Plan educativo a pacientes adultos que reciben citostáticos orales en el hogar / Educational plan for adult patients receiving oral cytostatics at home

La quimioterapia oral comenzó a surgir entre 1940 y 1950, se estima que al menos el 25% de los agentes neoplásicos existentes, están previstos para ser orales y de este modo se espera que su administración aumente en los próximos años. El uso de estas drogas oncológicas oral trae ventajas para el paciente como mayor comodidad, participación activa en su tratamiento, menor interferencia con la vida laboral y social y aumento de la calidad de vida. Objetivo: diseñar un programa educativo sobre el autocuidado en el tratamiento de quimioterapia oral en los pacientes adultos oncológicos en su hogar. diseño metodológico: se realizó una búsqueda de diferentes bases de datos como PUBMED, BVS, SCIELO, obteniendo como resultados 104 artículos de los cuales se seleccionan 10 que respondían a la pregunta de investigación. Resultados: tras el análisis de los artículos seleccionados podemos asegurar que educar a los pacientes y sus familias sobre quimioterapia oral, es un gran desafío que necesita de ajustes y mejoras permanentemente. La educación al paciente debe ser constante y permanente[AU]

Oral chemotherapy began to emerge between 1940 and 1950, it is estimated that at least 25% of existing neoplastic agents are expected to be oral and thus its administration is expected to increase in the coming years. The use of these oral cancer drugs brings advantages for the patient such as greater comfort, active participation in their treatment, less interference with work and social life and increased quality of life. Objective: To design an educational program on self-care in the treatment of oral chemotherapy in adult cancer patients at home. Methodological Design: A search of different databases such as Pubmed, BVS, Scielo was carried out, obtaining as results 104 articles of which 10 were selected that responded to the research question. Results: After analyzing the selected articles, we can ensure that educating patients and their families about oral chemotherapy is a great challenge that needs permanent adjustments and improvements. Patient education must be constant and permanent[AU]

A quimioterapia oral começou a surgir entre 1940 e 1950, estima-se que pelo menos 25% dos agentes neoplásicos existentes sejam orais e, portanto, sua administração deverá aumentar nos próximos anos. O uso desses medicamentos para o câncer oral NE | 22Plan educativo a pacientes adultos que reciben citostáticos orales en el hogar / Paola Natalia Oyola / Trabajo recibido: 2 de febrero 2021 · Trabajo aprobado: 29 de abril 2021traz vantagens para o paciente como maior conforto, participação ativa no seu tratamento, menor interferência no trabalho e na vida social e aumento da qualidade de vida. Objetivo: Elaborar um programa educacional sobre autocuidado no tratamento da quimioterapia oral em pacientes adultos com câncer no domicílio. Delineamento metodológico: Foi realizada uma busca em diferentes bases de dados como Pubmed, BVS, Scielo, obtendo-se como resultados 104 artigos dos quais 10 foram selecionados que responderam à questão de pesquisa. Resultados: Após a análise dos artigos selecionados, podemos assegurar que educar os pacientes e seus familiares sobre a quimioterapia oral é um grande desafio que necessita de ajustes e melhorias permanentes. A educação do paciente deve ser constante e permanente[AU]

Recent Advances and Trends in Chemical CPP-Drug Conjugation Techniques.

This review summarizes recent developments in conjugation techniques for the synthesis of cell-penetrating peptide (CPP)-drug conjugates targeting cancer cells. We will focus on small organic molecules as well as metal complexes that were used as cytostatic payloads. Moreover, two principle ways of coupling chemistry will be discussed direct conjugation as well as the use of bifunctional linkers. While direct conjugation of the drug to the CPP is still popular, the use of bifunctional linkers seems to gain increasing attention as it offers more advantages related to the linker chemistry. Thus, three main categories of linkers will be highlighted, forming either disulfide acid-sensitive or stimuli-sensitive bonds. All techniques will be thoroughly discussed by their pros and cons with the aim to help the reader in the choice of the optimal conjugation technique that might be used for the synthesis of a given CPP-drug conjugate.

Clinical and Prognostic Features of Essential Thrombocythemia: Comparison of 2001 WHO Versus 2008/2016 WHO Criteria in a Large Single-center Cohort.

BACKGROUND: According to 2008/2016 classification of the World Health Organization (WHO), a platelet (PLT) count ≥ 450 × 109/L, reduced from the previously published WHO 2001 indicated level ≥ 600 × 109/L, was considered the new PLT threshold for the diagnosis of essential thrombocythemia (ET). PATIENTS AND METHODS: To validate this important diagnostic change in a setting of current clinical practice, we retrospectively analyzed clinical and hematologic features at diagnosis and during follow-up of 162 patients with ET, diagnosed in our center from January 2008 to December 2017. We subdivided patients according to PLT value at baseline into Group A (PLT ≥ 600 × 109/L) (124 patients; 76.5%) and Group B (PLT ≥ 450 × 109/L < 600 × 109/L) (38 patients; 23.5%). RESULTS: Among clinical features, only the median value of leukocytes (P < .001) was significantly higher in Group A. Cytostatic treatment was administered in 103 patients, with a significantly higher rate in patients of group A (P < .001). After a median follow-up of 42.4 months (interquartile range, 22.1-70.6 months), 8 thrombotic events were recorded in the entire cohort, without differences between the 2 groups (P = .336). The 5-year overall survival (OS) of the entire cohort was 96.9% (95% confidence interval, 92.6%-100%), without differences between the 2 groups (P = .255). CONCLUSIONS: Our data indicate a substantial homogeneity among patients with ET regardless of the PLT count at diagnosis, thus confirming the usefulness of the 2008/2016 WHO diagnostic criteria.

Bomba elastomérica, aplicación de citostáticos en hospital de día oncológico / Elastomeric pump, application of cytostatics

Introducción. Este espacio es acerca del empleo de bombas elastoméricas en la administración de citostáticos de infusión continua con pacientes oncológicos que reciben tratamiento endovenoso, de infusión continua en el domicilio, mejorando así la calidad de vida del paciente, (esta experiencia es sólo en relación a aplicación de 5 fluorouracilo).Material y método: Al inicio, la primera dosis de quimioterapia, se realiza en el internado común para observar la tolerancia a la medicación, y en la segunda o tercera aplicación se realiza la misma en el hospital de día la primera parte del esquema, y luego se realiza la conexión de la bomba elastomérica que infundirá durante 46hs con el 5 fluorouracilo. El paciente asistirá al hospital oncológico para realizar la desconexión. Nuestro rol enfermero de contención y capacitación es necesario y así poder asegurar el buen manejo del dispositivo y brindar seguridad a los pacientes, para que logren un cuidado autónomo, seguro y eficaz. Para tal fin se les provee un instructivo. Poseer catéter implantable es requisito obligatorio para esta modalidad. Beneficios encontrados: es portátil y ergonómico, Mejora la movilidad y autocuidado, tasa de infusión exacta. Características de seguridad, que incluyan la protección del reservorio frente a posibles daños; Descomprimimos las internaciones, reducimos la espera de camas para internación de pacientes. Reducimos el uso de bombas comunes eléctricas del internado quedando a disponibilidad para otros pacientes hospitalizados. Dificultades halladas: Desconocimiento del paciente sobre el insumo (bomba). Inseguridad del paciente al encontrarse en el hogar por primera vez. Trámites burocráticos para autorización de la bomba. Conclusión: esta implementación innovadora requiere aún más aprendizaje, contamos con el apoyo del Departamento de Enfermería y la jefatura del servicio del Hospital de Día Oncológico, para el uso de las bombas. Para esta experiencia se utilizaron 10 bombas elastoméricas. Experiencia práctica, positiva para el paciente, además él mismo se compromete con su autocuidado y tratamiento, se logra evitar las exposiciones nosocomiales minimizando así los riesgos de contagios. Reducimos el uso de bombas comunes eléctricas del internado quedando a disposición para otros pacientes que lo requieran. Descomprimimos el internado común permitiendo así contar con más camas y mayor fluidez para satisfacer la demanda de internación de pacientes con otras patologías[AU]

Introduction. This space is about the use of elastomeric pumps in the administration of cytostatics of continuous infusion with cancer patients who receive intravenous treatment, of continuous infusion of qmt at home, thus improving the quality of life of the patient, (this experience is only in relation to to application of 5 fluorouracil). Material and method: At the beginning, the first dose of chemotherapy is carried out in the common boarding school to observe the tolerance to the medication, and in the second or third application it is carried out in the day hospital the first part of the scheme, and then the elastomeric pump is connected, which will infuse for 46 hours with 5 fluorouracil. The patient will attend the cancer hospital at hour 46 to perform the disconnection. Our nursing role of containment and training is necessary in order to ensure the proper handling of the device and provide safety to patients, so that they achieve autonomous, safe and effective care. For this purpose, an instruction manual is provided. Having an implantable catheter is a mandatory requirement for this modality; Benefits found: It is portable and ergonomic, Improves mobility and self-care, exact infusion rate. Safety features, including protection of the reservoir against possible damage; We decompressed hospitalizations, we reduced the wait for beds for patient admission. We reduced the use of common electric pumps in the internship, making them available for other hospitalized patients. Difficulties encountered: Lack of knowledge of the patient about the input (pump). Patient insecurity when being at home for the first time. Bureaucratic procedures for authorization of the pump. Conclusion. This innovative implementation requires even more learning, we have the support of the Nursing Department and the head of the Oncology Day Hospital service, for the use of the pumps. For this experiment 10 elastomeric pumps were used. Practical experience, positive for the patient, he also commits himself to self-care and treatment, it is possible to avoid nosocomial exposures, thus minimizing the risks of contagion. We reduce the use of common electric pumps in the internship by being available for other patients who require it. We decompress the common boarding school, thus allowing us to have more beds and greater fluidity to satisfy the demand for hospitalization of patients with other pathologies[AU]

Introdução. Este espaço trata da utilização de bombas elastoméricas na administração de citostáticos de infusão contínua em pacientes oncológicos que recebem tratamento intravenoso, de infusão contínua de qmtem casa, melhorando assim a qualidade de vida do paciente, (esta experiência é apenas emrelação a aplicação de 5 fluorouracil). Material e método: No início, a primeira dose de quimioterapia é realizada no colégio interno comum para observar a tolerânciaao medicamento, e na segunda ou terceira aplicação é realizada em hospital dia a primeira parte do esquema, e em seguida, a bomba elastomérica é conectada, que fará a infusão de 5 fluorouracil por 46 horas. O paciente comparecerá ao hospital oncológico na hora 46 para realizar o desligamento. Nosso papel de enfermagem de contenção e treinamento é necessário a fim de garantir o correto manuseio do dispositivo e dar segurançaaos pacientes, para que alcancem um cuidado autônomo, seguro e eficaz. Para tal, é fornecido um manual de instruções. Ter Um catéter implantável é requisito obrigatório para esta modalidade; Benefícios encontrados: É portátil e ergonômico, melhora a mobilidade e o autocuidado, taxa de infusão exata. Recursos de segurança, incluindo proteção do reservatório contra possíveis danos; Descomprimimos internações, reduzimos a espera por leitos para admissão de pacientes .Reduzimos o uso de bombas elétricas comuns no internato, disponibilizando-as para outros pacientes internados. Dificuldades encontradas: Falta de conhecimento do paciente sobre o insumo (bomba). Insegurança do paciente ao estar em casa pela primeira vez. Procedimentos burocráticos para autorização da bomba. Conclusão. Esta implementação inovadora exige ainda mais aprendizagem, contamos com o apoio do Departamento de Enfermagem e do chefe do serviço de Oncologia-Dia Hospital, para utilização das bombas. Para esta experiencia foram utilizadas 10 bombas elastoméricas. Experiência prática, positiva para o paciente, ele também se compromete com o autocuidado e o tratamento, sendo possível evitar exposições nosocomiais, minimizando assim os riscos de contágio. Reduzimos o uso de bombas elétricas comuns no estágio, disponibilizando para outros pacientes que necessitem. Descomprimimos o internato comum, permitindo assim ter Mais leitos e maior fluidez para atender a demanda de internação de pacientes como utras patologias[AU]

Hypoxia and hyperglycaemia determine why some endometrial tumours fail to respond to metformin.

BACKGROUND: High expression of Ki67, a proliferation marker, is associated with reduced endometrial cancer-specific survival. Pre-surgical metformin reduces tumour Ki-67 expression in some women with endometrial cancer. Metformin's anti-cancer activity may relate to effects on cellular energy metabolism. Since tumour hypoxia and glucose availability are major cellular redox determinants, we evaluated their role in endometrial cancer response to metformin. METHODS: Endometrial cancer biopsies from women treated with pre-surgical metformin were tested for the hypoxia markers, HIF-1α and CA-9. Endometrial cancer cell lines were treated with metformin in variable glucose concentrations in normoxia or hypoxia and cell viability, mitochondrial biogenesis, function and energy metabolism were assessed. RESULTS: In women treated with metformin (n = 28), Ki-67 response was lower in hypoxic tumours. Metformin showed minimal cytostatic effects towards Ishikawa and HEC1A cells in conventional medium (25 mM glucose). In low glucose (5.5 mM), a dose-dependent cytostatic effect was observed in normoxia but attenuated in hypoxia. Tumours treated with metformin showed increased mitochondrial mass (n = 25), while in cultured cells metformin decreased mitochondrial function. Metformin targets mitochondrial respiration, however, in hypoxic, high glucose conditions, there was a switch to glycolytic metabolism and decreased metformin response. CONCLUSIONS: Understanding the metabolic adaptations of endometrial tumours may identify patients likely to derive clinical benefit from metformin.

Doxorubicin-polyglycerol-nanodiamond conjugate is a cytostatic agent that evades chemoresistance and reverses cancer-induced immunosuppression in triple-negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) has the poorest prognosis of all breast cancer subtypes and is one of the most fatal diseases for women. Combining cytotoxic chemotherapy with immunotherapy has shown great promise for TNBC treatment. However, chemotherapy often leads to the development of chemoresistance and severe systemic toxicity compromising the immune functions that are crucial to anti-TNBC immune therapy. Tumor-induced immunosuppression also poses a great hindrance to efficacious anti-TNBC immunotherapy. Nanomedicine holds great promise to overcome these hurdles. RESULTS: Doxorubicin-polyglycerol-nanodiamond conjugate (Nano-DOX) was firstly found to be a cytostatic agent to the 4T1 cells and displayed a lower apparent therapeutic potency than DOX. However, the tumor-bearing animals, particularly some key immune cells thereof, showed good tolerance of Nano-DOX as opposed to the severe toxicity of DOX. Next, Nano-DOX did not induce significant upregulation of P-gp and IL-6, which were demonstrated to be key mediators of chemoresistance to DOX in the 4T1 cells. Then, Nano-DOX was shown to downregulate tumor-derived granulocyte-colony stimulating factor (G-CSF) and suppresses the induction and tissue filtration of myeloid-derived suppressor cells (MDSCs) that are the principal effectors of cancer-associated systemic immunosuppression. Nano-DOX also alleviated the phenotype of MDSCs induced by 4T1 cells. Finally, Nano-DOX induced the 4T1 cells to emit damage associated molecular patterns (DAMPs) that stimulated the tumor immune microenvironment through activating key immune effector cells involved in anti-tumor immunity, such as macrophages, dendritic cells and lymphocytes in the tumor tissue. CONCLUSIONS: Nano-DOX is a cytostatic agent with good host tolerance which is capable of evading chemoresistance and reversing cancer-induced immunosuppression both at the systemic level and in the tumor microenvironment in TNBC. Our work presents Nano-DOX as an interesting example that a chemotherapeutic agent in nano-form may possess distinct biochemical properties from its free form, which can be exploited to join chemotherapy with immunotherapy for better treatment of cancer.

Organoseleno cytostatic derivatives: Autophagic cell death with AMPK and JNK activation.

Selenocyanates and diselenides are potential antitumor agents. Here we report two series of selenium derivatives related to selenocyanates and diselenides containing carboxylic, amide and imide moieties. These compounds were screened for their potency and selectivity against seven tumor cell lines and two non-malignant cell lines. Results showed that MCF-7 cells were especially sensitive to the treatment, with seven compounds presenting GI50 values below 10 µM. Notably, the carboxylic selenocyanate 8b and the cyclic imide 10a also displayed high selectivity for tumor cells. Treatment of MCF-7 cells with these compounds resulted in cell cycle arrest at S phase, increased levels of pJNK and pAMPK and caspase independent cell death. Autophagy inhibitors wortmannin and chloroquine partially prevented 8b and 10a induced cell death. Consistent with autophagy, increased Beclin1 and LC3-IIB and reduced SQSTM1/p62 levels were detected. Our results point to 8b and 10a as autophagic cell death inducers.

Perfusión aislada de extremidad inferior con fuga de quimioterapéutico / Isolated limb perfusion with cytostatic drug leakage

La perfusión aislada de la extremidad es el tratamiento del melanoma en estadio iii, con metástasis en tránsito. Esta técnica permite la administración de citostáticos a concentración y temperatura eficaces, que no podrían ser administrados de manera sistémica debido a su toxicidad. La toxicidad debido al paso a la circulación sistémica de quimioterápico procedente de la extremidad es la complicación más grave a corto plazo, y se manifiesta mediante el síndrome de respuesta inflamatoria sistémica en el postoperatorio inmediato. La detección precoz de esta complicación y su manejo perioperatorio requiere un abordaje multidiscilplicar, en el que el anestesiólogo tiene un papel clave. Presentamos un caso de perfusión aislada de la extremidad inferior en el que el procedimiento tuvo que ser interrumpido por paso de factor de necrosis tumoral a la circulación sistémica, con grave repercusión hemodinámica intraoperatoria (AU)

Isolated limb perfusion is the treatment of stage III melanoma with in-transit metastasis. This technique allows the administration of cytostatics at an effective concentration and temperature, which could not be administered systemically because of their toxicity. The toxicity due to leakage of the chemotherapy agent from the limb into the systemic circulation is the most serious short-term complication, and is manifested by a systemic inflammatory response syndrome in the immediate post-intervention period. Early detection of this complication and its peri-operative management requires a multidisciplinary approach, in which the anaesthesiologist plays a key role. A case of isolated lower limb perfusion is reported in which the procedure had to be interrupted due to the passage of tumour necrosis factor into the systemic circulation, with severe intra-operative haemodynamic repercussions (AU)

Vitamin D derivatives potentiate the anticancer and anti-angiogenic activity of tyrosine kinase inhibitors in combination with cytostatic drugs in an A549 non-small cell lung cancer model.

Numerous in vitro and in vivo studies have demonstrated that calcitriol [1,25(OH)2D3] and different vitamin D analogs possess antineoplastic activity, regulating proliferation, differentiation and apoptosis, as well as angiogenesis. Vitamin D compounds have been shown to exert synergistic effects when used in combination with different agents used in anticancer therapies in different cancer models. The aim of this study was to evaluate the mechanisms of the cooperation of the vitamin D compounds [1,24(OH)2D3 (PRI­2191) and 1,25(OH)2D3] with tyrosine kinase inhibitors (imatinib and sunitinib) together with cytostatics (cisplatin and docetaxel) in an A549 non-small cell lung cancer model. The cytotoxic effects of the test compounds used in different combinations were evaluated on A549 lung cancer cells, as well as on human lung microvascular endothelial cells (HLMECs). The effects of such combinations on the cell cycle and cell death were also determined. In addition, changes in the expression of proteins involved in cell cycle regulation, angiogenesis and the action of vitamin D were analyzed. Moreover, the effects of 1,24(OH)2D3 on the anticancer activity of sunitinib and sunitinib in combination with docetaxel were examined in an A549 lung cancer model in vivo. Experiments aiming at evaluating the cytotoxicity of the combinations of the test agents revealed that imatinib and sunitinib together with cisplatin or docetaxel exerted potent anti-proliferative effects in vitro on A549 lung cancer cells and in HLMECs; however, 1,24(OH)2D3 and 1,25(OH)2D3 enhanced the cytotoxic effects only in the endothelial cells. Among the test agents, sunitinib and cisplatin decreased the secretion of vascular endothelial growth factor (VEGF)­A from the A549 lung cancer cells. The decrease in the VEGF­A level following incubation with cisplatin correlated with a higher p53 protein expression, while no such correlation was observed following treatment of the A549 cells with sunitinib. Sunitinib together with docetaxel and 1,24(OH)2D3 exhibited a more potent anticancer activity in the A549 lung cancer model compared to double combinations and to treatment with the compounds alone. The observed anticancer activity may be the result of the influence of the test agents on the process of tumor angiogenesis, for example, through the downregulation of VEGF­A expression in tumor and also on the induction of cell death inside the tumor.

Cytostatic hydroxycoumarin OT52 induces ER/Golgi stress and STAT3 inhibition triggering non-canonical cell death and synergy with BH3 mimetics in lung cancer.

Coumarins are natural compounds with antioxidant, anti-inflammatory and anti-cancer potential known to modulate inflammatory pathways. Here, non-toxic biscoumarin OT52 strongly inhibited proliferation of non-small cell lung cancer cells with KRAS mutations, inhibited stem-like characteristics by reducing aldehyde dehydrogenase expression and abrogated spheroid formation capacity. This cytostatic effect was characterized by cell cycle arrest and onset of senescence concomitant with endoplasmic reticulum and Golgi stress, leading to metabolic alterations. Mechanistically, this cellular response was associated with the novel capacity of biscoumarin OT52 to inhibit STAT3 transactivation and expression of its target genes linked to proliferation. These results were validated by computational docking of OT52 to the STAT3 DNA-binding domain. Combination treatments of OT52 with subtoxic concentrations of Bcl-xL and Mcl-1-targeting BH3 protein inhibitors triggered synergistic immunogenic cell death validated in colony formation assays as well as in vivo by zebrafish xenografts.

Implementation of safeguards to improve patient safety in chemotherapy

Purpose. To evaluate the effectiveness of safeguards introduced in the process of using cytostatic agents for increasing the safety of oncology patients. Methods. Prospective hospital study conducted in two stages, before and after the implementation of safeguards: staff training, standardized procedures, computerized prescription, pharmaceutical validation, implementation of bar codes, and a new manual on drug interactions. Medication errors (MEs) were actively recorded during the process of administering chemotherapy in the Medical Oncology Department. The study classified MEs by the stage of the medication process in which they occurred and assessed their severity. Results. 500 patients, 250 before implementing safeguards and 250 afterward, were included in this study . Out of all patients included before, 43.1% had at least 1 error, compared to 27% of those included later. The number of MEs detected before and after was 144 vs. 95: 125 vs. 55 prescription errors, 2 vs. 5 validation errors, 14 vs. 4 preparation errors, 3 vs. 1 dispensation errors and 0 vs. 30 administration errors. The number of MEs that reached the patient before and after safeguard implementation was 16.7% vs. 6.3%. After the safeguards were introduced, all MEs that could have caused harm or required monitoring of some kind were prevented. Conclusions. Implementing safeguards in the hospital’s cytostatic treatment cycle is useful for preventing MEs. Computerized prescription, pharmaceutical validation, and the creation/dissemination of proper work procedures are effective barriers that keep MEs from reaching the patient. Administering chemotherapy with a bar-code system facilitates detection error detection at this stage of the cycle and prevents them from reaching the patient (AU)

No disponible

Degree of technological implementation in intravenous chemotherapy management in hospitals of the Autonomous Community of Madrid / Grado de implantación tecnológica en el manejo de quimioterapia intravenosa en los hospitales de la Comunidad de Madrid

Objective: To understand the degree of technological implementation in the processes of preparation and administration of cytostatics drugs that is available in those hospitals of the Autonomous Community of Madrid where intravenous chemotherapy is prepared. Method: A descriptive observational study through the completion of a survey targeted to the staff responsible for the preparation of this type of treatments. Results: The degree of implementation of assisted electronic prescription is high, there is a medium degree in the case of bar code reading technology, and low in terms of vial re-labelling and gravimetric and voice control for preparation. Conclusions: There is a large room for improvement regarding traceability in the process of preparation and administration of intravenous chemotherapy (AU)

Objetivo: Conocer el grado de implantación tecnológica en los procesos de preparación y administración de citostáticos del que disponen los hospitales de la Comunidad de Madrid en los que se elabora quimioterapia intravenosa. Método: Estudio observacional descriptivo mediante la cumplimentación de una encuesta dirigida al personal responsable de la elaboración de este tipo de tratamientos. Resultados: El grado de implantación de la prescripción electrónica asistida es elevado, medio en el caso de tecnología de lectura de código de barras y bajo en reetiquetado de viales y control gravimétrico y por voz de la elaboración. Conclusiones: Existe un amplio margen de mejora en lo que se refiere a la trazabilidad del proceso de elaboración y administración de mezclas intravenosas de quimioterapia (AU)

Extravasación de citostáticos por vía periférica. tratamiento quirúrgico: ¿cuándo y cómo? / Extravasation of peripheral cytostatic. surgical treatment: when and how?

Se analiza el tratamiento quirúrgico en las extravasaciones de citostáticos por vía periférica. Se discute cuándo y cómo realizarlo. Se lo ubica dentro del contexto de los otros dos tratamientos: el de urgencia y el clínico. Se señala que el tipo de citostático utilizado y el estado clínico de paciente influyen en esta decisión.

Surgical treatment in peripheral cytostatic extravasations is analysed. It discusses when and how to perform it. It is placed within the context of the other two treatments: the emergency and the clinical. It is pointed out that the type of cytostatic used and the clinical status of the patient influence this decision.

Characterisation of sol-gel method synthesised MgZnFe2O4 nanoparticles and its cytotoxic effects on breast cancer cell line, MDA MB-231 in vitro.

In this study, nanocrystalline magnesium zinc ferrite nanoparticles were successfully prepared by a simple sol-gel method using copper nitrate and ferric nitrate as raw materials. The calcined samples were characterised by differential thermal analysis/thermogravimetric analysis, Fourier transform infrared spectroscopy and X-ray diffraction. Transmission electron microscopy revealed that the average particle size of the calcined sample was in a range of 17-41 nm with an average of 29 nm and has spherical size. A cytotoxicity test was performed on human breast cancer cells (MDA MB-231) and (MCF-7) at various concentrations starting from (0 µg/ml) to (800 µg/ml). The sample possessed a mild toxic effect toward MDA MB-231 and MCF-7 after being examined with MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide) assay for up to 72 h of incubation. Higher reduction of cells viability was observed as the concentration of sample was increased in MDA MB-231 cell line than in MCF-7. Therefore, further cytotoxicity tests were performed on MDA MB-231 cell line.

Simultaneous Interference with HER1/EGFR and RAC1 Signaling Drives Cytostasis and Suppression of Survivin in Human Glioma Cells in Vitro.

We have previously reported that combined inhibition of the epidermal growth factor receptor by erlotinib and of RAC1 by NSC23766 yielded a synergistic antiproliferative effect on established and primary cultured glioblastoma cells. The current study aimed at identifying the molecular mechanism. Staining for annexin V/PI or carboxyfluorescein succinimidyl ester was performed in order to determine the induction of apoptosis, necrosis or cytostasis in established and primary cultured glioblastoma cells. Moreover, expression of Ki-67 was determined by immunofluorescence, and the expression of cell cycle proteins was analysed by Western blot. Our data show that combined treatment with erlotinib and NSC23766 resulted in a reduced number of cell divisions, a significantly decreased Ki-67 expression, increased apoptosis and autophagy when compared to single agent treatments. On the molecular level, concomitant treatment with both agents resulted in a pronounced downregulation of cyclin D1, cyclin-dependent kinases 2, 4 and 6, as well as of survivin when compared to treatments with either agent alone. In conclusion, we demonstrate that combined treatment of human glioma cell lines in vitro with erlotinib and NSC23766 markedly inhibits cell division, induces apoptosis independent of caspase-3 activation and induces autophagy concomitant with suppression of survivin.

Drug-drug interactions of cytostatics with regular medicines in lung cancer patients.

Background Lung cancer patients have a high risk for drug-drug interactions, as they use numerous types of concomitant medicines including antineoplastic agents, cancer treatment co-medication, and medicines aimed at several types of comorbidities. Objective The primary objective of this study is to determine the incidence and the clinical relevance of the drug-drug interactions between antineoplastic agents and regular medication used by lung cancer patients. Secondary objectives are (i) to determine the effectiveness of the medication review by the hospital pharmacists concerned, (ii) to establish which patients are most at risk of drug-drug interactions and (iii) to determine whether physicians comply with advice given by hospital pharmacists. Setting This prospective study was undertaken in a Dutch hospital pharmacy, at Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam. Methods All lung cancer patients receiving one or more cytotoxic agents during the period 21 June 2010 till 2 December 2014 at OLVG were included. The medication list of the patients was obtained electronically from the community pharmacy and checked for interactions by a hospital pharmacist. Interactions that required intervention according to the national database were the only ones taken into account. Interventions were recorded in the patients' electronic charts. All medication reviews were cross-checked and analyzed by an independent pharmacist at the end of the study period. Main outcome measure Prevalence and clinical relevance of drug-drug interactions between antineoplastic agents and other types of medication in lung cancer patients. Results A total of 298 lung cancer patients were included in this study. In 53 patients (18%), a total of 73 interactions with potential clinical relevance were found. The most frequent interaction was between cytostatics and coumarins while the most relevant one was between cisplatin and furosemide. According to statistical analysis, gender as well as the number of drugs prescribed were significant predictors for drug-drug interactions. Eighty-four percent of the interactions were discovered by pharmacists during daily routine. In 92% of the cases, the pulmonary physicians complied with the advice of the pharmacist. Conclusion Eighteen percent of lung cancer patients treated with cytotoxic therapy had one or more relevant drug-drug interactions. This study shows that medication surveillance by a hospital pharmacist is necessary to prevent possible negative drug-drug interactions. Further research should focus on the clinical outcome of the interactions as well as on interactions between cytostatics and alternative medicines and/or over-the-counter medicines.

Overcoming multidrug resistance via simultaneous delivery of cytostatic drug and P-glycoprotein inhibitor to cancer cells by HPMA copolymer conjugate.

Multidrug resistance (MDR) is a common cause of failure in chemotherapy for malignant diseases. MDR is either acquired as a result of previous repeated exposure to cytostatic drugs (P388/MDR cells) or naturally, as some tumors are congenitally resistant to chemotherapy (CT26 cells). One of the most common mechanisms of MDR is upregulation of P-glycoprotein (P-gp) expression. Here, we used HPMA copolymer conjugates, whereby the cytostatic drug doxorubicin (Dox) or the derivative of the P-gp inhibitor reversin 121 (R121) or both were covalently bound through a degradable pH-sensitive hydrazone bond. We proved that R121, when bound to a polymeric carrier, is capable of inhibiting P-gp in P388/MDR cells and sensitizing them in relation to the cytostatic activity of Dox. Conjugate bearing both Dox and R121 was found to be far more potent in P388/MDR cells than conjugate bearing Dox alone or a mixture of conjugates bearing either Dox or R121 when cytostatic activity in vitro, cell cycle arrest, accumulation of Dox in cells and induction of apoptosis were determined. Importantly, conjugate bearing R121 is also effective in vivo as it inhibits P-gp in P388/MDR tumors after intraperitoneal administration, while both the conjugate bearing Dox and R121 induces apoptosis in P388/MDR tumors more effectively than conjugate bearing Dox alone. Only conjugate bearing Dox and R121 significantly inhibited P388/MDR tumor growth and led to the prolonged survival of treated mice. However, the most dramatic antitumor activity of this conjugate was found in the CT26 tumor model where it completely cured six out of eight experimental mice, while conjugate bearing Dox alone cured no mice.

The polysialic acid mimetics 5-nonyloxytryptamine and vinorelbine facilitate nervous system repair.

Polysialic acid (PSA) is a large negatively charged glycan mainly attached to the neural cell adhesion molecule (NCAM). Several studies have shown that it is important for correct formation of brain circuitries during development and for synaptic plasticity, learning and memory in the adult. PSA also plays a major role in nervous system regeneration following injury. As a next step for clinical translation of PSA based therapeutics, we have previously identified the small organic compounds 5-nonyloxytryptamine and vinorelbine as PSA mimetics. Activity of 5-nonyloxytryptamine and vinorelbine had been confirmed in assays with neural cells from the central and peripheral nervous system in vitro and shown to be independent of their function as serotonin receptor 5-HT1B/1D agonist or cytostatic drug, respectively. As we show here in an in vivo paradigm for spinal cord injury in mice, 5-nonyloxytryptamine and vinorelbine enhance regain of motor functions, axonal regrowth, motor neuron survival and remyelination. These data indicate that 5-nonyloxytryptamine and vinorelbine may be re-tasked from their current usage as a 5-HT1B/1D agonist or cytostatic drug to act as mimetics for PSA to stimulate regeneration after injury in the mammalian nervous system.

Combined Treatment of MCF-7 Cells with AICAR and Methotrexate, Arrests Cell Cycle and Reverses Warburg Metabolism through AMP-Activated Protein Kinase (AMPK) and FOXO1.

Cancer cells are characterized by metabolic alterations, namely, depressed mitochondrial oxidation, enhanced glycolysis and pentose phosphate shunt flux to support rapid cell growth, which is called the Warburg effect. In our study we assessed the metabolic consequences of a joint treatment of MCF-7 breast cancer cells with AICAR, an inducer of AMP-activated kinase (AMPK) jointly with methotrexate (MTX), a folate-analog antimetabolite that blunts de novo nucleotide synthesis. MCF7 cells, a model of breast cancer cells, were resistant to the individual application of AICAR or MTX, however combined treatment of AICAR and MTX reduced cell proliferation. Prolonged joint application of AICAR and MTX induced AMPK and consequently enhanced mitochondrial oxidation and reduced the rate of glycolysis. These metabolic changes suggest an anti-Warburg rearrangement of metabolism that led to the block of the G1/S and the G2/M transition slowing down cell cycle. The slowdown of cell proliferation was abolished when mitotropic transcription factors, PGC-1α, PGC-1ß or FOXO1 were silenced. In human breast cancers higher expression of AMPKα and FOXO1 extended survival. AICAR and MTX exerts similar additive antiproliferative effect on other breast cancer cell lines, such as SKBR and 4T1 cells, too. Our data not only underline the importance of Warburg metabolism in breast cancer cells but nominate the AICAR+MTX combination as a potential cytostatic regime blunting Warburg metabolism. Furthermore, we suggest the targeting of AMPK and FOXO1 to combat breast cancer.