interconexões entre a instabilidade de microssatélites, inflamação e o estresse oxidativo em pacientes com câncer colorretal.

Microsatellite instability is a genetic phenomenon characterized by changes in the repetition of nucleotide sequences known as microsatellites. This instability may occur due to defects in DNA repair genes, such as the MLH1, MSH2, MSH6 and PMS2 genes. Chronic inflammation has been linked to the development of colorectal cancer. Microsatellite instability genes are involved in regulating the inflammatory response and may influence tumor progression. Studies have shown that the presence of microsatellite instability in colorectal tumors is related to a greater infiltration of immune cells, such as T lymphocytes, macrophages and neutrophils, which can modulate the inflammatory response in the tumor microenvironment. Oxidative stress is characterized by the imbalance between the production of reactive oxygen species and the body's antioxidant capacity and plays an important role in carcinogenesis. Microsatellite instability genes can influence the response to oxidative stress, affecting the ability of tumor cells to deal with oxidative damage and promoting cell survival. The objective of this work is to understand the genes involved in microsatellite instability in colorectal cancer and how they contribute to the development of the disease, relating it to inflammatory processes and oxidative stress in tumor cells. It is justified by the need to understand the interconnections between microsatellite instability, inflammation and oxidative stress in patients with colorectal cancer.

In vitro models to evaluate multidrug resistance in cancer cells: Biochemical and morphological techniques and pharmacological strategies.

The overexpression of ATP-binding cassette (ABC) transporters contributes to the failure of chemotherapies and symbolizes a great challenge in oncology, associated with the adaptation of tumor cells to anticancer drugs such that these transporters become less effective, a mechanism known as multidrug resistance (MDR). The aim of this review is to present the most widely used methodologies for induction and comprehension of in vitro models for detection of multidrug-resistant (MDR) modulators or inhibitors, including biochemical and morphological techniques for chemosensitivity studies. The overexpression of MDR proteins, predominantly, the subfamily glycoprotein-1 (P-gp or ABCB1) multidrug resistance, multidrug resistance-associated protein 1 (MRP1 or ABCCC1), multidrug resistance-associated protein 2 (MRP2 or ABCC2) and cancer resistance protein (ABCG2), in chemotherapy-exposed cancer lines have been established/investigated by several techniques. Amongst these techniques, the most used are (i) colorimetric/fluorescent indirect bioassays, (ii) rhodamine and efflux analysis, (iii) release of 3,30-diethyloxacarbocyanine iodide by fluorescence microscopy and flow cytometry to measure P-gp function and other ABC transporters, (iv) exclusion of calcein-acetoxymethylester, (v) ATPase assays to distinguish types of interaction with ABC transporters, (vi) morphology to detail phenotypic characteristics in transformed cells, (vii) molecular testing of resistance-related proteins (RT-qPCR) and (viii) 2D and 3D models, (ix) organoids, and (x) microfluidic technology. Then, in vitro models for detecting chemotherapy MDR cells to assess innovative therapies to modulate or inhibit tumor cell growth and overcome clinical resistance. It is noteworthy that different therapies including anti-miRNAs, antibody-drug conjugates (to natural products), and epigenetic modifications were also considered as promising alternatives, since currently no anti-MDR therapies are able to improve patient quality of life. Therefore, there is also urgency for new clinical markers of resistance to more reliably reflect in vivo effectiveness of novel antitumor drugs.

Association between visceral adiposity index and cancer risk in the UK Biobank cohort.

BACKGROUND: The visceral adiposity index (VAI) is a marker of visceral fat accumulation and metabolic dysfunction, but there is limited evidence of its association with cancer. The objective of this study was to investigate associations between the VAI and both incident cancer at 23 sites and all-cause cancer. METHODS: In total, 385,477 participants (53.3% women; mean age, 56.3 years) from the UK Biobank prospective cohort were included in this study. The median follow-up was 8.2 years (interquartile range, 7.3-8.9 years). The VAI was calculated using formula the published by Amato et al. and was categorized into sex-specific tertiles. Twenty-four incident cancers were the outcomes. Cox proportional hazard models were adjusted for sociodemographics, lifestyle factors, and multimorbidity counts. RESULTS: Over the follow-up period, 47,882 individuals developed cancer. In the fully adjusted models, the VAI was associated with a higher risk of six cancer sites. Individuals in the highest tertile, compared with those in the lowest tertile, had higher risks of uterine (hazard ratio [HR], 2.09; 95% confidence interval [CI], 1.76-2.49), gallbladder (HR, 1.83; 95% CI, 1.26-2.66), kidney (HR, 1.39; 95% CI, 1.18-1.64), liver (HR, 1.25; 95% CI, 1.00-1.56), colorectal (HR, 1.14; 95% CI, 1.05-1.24), and breast (HR, 1.11; 95% CI, 1.03-1.19) cancers and of all-cause cancer (HR, 1.05). There was no evidence of a nonlinear association between the VAI and cancer risk. CONCLUSIONS: The VAI was associated with six cancer sites and with all-cause cancer. The prognostic and etiologic roles of visceral fat accumulation and dysfunction in cancer warrant further research.

Retrospective study assessing the role of the androgen receptor in clear cell renal cell cancer patients treated with VEGFR inhibitors in monotherapy.

BACKGROUND AND PURPOSE: Despite that incorporating antiangiogenic in combination with immune-checkpoint inhibitors as the standard first-line treatment for advanced clear cell renal cell cancer (ccRCC) yields promising outcomes, these regimens often lead to significant toxicity. However, a subgroup of patients has shown responsiveness to VEGFR tyrosine-kinase inhibitors (TKIs) in monotherapy, leading to the question of whether employing combination therapies can significantly enhance overall survival in all patients over monotherapy. Thus, we aim to identify gene expression signatures that can predict TKI response within subpopulations that might benefit from single-agent therapies, to minimize unnecessary exposure to combination therapies and their associated toxicities, as well as to discover new potential therapeutic targets to improve ccRCC treatment. Based on prior data, the androgen receptor (AR) might meet both conditions. PATIENTS AND METHODS: We evaluated the association between AR expression, assessed through NanoString® technology-derived mRNA counts, and the clinical outcomes of 98 ccRCC patients treated with first-line antiangiogenics and determined its association with other genes implicated in ccRCC tumorigenesis. RESULTS: Higher AR-expression correlates significantly with better prognosis and survival based on the MSKCC risk score, and longer PFS. Furthermore, we have identified a gene set signature associated with AR-overexpression and several genes involved in angiogenesis and transcriptional targets of the hypoxia-inducible factor, a cornerstone of ccRCC. CONCLUSIONS: AR-overexpression and its association with other genes could favor a transcriptomic signature set to aid in identifying patients suitable for TKI in monotherapy, rather than aggressive combinations, enhancing thus, precision and personalized therapeutic decisions.

Multidrug Resistance Reversed by Maleimide Interactions. A Biological and Synthetic Overview for an Emerging Field.

Multidrug Resistance (MDR) can be considered one of the most frightening adaptation types in bacteria, fungi, protozoa, and eukaryotic cells. It allows the organisms to survive the attack of many drugs used in the daily basis. This force the development of new and more complex, highly specific drugs to fight diseases. Given the high usage of medicaments, poor variation in active chemical cores, and self-medication, the appearance of MDR is more frequent each time, and has been established as a serious medical and social problem. Over the years it has been possible the identification of several genes and proteins responsible for MDR and with that the development of blockers of them to reach MDR reversion and try to avoid a global problem. These mechanisms also have been observed in cancer cells, and several calcium channel blockers have been successful in MDR reversion, and the maleimide can be found included in them. In this review we explore the history, mechanisms, reversion efforts, and we specifically focused on the maleimide synthesis as MDR-reversers in co-administration, as well as their biological applications in a urge to expand the available information and explore a very plausible MDR reversion source.

Physical exercise in Chilean breast cancer survivors: Qualitative study of barriers, facilitators and preferences. / Actividad física en chilenas sobrevivientes de cáncer de mama: estudio cualitativo de barreras, facilitadores y preferencias.

Introduction: Breast cancer survivors often experience pre and post-treatment physical and psychological symptoms, negatively affecting their quality of life. Regular physical exercise is associated with better quality of life and lower recurrence of cancer, and therefore all oncological patients are recommended to practice it in a regular basis. Despite this, breast cancer survivors have low adherence to physical exercise. The purpose of this study is to identify barriers, facilitators and preferences of Chilean breast cancer survivors to practice physical exercise. Methods: Phenomenological qualitative study of 12 in-depth interviews with adjuvant radiation therapy concluded at least three months ago. Results: Breast cancer survivors ignored the benefits of physical exercise during and after treatment. The barriers were physical symptoms, psychological barriers, sociocultural barriers, health system barriers, disinformation and sedentary lifestyle. Facilitators were coping with physical symoptoms, psychological issues, having information and active lifestyle. The preferences were painless and familiar exercises. Preferred exercise was walking. Conclusions: Breast cancer survivors may adhere to physical exercise despite barriers when certain facilitators are present, which may be promoted by the health team when reporting the benefits of the physical exercise, prescribing personalized, safe and painless physical exercise and educating both patient and her family about the role of the physical exercise in cancer recovering process.

Introducción: Las sobrevivientes de cáncer de mama suelen ver afectada negativamente su calidad de vida por síntomas físicos y psicológicos pre y post tratamiento. La práctica regular de ejercicio físico se asocia a mejor calidad de vida y menor recurrencia del cáncer, por esto es recomendado a todos los pacientes oncológicos. Sin embargo, existe baja adherencia a este. El propósito de este artículo es identificar barreras, facilitadores y preferencias de sobrevivientes de cáncer de mama chilenas para realizar ejercicio físico. Métodos: Estudio cualitativo fenomenológico, basado en entrevistas en profundidad a 12 sobrevivientes de cáncer de mama que terminaron la radioterapia adyuvante hace tres o más meses. Resultados: Las sobrevivientes de cáncer de mama desconocían la importancia del ejercicio físico durante y después del tratamiento. Las barreras identificadas fueron síntomas físicos, barreras psicológicas, socioculturales, del sistema de salud; desinformación y sedentarismo. Los facilitadores fueron físicos, psicológicos, contar con información y práctica de ejercicio físico antes del diagnóstico. Las preferencias fueron ejercicios indoloros y familiares. El ejercicio preferido fue caminar. Conclusiones: Es posible que las sobrevivientes de cáncer de mama adhieran al ejercicio físico, a pesar de las barreras cuando hay ciertos facilitadores presentes. Estos pueden ser generados por el equipo médico al informar los beneficios del ejercicio físico, prescribir ejercicio físico personalizado, seguro e indoloro y educar a la paciente y a su familia sobre el rol del ejercicio físico en la recuperación de sobrevivientes de cáncer de mama.

Realizing active targeting in cancer nanomedicine with ultrasmall nanoparticles.

Ultrasmall nanoparticles (usNPs) have emerged as promising theranostic tools in cancer nanomedicine. With sizes comparable to globular proteins, usNPs exhibit unique physicochemical properties and physiological behavior distinct from larger particles, including lack of protein corona formation, efficient renal clearance, and reduced recognition and sequestration by the reticuloendothelial system. In cancer treatment, usNPs demonstrate favorable tumor penetration and intratumoral diffusion. Active targeting strategies, incorporating ligands for specific tumor receptor binding, serve to further enhance usNP tumor selectivity and therapeutic performance. Numerous preclinical studies have already demonstrated the potential of actively targeted usNPs, revealing increased tumor accumulation and retention compared to non-targeted counterparts. In this review, we explore actively targeted inorganic usNPs, highlighting their biological properties and behavior, along with applications in both preclinical and clinical settings.

Prophylactic ureteral stent in colorectal surgery: a meta-analysis and systematic review.

PURPOSE: Accidental ureteric injury during colorectal surgery is a rare but dreadful event. It is associated with a higher risk of urinary tract infection (UTI) and acute kidney injury (AKI). Prophylactic placement of double J stents could improve ureteral identification and decrease the chance of accidental ureteral injury. METHODS: We searched MEDLINE, Cochrane, Central Register of Clinical Trials, and Web of Science for studies published until March 2024. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Statistical significance was defined as p < 0.05. Heterogeneity was assessed using the Cochran Q test and I2 statistics, with p-values inferior to 0.10 and I2 > 25% considered significant. Statistical analysis was conducted in RStudio version 4.4.1. RESULTS: Eleven observational studies were included, comprising 71,784 patients. Among them, 11,723 (16.4%) were submitted to a prophylactic ureteral stent while 59,961 (83.6%) were not. There was no significant difference in ureteral injury between the groups (0.66% vs 0.8%; OR 1.45; 95% CI 0.43-4.87; p = 0.552; I2 = 56%). Prophylactic stent placement was associated with an increase in AKI (1.7% vs. 0.56%; OR 1.54; 95% CI 1.24-1.91; p < 0.001; I2 = 44%), operative time (MD 24.8 min; 95% CI 4.9-44.8; p = 0.01; I2 = 91%), and a decrease in mortality (OR 0.11; 95% CI 0.05-0.23; p < 0.001; I2 = 42%). No differences were observed in UTI, hematuria, length of hospital stays, and reoperation. CONCLUSION: In colorectal surgery, prophylactic ureteral stents were associated with increased AKI and operative time. No significant difference was observed in ureteral injury, UTI, hematuria, length of hospital stays, and reoperation.

Impact of Preoperative Counseling and Education on Decreasing Anxiety in Patients With Gynecologic Tumors: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the impact of counseling and preoperative education on reducing anxiety in patients undergoing surgery for gynecologic cancer. METHODS: In this randomized clinical trial, patients with gynecological tumors undergoing surgical treatment between 15 and 60 days preoperatively, were included. The group was randomized to receive preoperative routine orientation plus preoperative counseling and education by nursing (experimental group [EG]) or receive preoperative routine orientation only (control group [CG]). We stratified the groups by surgical approach: open, laparoscopy, and robotic. We excluded patients treated in another service and with the need for an intensive care unit after surgery. We used the Hospital Anxiety and Depression Scale (HADS) to evaluate symptoms of anxiety and depression. The severity of symptoms was evaluated using the Edmonton Symptom Assessment System (ESAS-Br). RESULTS: We analyzed 54 women (CG 27, EG 27). No significant differences were observed regarding ESAS scores (total, physical, emotional, well-being, and anxiety) between preoperative and postoperative evaluation. However, in the EG, comparing the preoperative versus postoperative moments, there was a significant reduction in total, emotional, and anxiety scores of ESAS (p = 0.012; p = 0.003; p = 0.001). No difference in anxiety symptoms by HADS scale was noted between the two groups, comparing preoperative and postoperative moments, CG (40.7% and 22.2%) and EG (37.0% and 25.9%) (p = 0.78; p = 0.75), respectively. Also, in depression symptoms (HADS scale), we found no difference comparing preoperative and postoperative moments (p = 0.34; p > 0.99). When we stratified by surgical approach or time between intervention and surgery ( ≤ 15, > 15 to ≤ 30, and > 30 days), no difference was observed in the anxiety and depression symptoms evaluation, in both groups. CONCLUSIONS: The preoperative education by nurse orientation reduced the total, emotional, and anxiety symptoms of ESAS score between preoperative and postoperative moments. However, by the HADS scale, there was no difference in anxiety and depression symptoms.

MicroRNA-1307-3p contributes to breast cancer progression through PRM2.

BACKGROUND: Despite advances in screening and therapy, breast cancer (BC) remains the predominant cancer in women globally. Dysregulation of microRNAs (miRNAs) is pivotal in carcinogenesis across various cancers, including BC. Evidence indicates that miR-1307-3p is upregulated in BC tumors, yet its target genes are not fully elucidated. This study aimed to explore how miR-1307-3p regulates BC proliferation, migration, invasion, and angiogenesis and to identify potential target genes. METHODS: Basal miR-1307-3p levels were quantified in BC cell lines MDA-MB-231 and MCF-7, as well as MCF-10A using quantitative real-time reverse transcription-PCR (RT-qPCR). The impact of miR-1307-3p inhibition on BC cell proliferation, migration, invasion, and angiogenesis was assessed. Nine miRNA-target prediction databases identified potential miR-1307-3p targets. Target expression was validated using RT-qPCR, Western blot, and dual-luciferase reporter assays. MiR-1307-3p was overexpressed in MDA-MB-231 and MCF-7 compared to MCF-10A. RESULTS: Inhibiting miR-1307-3p significantly reduced BC cell proliferation, migration, invasion, and angiogenesis. Bioinformatics analysis identified 17 potential miR-1307-3p targets, with protamine 2 (PRM2) overexpression confirmed via Western blot and dual-luciferase assays. CONCLUSION: MiR-1307-3p overexpression in BC promotes proliferation, migration, invasion, and angiogenesis. PRM2 emerges as a novel miR-1307-3p target in BC.

Cruciferous Plant Extracts, Their Isothyocianate or Indol Derivatives, and Their Effect on Cellular Viability of Breast Cancer Cell Lines.

Brassicaceaes are rich in glucosinolates (GSL), whose derivatives, the isothyocianates sulforaphane (SFN), iberine (IB), or indole derivatives as indole-3-carbinol (I3C), have anticancer activities. We evaluated the effects of a broccoli sprout (Brassica oleracea var italica) and red cabbage (B. oleracea L. var capitata f. rubra) extracts and their GSL derivatives on breast cancer cells. Broccoli sprout aqueous extract (BSE) and red cabbage aqueous (RCA) or ethanolic (RCE) extracts were high in SFN, IB, and/or I3C. BSE and RCA decreased proliferation at doses of 2.5-5 mg/mL but induced proliferation at lower doses. RCE decreased proliferation starting at 10 µg/mL with selectivity toward cancer cells. SFN, IB, or I3C alone or in combination did not decrease proliferation similarly, suggesting synergistic effects with other phytochemicals in the extract. RCE showed selectivity toward breast cancer cells, but the effect of the individual metabolites or their combination did not reduce proliferation to the same extent. It will be important to determine the combination responsible for this effect to characterize their use for breast cancer treatment.

Anticancer Drug Discovery from Natural Compounds Targeting PI3K/AKT/mTOR Signaling Pathway.

The term cancer is used to describe a complex pathology characterized by the uncontrollable proliferation of cells, which displays a fast metastatic spread, being a disease with difficult treatment. In this context, Phosphatidylinositol 3-kinase (PI3K) represents a promising pathway to be inhibited, aiming to develop anticancer agents, since it performs a pivotal role in regulating essential cellular processes, including cell proliferation, growth, autophagy, and apoptosis. In parallel, natural compounds can effectively represent a therapeutic strategy to fight against malignant cells. Then, compounds derived from various plant sources, such as flavonoids, terpenoids, alkaloids, coumarins, and lignans, have exhibited remarkable in vitro and in vivo anticancer properties. This review focused in the exploration of natural products targeting the PI3K/AKT/m-TOR signaling pathway, demonstrating that these compounds could even further investigated to reveal novel and effective anticancer drugs in the future.

Real-world evidence of survival outcomes in breast cancer subtypes after neoadjuvant chemotherapy in a Brazilian reference center.

BACKGROUND: Neoadjuvant chemotherapy (NAC), traditionally used for locally advanced disease, is now applied for operable disease, particularly to treat aggressive breast cancer (BC). This study aimed to characterize the pathological complete response (pCR) and its relationship with overall survival (OS) and disease-free survival (DFS) among BC patients receiving NAC in a Brazilian public reference center, as well as the association between pCR and BC subtypes. METHODS: A retrospective cohort study used a comprehensive BC database from a Brazilian women's health reference center, including patients diagnosed between 2011 and 2020 who underwent NAC. We collected demographic, cancer-specific, and treatment-related data, analyzing OS and DFS based on pCR status using the semiparametric Kaplan-Meier method, with the date of BC diagnosis as the starting point. RESULTS: The study included 1,601 patients, with an average age of 49 years and a majority presenting stage IIIa disease (35%). Most had invasive nonspecial type (NST) BC (94%), and a significant portion (86.7%) exhibited a Ki-67 index <14. The overall pCR rate was 22.7%, with higher frequencies observed in the triple negative and luminal B subtypes. Patients who achieved pCR had significantly higher survival rates (89% alive vs. 61%, P<0.001) and better DFS (90% vs. 66%, P<0.001), except in the luminal A subtype, where pCR did not correlate with improved OS or DFS. CONCLUSIONS: These updated real-world data (RWD) from BC patients who underwent NAC in Brazil revealed a pCR rate of 22.7% in all cancer subtypes and stages. pCR was not associated with better outcomes in patients with luminal A, contrasting with other subtypes.

Patterns of beverages consumption and prevalence of non-communicable chronic diseases.

Beverages consumption influences diet quality in general and has been associated with the development of non-communicable chronic diseases (NCCD). We aimed to verify the association between beverage consumption patterns and the prevalence of NCCD. A cross-sectional household and population-based study was conducted with 489 individuals aged 20 years and older. The presence of NCCD (arterial hypertension, diabetes, cancer and hypercholesterolemia) was obtained by self-report, while obesity was diagnosed by measuring body weight, height and waist circumference. Beverage consumption patterns were obtained by principal component analysis. The association between beverages patterns and the prevalence of NCCD was verified using Poisson regression, expressed as prevalence ratio (PR) and adjusted for potential confounding factors. Three beverage patterns were identified: 'ultra-processed beverages', 'alcoholic beverages' and 'healthy beverages'. Individuals with greater adherence to the Ultra-processed Beverages Pattern had a 2·77 times higher prevalence of cancer (PR: 3·77; 95 % CI 1·57, 9·07). Higher adherence to the Alcoholic Beverages Pattern was associated with a higher prevalence of obesity (PR: 1·97; 95 % CI 1·13, 3·44). In contrast, individuals in the second tertile of adherence to the Healthy Beverages Pattern had a 39 % lower prevalence of hypercholesterolemia (PR: 0·61; 95 % CI 0·40, 0·92), and individuals in the third tertile had a 10 % lower prevalence of abdominal obesity estimated by the waist-to-height ratio (PR: 0·90; 95 % CI 0·83, 0·97). Beverage consumption patterns may be associated with a higher prevalence of NCCD, regardless of other risk factors. It is therefore important to conduct more studies investigating the impact of beverages patterns on health.

Combining serum CDK1 with tumor markers for the diagnosis of small cell lung cancer.

OBJECTIVE: An investigation of the diagnostic and clinical value of cell cycle-dependent kinase 1 (CDK1) in small cell lung cancer (SCLC). METHODS: A large tertiary hospital in Jiangxi Province enrolled 80 SCLC cases, 105 cases of non-small cell lung cancer (NSCLC), 114 cases of pulmonary nodule (PN) and 60 control cases from December 2022 to December 2023. ELISA was used to measure CDK1 levels in serum. The expression levers of neuron-specific enolase (NSE), Pro gastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCA), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and cytokeratin 19 fragment (YFRA21-1) were detected by electrochemiluminescence immunoassay. RESULTS: ①CDK1, ProGRP, NSE, and CA199 expressions were significantly higher in the SCLC group compared to the NSCLC, PN and Control groups (P < 0.01). ②Spearman correlation analysis showed that serum levels of CDK1, NSE, and ProGRP were associated with clinical staging and lymph node metastasis in SCLC patients (P < 0.05). ③The serum levels of CDK1, NSE, and ProGRP in patients with extensive-disease (ED) SCLC were higher than those in patients with limited-disease (LD) SCLC (P < 0.05), and the serum levels of CDK1, NSE, and ProGRP in SCLC patients with lymph node metastasis were higher than those without lymph node metastasis (P < 0.05). ④Compared with the NSCLC group, the AUC of subjects diagnosed with SCLC by CDK1 was the largest and the sensitivity was the highest, 0.831 and 72.50%, the specificity of ProGRP in diagnosing SCLC is the highest, at 95.20% (P < 0.01). Compared with the PN group, CDK1 had the highest AUC, sensitivity, and specificity in diagnosing SCLC, with values of 0.93%, 88.80%, and 94.70%, respectively (P < 0.01). ⑤The combination of CDK1, ProGRP and NSE had the highest AUC and sensitivity of 0.903 and 86.30% for the diagnosis of SCLC (P < 0.01). CONCLUSION: CDK1 not only plays an important role in assisting the diagnosis of SCLC but also in the differential diagnosis between SCLC and NSCLC. The combination of CDK1 and NSE and ProGRP can significantly improve the diagnostic performance and provide new ideas for the clinical diagnosis of SCLC.