Polineuropatía axonal distal secundaria a nivolumab: reporte de caso / Distal axonal polineuropathy secondary to nivolumab: case report

Nivolumab es un anticuerpo monoclonal contra la proteína de muerte celular programada 1 (PD-1) y actúa como un inhibidor del punto de control inmunitario al interrumpir la interacción del receptor PD-1 con sus ligandos. Nivolumab se ha convertido en un tratamiento eficaz para cánceres avanzados como el melanoma. La colitis, la disfunción endocrina y la miastenia grave (MG) son eventos1 conocidos inducidos por nivolumab. Los eventos adversos neurológicos relacionados con el sistema inmunitario son raros y ocurren en < 1 % de los pacientes tratados en grandes ensayos clínicos2. En este estudio describimos un caso de neuropatía axonal distal después del tratamiento con nivolumab en un paciente con melanoma metastásico.

Nivolumab is a monoclonal antibody against the programmed cell death protein 1 (PD-1) and acts as an imune checkpoint inhibitor by disrupting the interaction of the PD-1 receptor with its ligands. Nivolumab has emerged as an effective treatment for advanced cancers such as melanoma. Colitis, endocrine dysfunction, and myasthenia gravis (MG) are known events1 induced by nivolumab. Immune-related neurological adverse events are rare, occurring in <1% of patients treated in large clinical trials. In this study, we describe a case of distal axonal neuropathy after nivolumab treatment in a patient with metastatic melanoma.

Ethnobotanical study of medicinal plants used for cancer treatment at the province of Nador, Morocco

Morocco has varied wealth of aromatic and medicinal plants (AMPs) which are commonly used for prevention and treatment of vario us diseases or as complementary therapy such for cancer diseases. An ethnobotanical study was carried out in the province of Nador, located northeast of Morocco. A total of 418 persons were interviewed, information about their profile, type of medicinal pl ants existing in this area, plant characteristics and uses of those existing plants. Results showed 35 species distributed in 23 families, the most represented were Lamiaceae (7), Apiaceae (5) and Fabaceae (3). This study revealed that the population mainl y used seeds (28%), leaves (26%), aerial parts (20%) and fruits (14%). Moreover, it has shown that Nerium oleander were used by the local population for cancer treatments. Biological activity of N. oleander showed an antimicrobial effect on Escherichia col i , Pseudomonas aeruginosa and Staphylococcus aureus

Marruecos tiene una riqueza vegetal muy variada de plantas aromáticas y medicinales (AMP) y se utilizan com únmente para la prevención y el tratamiento de diversas enfermedades o como terapia complementaria, como las enfermedades del cáncer. Se llevó a cabo un estudio etnobotánico en la provincia de Nador, situada al noreste de Marruecos. Se entrevistó a un tota l de 418 personas, información sobre su perfil, tipo de plantas medicinales existentes en esta zona, características de las plantas, usos de las plantas existentes, etc. Los resultados mostraron una alta riqueza de especies de 35 especies distribuidas en 2 3 familias, las más representadas fueron Lamiaceae (7), Apiaceae (5) y Fabaceae (3). Este estudio reveló que la población utilizó preferentemente semillas (28%), hojas (26%), partes aéreas (20%) y frutos (14%). Además, se ha demostrado que la población loc al utilizaba Nerium oleander para tratamientos contra el cáncer. La actividad biológica de N. oleander mostró un efecto antimicrobiano sobre Escherichia coli , Pseudomonas aeruginosa y Staphylococcus aureus

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.

Flavonoid Myricetin as Potent Anticancer Agent: A Possibility towards Development of Potential Anticancer Nutraceuticals / 中国结合医学杂志

Good nutrition plays a crucial role in maintaining a balanced lifestyle. The beneficial effects of nutrition have been found to counteract nutritional disturbances with the expanded use of nutraceuticals to treat and manage cardiovascular diseases, cancer, and other developmental defects over the last decade. Flavonoids are found abundantly in plant-derived foods such as fruits, vegetables, tea, cocoa, and wine. Fruits and vegetables contain phytochemicals like flavonoids, phenolics, alkaloids, saponins, and terpenoids. Flavonoids can act as anti-inflammatory, anti-allergic, anti-microbial (antibacterial, antifungal, and antiviral) antioxidant, anti-cancer, and anti-diarrheal agents. Flavonoids are also reported to upregulate apoptotic activity in several cancers such as hepatic, pancreatic, breast, esophageal, and colon. Myricetin is a flavonol which is naturally present in fruits and vegetables and has shown possible nutraceutical value. Myricetin has been portrayed as a potent nutraceutical that may protect against cancer. The focus of the present review is to present an updated account of studies demonstrating the anticancer potential of myricetin and the molecular mechanisms involved therein. A better understanding of the molecular mechanism(s) underlying its anticancer activity would eventually help in its development as a novel anticancer nutraceutical having minimal side effects.

Elemene Antitumor Drugs Development Based on "Molecular Compatibility Theory" and Clinical Application: A Retrospective and Prospective Outlook / 中国结合医学杂志

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".

Fatores associados à punção venosa periférica difícil em adultos submetidos à quimioterapia antineoplásica / Factors associated with difficult peripheral venipuncture in adults undergoing antineoplastic chemotherapy / Factores asociados a la venopunción periférica difícil en adultos sometidos a quimioterapia antineoplásica

Objetivo: identificar os fatores associados à punção venosa periférica difícil em adultos submetidos à quimioterapia antineoplásica. Método: estudo transversal, observacional, analítico e quantitativo realizado em uma Unidade de Alta Complexidade em Oncologia (UNACON) da região amazônica brasileira. Os dados foram analisados por meio de estatística descritiva e inferencial, onde a razão de possibilidades foi calculada. Resultados: a maioria dos participantes foi do sexo feminino (64,6%), autodeclarados como pardos (51,2%). Em relação à localização do câncer, a maioria possuía a doença no aparelho digestório (46,4%) ou reprodutor (45,2%). Pacientes que tinham histórico de punção venosa difícil, veias não visíveis ou não palpáveis apresentaram mais chance de apresentar a punção venosa difícil (OR 1,6, 1,5 e 1,3, respetivamente). Conclusão: os preditores encontrados relacionados à punção venosa periférica difícil em pacientes adultos submetidos à quimioterapia antineoplásica foram: histórico de punção difícil e veias não visíveis ou não palpáveis(AU)

Objective: to identify factors associated with difficult peripheral venipuncture in adults undergoing antineoplastic chemotherapy. Method: cross-sectional, observational, analytical, and quantitative study carried out in a High Complexity Oncology Unit (UNACON) in the Brazilian Amazon region. Data were analyzed using descriptive and inferential statistics, where the odds ratio was calculated. Results: majority of participants were female (64.6%), self-declared as brown (51.2%). Regarding the location of the cancer, the majority had the disease in the digestive (46.4%) or reproductive (45.2%) systems. Patients who had a history of difficult venipuncture, non-visible or non-palpable veins were more likely to have difficult venipuncture (OR 1.6, 1.5 and 1.3, respectively). Conclusion: found predictors related to difficult peripheral venipuncture in adult patients undergoing antineoplastic chemotherapy were: history of difficult puncture and non-visible or non-palpable veins(AU)

Objetivo: identificar los factores asociados a la dificultad de la venopunción periférica en adultos sometidos a la quimioterapia antineoplásica. Método: estudio transversal, observacional, analítico y cuantitativo realizado en una Unidad de Oncología de Alta Complejidad (UNACON) en la Amazonía brasileña. Se analizaron los datos mediante estadística descriptiva e inferencial, donde se calculó el odds ratio. Resultados: la mayoría de los participantes era del sexo femenino (64,6%), se auto declaró morena (51,2%). En cuanto a la ubicación del cáncer, la mayoría tenía la enfermedad en el sistema digestivo (46,4%) o reproductivo (45,2%). Los pacientes que tenían antecedentes de venopunción difícil, venas no visibles o no palpables tenían más probabilidades de tener venopunción difícil (OR 1,6, 1,5 y 1,3, respectivamente). Conclusión: Los predictores encontrados relacionados con la punción venosa periférica difícil en pacientes adultos sometidos a quimioterapia antineoplásica fueron antecedente de punción difícil y venas no visibles o no palpables(AU)

Toxicidad sistémica y pulmonar por inmunoterapia: revisión narrativa a propósito de un caso / Systemic and pulmonary toxicity from immunotherapy: A narrative review and a clinical case report

En el último tiempo, la inmunoterapia se ha convertido en una opción terapéutica para diversos tipos de neoplasias, aumentando la sobrevida en muchos casos, pero también los efectos adversos asociados. Existen tres tipos de inmunoterapia utilizados en cáncer: Terapia de células T con receptor de antígeno quimérico (CAR-T), destacando como reacciones adversas el síndrome liberador de citoquinas (CRS) y el síndrome de neurotoxicidad (ICANS); Anticuerpos monoclonales (AcM), cuyos efectos adversos más comunes están relacionados con reacciones de hipersensibilidad; y los Inhibidores de puntos de control inmunitario (ICI) con toxicidad pulmonar claramente reportada. Para un correcto manejo de estas reacciones adversas se requiere un alto índice de sospecha, un adecuado diagnóstico diferencial y un tratamiento oportuno, basado principalmente en corticoides y guiado por criterios de gravedad. Se presenta el caso de un paciente con reacción granulomatosa sarcoidea posterior al uso de Nivolumab.

In recent times, immunotherapy has emerged as a therapeutic option for various neoplasms, significantly improving survival rates in many cases, albeit with associated adverse effects. There are three types of immunotherapy commonly used in cancer treatment: Chimeric Antigen Receptor T-cell Therapy (CAR-T), notable for adverse reactions such as Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS); Monoclonal Antibodies (mAbs), with the most common adverse effects being hypersensitivity reactions; and Immune Checkpoint Inhibitors (ICI), with well-documented pulmonary toxicity. Adequate management of these adverse reactions requires a high index of suspicion, accurate differential diagnosis, and timely treatment, primarily based on corticosteroids and guided by severity criteria. We present a case of a patient with granulomatous sarcoid-like reaction following the use of Nivolumab.

Neurotoxidad inducida por ifosfamida / Ifosfamide-induced neurotoxicity

Introducción: La ifosfamida es un agente alquilante utilizado para el tratamiento de enfermedades oncohematológicas. Entre sus eventos adversos agudos se encuentra la neurotoxicidad. Esta puede presentarse desde el inicio de la infusión hasta tres días después. El tratamiento consiste en suspender la administración y asegurar una adecuada hidratación. Objetivo: Describir eventos neurológicos asociados al uso de ifosfamida en pacientes pediátricos con enfermedades oncohematológicas. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo y transversal. Los datos se obtuvieron de historias clínicas de pacientes internados en el Hospital Garrahan que infundieron ifosfamida y desarrollaron síntomas neurológicos. Se analizaron edad, diagnóstico de base, dosis de ifosfamida, síntomas neurológicos y su relación con la infusión, tratamiento instaurado, exámenes complementarios y posibles factores de riesgo asociados. Resultados: Se registraron un total de catorce eventos neurológicos en doce pacientes, sin diferencia de sexo, con una mediana de edad de 9,5 años. La enfermedad de base más prevalente fue osteosarcoma. Las convulsiones fueron el síntoma más frecuente (50%), seguido de somnolencia y paresias. La combinación de ifosfamida y etopósido con/sin carboplatino se asoció en un 36% cada uno. El 64% desarrolló neurotoxicidad dentro de las primeras cuatro horas. Ningún paciente presentó alteraciones en los exámenes complementarios. Todos presentaron recuperación ad integrum. Conclusión: Este estudio brinda información acerca del tiempo de aparición de esta complicación, lo cual facilitará su detección precoz y tratamiento oportuno (AU)

Introduction: Ifosfamide is an alkylating agent used for the treatment of cancer. Among its acute adverse events is neurotoxicity. This can occur from the beginning of the infusion up to three days afterwards. Treatment consists of discontinuing administration and ensuring adequate hydration. Objective: To describe neurological events associated with the use of ifosfamide in children with cancer. Materials and methods: Observational, descriptive, retrospective, and cross-sectional study. Data were obtained from clinical records of patients admitted to the Garrahan Hospital who received ifosfamide infusion and developed neurological symptoms. Age, baseline diagnosis, ifosfamide dose, neurological symptoms and their relationship with the infusion, treatment, complementary tests, and possible associated risk factors were analyzed. Results: A total of fourteen neurological events were recorded in twelve patients, without difference in sex and with a median age of 9.5 years. The most prevalent underlying disease was osteosarcoma. Seizures were the most frequent symptom (50%), followed by drowsiness and paresis. The combination of ifosfamide and etoposide with/without carboplatin was associated in 36% each. Sixty-four percent developed neurotoxicity within the first four hours. None of the patients presented with abnormalities in the complementary examinations. All recovered ad integrum. Conclusion: This study provides information about the time of onset of this complication, which will facilitate its early detection and timely treatment (AU)

Inductores de ferroptosis para el tratamiento del cáncer / Ferroptosis Inducers for Cancer Treatment

Introducción: La ferroptosis es un proceso no apoptótico de muerte celular regulada que depende de la presencia de iones hierro en el medio intracelular. Se caracterizada por la acumulación de especies reactivas de lípidos oxidados y radicales libres en las membranas celulares. Los inductores e inhibidores de este proceso inciden de manera circunstancial en él, con cuya respuesta celular se trabaja en función de elaborar modelos para el tratamiento del cáncer. Objetivo: Profundizar en el proceso de ferroptosis con un enfoque hacia los inductores e inhibidores, el establecimiento de modelos biofisicoquímicos y las estrategias terapéuticas para el tratamiento del cáncer. Métodos: Se realizó una revisión de los estudios más significativos sobre el tema, publicados en la Web of Science, PubMed, EBSCO, y Scopus. Resultados: Gracias al novedoso descubrimiento de la ferroptosis como impulsor de la muerte de células tumorales para tratar el cáncer, se han comenzado a desarrollar modelos teóricos que simulan el comportamiento de estas células y la complejidad en sistemas biológicos; que permiten encontrar procedimientos alternativos y menos invasivos contra esta y otras enfermedades. Conclusiones: Los inductores e inhibidores tienen una función primordial a la hora de predecir la influencia en la sensibilidad a la ferroptosis; por lo que se indagó en los mecanismos de funcionamiento de estos, que facilitará la forma de inducir en mayor o menor grado la muerte celular y disminuir la población de células cancerígenas(AU)

Introduction: Ferroptosis is a non-apoptotic process of regulated cell death that depends on the presence of iron ions in the intracellular medium. It is characterized by the accumulation of reactive species of oxidized lipids and free radicals in cell membranes. The inducers and inhibitors of this process circumstantially affect it, whose cellular response is used to develop models for cancer treatment. Objective: To deepen the ferroptosis process focusing on inducers and inhibitors, the establishment of biophysiochemical models and therapeutic strategies for cancer treatment. Methods: A review was carried out of the most significant studies on the subject, published in the Web of Science, PubMed, EBSCO and Scopus. Results: Thanks to the novel discovery of ferroptosis as a conductor of tumor cell death to treat cancer, theoretical models have begun to be developed that simulate the behavior of these cells and the complexity in biological systems; that allow finding alternative and less invasive procedures against this and other diseases. Conclusions: Inductors and inhibitors have a primary role in predicting the influence on sensitivity to ferroptosis; therefore, the mechanisms of operation of these were investigated, which will facilitate the way to induce cell death to a greater or lesser degree and reduce the population of cancer cells(AU)

Can pumpkin save us of doxorubicin induced cardiotoxicity? / ¿Puede la calabaza salvarnos de la cardiotoxicidad inducida por doxorrubicina?

SUMMARY: Doxorubicin (DOX) is one of the drugs necessary for the treatment of the 10 most common types of cancer. The leading adverse effect limiting clinical use of DOX is cardiotoxicity. Given that literature data indicate a protective role of carotenoids in doxorubicin-induced toxicity, in our study we compared the cardioprotective effect of a mixture of pumpkin carotenoids and a commercially available antioxidant preparation. Animals were distributed in 8 groups (Control - S; NADES - N; Doxorubicin - Dox; Carotenoids - Car; CardiofortIN - CF; NADES-Doxorubicin - N-Dox; Carotenoids-Doxorubicin - Car-Dox; CardiofortIN-Doxorubicin - CF-Dox). Histological sections were stained with the hematoxylin-eosin (HE) and analyzed for the presence of myocardial damage by doxorubicin damage score (DDS). From the heart tissue homogenate were determined the intensity of lipid peroxidation and specific antioxidative enzyme activity (superoxide dismutase; catalase; glutathione S-transferase; glutathione peroxidase). In Car-DOX and CF-DOX groups, lipid peroxidation is significantly reduced compared to DOX group. Pretreatment of animals with carotenoids and in lesser extent with CardiofortIN led to higher antioxidative enzymes activity, compared to DOX group. Pretreated with carotenoids, only 50 % of animals had some degree of myocardial damage, and no animals had extensive damage. CardiofortIN pretreatment showed less protective effect. Pretreatment with carotenoid extract, reduced DDS significantly, so Car-DOX group has changes equivalent to mild myocardial damage. Although CardiofortIN pretreatment lowered DDS score values, animals still had moderate level of myocardium damage. This in vivo study and its findings indicate that carotenoids extracted from pumpkin may be a promising cardioprotective agent against doxorubicin induced cardiotoxicity, at least in part mediated through inhibition of DOX-induced oxidative stress.

La doxorrubicina (DOX) es uno de los fármacos necesarios para el tratamiento de los 10 tipos más comunes de cáncer. El principal efecto adverso que limita el uso clínico de DOX es la cardiotoxicidad. Debido a que los datos de la literatura indican un papel protector de los carotenoides en la toxicidad inducida por doxorrubicina, en nuestro estudio comparamos el efecto cardioprotector de una mezcla de carotenoides de calabaza y una preparación antioxidante disponible comercialmente. Los animales se distribuyeron en 8 grupos (Control - S; NADES - N; Doxorrubicina - Dox; Carotenoides - Car; CardiofortIN - CF; NADES-Doxorrubicina - N-Dox; Carotenoides-Doxorrubicina - Car-Dox; CardiofortIN- Doxorrubicina - CF-Dox). Las secciones histológicas se tiñeron con hematoxilina-eosina (HE) y se analizaron para detectar la presencia de daño miocárdico mediante la puntuación de daño por doxorrubicina (DDS). A partir del homogeneizado de tejido cardíaco se determinó la intensidad de la peroxidación lipídica y la actividad enzimática antioxidante específica (superóxido dismutasa, catalasa, glutatión S-transferasa, glutatión peroxidasa). En los grupos Car-DOX y CF-DOX, la peroxidación lipídica se redujo significativamente en comparación con el grupo DOX. El pre tratamiento de los animales con carotenoides y, en menor medida, con CardiofortlN condujo a una mayor actividad de las enzimas antioxidantes, en comparación con el grupo DOX. Al ser pre tratados con carotenoides, solo el 50 % de los animales tenían algún grado de daño miocárdico y ningún animal tenía daño extenso. El pre tratamiento con CardiofortIN mostró un efecto protector menor. El pre tratamiento con extracto de carotenoides redujo significativamente el DDS, por lo que el grupo Car-DOX mostró cambios equivalentes a un daño miocárdico leve. Aunque el pre tratamiento con CardiofortIN redujo los valores de la puntuación DDS, los animales aún tenían un nivel moderado de daño al miocardio. Este estudio in vivo y sus hallazgos indican que los carotenoides extraídos de la calabaza pueden ser un agente cardioprotector prometedor contra la cardiotoxicidad inducida por doxorrubicina, al menos en parte mediada por la inhibición del estrés oxidativo inducido por DOX.

Reações adversas medicamentosas em pacientes em quimioterapia e estratégias de intervenções / Adverse drug reactions in chemotherapy patients and intervention strategies / Reacciones adversas a medicamentos en pacientes quimioterápicos y estrategias de intervención

A quimioterapia do câncer pode ocasionar reações adversas medicamentosas (RAM), podendo resultar de interações medicamentosas (IM) e impactar na adesão. O presente estudo relatou as RAM apresentadas por pacientes em quimioterapia (QT) e propôs estratégias de intervenções. Este trabalho foi aprovado em comité de ética (5.160.503), sendo incluídos 23 pacientes em quimioterapia (oral- VO e/ou endovenosa- EV) e todos foram entrevistados. Recebiam apenas o QTEV, 20 pacientes e 2 QTEV e VO, a maioria em tratamento paliativo (50%), predomínio de estadiamento IV, sendo as doenças mais presentes de pâncreas (27,3%), estômago (22,7%) e mama (18,2%) e esquema mais usado foi Carboplatina + Paclitaxel. As principais comorbidades foram diabetes e hipertensão arterial. As interações medicamentosas foram classificadas em graves (45%), moderadas (55%) e intencional (75%), sendo necessário introdução de medicamentos de suporte (61%). Houve RAM de maior gravidade, neutropenia, sendo necessário a suspensão temporária, e de menor gravidade náuseas. Houve um óbito relacionado a evolução de doença e, talvez, o tratamento possa ter contribuído. Ao final, foram feitas as intervenções para cada caso e validado o formulário para a consulta farmacêutica a pacientes oncológicos.

Cancer chemotherapy can cause adverse drug reactions (ADRs), which can result from drug interactions (IM) and impact adherence. The present study reported the ADRs presented by patients undergoing chemotherapy (CT) and proposed intervention strategies. This work was approved by the ethics committee (5,160,503), and 23 patients on chemotherapy (oral-VO and/or intravenous-IV) were included and all were interviewed. Only received CTIV, 20 patients and 2 CTIV and VO, most in palliative treatment (50%), predominance of stage IV, being the most common diseases of pancreas (27.3%), stomach (22.7%) and breast (18.2%) and the most used regimen was Carboplatin + Paclitaxel. The main comorbidities were diabetes and arterial hypertension. Drug interactions were classified as severe (45%), moderate (55%) and intentional (75%), requiring the introduction of supportive drugs (61%). There were more severe ADRs, neutropenia, requiring temporary suspension, and less severe nausea. There was one death related to the evolution of the disease and, perhaps, the treatment may have contributed. At the end, interventions were made for each case and the form for the pharmaceutical consultation to cancer patients was validated.

La quimioterapia contra el cáncer puede causar reacciones adversas a los medicamentos (RAM), que pueden ser consecuencia de interacciones farmacológicas (IM) y repercutir en la adherencia. El presente estudio reportó las RAM presentadas por pacientes en quimioterapia (QT) y propuso estrategias de intervención. Este trabajo fue aprobado en comité de ética (5.160.503), se incluyeron 23 pacientes en quimioterapia (oral- VO y/o endovenosa-EV) y todos fueron entrevistados. Recibieron sólo QTEV, 20 pacientes y 2 QTEV y VO, la mayoría en tratamiento paliativo (50%), predominio de estadiaje IV, siendo las enfermedades más presentes las de páncreas (27,3%), estómago (22,7%) y mama (18,2%) y el esquema más utilizado fue Carboplatino + Paclitaxel. Las principales comorbilidades fueron la diabetes y la hipertensión arterial. Las interacciones farmacológicas se clasificaron como graves (45%), moderadas (55%) e intencionadas (75%), requiriendo la introducción de fármacos de apoyo (61%). La RAM más grave fue la neutropenia, que requirió la suspensión temporal, y la menos grave las náuseas. Hubo una muerte relacionada con la evolución de la enfermedad y, tal vez, el tratamiento pudo haber contribuido. Al final, se realizaron intervenciones para cada caso y se validó el formulario de consulta farmacéutica a pacientes oncológicos.

Conhecimento e percepção de enfermeiros frente à sedação paliativa na oncologia / Knowledge and perception of nurses dealing with palliative sedation in oncology / Conocimiento y percepción de los enfermeros frente a la sedación paliativa en oncología

Objetivo: compreender o conhecimento e a percepção de enfermeiros quanto à sedação paliativa em oncologia. Método: estudo qualitativo, exploratório e descritivo, com delineamento transversal. Participaram do estudo 16 enfermeiros atuantes na oncologia de um hospital de referência localizado ao norte do Rio Grande do Sul. A coleta de dados ocorreu por meio de entrevista gravada com duração de aproximadamente 10 minutos, sendo aplicado um roteiro de perguntas fechadas com a finalidade de caracterizar os enfermeiros participantes da pesquisa, e perguntas abertas e específicas para contemplar o objetivo do estudo. O método utilizado para o diagnóstico e verificação dos dados da pesquisa foi a análise de conteúdo de Bardin. Os dados foram analisados e codificados por meio do software NVivo 10, que gerou categorias de similaridade e correlações. Resultados: surgiram cinco categorias intituladas "Conhecimento sobre sedação paliativa; Percepção sobre sedação paliativa na oncologia; Sentimentos em relação à sedação paliativa aos pacientes oncológicos; Vivência em relação à sedação paliativa em pacientes oncológicos e Participação do enfermeiro no procedimento de sedação paliativa". Conclusão: o enfermeiro atua de forma efetiva e fundamental na prestação do cuidado e na avaliação do paciente em sedação paliativa, mas ainda encontram-se diversos obstáculos relacionados à participação na tomada de decisões. Evidencia-se a importância de novas pesquisas sobre a temática, como também a implementação de protocolos que subsidiem na indicação da sedação paliativa.(AU)

Objective: to understand the knowledge and perception of nurses dealing with palliative sedation in oncology. Method: this is a qualitative, exploratory, and descriptive study, with a cross-sectional design. The study included 16 nurses working in oncology at a reference hospital located in the north of Rio Grande do Sul. Data were collected through recorded interviews lasting approximately 10 minutes, with a script of closed questions being applied to characterize the nurses participating in the research, and open and specific questions, to contemplate the objective of the study. The method used for the diagnosis and verification of research data was Bardin's content analysis. Data were analyzed and coded using the NVivo 10 software, which generated categories of similarity and correlations. Results: five categories emerged: (i) Knowledge about palliative sedation; (ii) Perception of palliative sedation in oncology; (iii) Feelings regarding palliative sedation in cancer patients; (iv) Experience with palliative sedation in cancer patients; and (v) Participation of the nurse in the palliative sedation procedure. Conclusion: nurses act effectively and fundamentally in providing care and evaluating patients undergoing palliative sedation, but there are still several obstacles related to their participation in decision-making. The importance of new research on the subject is evident, as well as the implementation of protocols that support the indication of palliative sedation.(AU)

Objetivo: comprender el conocimiento y la percepción de los enfermeros sobre la sedación paliativa en oncología. Método: estudio cualitativo, exploratorio y descriptivo, con diseño transversal. El estudio abarcó 16 enfermeros que trabajaban en oncología en un hospital de referencia localizado en el norte de Rio Grande do Sul. La colecta de datos ocurrió por medio de entrevista grabada con duración aproximada de 10 minutos, siendo aplicado un guión de preguntas cerradas con la finalidad de caracterizar los enfermeros participantes de la investigación, y preguntas abiertas y específicas para contemplar el objetivo del estudio. El método utilizado para el diagnóstico y verificación de los datos de la investigación fue el análisis de contenido de Bardin. Los datos fueron analizados y codificados utilizando el software NVivo 10, que generó categorías de similitud y correlaciones. Resultados: surgieron cinco categorías tituladas "Conocimientos sobre sedación paliativa; Percepción de la sedación paliativa en oncología; Sentimientos con respecto a la sedación paliativa para pacientes con cáncer; Experiencia con sedación paliativa en pacientes oncológicos y participación de Enfermeros en el procedimiento de sedación paliativa". Conclusión: el enfermero actúa de forma eficaz y fundamental en la prestación del cuidado y en la evaluación del paciente en sedación paliativa, pero aún existen varios obstáculos relacionados con la participación en la toma de decisiones. Es evidente la importancia de seguir investigando sobre el tema, así como la implementación de protocolos que sustenten la indicación de la sedación paliativa.(AU)

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).

Aldehyde dehydrogenase 2 rs671 genetic polymorphisms are associated with chemotherapy-induced nausea and vomiting / 南方医科大学学报

OBJECTIVE@#To investigate the correlation between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and chemotherapy-induced nausea and vomiting (CINV).@*METHODS@#A total of 90 Chinese patients with malignant tumors receiving chemotherapy for the first time were recruited in this study. The occurrence of CINV was observed within 120 h after treatment with docetaxel and cis-platinum chemotherapy (DP regimen). The data of the patients (including age, gender, tumor stage, habitual alcohol consumption, motion sickness, morning sickness, and average sleep time prior to chemotherapy) were collected through a questionnaire. ALDH2 rs671 polymorphisms of the patients were analyzed using a multiple single nucleotide polymorphism genotyping, and the Hardy-Weinberg equation was used for genetic linkage analysis. The correlations between the factors including ALDH2 rs671 polymorphisms and the occurrence of CINV were analyzed.@*RESULTS@#The incidence of CINV was 48.9% among the patients receiving their first chemotherapy with DP regimen. Univariate analysis indicated that the genetic polymorphisms of ALDH2 rs671 were significantly correlated with the occurrence of CINV (P < 0.05). Multivariate logistic analysis indicated that ALDH2 rs671 mutation (OR: 3.019, 95% CI: 1.056-8.628, P < 0.05) and average sleep time prior to chemotherapy no longer than 6 h (OR: 2.807, 95% CI: 1.033-7.628, P < 0.05) were risk factors for CINV in patients with malignant tumors receiving the first chemotherapy with DP regimen.@*CONCLUSION@#ALDH2 gene mutation at rs671 is a risk factor contributing to the occurrence of CINV, and understanding of the underlying mechanism may help to more effectively control the occurrence of CINV.

Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms and strategies / 医学前沿

Immunotherapies based on immune checkpoint blockade (ICB) have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade. To date, immune checkpoint inhibitors (ICIs) of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy. Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers, however, a large subset of refractory patients presents poor responsiveness to ICB therapy; and the underlying mechanism remains elusive. Recently, numerous studies have revealed that metabolic reprogramming of tumor cells restrains immune responses by remodeling the tumor microenvironment (TME) with various products of metabolism, and combination therapies involving metabolic inhibitors and ICIs provide new approaches to cancer therapy. Nevertheless, a systematic summary is lacking regarding the manner by which different targetable metabolic pathways regulate immune checkpoints to overcome ICI resistance. Here, we demonstrate the generalized mechanism of targeting cancer metabolism at three crucial immune checkpoints (CTLA-4, PD-1, and PD-L1) to influence ICB therapy and propose potential combined immunotherapeutic strategies co-targeting tumor metabolic pathways and immune checkpoints.

Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients

INTRODUCTION@#Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity.@*METHOD@#Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases.@*RESULTS@#A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection.@*CONCLUSION@#This study demonstrates the benefit of early administration of the third dose among cancer patients.

Application of traditional Chinese medicine theory in modern traditional Chinese medicine nano-preparation: taking tumor treatment as an example / 中国中药杂志

With Zang-Fu organs, meridians, Qi and blood, and body fluid as the physiological and pathological basis, traditional Chinese medicine(TCM) theory is guided by the holistic concept and characterized by syndrome differentiation. It has made significant contributions to human health maintenance and disease prevention. Modern TCM preparation is developed on the basis of inheriting and developing TCM preparations using modern science and technology under the guidance of TCM theory. At present, the incidence and mortality of common tumors are increasing. TCM has rich clinical experience in the treatment of tumors. However, in the current stage, some TCM preparations have a tendency to deviate from the guidance of TCM theory. With the modernization of TCM, it is worth considering how TCM theory guides modern TCM preparations. Taking tumor treatment as an example, this paper introduced the development of TCM nano-preparation under the influence of modern nanotechnology, summarized the research on the development of modern TCM nano-preparation from the aspects of TCM holistic concept, TCM treatment principles, and TCM theory application, and discussed the application prospect of TCM nano-preparation in overall therapy, drug pairing, carrier selection, and targeted substance selection under the guidance of TCM theory. This paper provides new references for further developing the combination of tradition and modernization of TCM nano-preparation.

Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis / 中华医学杂志(英文版)

As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.

Advances in targeted delivery of proteolysis targeting chimeras in cancer therapy / 生物工程学报

Small-molecule anticancer drugs inhibited tumor growth based on targeted inhibition of specific proteins, while most of oncogenic proteins are "undruggable". Proteolysis targeting chimeras (PROTAC) is an attractive and general strategy for treating cancer based on targeted degradation of oncogenic proteins. This review briefly describes the peptide-based PTOTAC and small molecule-based PROTAC. Subsequently, we summarize the development of targeted delivery of PROTAC, such as targeting molecule-mediated targeted delivery of PROTAC, nanomaterial-mediated targeted delivery of PROTAC and controllable activation of small-molecular PROTAC prodrug. Such strategies show potential application in improving tumor selectivity, overcoming off-target effect and reducing biotoxicity. At the end, the druggability of PROTAC is prospected.

Research progress on anti-tumor effects by traditional Chinese medicine based on "soothing" or "blockage" regulation of tumor vessels / 中国中药杂志

Regulation of tumor vessels has become one of the most common strategies for clinical anti-tumor therapy. In recent years, studies have found that the anti-tumor effect of limotherapy, which routinely inhibits tumor angiogenesis, is not ideal and may even deteriorate the tumor microenvironment, causing tumor resistance and distal metastasis and increasing the risk of tumor metastasis and recurrence. However, the proper use of anti-angiogenic drugs can promote the normalization of tumor vessels, improve the structure and function of tumor vessels, increase the number of functional vessels in the tumor, and reduce the number of ineffective vessels. It is beneficial to promote the penetration of anti-tumor drugs into the tumor, improve the microenvironment of tumor hypoxia and immunosuppression, and enhance the anti-tumor effect. Traditional Chinese medicine(TCM) has a long history of understanding the etiology and pathogenesis of tumors and has accumulated rich experience in tumor treatment, with significant clinical advantages and broad application prospects. In this study, from the perspective of bidirectional "soothing" or "blockage" regulation of tumor vessels, the commonly used molecular targets were sorted out, and the research status of anti-tumor regulation of tumor vessels by monomer-single herb-compound(herb pair) of TCM in recent years was summarized. The research on the anti-tumor effects of TCM compounds and active ingredients by regulating tumor vessels combined with other therapies was analyzed and sorted out, so as to provide ideas for the clinical application of TCM in regulating functions and anti-tumor effects of tumor vessels.