Psychoneuroimmunology and oncology nursing: a theoretical study.

OBJECTIVE: To discuss the evolution of research in cancer psychoneuroimmunology, the advances in the management of neuropsychological symptom clusters and their interface with mid-range theories, and practical applications in Nursing. METHOD: This is a theoretical-reflective study anchored in recent literature, as well as in the critical analysis of the authors. RESULTS: This is a promising field of investigation, which emphasizes the complexity and interaction of symptoms, the interrelationships among them, the factors influencing them, and their consequences. Subsidized by mid-range theories in Nursing, such as the Theory of Unpleasant Symptoms and the Theory of Symptom Management, analyses of these interrelationships support Oncology Nursing diagnoses and interventions. CONCLUSION: An innovative approach is proposed to qualify Oncology Nursing care based on the integration of recent advances in cancer psychoneuroimmunology, Nursing mid-range theories, and practical tools such as health coaching. The approach proposed may strengthen clinical nursing practice in the management of neuropsychological symptom clusters in oncology and shall be integrated into decision-making during cancer treatment, favoring person-centered care.

Psychoneuroimmunology and oncology nursing: a theoretical study / Psiconeuroinmunología y la enfermería oncológica: estudio teórico / Psiconeuroimunologia e a enfermagem oncológica: estudo teórico

ABSTRACT Objective: To discuss the evolution of research in cancer psychoneuroimmunology, the advances in the management of neuropsychological symptom clusters and their interface with mid-range theories, and practical applications in Nursing. Method: This is a theoretical-reflective study anchored in recent literature, as well as in the critical analysis of the authors. Results: This is a promising field of investigation, which emphasizes the complexity and interaction of symptoms, the interrelationships among them, the factors influencing them, and their consequences. Subsidized by mid-range theories in Nursing, such as the Theory of Unpleasant Symptoms and the Theory of Symptom Management, analyses of these interrelationships support Oncology Nursing diagnoses and interventions. Conclusion: An innovative approach is proposed to qualify Oncology Nursing care based on the integration of recent advances in cancer psychoneuroimmunology, Nursing mid-range theories, and practical tools such as health coaching. The approach proposed may strengthen clinical nursing practice in the management of neuropsychological symptom clusters in oncology and shall be integrated into decision-making during cancer treatment, favoring person-centered care.

RESUMEN Objetivo: Discutir la evolución de las investigaciones en psiconeuroinmunología del cáncer, los avances en el manejo de los clusters de síntomas neuropsicológicos y su interface con teorías de rango medio y aplicaciones prácticas por la Enfermería. Método: Estudio teórico-reflexivo ancorado en literatura reciente, así como en el análisis crítico de los autores. Resultados: Este es un campo promisor de investigación, que tiene énfasis en la complejidad y la interacción de los síntomas, las interrelaciones entre ellos, los factores que los influyen y sus consecuencias. Subsidiadas por teorías de rango medio en Enfermería, como la Teoría de los Síntomas Desagradables y la Teoría del Manejo de Síntomas, análisis de estas interrelaciones corroboran los diagnósticos y las intervenciones de Enfermería en Oncología. Consideraciones Finales: Se ha propuesto un abordaje innovador para calificar el cuidado de Enfermería Oncológica a partir de la integración de avances recientes en psiconeuroinmunología del cáncer, teorías de rango medio de Enfermería y herramientas prácticas como coaching de salud. El abordaje propuesto puede fortalecer la práctica clínica de Enfermería en la gestión de los clusters de síntomas neuropsicológicos en oncología y debe ser integrado en las acciones y decisiones durante el tratamiento oncológico que favorezcan el cuidado centrado en las personas.

RESUMO Objetivo: Discutir a evolução das pesquisas em psiconeuroimunologia do câncer, os avanços no manejo dos clusters de sintomas neuropsicológicos e sua interface com teorias de médio alcance e aplicações práticas pela Enfermagem. Método: Estudo teórico-reflexivo ancorado em literatura recente, bem como na análise crítica dos autores. Resultados: Este é um campo promissor de investigação, que enfatiza a complexidade e a interação dos sintomas, as inter-relações entre os mesmos, os fatores que os influenciam e suas consequências. Subsidiadas por teorias de médio alcance em Enfermagem, como a Teoria dos Sintomas Desagradáveis e a Teoria de Gerenciamento de Sintomas, análises destas inter-relações corroboram os diagnósticos e as intervenções de Enfermagem em Oncologia. Conclusão: Propõe-se uma abordagem inovadora para qualificar o cuidado de Enfermagem Oncológica a partir da integração de avanços recentes em psiconeuroimunologia do câncer, teorias de médio alcance de Enfermagem, e ferramentas práticas como coaching de saúde. A abordagem proposta pode fortalecer a prática clínica da Enfermagem no manejo dos clusters de sintomas neuropsicológicos em oncologia e deve ser integrada na tomada de decisões durante o tratamento oncológico, favorecendo o cuidado centrado na pessoa.

Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200.

The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual ovarian cancer with 211At-Rebmab200. Here, the biodistribution of 211At-Rebmab200 was evaluated, as was the utility of 99mTc-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that 99mTc-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.

Rebmab200, a humanized monoclonal antibody targeting the sodium phosphate transporter NaPi2b displays strong immune mediated cytotoxicity against cancer: a novel reagent for targeted antibody therapy of cancer.

NaPi2b, a sodium-dependent phosphate transporter, is highly expressed in ovarian carcinomas and is recognized by the murine monoclonal antibody MX35. The antibody had shown excellent targeting to ovarian cancer in several early phase clinical trials but being murine the antibody's full therapeutic potential could not be explored. To overcome this impediment we developed a humanized antibody version named Rebmab200, expressed in human PER.C6® cells and cloned by limiting dilution. In order to select a clone with high therapeutic potential clones were characterized using a series of physicochemical assays, flow cytometry, real-time surface plasmon resonance, glycosylation analyses, immunohistochemistry, antibody-dependent cell-mediated cytotoxicity, complement-dependent-cytotoxicity assays and quantitative PCR. Comparative analyses of Rebmab200 and MX35 monoclonal antibodies demonstrated that the two antibodies had similar specificity for NaPi2b by flow cytometry with a panel of 30 cell lines and maintained similar kinetic parameters. Robust and high producer cell clones potentially suitable for use in manufacturing were obtained. Rebmab200 antibodies were assessed by immunohistochemistry using a large panel of tissues including human carcinomas of ovarian, lung, kidney and breast origin. An assessment of its binding towards 33 normal human organs was performed as well. Rebmab200 showed selected strong reactivity with the tested tumor types but little or no reactivity with the normal tissues tested confirming its potential for targeted therapeutics strategies. The remarkable cytotoxicity shown by Rebmab200 in OVCAR-3 cells is a significant addition to the traits of stability and productivity displayed by the top clones of Rebmab200. Antibody-dependent cell-mediated toxicity functionality was confirmed in repeated assays using cancer cell lines derived from ovary, kidney and lung as targets. To explore use of this antibody in clinical trials, GMP production of Rebmab200 has been initiated. As the next step of development, Phase I clinical trials are now planned for translation of Rebmab200 into the clinic.

In silico analysis and immunohistochemical characterization of NaPi2b protein expression in ovarian carcinoma with monoclonal antibody Mx35.

INTRODUCTION: Ovarian adenocarcinoma is frequently detected at the late stage, when therapy efficacy is limited and death occurs in up to 50% of the cases. A potential novel treatment for this disease is a monoclonal antibody that recognizes phosphate transporter sodium-dependent phosphate transporter protein 2b (NaPi2b). MATERIALS AND METHODS: To better understand the expression of this protein in different histologic types of ovarian carcinomas, we immunostained 50 tumor samples with anti-NaPi2b monoclonal antibody MX35 and, in parallel, we assessed the expression of the gene encoding NaPi2b (SCL34A2) by in silico analysis of microarray data. RESULTS: Both approaches detected higher expression of NaPi2b (SCL34A2) in ovarian carcinoma than in normal tissue. Moreover, a comprehensive analysis indicates that SCL34A2 is the only gene of the several phosphate transporters genes whose expression differentiates normal from carcinoma samples, suggesting it might exert a major role in ovarian carcinomas. Immunohistochemical and mRNA expression data have also shown that 2 histologic subtypes of ovarian carcinoma express particularly high levels of NaPi2b: serous and clear cell adenocarcinomas. Serous adenocarcinomas are the most frequent, contrasting with clear cell carcinomas, rare, and with worse prognosis. CONCLUSION: This identification of subgroups of patients expressing NaPi2b may be important in selecting cohorts who most likely should be included in future clinical trials, as a recently generated humanized version of MX35 has been developed.

Antitumor Activity of IMC-038525, a Novel Oral Tubulin Polymerization Inhibitor.

Microtubules are a well-validated target for anticancer therapy. Molecules that bind tubulin affect dynamic instability of microtubules causing mitotic arrest of proliferating cells, leading to cell death and tumor growth inhibition. Natural antitubulin agents such as taxanes and Vinca alkaloids have been successful in the treatment of cancer; however, several limitations have encouraged the development of synthetic small molecule inhibitors of tubulin function. We have previously reported the discovery of two novel chemical series of tubulin polymerization inhibitors, triazoles (Ouyang et al. Synthesis and structure-activity relationships of 1,2,4-triazoles as a novel class of potent tubulin polymerization inhibitors. Bioorg Med Chem Lett. 2005; 15:5154-5159) and oxadiazole derivatives (Ouyang et al. Oxadiazole derivatives as a novel class of antimitotic agents: synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines. Bioorg Med Chem Lett. 2006; 16:1191-1196). Here, we report on the anticancer effects of a lead oxadiazole derivative in vitro and in vivo. In vitro, IMC-038525 caused mitotic arrest at nanomolar concentrations in epidermoid carcinoma and breast tumor cells, including multidrug-resistant cells. In vivo, IMC-038525 had a desirable pharmacokinetic profile with sustained plasma levels after oral dosing. IMC-038525 reduced subcutaneous xenograft tumor growth with significantly greater efficacy than the taxane paclitaxel. At efficacious doses, IMC-038525 did not cause substantial myelosuppression or peripheral neurotoxicity, as evaluated by neutrophil counts and changes in myelination of the sciatic nerve, respectively. These data indicate that IMC-038525 is a promising candidate for further development as a chemotherapeutic agent.