Cancer Vaccines in Ovarian Cancer: How Can We Improve?

Epithelial ovarian cancer (EOC) is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago) but, as the disease is usually diagnosed at an advanced stage, its prognosis remains very poor. Clearly, there is a critical need for new treatment options, and immunotherapy is one attractive alternative. Prophylactic vaccines for prevention of infectious diseases have led to major achievements, yet therapeutic cancer vaccines have shown consistently low efficacy in the past. However, as they are associated with minimal side effects or invasive procedures, efforts directed to improve their efficacy are being deployed, with Dendritic Cell (DC) vaccination strategies standing as one of the more promising options. On the other hand, recent advances in our understanding of immunological mechanisms have led to the development of successful strategies for the treatment of different cancers, such as immune checkpoint blockade strategies. Combining these strategies with DC vaccination approaches and introducing novel combinatorial designs must also be considered and evaluated. In this review, we will analyze past vaccination methods used in ovarian cancer, and we will provide different suggestions aiming to improve their efficacy in future trials

Home in the Dharma: Transgender Buddhists on the West Coast of the U.S. and Canada, 1998-2019

Research on LGBTQ+ people and religion focuses on how religion has done harm. This violence is vital to recognize. But as a result, histories of how religion has benefitted transgender people are silenced. I will respond to this lack of scholarship on trans and queer religious history. I will analyze how transgender Buddhists on the West Coast of the U.S. and Canada negotiated gender identity with religion between 1998 and 2019. What factors led these individuals to Buddhism in this place and time? What aspects of the religion did they find (un)appealing? How did differences of identity—race, age, (dis)ability—affect how they related to and accessed Buddhism? I will add to the small but growing body of scholarship on trans religious history. In a broader context, this project continues the urgent work of decolonizing the cis-centric academic landscape, bringing trans epistemologies and subjectivities to the fore

Effect of single peak overloading on fatigue crack propagation

The macroscopic and electronmicroscopic crack propagation behavior of 2024-T3 aluminum alloy resulting from the application of a single 50% overload in an otherwise uniform alternating fatigue load is examined

Análisis automático en lo industria del cemento por espectrometría de rayos X y calculador asociado

No availableLa Sociedad de Ciments Français emplea desde hace tres años, en su Laboratorio Central de Levallois, un espectrómetro automático de rayos X, PW 1210. Las materias controladas son los productos empleados y fabricados corrientemente en la industria del cemento. Se han hecho patrones por fusión de mezclas puras. Estos patrones han permitido calcular para cada elemento la ecuación de una recta de referencia, a partir de la cual se efectúan los cálculos que dan la composición elemental de las muestras analizadas. Estos cálculos necesitan dos operadores, y los procesos verbales de análisis deben ser dactilografiados enseguida. Se ha considerado útil asociar al espectrómetro un calculador PR 8000, que realiza el conjunto de los cálculos y la redacción de los procesos verbales de análisis. Con este conjunto, se llega a un trabajo de análisis completamente automatizado entre la introducción de la muestra en el espectrómetro y la salida de los resultados imprimidos. Gracias al calculador a él asociado, el espectrómetro puede ser utilizado a pleno rendimiento

Edgardo Von Euw: “Sin racionalidad en la incorporación de tecnología, el sistema no tendrá sustentabilidad”

Es egresado de la Universidad Nacional de Córdoba (UNC), tiene una amplia trayectoria como médico sanitarista e integra el equipo multidisciplinario del Centro de Evaluación de Tecnología en Salud (Cetsa), de la Universidad ISALUD. Su experiencia previa le sirvió para capitalizar aún más su paso por la Maestría en Economía y Gestión de la Salud, de nuestra Universidad. En esta entrevista, se refiere a los desafíos que se avecinan frente a los avances tecnológicos

Enhancing the immunogenicity of tumour lysate-loaded dendritic cell vaccines by conjugation to virus-like particles

BACKGROUND: Tumour cell lysates are an excellent source of many defined and undefined tumour antigens and have been used clinically in immunotherapeutic regimes but with limited success. METHODS: We conjugated Mel888 melanoma lysates to rabbit haemorrhagic disease virus virus-like particles (VLP), which can act as vehicles to deliver multiple tumour epitopes to dendritic cells (DC) to effectively activate antitumour responses. RESULTS: Virus-like particles did not stimulate the phenotypic maturation of DC although, the conjugation of lysates to VLP (VLP-lysate) did overcome lysate-induced suppression of DC activation. Lysate-conjugated VLP enhanced delivery of antigenic proteins to DC, while the co-delivery of VLP-lysates with OK432 resulted in cross-priming of naïve T cells, with expansion of a MART1(+) population of CD8(+) T cells and generation of a specific cytotoxic response against Mel888 tumour cell targets. The responses generated with VLP-lysate and OK432 were superior to those stimulated by unconjugated lysate with OK432. CONCLUSION: Collectively, these results show that the combination of VLP-lysate with OK432 delivered to DC overcomes the suppressive effects of lysates, and enables priming of naïve T cells with superior ability to specifically kill their target tumour cells

Checks and Balances in Autoimmune Vasculitis

Age-associated changes in the immune system including alterations in surface protein expression are thought to contribute to an increased susceptibility for autoimmune diseases. The balance between the expression of coinhibitory and costimulatory surface protein molecules, also known as immune checkpoint molecules, is crucial in fine-tuning the immune response and preventing autoimmunity. The activation of specific inhibitory signaling pathways allows cancer cells to evade recognition and destruction by the host immune system. The use of immune checkpoint inhibitors (ICIs) to treat cancer has proven to be effective producing durable antitumor responses in multiple cancer types. However, one of the disadvantages derived from the use of these agents is the appearance of inflammatory manifestations termed immune-related adverse events (irAEs). These irAEs are often relatively mild, but more severe irAEs have been reported as well including several forms of vasculitis. In this article, we argue that age-related changes in expression and function of immune checkpoint molecules lead to an unstable immune system, which is prone to tolerance failure and autoimmune vasculitis development. The topic is introduced by a case report from our hospital describing a melanoma patient treated with ICIs and who subsequently developed biopsy-proven giant cell arteritis. Following this case report, we present an in-depth review on the role of immune checkpoint pathways in the development and progression of autoimmune vasculitis and its relation with an aging immune system

CTLA4 blockade increases Th17 cells in patients with metastatic melanoma

<p>Abstract</p> <p>Background</p> <p>Th17 cells are CD4+ cells that produce interleukin 17 (IL-17) and are potent inducers of tissue inflammation and autoimmunity. We studied the levels of this T cell subset in peripheral blood of patients treated with the anti-CTLA4 antibody tremelimumab since its major dose limiting toxicities are inflammatory and autoimmune in nature.</p> <p>Methods</p> <p>Peripheral blood mononuclear cells (PBMC) were collected before and after receiving tremelimumab within two clinical trials, one with tremelimumab alone (21 patients) and another together with autologous dendritic cells (DC) pulsed with the melanoma epitope MART-1_26–35(6 patients). Cytokines were quantified directly in plasma from patients and after <it>in vitro </it>stimulation of PBMC. We also quantified IL-17 cytokine-producing cells by intracellular cytokine staining (ICS).</p> <p>Results</p> <p>There were no significant changes in 13 assayed cytokines, including IL-17, when analyzing plasma samples obtained from patients before and after administration of tremelimumab. However, when PBMC were activated <it>in vitro</it>, IL-17 cytokine in cell culture supernatant and Th17 cells, detected as IL-17-producing CD4 cells by ICS, significantly increased in post-dosing samples. There were no differences in the levels of Th17 cells between patients with or without an objective tumor response, but samples from patients with inflammatory and autoimmune toxicities during the first cycle of therapy had a significant increase in Th17 cells.</p> <p>Conclusion</p> <p>The anti-CTLA4 blocking antibody tremelimumab increases Th17 cells in peripheral blood of patients with metastatic melanoma. The relation between increases in Th17 cells and severe autoimmune toxicity after CTLA4 blockade may provide insights into the pathogenesis of anti-CTLA4-induced toxicities.</p> <p>Trial Registration</p> <p><b>Clinical trial registration numbers</b>: NCT0090896 and NCT00471887</p

Reconstructing Dryopteris “semicristata” (Dryopteridaceae): Molecular profiles of tetraploids verify their undiscovered diploid ancestor

This is the publisher's version, also available electronically from http://www.amjbot.org.• Premise of the study: Discovering missing ancestors is essential to understanding the evolutionary history of biodiversity on Earth. Evidence from extinct species can provide links for reconstructing intricate patterns of reticulate relationships among extant descendents. When fossils are unavailable and other evidence yields competing hypotheses to explain species ancestry, data from proteins and DNA can help resolve conflicts and generate novel perspectives. The identity of a parent shared by two tetraploid species in the cosmopolitan fern genus Dryopteris has remained elusive for more than 50 years. Based on available data, four hypotheses were developed previously, each providing a different resolution to this uncertainty. • Methods: New molecular evidence from studies of isozymes and restriction site analysis of chloroplast DNA tested the competing hypotheses about the diploid ancestors of these two extant Dryopteris polyploids. • Key results: The results falsify two of the hypotheses, resolve the uncertainty in the third, and support the fourth. • Conclusions: Our data validate the prior existence of Dryopteris “semicristata,” which was proposed 38 years ago as a diploid progenitor of the allotetraploids D. cristata and D. carthusiana but has never been collected. After developing a phylogeny using the new molecular data, we describe a plausible morphology for D. “semicristata” by extrapolating likely character states from related extant species