Celecoxib: Antiangiogenic and Antitumoral Action / Celecoxib: Acción Antiangiogénica y Antitumoral

SUMMARY: Angiogenesis, a process by which new blood vessels are generated from pre-existing ones, is significantly compromised in tumor development, given that due to the nutritional need of tumor cells, pro-angiogenic signals will be generated to promote this process and thus receive the oxygen and nutrients necessary for its development, in addition to being a key escape route for tumor spread. Although there is currently an increase in the number of studies of various anti-angiogenic therapies that help reduce tumor progression, it is necessary to conduct a review of existing studies of therapeutic alternatives to demonstrate their importance.

La angiogénesis, proceso por el cual se generan nuevos vasos sanguíneos a partir de otros preexistentes, se encuentra comprometida de forma importante en el desarrollo tumoral, dado que por necesidad nutritiva de las células tumorales se generarán señales pro angiogénicas para promover este proceso y así recibir el oxígeno y los nutrientes necesarios para su desarrollo, además de ser una ruta de escape clave para la diseminación tumoral. Si bien, actualmente existe un aumento en la cantidad de estudios de diversas terapias anti angiogénicas que ayudan a reducir el avance tumoral, es necesario realizar una revisión de los estudios existentes de alternativas terapéuticas para demostrar su importancia.

Percepção dos profissionais de enfermagem sobre manejo de reação infusional a antineoplásicos: estudo qualitativo / Perception of nursing professionals on the management of infusion reactions to antineoplastics: qualitative study

Identificar a percepção dos profissionais de enfermagem sobre o manejo de reação infusional imediata a antineoplásicos. Método: Trata-se de um estudo descritivo de caráter exploratório com abordagem qualitativa realizado em um hospital no Rio Grande do Sul. Resultados: Todos os participantes afirmaram saber identificar uma reação infusional. Após a identificação da reação, nota-se que a maioria obedeceu a uma ordem de condutas a serem realizadas. Quanto aos cuidados para prevenção das reações infusionais, a maioria dos participantes mencionou a administração de medicamentos pré-quimioterápicos, como antialérgicos e antieméticos. Conclusão: Os achados demonstram que a maioria dos profissionais sabe reconhecer e manejar, porém há a necessidade de treinamentos e padronização das ações.(AU)

To identify the perception of nursing professionals about the management of immediate infusion reactions to antineoplastic drugs. Method: This is a descriptive, exploratory study with a qualitative approach carried out in a hospital in Rio Grande do Sul. Results: All the participants said they knew how to identify an infusion reaction. After identifying the reaction, it was noted that the majority followed an order of conduct to be carried out. As for precautions to prevent infusion reactions, most of the participants mentioned the administration of pre-chemotherapy drugs, such as anti-allergic and anti-emetic drugs. Conclusion: The findings show that most professionals know how to recognize and manage them, but there is a need for training and standardization of actions.(AU)

Identificar la percepción de los profesionales de enfermería sobre el manejo de las reacciones infusionales inmediatas a medicamentos antineoplásicos. Método: Se trata de un estudio descriptivo, exploratorio, con abordaje cualitativo, realizado en un hospital de Rio Grande do Sul. Resultados: Todos los participantes afirmaron saber identificar una reacción a la infusión. Después de identificar la reacción, la mayoría siguió un orden de conducta. En cuanto a las precauciones para prevenir las reacciones a la infusión, la mayoría de los participantes mencionó la administración de fármacos prequimioterápicos, como antialérgicos y antieméticos. Conclusión: Los hallazgos muestran que la mayoría de los profesionales saben reconocerlas y manejarlas, pero es necesaria la formación y la estandarización de actuaciones.(AU)

Modalidades Fisioterapêuticas no Manejo da Dor Neuropática Induzida pelo Tratamento do Câncer de Mama: Revisãoda Literatura / Physiotherapeutic Modalities in the Management of Neuropathic Pain Induced by Breast Cancer Treatment: Literature Review / Modalidades Fisioterapéuticas en el Manejo Del Dolor Neuropático Inducido por el Tratamiento del Cáncer de Mama: Revisión de la Literatura

A sobrevida de mulheres após o tratamento do câncer de mama tem aumentado em virtude de avanços na detecção precoce e terapias disponíveis. Porém, as sobreviventes comumente enfrentam efeitos adversos após o tratamento que representam grande carga física e psicológica. Além da fadiga, a dor é o sintoma persistente mais frequente após o tratamento. Objetivo: Sistematizar os resultados de ensaios clínicos randomizados sobre a intervenção fisioterapêutica na dor neuropática periférica induzida pelos tratamentos para o câncer de mama. Método: Busca realizada nas bases de dados MEDLINE via portal PubMed e Cochrane. Foram selecionados ensaios clínicos randomizados publicados a partir de 2017, em língua inglesa, que abordassem as modalidades fisioterapêuticas como intervenção, a dor neuropática periférica induzida por tratamentos oncológicos como desfecho, e mulheres sobreviventes ao câncer de mama como população de interesse. A qualidade metodológica dos estudos foi avaliada pela ferramenta Cochrane para o risco de viés. Resultados: Quatro estudos foram revisados na íntegra. Majoritariamente, os efeitos adversos do tratamento oncológico se devem a regimes quimioterápicos à base de taxanos. Os desfechos avaliados incluem, além da dor, demais sinais neuropáticos e influência nas atividades de vida diária. Os estudos variaram quanto à intervenção e fase de tratamento. Apenas um dos estudos demonstrou resultado significativamente positivo a favor do grupo intervenção. Conclusão: Estudos clínicos randomizados disponibilizam evidências escassas quanto aos efeitos positivos da intervenção fisioterapêutica na dor neuropática periférica induzida pelos tratamentos para o câncer de mama.

Women's survival after breast cancer treatment has increased due to advances in early detection and available therapies. However, great physical and psychological burden are the result of adverse effects that survivors commonly face. In addition to fatigue, pain is the most common persistent symptom after cancer treatment. Objective: Systematize the results of randomized clinical trials on physiotherapeutic intervention in peripheral neuropathic pain induced by breast cancer treatments . Method:The search was carried out on the MEDLINE databases via PubMed and Cochrane portals. Randomized clinical trials published since 2017 in English, that addressed physiotherapeutic modalities as intervention, peripheral neuropathic pain induced by oncological treatments as outcome were selected, and the population of interest were women surviving breast cancer. The Cochrane-risk-of-bias tool was applied to evaluate the methodological quality of the studies. Results: Four studies were fully reviewed. Most of the adverse effects of cancer treatment are due to taxane-based chemotherapy regimens. The outcomes assessed include, in addition to pain, other neuropathic signs and influence on activities of daily living. The studies varied in terms of intervention and treatment phase. Only one of the studies demonstrated a significantly positive result in favor of the intervention group. Conclusion: Randomized clinical studies provide scant evidence regarding the positive effects of physiotherapeutic intervention on peripheral neuropathic pain induced by breast cancer treatments.

La supervivencia de las mujeres después del tratamiento del cáncer de mama ha aumentado debido a los avances en la detección temprana y las terapias disponibles. Sin embargo, los supervivientes suelen enfrentarse a efectos adversos después del tratamiento que representan una gran carga física y psicológica. Además de la fatiga, el dolor es el síntoma persistente más común después del tratamiento del cáncer. Objetivo: Sistematizar los resultados de ensayos clínicos aleatorizados sobre intervención fisioterapéutica en el dolor neuropático periférico inducido por tratamientos para el cáncer de mama. Método: La búsqueda se realizó en las bases de datos MEDLINE a través de los portales PubMed y Cochrane. Se seleccionaron ensayos clínicos aleatorizados publicados desde 2017, en inglés, que abordaron modalidades fisioterapéuticas como intervención, dolor neuropático periférico inducido por tratamientos oncológicos como resultado y mujeres sobrevivientes de cáncer de mama como población de interés. La calidad metodológica de los estudios se evaluó mediante la herramienta Cochrane de Riesgo de Sesgo. Resultados: Se revisaron en su totalidad cuatro estudios. La mayoría de los efectos adversos del tratamiento del cáncer se deben a los regímenes de quimioterapia basados en taxanos. Los resultados evaluados incluyen, además del dolor, otros signos neuropáticos y su influencia en las actividades de la vida diaria. Los estudios variaron en términos de intervención y fase de tratamiento. Sólo uno de los estudios demostró un resultado significativamente positivo a favor del grupo de intervención. Conclusión: Los estudios clínicos aleatorizados aportan escasa evidencia sobre los efectos positivos de la intervención fisioterapéutica sobre el dolor neuropático periférico inducido por los tratamientos del cáncer de mama

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse / Avaliação genotóxica e citotóxica da venlafaxina em ensaio agudo e subcrônico em camundongos

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Antitumor and immunomodulatory activity of fucoidan from the brown alga Lessonia trabeculata (Lessoniaceae) on breast cancer spheroids / Actividad antitumoral e inmunomoduladora de fucoidan del alga parda Lessonia trabeculata (Lessoniaceae) en esferoides de cáncer de mama

Abstract Introduction: The therapeutic benefits of the brown algae fucoidan in the treatment of breast cancer have attracted considerable interest in recent years. However, research using spheroids which provide relevant results in trials for antitumor and immunomodulatory products because they adequately simulate the tumor microenvironment, is limited. Objective: To evaluate the antitumor and immunomodulatory activity of Lessonia trabeculata fucoidan (LtF), native to the Peruvian Sea, on two types of multicellular tumor spheroids. Methods: The study was conducted from January to December 2021. Two types of spheroides were elaborated: from 4T1 tumor cells (MTS), and from 4T1 tumor cells+mouse splenocytes (MTSs). The antitumor activity of LtF was evaluated in MTS by quantifying cell viability with MTT. Immunomodulatory activity was determined in MTSs using the IC50 for two types of treatment: simple, fucoidan alone (LtF) and combined, fucoidan+doxorubicin (LtF+Dox). Pro-inflammatory (TNF-α, IL-6) and anti-inflammatory (IL-10, TGF-β) cytokine production was quantified by sandwich ELISA 72 h after treatment. Dox was used as positive control in all assays. Results: LtF exerted antitumor activity as evidenced by increased necrotic zone and cell debris formation compared to the untreated control. Antitumor activity was concentration dependent between 100 and 6 000 μg/ml. In MTSs, simple treatment increased IL-6 and decreased IL-10 and TGF-β production. The combined treatment significantly reduced TGF-β production. In both treatments and Dox, there was an increase in IL-6 compared to the untreated control. The highest production of IL-10 and TGF-β was observed in the untreated control, compatible with a highly immunosuppressive tumor microenvironment. Conclusions: LtF is a good candidate for the treatment of breast cancer and can immunomodulate the tumor microenvironment alone or in combination with Dox.

Resumen Introduccción: Los beneficios terapéuticos del fucoidan de algas pardas en el tratamiento del cáncer de mama han despertado gran interés en los últimos años. Sin embargo, las investigaciones con esferoides son limitadas, éstos proporcionan resultados relevantes en ensayos de productos antitumorales e inmunomoduladores porque simulan adecuadamente el microambiente tumoral. Objetivo: Evaluar la actividad antitumoral e inmunomoduladora del fucoidan de Lessonia trabeculata (LtF), nativa del Mar Peruano, en dos tipos de esferoides tumorales multicelulares. Métodos: El estudio se realizó de enero a diciembre de 2021. Se elaboraron dos tipos de esferoides: con células tumorales 4T1 (MTS) y con células tumorales 4T1+esplenocitos de ratón (MTSs). La actividad antitumoral de LtF se evaluó en MTS cuantificando la viabilidad celular con MTT. La inmunomodulación se determinó en MTSs utilizando la IC50 para dos tipos de tratamiento: simple, fucoidan solo (LtF) y combinado, fucoidan+doxorubicina (LtF+Dox). La producción de citoquinas proinflamatorias (TNF-α, IL-6) y antiinflamatorias (IL-10, TGF-β) se cuantificó mediante ELISA sándwich 72 h post-tratamiento. En todos los ensayos se utilizó Dox como control positivo. Resultados: En los MTS, el LtF ejerció actividad antitumoral evidenciada por aumento de la zona necrótica y formación de restos celulares respecto al control no tratado. La actividad antitumoral fue concentración-dependiente entre 100 y 6 000 μg/ml. En los MTSs, con el tratamiento simple se incrementó IL-6 y disminuyeron IL-10 y TGF-β. El tratamiento combinado redujo significativamente la producción de TGF-β. Los dos tratamientos y Dox incrementaron IL-6 respecto al control no tratado. La mayor producción de IL-10 y TGF-β se observó en los no tratados, compatible con un microambiente tumoral altamente inmunosupresor. Conclusiones: El LtF es un buen candidato para tratar el cáncer de mama y puede inmunomodular el microambiente tumoral solo o en combinación con Dox.

¿Qué hay de nuevo en el tratamiento de amiloidosis por cadenas livianas? Parte 1: cadenas livianas / What is new in light chain amyloidosis treatment? Part 1: lightweight chains

La amiloidosis AL es una enfermedad debida al depósito, en órganos y tejidos, de fibrillas formadas por cadenas livianas producidas de forma patológica por plasmocitos clonales. Su tratamiento actualmente está orientado a erradicar el clon de células plasmáticas; este históricamente se extrapoló de tratamientos disponibles y estudiados para otras discrasias sanguíneas. En el año 2020, el Grupo de Estudio de Amiloidosis (GEA) confeccionó distintas guías de práctica clínica para el tratamiento de la amiloidosis AL. Desde entonces se han publicado ensayos clínicos que arrojan contundencia al conocimiento disponible hasta el momento, y están en desarrollo nuevas líneas de investigación que robustecen y estimulan el estudio en el área. En esta revisión se realiza una actualización de las guías existentes en lo que respecta al tratamiento de la amiloidosis por cadenas livianas.Como evidencia de relevancia, en el último año estuvieron disponibles resultados de ensayos clínicos que respaldan el uso de esquemas basados en daratumumab (un anticuerpo monoclonal anti-CD38+) para pacientes con diagnóstico reciente de amiloidosis AL como primera línea. Además, para el tratamiento de la amiloidosis AL refractaria o recaída, la disponibilidad de bibliografía respaldatoria es escasa y extrapolada del tratamiento del mieloma múltiple; sin embargo, actualmente existe evidencia de calidad para recomendar el uso de ixazomib, un inhibidor de proteosoma reversible por vía oral disponible en la Argentina desde 2020. Por último, se mencionan algunas líneas de investigación con otros anticuerpos monoclonales y terapéuticas basadas en el uso de CAR-T cells. (AU)

AL amyloidosis is a disease caused by the deposit in different organs and tissues of protein fibrils formed by light chains synthetized by pathological clonal plasma cells. Its treatment is currently aimed at eradicating this plasma cell clone and it has been historically extrapolated from available and validated treatments for other blood dyscrasias. In 2020, the Amyloidosis Study Group prepared different clinical practice guidelines for the treatment of AL amyloidosis.Since then, clinical trials have been published that confirm and strengthen the knowledge available up to now, and new lines of research are being developed that stimulate study in the area. In this review, an update of the existing guidelines regarding the treatment of AL amyloidosis is made. As relevant evidence, in the last year, results of clinical trials have been made available that support the use of regimens based on Daratumumab (an anti-CD38+ monoclonal antibody) for patients with newly diagnosed AL amyloidosis as first line therapy. In addition, for the treatment of refractory or relapsed AL amyloidosis, where the availability of supporting literature is scant and extrapolated from the treatment of multiple myeloma, there is currently quality evidence to recommend the use of ixazomib, an oral reversible proteasome inhibitor, only available in Argentina since 2020. Finally, some research lines exploring the efficacy of other monoclonal antibodies and therapeutic experiments based on the use of CAR-T cells are mentioned. (AU)

Protective Autophagy in 5-Fluorouracil-Resistant Colorectal Cancer Cells and ERK-RSK-ABCG2 Linkage / Autofagia Protectora en Células de Cáncer Colorrectal Resistentes al 5-Fluorouracilo y Enlace ERK-RSK-ABCG2

SUMMARY: To evaluate the anti-cancer effects of yeast extract on resistant cells, autophagy and necroptosis were investigated in 5-fluorouracil (5-FU)-resistant colorectal cancer cells. Further underlying characteristics on drug resistance were evaluated, focused on ERK-RSK-ABCG2 linkage. SNU-C5 and 5-FU resistant SNU-C5 (SNU-C5/5-FUR) colorectal cancer cells were adopted for cell viability assay and Western blotting to examine the anti-cancer effects of yeast extract. Yeast extract induced autophagy in SNU-C5 cells with increased Atg7, Atg12-5 complex, Atg16L1, and LC3 activation (LC3-II/LC3-I), but little effects in SNU-C5/5-FUR cells with increased Atg12-5 complex and Atg16L1. Both colorectal cancer cells did not show necroptosis after yeast extract treatment. Based on increased ABCG2 and RSK expression after yeast extract treatment, drug resistance mechanisms were further evaluated. As compared to wild type, SNU-C5/5-FUR cells showed more ABCG2 expression, less RSK expression, and less phosphorylation of ERK. ABCG2 inhibitor, Ko143, treatment induces following changes: 1) more sensitivity at 500 mM 5-FU, 2) augmented proliferation, and 3) less phosphorylation of ERK. These results suggest that protective autophagy in SNU-C5/5-FUR cells with increased ABCG2 expression might be candidate mechanisms for drug resistance. As the ERK responses were different from each stimulus, the feasible mechanisms among ERK-RSK-ABCG2 should be further investigated in 5-FU-resistant CRC cells.

Para evaluar los efectos anticancerígenos del extracto de levadura en células resistentes, se investigaron la autofagia y la necroptosis en células de cáncer colorrectal resistentes al 5-fluorouracilo (5-FU). Además se evaluaron otras características subyacentes de la resistencia a los medicamentos centrándose en el enlace ERK-RSK-ABCG2. Se usaron células de cáncer colorrectal SNU-C5 (SNU-C5/5-FUR) resistentes a SNU-C5 y 5- FU para el ensayo de viabilidad celular y la transferencia Western para examinar los efectos anticancerígenos del extracto de levadura. El extracto de levadura indujo autofagia en células SNU-C5 con mayor activación de Atg7, complejo Atg12-5, Atg16L1 y LC3 (LC3-II/LC3-I), pero pocos efectos en células SNU-C5/5-FUR con aumento de Atg12-5 complejo y Atg16L1. Ambas células de cáncer colorrectal no mostraron necroptosis después del tratamiento con extracto de levadura. Se evaluaron los mecanismos de resistencia a los medicamentos. en base al aumento de la expresión de ABCG2 y RSK después del tratamiento con extracto de levadura.En comparación con las de tipo salvaje, las células SNU-C5/5-FUR mostraron más expresión de ABCG2, menos expresión de RSK y menos fosforilación de ERK. El tratamiento con inhibidor de ABCG2, Ko143, induce los siguientes cambios: 1) más sensibilidad a 5-FU 500 mM, 2) proliferación aumentada y 3) menos fosforilación de ERK. Estos resultados sugieren que la autofagia protectora en células SNU-C5/5-FUR con mayor expresión de ABCG2 podría ser un mecanismo candidato para la resistencia a los medicamentos. Como las respuestas de ERK fueron diferentes de cada estímulo, los mecanismos factibles entre ERK-RSK- ABCG2 deberían investigarse más a fondo en células CCR resistentes a 5-FU.

In vivo Gonadoprotective Effects of Myricetin on Cisplatin- Induced Testicular Damage via Suppression of TLR4/NF-kB Inflammation Pathway and Heat-Shock Response / Efectos Gonadoprotectores in vivo de la Miricetina sobre el Daño Testicular Inducido por Cisplatino Mediante la Supresión de la Vía de Inflamación TLR4/NF-kB y la Respuesta al Choque Térmico

SUMMARY: The aim of this study is to reveal the gonadoprotective effects of myricetin (MYC), which has many biological properties, on cisplatin (CP)-induced testicular damage in rats. For this purpose, 40 male Wistar albino rats were divided into 4 groups as Control (group given no treatment), MYC (group given 5 mg/kg/i.p myricetin for 7 days), CP (group given 7 mg/kg/i.p cisplatin at 7th day) and MYC + CP (group given 5 mg/kg/i.p myricetin for 7 days before 7 mg/kg/i.p cisplatin injection). After administrations, testicular tissues of animals were extracted and processed according to tissue processing protocol. Hematoxylin & Eosin staining were performed to evaluate the histopathological changes and Johnsen'sTesticular Biopsy Score (JTBS) was applied and mean seminiferous tubule diameters (MSTD) were measured to compare experimental groups in terms of histopathological changes. Moreover, TLR4, NF-kB, HSP70 and HSP90 expression levels were detected by immunohistochemical staining and the density of immunoreactivity were measured to determine the difference in the expression levels of these factors among groups. Additionally, testicular apoptosis was detected via TUNEL assay. JTBS and MSTD data were significantly lower in CP group compared to other groups and MYC administrations significantly protects testicular tissue against CP-induced damage. Moreover, TLR4, NF-kB, HSP70 and HSP90 expressions and apoptotic cells significantly increased in the CP group (p<0.05). However, MYC administrations exerted a strong gonadoprotective effect on testicular tissue in terms of these parameters in MYC+CP group (p<0.05). According to our results, we suggested that MYC can be considered as a protective agent against cisplatin-induced testicular damage.

El objetivo de este estudio es revelar los efectos gonadoprotectores de la miricetina (MYC), que tiene muchas propiedades biológicas, sobre el daño testicular inducido por cisplatino (CP) en ratas. Para este propósito, se dividieron 40 ratas albinas Wistar macho en 4 grupos: Control (grupo que no recibió tratamiento), MYC (grupo que recibió 5 mg/kg/i.p de miricetina durante 7 días), CP (grupo que recibió 7 mg/kg/i.p de cisplatino al séptimo día) y MYC + CP (grupo que recibió 5 mg/ kg/i.p de miricetina durante 7 días antes de la inyección de 7 mg/ kg/i.p de cisplatino). Después de las administraciones, se extrajeron y procesaron tejidos testiculares de animales según el protocolo de procesamiento de tejidos. Se realizó tinción con hematoxilina y eosina para evaluar los cambios histopatológicos y se aplicó la puntuación de biopsia testicular de Johnsen (JTBS) y se midieron los diámetros medios de los túbulos seminíferos (MSTD) para comparar los grupos experimentales en términos de cambios histopatológicos. Además, los niveles de expresión de TLR4, NF-kB, HSP70 y HSP90 se detectaron mediante tinción inmunohistoquímica y se midió la densidad de inmunorreactividad para determinar la diferencia en los niveles de expresión de estos factores entre los grupos. Además, se detectó apoptosis testicular mediante el ensayo TUNEL. Los datos de JTBS y MSTD fueron significativamente más bajos en el grupo CP en comparación con otros grupos y las administraciones de MYC protegen significativamente el tejido testicular contra el daño inducido por CP. Además, las expresiones de TLR4, NF-kB, HSP70 y HSP90 y las células apoptóticas aumentaron significativamente en el grupo CP (p<0,05). Sin embargo, las administraciones de MYC ejercieron un fuerte efecto gonadoprotector sobre el tejido testicular en términos de estos parámetros en el grupo MYC+CP (p<0,05). Según nuestros resultados, sugerimos que MYC puede considerarse como un agente protector contra el daño testicular inducido por cisplatino.

Toxicidad pulmonar secundaria a bleomicina. Reporte de un caso / Pulmonary Toxicity Secondary to Bleomycin. A Case Report

La toxicidad pulmonar por antineoplásicos es muy variable dependiente del grupo far-macológico; la bleomicina es uno de los medicamentos en los que se ha reportado este evento. Este citostático puede lesionar el endotelio pulmonar y el epitelio alveolar para llevar a un proceso inflamatorio y fibrótico del intersticio con repercusiones potencial-mente fatales.A continuación, se presenta un caso de enfermedad intersticial tipo neumonía organi-zada asociada a bleomicina en un paciente de 68 años con diagnóstico linfoma Hodg-kin clásico de tipo esclerosis nodular, con estudio imagenológico normal previo al tratamiento

Antineoplastic pulmonary toxicity is highly variable depending on the pharmacological group; bleomycin is one of the drugs in which this event has been reported. This cyto-static can injure the pulmonary endothelium and the alveolar epithelium to lead to an in-flammatory and fibrotic process of the interstitium with potentially fatal repercussions. The following is a case of interstitial disease type organizing pneumonia associated with bleomycin in a 68-year-old patient diagnosed with classical Hodgkin lymphoma of nodular sclerosis type, with imaging study prior to normal treatment

Alterações bucais associadas ao tratamento antineoplásico e a importância da assistência odontológica ao paciente oncológico: uma revisão integrativa / Oral alterations associated with antineoplastic treatment and the importance of dental care for oncology patients: an integrative review / Alteraciones orales asociadas al tratamiento antineoplásico y la importancia de la atención dental en pacientes oncológicos: una revisión integrativa

O tratamento oncológico por meio da quimioterapia e radioterapia consiste em destruir ou impedir o crescimento das células tumorais, visando a cura ou controle da doença. No entanto, esses tratamentos podem ocasionar danos às células saudáveis e consequentes efeitos colaterais, especialmente na cavidade oral, causando alterações como: mucosite, xerostomia, disgeusia, infecções orais, trismo e osteorradionecrose. Objetivo:Sumarizar estudos sobre a importância da prevenção ecuidado das alterações bucais no manejo odontológico a pacientes em tratamento oncológico.Metodologia:Revisão integrativa, a partir da identificação do tema e elaboração da questão norteadora com busca sistematizada da literatura realizada entre os meses de setembro e novembro de 2022. Foram realizadas buscasnas bases de dados da Biblioteca Virtual em Saúde, Google Acadêmicoe PubMed, excluindo-se artigos publicados há mais de cinco anos.Resultados:Obteve-se uma amostra final de seteestudos, após aplicação dos critérios de inclusão e exclusão.Houve concordância entre todos eles acerca das alterações bucais durante o tratamento oncológico, enfatizando a necessidade de assistência odontológica nesses pacientes antes, durante e após a terapia antineoplásica, além deminimizar efeitos desta intervenção. Conclusões:A atuação do cirurgião-dentista no cuidado aos pacientes oncológicos tem grande relevância, uma vez que as condições de saúde bucal impactam a qualidade de vida desses indivíduos. Em suma, o presente estudo contribuino entendimento das alterações bucais e cuidados para o bem-estar do paciente (AU).

Oncologicaltreatment through chemotherapy and radiotherapy consists of destroying or preventing the growth of tumor cells, aiming at curing or controlling the disease. However, these treatments can cause damage to healthy cells and consequent side effects, especially in the oral cavity, causing changes such as: mucositis, xerostomia, dysgeusia, oral infections, trismus and osteoradionecrosis. Objective:To summarize studies on the importance of prevention and care for oral changes in the dental management for patients undergoing oncologicaltreatment.Methodology:Integrative reviewfrom theidentification of the theme and elaboration of the guiding question with a systematic search of the literature carried out between September and November 2022. They were carried out searchesin the Virtual Health Librarydatabase, Google Scholar and PubMed, excluding articles published more than five years ago.Results:A final sample of 07 studies was obtained, after applying the inclusion and exclusion criteria. There was agreement among all of them about oral changes during cancer treatment, emphasizing the need for dental care in these patients before, during and after antineoplastic therapy, in addition to minimizing the effects of this intervention.Conclusions:The performance of the dental surgeon in the care of cancer patients is of great relevance, since oral health conditions impact the quality of life of these individuals. In short, the presentstudy contributesto the of oral changesand care for the patient's well-being (AU).

El tratamiento oncológicopor mediodequimioterapia y radioterapia consiste en destruir o impedir el crecimiento de las células tumorales, visando lacurar o controla de la enfermedad. Sin embargo, estos tratamientos pueden causar daño a las células sanasy en consecuenciaefectos secundarios, especialmenteen la cavidad oral, causandoalteraciones como: mucositis, xerostomía, disgeusia, infecciones orales, trismoy osteorradionecrosis.Objetivo: Resumir estudios acerca de la importancia de la prevención y cuidados de las alteracionesorales en el manejo dental apacientes en tratamiento oncológico.Metodología: Revisión integrativa, apartir de la identificación detema y elaboración de la pregunta guía con buscasistematizadade la literatura realizada entre los meses de septiembre y noviembre de 2022. Fueron realizadas búsquedas en las bases de datos de la Biblioteca Virtual en Salud, Google Académico y PubMed, excluyéndoseartículos publicados hace más de cinco años. Resultados: Se obtuvo una muestra final de siete estudios, después aplicaciones de los criterios de inclusión y exclusión. Hubo concordancia entre todos acerca de las alteracionesorales durante el tratamiento oncológico, enfatizando la necesidad de asistencia odontológica en esespacientes antes, durante y después de la terapia antineoplásica, además de minimizar efectos de esta intervención.Conclusiones: La actuación del cirujano dentistaen el cuidado a lospacientes oncológicos tienegran relevancia, una vez que las condiciones de salud oral impactan la calidad de vida de los individuos. En suma, el presente estudio contribuyeen el entendimientode las alteraciones orales y cuidados para el bienestar del paciente (AU).

Percepção do enfermeiro sobre os cuidados relacionados ao extravasamento de drogas antineoplásicas / Percepción de profesionales de enfermería sobre los cuidados relacionados con la extravasación de medicamentos antineoplásicos / Perception of the nursing professional about the care related to extravasation of antineoplastic drugs

Introdução: O uso de quimioterapias antineoplásicas atuando a nível celular com objetivo de tratar as neoplasias malignas, pode levar ao surgimento da toxicidade dermatológica, ocasionada pelo extravasamento, que consiste em um dano tecidual decorrente da infiltração, por via endovenosa, dos quimioterápicos aos tecidos circunvizinhos do local puncionado, necessitando de uma atuação profissional rápida e efetiva para evitar desfechos desfavoráveis para o paciente. Objetivo: Compreender a percepção do enfermeiro sobre os cuidados relacionados ao extravasamento de drogas antineoplásicas. Método: Trata-se de um estudo de campo, descritivo-exploratório com abordagem qualitativa, realizado com quinze enfermeiros que atuam no ambulatório e enfermarias da oncologia adulto de uma instituição hospitalar filantrópica localizada em Recife/Pernambuco, Brasil. Os dados foram coletados entre janeiro e dezembro de 2020 através de entrevista e passaram por análise de conteúdo temática-categorial. Resultados: Emergiram duas categorias. Cuidados preventivos: da identificação dos fatores de riscos à educação do paciente e equipe de saúde; Cuidados diretos: da identificação da ocorrência ao gerenciamento institucional do evento. Conclusão: Compreendeu-se que a percepção do enfermeiro destaca a importância do planejamento da assistência, incluindo a intervenção imediata, o registro do evento e o acompanhamento do paciente após o extravasamento, como forma de realizar um cuidado especializado e com maior segurança.

Introducción: El uso de quimioterapias antineoplásicas que actúan a nivel celular con el objetivo de tratar neoplasias malignas puede conducir a la aparición de toxicidad dermatológica. Esta es causada por extravasación, que consiste en daño tisular producto de la infiltración, por vía endovenosa, de los agentes quimioterápicos a los tejidos circundantes del sitio de punción. Lo anterior, requiere una actuación profesional rápida y eficaz para evitar resultados desfavorables para la persona. Objetivo: Comprender la percepción de profesionales de enfermería sobre el cuidado relacionado con la extravasación de fármacos antineoplásicos. Método: Se trata de un estudio de campo descriptivo-exploratorio con abordaje cualitativo, realizado con quince personas enfermeras que actúan en las salas de oncología de población adulta y ambulatoria de un hospital filantrópico ubicado en Recife/Pernambuco, Brasil. Los datos fueron recolectados entre enero y diciembre de 2020, a través de entrevistas y fueron sometidos a análisis de contenido por categorías temáticas. Resultados: Emergieron dos categorías: atención preventiva (desde la identificación de factores de riesgo hasta la educación de la persona y del equipo de salud) y atención directa (desde la identificación de la ocurrencia hasta la gestión institucional del evento). Conclusión: Se entendió que la percepción de la persona profesional de enfermería destaca la importancia de la planificación del cuidado, incluyendo la intervención inmediata, el registro de eventos y el seguimiento después de la extravasación, como forma de realizar cuidados especializados y con mayor seguridad.

Introduction: The use of antineoplastic chemotherapies acting at the cellular level with the aim of treating malignant neoplasms can lead to the emergence of dermatological toxicity caused by extravasation. This toxicity consists of tissue damage resulting from the infiltration, by intravenous route, of the chemotherapeutic agents to the surrounding tissues, requiring quick and effective professional action to avoid unfavorable outcomes for the patient. Objective: To understand the nurses' perception of care related to extravasation of antineoplastic drugs. Method: This is a descriptive-exploratory field study with a qualitative approach; it was carried out with fifteen nurses who work in the outpatient and adult oncology wards of a philanthropic hospital located in Recife/Pernambuco, Brazil. Data were collected between January and December 2020 through interviews and underwent thematic-category content analysis. Results: Two categories emerged: Preventive Care: from the identification of risk factors to the patient and health team education; and Direct Care: from the identification of the occurrence to the institutional management of the event. Conclusion: It was understood that the nurse's perception highlights the importance of care planning, including immediate intervention, event registration, and patient follow-up after extravasation, to perform specialized care and with greater safety.

Manejo de reações adversas dermatológicas em pacientes submetidos à terapia quimioterápica antineoplásica / Management of dermatological adverse reactions in patients undergoing antineoplastic chemotherapy

Objetivo: o presente estudo tem como objetivo reunir recomendações de cuidados considerando a prevenção e tratamento de lesões de pele induzidas pelo tratamento com quimioterápicos antineoplásicos, de acordo com os estudos e consensos atuais. Metodologia: realizou-se um estudo bibliográfico para levantamento das relações entre os principais fármacos antineoplásicos e suas intercorrências dermatológicas, bem como seus respectivos manejos, para subsidiar a orientação e aconselhamento aos profissionais de saúde que acompanham o paciente oncológico. Resultado: os principais problemas dermatológicos decorrentes do uso de antineoplásicos correspondem às lesões de pele, tais como a descoloração, hiperpigmentação, fotossensibilidade, eritemas, descamação e prurido. Também são recorrentes os efeitos adversos que acometem os pelos e cabelos, resultando em alopecia, e a modificação do crescimento e lesões nas unhas. Tratamentos específicos para cada caso são capazes de amenizar ou reverter os problemas. Conclusão: as reações adversas aos medicamentos envolvendo quimioterapia são frequentes na prática oncológica, e variam em termos de frequência e gravidade, atingindo diversos anexos cutâneos. O adequado manejo destes efeitos melhora a integridade da pele e demais estruturas, proporcionando a esses pacientes a melhoria da autoestima e da qualidade de vida.

Objective: the present study aims to gather care recommendations considering the prevention and treatment of skin lesions induced by treatment with antineoplastic chemotherapy, according to current studies and consensus. Methodology: a bibliographical study was carried out to survey the relationships between the main antineoplastic drugs and their dermatological intercurrences, as well as their respective management, to subsidize the guidance and counselling of health professionals who treat cancer patients. Result: the main dermatological problems arising from the use of antineoplastic agents correspond to skin lesions, such as discoloration, hyperpigmentation, photosensitivity, erythema, scaling and pruritus. Adverse effects that affect hair and body hair are also recurrent, resulting in alopecia, and the modification of growth and lesions on the nails. Specific treatments for each case can alleviate or reverse the problems. Conclusion: adverse drug reactions involving chemotherapy are frequent in oncology practice, and vary in terms of frequency and severity, affecting various skin appendages. Proper management of these effects improves the integrity of the skin and other structures, providing these patients with improved self-esteem and quality of life.

Perfil clínico-epidemiológico de pacientes pediátricos de um centro de oncohematologia de pernambuco / Clinical-epidemiological profile of pediatric patients at a center of oncohematology in Pernambuco / Perfil clínico-epidemiológico de pacientes pediátricos en un centro de oncohematología de Pernambuco

ntrodução:O câncer infantojuvenil corresponde a um grupo de várias doenças que têm em comum a proliferação descontrolada de células anormais e que pode ocorrer em qualquer local do organismo. Objetivo:Identificar os tipos de neoplasias mais frequentes na infância e adolescência e analisar o perfil clínico-epidemiológicodos pacientes. Metodologia:Estudo de transversal exploratório, de natureza aplicada com análise documental, realizado no Centro de Oncohematologia Pediátrica do Hospital Universitário Oswaldo Cruz, Recife, Pernambuco.Foram incluídos crianças e adolescentes diagnosticados com neoplasia e tratados por terapia antineoplásica.Os critérios de exclusão foram crianças e adolescentes normorreativas e/ou com doenças sistêmicas; prontuários ilegíveis ou com falta de informações clínicas.Resultados:Identificou-se que 54,21% dos pacientes eram dosexo feminino, seguido por 44,86% do sexo masculino.A faixa etária prevalente no estudo foi o de crianças de 5 a 14 anos (54,21%), ainda sobre o perfil dos pacientes, identificou-se que população autodeclarada como negra foi a mais prevalente representando 44,86% do total, seguido dos brancos com 43,93%. O diagnóstico que prevaleceu foi o de Leucemia Linfoide Aguda(23,36%), seguido pela Retinoblastoma (7,48%) e pela Rabdomiossarcoma embrionário (6,54%), e consequentemente o local da neoplasia primária que prevaleceu foi a Medula óssea (27,10%) seguido do olho (10,28%), deste total nota-se que o tratamento antineoplásico mais utilizado foi a quimioterapia (40,19%) seguido da quimioterapia associada à radioterapia(12,15%) e pela quimioterapia associada a cirurgia (10,28%). Conclusões:A leucemia linfoide aguda foi a neoplasia mais frequente na infância e adolescência, com prevalência na idade entre 5 e 14 anos, no sexo feminino e na etnia negra. A terapia antineoplásica mais utilizada foi a quimioterapia, seguida da associação entre quimioterapia e radioterapia (AU).

Introduction:Childhood cancer correspondsto a group of several diseases that have in common the uncontrolled proliferation of abnormal cells and that can occur anywhere in the body. Objective:Identify the most frequent types of neoplasms in childhood and adolescence and analyze the clinical-epidemiological profile of patients. Methodology:Exploratory cross-sectional study, applied in nature with document analysis, carried out at the Pediatric Oncohematology Center of Oswaldo Cruz University, Recife, Pernambuco. Children and adolescents diagnosed with neoplasia and treated with antineoplastic therapy were included. Exclusion criteria were normoreactive children and adolescents and/or with systemic diseases; illegible medical records or lacking clinical information. Results:It was identified that54.21% of the patients were female, followed by 44.86% male. The prevalent age group in the study was children from 5 to 14 years old (54.21%), still regarding the patients'profile , it was identified that the population self-declared as black was the most prevalent, representing 44.86% of the total, followed by of whites with 43.93%. The diagnosis that prevailed was Acute Lymphoid Leukemia (23.36%), followed by Retinoblastoma (7.48%) and Embryonic Rhabdomyosarcoma (6.54%), and consequently,the site of the primary neoplasm that prevailed was Bone marrow (27.10%) followed by the eye (10.28%), of this total it is noted that the most used anticancer treatment was chemotherapy (40.19%) followed by chemotherapy associated with radiotherapy (12.15% ) and chemotherapy associated with surgery (10.28%). Conclusions:Acute lymphoblastic leukemia was the most frequent neoplasm in childhood and adolescence, with a prevalence between 5 and 14 years of age, in females,and black ethnicity. The most used antineoplastic therapy was chemotherapy, followed by the association between chemotherapy and radiotherapy (AU).

ntroducción: El cáncer infantil corresponde a un grupo de varias enfermedades que tienen en común la proliferación descontrolada de células anormales y que pueden presentarse en cualquier parte del cuerpo. Objetivo: Identificar los tipos de neoplasias más frecuentes en la infancia y la adolescencia y analizar el perfil clínico-epidemiológico de los pacientes. Metodología: Estudio transversal exploratorio, aplicado en la naturaleza con análisis de documentos, realizado en el Centro de Oncohematología Pediátrica del Hospital Universitario Oswaldo Cruz, Recife, Pernambuco. Se incluyeron niños y adolescentes con diagnóstico de neoplasia y tratados con terapia antineoplásica. Los criterios de exclusión fueron niños y adolescentes normorreactivos y/o con enfermedades sistémicas; registros médicos ilegibles o carentes de información clínica. Resultados: Se identificó que el 54,21% de los pacientes eran del sexo femenino, seguido del 44,86% del masculino. El grupo etario prevalente en el estudio fueron los niños de 5 a 14 años (54,21%), en cuanto al perfil de los pacientes, se identificó que la población autodeclarada afrodescendiente fue la más prevalente, representando el 44,86% del total, seguido de los blancos con un 43,93%. El diagnóstico que predominó fue Leucemia Linfoide Aguda (23,36%), seguido de Retinoblastoma (7,48%) yRabdomiosarcoma Embrionario (6,54%), y en consecuencia el local de la neoplasia primaria que predominó fue Médula Ósea (27,10%) seguido de ocular (10,28%), de este total se destaca que el tratamiento anticancerígeno más utilizado fue la quimioterapia (40,19%) seguida de la quimioterapia asociada a radioterapia (12,15%) y la quimioterapia asociada a cirugía (10,28%). Conclusiones: La leucemia linfoblástica aguda fue la neoplasia más frecuente en la infancia y la adolescencia, con prevalencia entre los 5 y los 14 años, en el sexo femenino y en la etnia negra. La terapia antineoplásica más utilizada fue la quimioterapia, seguida de la asociación entre quimioterapia y radioterapia (AU).

Use of artificial intelligence to predict response to neoadjuvant chemotherapy in breast cancer

:Breast cancer is the object of thousands of studies worldwide. Nevertheless, few tools are available to corroborate prediction of response to neoadjuvant chemotherapy. Artificial intelligence is being researched for its potential utility in several fields of knowledge, including oncology. The development of a standardized Artificial intelligence-based predictive model for patients with breast cancer may help make clinical management more personalized and effective. We aimed to apply Artificial intelligence models to predict the response to neoadjuvant chemotherapy based solely on clinical and pathological data. Methods: Medical records of 130 patients treated with neoadjuvant chemotherapy were reviewed and divided into two groups: 90 samples to train the network and 40 samples to perform prospective testingand validate the results obtained by the Artificial intelligence method. Results: Using clinicopathologic data alone, the artificial neural network was able to correctly predict pathologic complete response in 83.3% of the cases. It also correctly predicted 95.6% of locoregional recurrence, as well as correctly determined whether patients were alive or dead at a given time point in 90% of the time. To date, no published research has used clinicopathologic data to predict the response to neoadjuvant chemotherapy in patients with breast cancer, thus highlighting the importance of the present study. Conclusions: Artificial neural network may become an interesting tool for predicting response to neoadjuvant chemotherapy, locoregional recurrence, systemic disease progression, and survival in patients with breast cancer (AU)

Carcinogenic drug exposure among health-sector workers: the need for exposure assessment and surveillance / Exposición a medicamentos cancerígenos en trabajadores del sector de la salud: necesidad de evaluación y vigilancia de la exposición / Exposição a fármacos carcinogênicos entre profissionais de saúde: necessidade de avaliação e vigilância da exposição

ABSTRACT Antineoplastic drugs (ANDs) used for chemotherapy can cause secondary cancers in treated patients and can pose carcinogenic risks to health-sector workers anywhere along these drugs' life cycle in a facility, from production to patient administration. Several PAHO/WHO Collaborating Centers (CCs) have experience addressing these hazards in the health sector. The objectives of this report are four-fold: 1) Provide an overview of longstanding research and prevention efforts, led by PAHO/WHO and its Occupational Health CCs, aimed at reducing the burden of occupational cancer in the Americas; 2) Discuss how robust AND exposure assessment and educational/outreach work by PAHO CCs can form the basis of exposure mitigation efforts among health-sector workers; 3) Through the presentation of original AND exposure assessment data from a pharmaceutical compounding facility in Chile, highlight relatively inexpensive methods by which such data can be generated; and 4) Discuss how effective, periodic environmental surveillance in healthcare facilities results in the identification of AND contamination in the work environment and enables the implementation of low-cost, high-impact interventions to reduce the risk of occupational cancer in health-sector workers, including in limited-resource settings. The risk of health-sector worker exposure to ANDs and other hazardous drugs is an important issue for inclusion within PAHO/WHO's broader efforts at reducing the impact of occupational cancer in the Americas. This report demonstrates that a wide range of accessible AND-exposure mitigation strategies are feasible at both a facility and a national policy level across the hemisphere.

RESUMEN Los medicamentos antineoplásicos empleados en quimioterapia pueden causar distintos tipos de tumores secundarios en pacientes tratados y presentar riesgos cancerígenos para los trabajadores del sector de la salud en cualquier momento del ciclo de vida de estos medicamentos en las instalaciones, desde su producción hasta su administración al paciente. Varios centros colaboradores de la OPS/OMS tienen experiencia en cuanto a cómo abordar estos peligros en el sector de la salud. Este informe persigue cuatro objetivos: 1) ofrecer una visión general de la labor de investigación y prevención de larga data, liderada por la OPS/OMS y sus centros colaboradores de salud ocupacional, encaminada a reducir la carga del cáncer ocupacional en la Región de las Américas; 2) abordar cómo una evaluación sólida de la exposición a los medicamentos antineoplásicos y la labor educativa y divulgativa de los centros colaboradores de la OPS pueden sentar las bases de los esfuerzos de mitigación de la exposición en los trabajadores del sector de la salud; 3) mediante la presentación de datos originales sobre la evaluación de la exposición a los medicamentos antineoplásicos en una instalación de compuestos farmacéuticos en Chile, destacar métodos relativamente asequibles gracias a los cuales se pueden recopilar dichos datos; y 4) examinar cómo la vigilancia ambiental efectiva y periódica en los centros de salud permite detectar casos de contaminación de medicamentos antineoplásicos en el entorno de trabajo y facilita la ejecución de intervenciones de bajo costo y alto impacto para reducir el riesgo de cáncer ocupacional en los trabajadores del sector de la salud, incluso en entornos de recursos limitados. El riesgo de exposición de los trabajadores del sector de la salud a los medicamentos antineoplásicos y otros medicamentos peligrosos es una cuestión importante para su inclusión en los esfuerzos más amplios de la OPS/OMS para reducir los efectos del cáncer ocupacional en la Región de las Américas. En este informe se demuestra que una amplia gama de estrategias accesibles de mitigación de la exposición a los medicamentos antineoplásicos es factible tanto a nivel de las instalaciones como de las políticas nacionales en toda la Región.

RESUMO Os medicamentos antineoplásicos usados para quimioterapia podem causar cânceres secundários em pacientes tratados e apresentar riscos carcinogênicos aos profissionais de saúde em qualquer momento do ciclo de vida desses fármacos dentro de um estabelecimento, desde sua produção até a administração ao paciente. Vários centros colaboradores da OPAS/OMS têm experiência em lidar com esses riscos no setor de saúde. Este relatório tem quatro objetivos: 1) fornecer uma visão geral dos esforços de longa data em pesquisa e prevenção liderados pela OPAS/OMS e por seus centros colaboradores de saúde ocupacional, cuja meta é reduzir a carga do câncer ocupacional nas Américas; 2) discutir como uma avaliação robusta da exposição aos antineoplásicos e o trabalho de extensão/educacional dos centros colaboradores da OPAS/OMS podem embasar os esforços de mitigação da exposição entre os profissionais de saúde; 3) por meio da apresentação de dados originais de avaliação da exposição a antineoplásicos obtidos de uma central de manipulação de medicamentos no Chile, destacar métodos relativamente econômicos para gerar esse tipo de dados; e 4) discutir como a vigilância ambiental eficaz e periódica em estabelecimentos de saúde resulta na identificação de contaminação por antineoplásicos no ambiente de trabalho e permite a implementação de intervenções de baixo custo e alto impacto para reduzir o risco de câncer ocupacional em profissionais de saúde, inclusive em contextos de recursos limitados. O risco de exposição dos profissionais de saúde aos medicamentos antineoplásicos e outros fármacos perigosos é uma questão importante a ser incluída nos esforços mais amplos da OPAS/OMS de reduzir o impacto do câncer ocupacional nas Américas. Este relatório demonstra a viabilidade de uma ampla gama de estratégias acessíveis de mitigação da exposição aos antineoplásicos, tanto no nível das instituições quanto no âmbito de políticas nacionais em todo o hemisfério.

Oral mucositis and microbial status in acute lymphoblastic leukemia subjects undergoing high-dose chemotherapy

Aim: To assess oral microbial status in patients with acute lymphoblastic leukemia (ALL) undergoing high-dose chemotherapy and to unravel possible associations between nosocomial pathogens and the establishment of chemotherapy-induced oral mucositis (CIOM). Methods: Oral mucosa, saliva, and peripheral blood samples were collected from 46 ALL subjects one day prior to chemotherapy (D0) and 2 weeks after treatment initiation (D14). Clinical intraoral inspection was performed by a single practitioner, with mucositis classification performed according to the WHO oral toxicity scale. Blood components were quantified by automatic flow cytometry, while oral Staphylococcus aureus and Pseudomonas aeruginosa were detected by Polymerase Chain Reaction with species-specific primers. Associations among bacteria and clinical findings were determined by Fisher's Exact test, longitudinal bacterial changes by paired Macnemar, and correlations among blood parameters and mucositis status or bacteria via Mann-Whitney. Results: S. aureus displayed higher detection rates at D14 (p < 0.05) and was positively associated with mucositis, adoption of a non-solid diet (all p < 0.001), nausea and fever (all p < 0.05). Conversely, P. aeruginosa did not correlate to CIOM clinical parameters. At the systemic standpoint, lower hemoglobin levels associated with CIOM and fever events (all p < 0.01). Conclusion: The study evidences S. aureus as a potential pathogen in ALL-CIOM, reaffirming microbial control as an important preventive measure during high-dose immunosuppressive therapy. The weight of non-white-blood-cell parameters should be validated as novel CIOM biomarkers in prospective research

Clinical tolerability and pharmacokinetics of troxacitabine / 中华肿瘤杂志

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).

TRPV1 participates in the protective effect of propolis on colonic tissue of ulcerative colitis / 中南大学学报(医学版)

OBJECTIVES@#Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly characterized by inflammation, ulceration and erosion of colonic mucosa and submucosa. Transient receptor potential vanilloid 1 (TRPV1) is an important mediator of visceral pain and inflammatory bowel disease. This study aims to investigate the protective effect of water soluble propolis (WSP) on UC colon inflammatory tissue and the role of TRPV1.@*METHODS@#Male SD rats were randomly divided into 6 groups (n=8): a normal control (NC) group, an ulcerative colitis model (UC) group, a low-WSP (L-WSP) group, a medium-WSP (M-WSP) group, a high-WSP (H-WSP) group, and a salazosulfapyridine (SASP) group. The rats in the NC group drank water freely, and the other groups drank 4% dextran sulfate sodium (DSS) solution freely for 7 d to replicate the ulcerative colitis model. Based on the successful replication of the UC, the L-WSP, M-WSP, and H-WSP groups were given 50, 100, and 200 mg/kg of water-soluble propolis by gavage for 7 d, and the SASP group was given 100 mg/kg of sulfasalazine by gavage for 7 d. The body weight of rats in each group was measured at the same time every day, the fecal traits and occult blood were observed to record the disease activity index (DAI). After intragastric administration, the animals were sacrificed after fasted 24 h. Serum and colonic tissue were collected, and the changes of MDA, IL-6 and TNF-α were detected. The pathological changes of colon tissues were observed by HE staining, and the expression of TRPV1 in colon tissues was observed by Western blotting, immunohistochemistry, and immunofluorescence.@*RESULTS@#The animals in each group that drank DSS freely showed symptoms such as weight loss, decreased appetite, depressed state, and hematochezia, indicating that the model was successfully established. Compared with the NC group, DAI scores of other groups were increased (all P<0.05). MDA, IL-6, TNF-α in serum and colon tissues of the UC group were increased compared with the NC group (all P<0.01), and they were decreased after WSP and SASP treatment (all P<0.01). The results of showed that the colon tissue structure was obviously broken and inflammatory infiltration in the UC group, while the H-WSP group and the SASP group significantly improved the colon tissue and alleviated inflammatory infiltration. The expression of TRPV1 in colon tissues in the UC group was increased compared with the NC group (all P<0.01), and it was decreased after WSP and SASP treatment.@*CONCLUSIONS@#WSP can alleviate the inflammatory state of ulcerative colitis induced by DSS, which might be related to the inhibition of inflammatory factors release, and down-regulation or desensitization of TRPV1.

Therapeutic Properties of Flavonoids in Treatment of Cancer through Autophagic Modulation: A Systematic Review / 中国结合医学杂志

Cancers have high morbidity and mortality rates worldwide. Current anticancer therapies have demonstrated specific signaling pathways as a target in the involvement of carcinogenesis. Autophagy is a quality control system for proteins and plays a fundamental role in cancer carcinogenesis, exerting an anticarcinogenic role in normal cells and can inhibit the transformation of malignant cells. Therefore, drugs aimed at autophagy can function as antitumor agents. Flavonoids are a class of polyphenolic secondary metabolites commonly found in plants and, consequently, consumed in diets. In this review, the systematic search strategy was used, which included the search for descriptors "flavonoids" AND "mTOR pathway" AND "cancer" AND "autophagy", in the electronic databases of PubMed, Cochrane Library, Web of Science and Scopus, from January 2011 to January 2021. The current literature demonstrates that flavonoids have anticarcinogenic properties, including inhibition of cell proliferation, induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, impaired cell migration, invasion, tumor angiogenesis and reduced resistance to multiple drugs in tumor cells. We demonstrate the available evidence on the roles of flavonoids and autophagy in cancer progression and inhibition. (Registration No. CRD42021243071 at PROSPERO).