63 research outputs found
Abstract LB-201: Durable remission of lethal canine hemangiosarcoma
No full textAbstract
Background: Angiosarcoma is an uncommon but deadly malignant neoplasm of the vascular endothelium. Primary disease may present at any vascularized site but often occurs in the dermis on the neck and scalp or in the radiation field of women previously-treated for breast cancer. Metastases are often present at first diagnosis, and five-year survival is an abysmal 10-30%. In contrast to the relative paucity of human diagnoses, angiosarcoma is a major killer in the companion canine population, responsible for an estimated 120,000 deaths per year in the United States. The canine disease (termed HSA) closely mimics the human disease in both pathology and genetics. It frequently presents in the dog as acute hemoabdomen secondary to splenic rupture. Even if life-saving splenectomy is performed, median OS is a scant 48 days, and one-year OS hovers at 0%. Given the lack of an analogous rodent model and the accelerated timeline of the canine disease, the outbred companion canine is an ideal system in which to translate novel therapeutic approaches. Here we report an interim analysis of a phase I multi-site, open-label veterinary trial of chemo-immunotherapy performed on consecutively-presenting splenectomized companion canines with histopathologically-verified HSA.
Methods: In addition to two cycles of 20 mg/m2 (low-dose) doxorubicin, enrolled study subjects received an autologous cell-therapy reported to generate durable CD8+ memory similar to that of physiologic viral infection. Vaccine was generated from mobilized peripheral blood and cryopreserved tumor antigen and was administered in four doses given in conjunction with type I interferon. Disease burden was monitored monthly by abdominal ultrasound, chest x-ray, and echocardiogram.
Results: At the time of abstract submission, median OS had not yet been reached in the per protocol population, with 75% of animals alive and healthy (NED or ongoing PR) at up to one year post-splenectomy (p<0.0002). Abdominal ultrasound documented the resolution of local mesenteric disease in one animal, sternal lymphadenopathy in another, and hepatic metastases in a third. In the intent-to-treat population, median OS was 109 days with 43% of animals alive and healthy at up to one year post-splenectomy. A single incidence of grade 1/2 uveitis resolved promptly with administration of ophthalmic corticosteroids.
Conclusions: Administration of autologous cell therapy in conjunction with low-dose doxorubicin is feasible, safe, and highly efficacious in the companion canine population. Generally, if subjects survived long enough to begin treatment, the prognosis became quite favorable. The results suggest that additional clinical studies in both canines and humans are warranted.
Citation Format: Matthew M. Halpert, Vanaja Konduri, Yunyu Chen, Dan Liang, Jonathan M. Levitt, Brittany Neal, Caleb Hudson, Heidi Hottinger, Sindy Piscoya, Nicola Wilson, Lisa DiBernardi, Shonda Stallings, Zharkyn Omarbekov, Lori Seelhof, Oscar Ramirez, Qizhi C. Yao, Ratan D. Bhardwaj, Vinod Ravi, Laurel Douglass, William K. Decker. Durable remission of lethal canine hemangiosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-201. doi:10.1158/1538-7445.AM2017-LB-201</jats:p
Maternal and professional identity change during the transition to motherhood
No full textBecoming a mother derails many women’s chances for career progression. One reason for this is that women leave organisations when they become mothers, or reduce their working hours. Another reason is that people within the organisation start to view them as less career-orientated as a result of being mothers. At the core of this issue is that who a woman is – her identity – is being redefined in the transition to motherhood, by herself and by those around her. But, little is known about how her professional identity develops during the transition to motherhood, or whether its development is related to her growing maternal identity. This paper, therefore, presents a systematic review of the literature concerning changes in maternal and professional identities, as well as the relationship between them. Based on the evidence, this review concludes that although the development of maternal identity has been well documented in the literature, little is known about how a woman’s professional identity develops, as she becomes a mother. Suggestions for further research and practice are discussed
The Impact of Chronic Stress on the Psychological Well-Being and Cognitive Functioning of Older Dementia Caregivers
No full textDegree awarded: Ph.D. Psychology. The Catholic University of AmericaOlder individuals caring for loved ones with memory problems, including dementia, are part of a dramatically expanding population in the United States. Caregivers are faced with the physically, emotionally, cognitively and financially daunting task of caring for those whose well-beings are expected to progressively decline over time. Currently, 9.9 million informal (i.e., unpaid) caregivers, typically spouses or adult children, care for individuals 50 and older who have dementia in the United States. This estimate will significantly increase as the number of individuals with Alzheimer's disease grows from 5.3 million to 16 million Americans in 2050.Not surprisingly, dementia caregivers frequently experience higher levels of stress than non-caregivers and other types of caregivers. Studies have shown that the added impact of chronic stress accelerates the aging process and precipitates subsequent impairments in psychological and cognitive health. We are particularly concerned with how cognition is influenced given the enormous cognitive responsibilities older caregivers undertake in providing care. If caregiver cognitive functions are compromised, this could adversely affect their abilities to take care of themselves as well as their patients.This study explored the impact of chronic stress on both psychological well-being and cognitive functioning in older dementia caregivers. Sixty-five caregivers and 64 non-caregivers participated in a two-part study which included a take-home packet of clinical measures and a cognitive battery administered over the telephone. As expected, we found that caregivers exhibited significantly higher levels of distress (e.g., stress, depression and anxiety) than non-caregivers. We also predicted that caregivers would be impaired in cognitive functions dependent on brain areas impacted by stress, including the prefrontal cortex and hippocampus. Caregivers did perform, as expected, worse compared to non-caregivers on four areas of executive functioning mediated by the frontal lobes: working memory, verbal fluency, attention-switching and processing speed. Contrary to our prediction, caregivers were not impaired relative to non-caregivers on hippocampally-dependant episodic verbal fluency. Finally, as hypothesized, caregivers demonstrated preserved implicit learning despite the double insult of stress and aging. The findings of this study alert us to the cognitive issues older dementia caregivers face and important implications are discussed.Made available in DSpace on 2011-02-24T20:46:49Z (GMT). No. of bitstreams: 1
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TLT2 Potentiates Neutrophil Antibacterial Activity and Chemotaxis in Response to G Protein-Coupled Receptor-Mediated Signaling
No full textAbstract
Receptors encoded within the Trem locus have been shown to play an important role in modulating the cellular response to pattern recognition receptor signaling. TREM-like transcript 2 (TLT2) is a member of the Trem locus that is conserved in mouse and human. TLT2 exhibits a unique expression pattern in that it is expressed on cells of the myeloid and lymphoid lineage, suggesting that it plays a role in both innate and adaptive immunity. In this work, studies reveal that TLT2 plays an important role in potentiating neutrophil antibacterial activity and chemotaxis. TLT2 ligation enhances the neutrophil response to the formylated peptide FMLF, leading to increased reactive oxygen species production, degranulation, and chemotaxis. Moreover, TLT2 has the ability to specifically potentiate neutrophil activation and chemotaxis in response to a range of agonists that bind to G protein-coupled receptors, as it does not potentiate the response of cells to growth factor receptor-, Fc receptor-, or TLR-mediated signaling. Finally, TLT2 ligation potentiates the recruitment of neutrophils to sites of inflammation in vivo. These findings reveal a novel functional role for TLT2 that involves potentiation of neutrophil responses to G protein-coupled receptor signaling. Thus, TLT2 appears to play an important role in enhancing the innate immune response via a novel molecular mechanism.</jats:p
Abstract LB-132: The potential role of the multienzyme aminoacyl-tRNA synthetase complex in Th-1 immunity: implications for cancer immunotherapy
No full textImmunotherapy for Invasive Mold Disease in Transplant Patients: Dendritic Cell Immunotherapy, Interferon Gamma, Recombinant Myeloid Growth Factors, and Healthy Donor Granulocyte Transfusions
No full textGeneration of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC
No full textPMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Evaluations for in vitro correlates of immunogenicity of inactivated influenza a H5, H7 and H9 vaccines in humans.
No full textBackgroundSerum antibody responses in humans to inactivated influenza A (H5N1), (H9N2) and A (H7) vaccines have been varied but frequently low, particularly for subunit vaccines without adjuvant despite hemagglutinin (HA) concentrations expected to induce good responses.DesignTo help understand the low responses to subunit vaccines, we evaluated influenza A (H5N1), (H9N2), (H7N7) vaccines and 2009 pandemic (H1N1) vaccines for antigen uptake, processing and presentation by dendritic cells to T cells, conformation of vaccine HA in antibody binding assays and gel analyses, HA titers with different red blood cells, and vaccine morphology in electron micrographs (EM).ResultsAntigen uptake, processing and presentation of H5, H7, H9 and H1 vaccine preparations evaluated in humans appeared normal. No differences were detected in antibody interactions with vaccine and matched virus; although H7 trimer was not detected in western blots, no abnormalities in the conformation of the HA antigens were identified. The lowest HA titers for the vaccines were SummaryAntigen uptake, processing and presentation to human T cells and conformation of the HA appeared normal for each inactivated influenza A vaccine. Low HA titer was associated with low immunogenicity and presence of particles or split virus pieces was associated with higher immunogenicity
Dendritic Cell Maturation and Cytokine Secretion by T Cells Stimulated in vitro with Influenza A Virus Vaccines and Hemagglutinin Proteins.<sup>1</sup>
No full text1<p>Immature dendritic cells loaded with antigen, matured with cytokines and used to present antigens to T cells that secrete cytokines.</p>2<p>Monovalent vaccine (manufacturer) or recombinant HA proteins described in M&M.</p>3<p>As determined in FACS for CD83 and HLADR.</p>4<p>Numbers of ELISpots for indicated cytokine secretion after T cell stimulation; unstimulated lymphocytes, DC only and medium controls did not show ELISpots.</p>5<p>The test was before and after dialysis in a repeat test, after dialysis result shown.</p>6<p>NT = not tested.</p
Dendritic Cell-Secreted Cytotoxic T-Lymphocyte-Associated Protein-4 Regulates the T-cell Response by Downmodulating Bystander Surface B7
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