Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: a phase I pilot study

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background: Overall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients. Methods: Five HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 x 107 DC cells administered subcutaneous and intravenously two times at two week intervals. The immunologic response, safety and tolerability to the vaccine were evaluated by the lymphoproliferation assay and clinical and laboratorial evolution, respectively. Results: The dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.005). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together. Conclusion: Despite the small sample size, the results on the immune response, safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment.30Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Radiology of the Hospital Estadual Sumare UNICAMPSCOGConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq [401327/05-1

Garetosmab in Fibrodysplasia Ossificans Progressiva: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths (5 of 44; 11.4%) occurred in the open-label period and, while considered unlikely to be related, causality cannot be ruled out. The primary efficacy end point in period 1 (total lesion activity by PET–CT) was not met (P = 0.0741). As the development of new HO lesions was suppressed in period 1, the primary efficacy end point in period 2 was prospectively changed to the number of new HO lesions versus period 1. No placebo patients crossing over to garetosmab developed new HO lesions (0% in period 2 versus 40.9% in period 1; P = 0.0027). Further investigation of garetosmab in FOP is ongoing

Urban vs. rural patients. Differences in stage and overall survival among patients treated surgically for lung cancer

Introduction. Besides the undoubted influence of risk factors on morbidity and survival time, there are also other environmental factors, such as awareness of the prevalence of risk factors and the availability of modern diagnosis and treatment methods. Objective. To evaluate differences in lung cancer 5-year overall survival rates between urban and rural patients hospitalized in the Department of Thoracic Surgery of the Medical University in Lublin, Poland, and possible influence of several risk factors on these rates. Materials and methods. The analysis was based on 125 lung cancer patients who underwent surgical procedures in years 2006-2007 and who agreed to take part in the survey. The study aimed at recognition of the health situation and selected demographic traits of people who had been treated surgically for lung cancer. The differences were evaluated between rural and urban inhabitants in gender, age, lung function, smoking habits, exposure to risk factors at work, family history of cancer, staging of the disease, histological type of cancer, post-surgical treatment, and their possible influence on overall survival. Results. The results showed that the only noted differences between urban and rural population were in tobacco smoking and lung function. Survival rates were very similar and did not differ from the European average. Conclusions. The assumption that Polish rural patients are presenting with later cancer stages at the time of diagnosis, and have worse chances for survival, has become invalid in modern times

Females and Autism

Females with autism are often undiagnosed, misdiagnosed, or receive a diagnosis of autism at a later age than males. This can result in adverse outcomes in their well-being, mental health, education, employment, and independence. Furthermore, the autism spectrum in females is associated with adverse outcomes after puberty, including anxiety, depression, high incidence of suicide, eating disorders, and high rates of other medical problems. The term “autism spectrum disorder” (ASD) and “autism spectrum condition” (ASC) and autism are used interchangeably, including in the citations of this article, and in the article itself. The term “autism spectrum condition” (ASC), coined by Simon Baron-Cohen, is used in the literature to respect both females and males on the autism spectrum who feel that the term “disorder” is stigmatizing, whereas ASC presents both the strengths and difficulties of individuals on the autism spectrum. Autism has traditionally been considered a male-dominated diagnosis, and its current features linked with descriptions in the major diagnostic classification systems are based primarily on males. While researchers continue to question the epidemiology, prevalence, and presentation of autism, there is an emerging awareness and growing clinical recognition that autism in females has a unique symptomatology and may, in fact, be more common in this population than previously acknowledged. Cultural and social aspects may also impact on the autistic characteristics presented by autistic females. Autism may also manifest itself differently, and more subtly, especially in individuals who are not recognized early in life or who do not have profound intellectual or communication difficulties. The current diagnostic assessments have mainly been developed for an autistic male population, and thus may lack the required sensitivity to identify autistic females. It is argued that these assessments may have an inhibitory potential in confirming the diagnosis of autism in females, as they do not reflect the unique presentation of autism in females, demonstrated by greater compensatory capacity and an ability to develop sophisticated methods of “camouflaging” and masquerading in order to blend in with neurotypical peers. Sex and gender stereotypes and differences in patterns of autistic behavior may contribute to females being overlooked in a diagnostic setting. Timely diagnosis and support, however, can reduce the difficulties that females with autism experience. Timely diagnosis can reduce abuse, exploitation, and certain co-occurring conditions, allowing us to better inform females’ needs in education, leisure, social relationships, and employment, so as to promote their well-being and independence

Myeloid and lymphoid dendritic cells in normal pregnancy and pre-eclampsia

The aim of our study was to estimate the populations of peripheral blood myeloid and lymphoid dendritic cells (CD1c(+), BDCA-2(+)) and the CD1c(+) : BDCA-2(+) ratio in normal pregnant women and in patients with pre-eclampsia. Fifteen women in the first, second and third trimesters of normal pregnancy, and 25 patients with pre-eclampsia were included in the study. The dendritic cells were isolated from peripheral blood, stained with monoclonal antibodies against blood dendritic cell antigens (anti-CD1c, anti-BDCA-2) and estimated using the flow cytometric method. CD1c(+) and BDCA-2(+) dendritic cells were present in women during all trimesters of physiological pregnancy and in pre-eclamptic patients. It was observed that the numbers of dendritic cells were significantly lower in the second trimester when compared with the first and third trimesters of normal pregnancy. Furthermore, in the second trimester, CD1c(+) : BDCA-2(+) ratio was higher than in the other trimesters of physiological pregnancy. All populations of dendritic cells and CD1c(+) : BDCA-2(+) ratio did not differ in the first and third trimesters of normal pregnancy. The percentage of BDCA-2(+) dendritic cells was significantly lower in pre-eclampsia in comparison with healthy women in the third trimester of physiological pregnancy, while CD1c(+) : BDCA-2(+) ratio was significantly higher in pre-eclamptic patients when compared with control groups. We concluded that dendritic cells may be involved in the immune regulation during physiological pregnancy. CD1c(+) and BDCA-2(+) cells can influence the Th2 phenomenon which is observed during physiological pregnancy. Furthermore, it seems possible that lower BDCA-2(+) cells percentage and higher CD1c(+) : BDCA-2(+) ratio can be associated with increased Th1-type immunity in patients with pre-eclampsia