Metastatic gastric cancer target lesion complete response with Claudin18.2-CAR T cells.

Treatment of hematologic malignancies with patient-derived anti-CD19 chimeric antigen receptor (CAR) T-cells has demonstrated long-term remissions for patients with otherwise treatment-refractory advanced leukemia and lymphoma. Conversely, CAR T-cell treatment of solid tumors, including advanced gastric cancer (GC), has proven more challenging due to on-target off-tumor toxicities, poor tumor T-cell infiltration, inefficient CAR T-cell expansion, immunosuppressive tumor microenvironments, and demanding preconditioning regimens. We report the exceptional results of autologous Claudin18.

Adenosine-related small molecules show utility of recall antigen assay to screen compounds for off-target effects on memory T cells.

Extracellular adenosine suppresses T cell immunity in the tumor microenvironment and in vitro treatment of memory T cells with adenosine can suppress antigen-mediated memory T cell expansion. We describe utilizing the recall antigen assay platform to screen small molecule drug off-target effects on memory T cell expansion/function using a dosing regimen based on adenosine treatment. As a proof of principle, we show low dose GS-5734, a monophosphoramidate prodrug of an adenosine analog, does not alter memory T cell recall at lower doses whereas toxicity observed at high dose favors antigen-specific memory T cell survival/proliferation over non-specific CD8 T cells.

Intranasal Therapeutic Peptide Vaccine Promotes Efficient Induction and Trafficking of Cytotoxic T Cell Response for the Clearance of HPV Vaginal Tumors.

Human papillomavirus (HPV)-induced cancers continue to affect millions of women around the world, and the five year survival rate under the current standard of care for these cancers is less than 60% in some demographics. Therefore there is still an unmet need to develop an effective therapy that can be easily administered to treat established HPV cervical cancer lesions. We sought to investigate the potential of an intranasal HPV peptide therapeutic vaccine incorporating the combination of α-Galactosylceramide (α-GalCer) and CpG-ODN adjuvants (TVAC) against established HPV genital tumors in a syngeneic C57BL/6J mouse model.

Targeting interferon signaling and CTLA-4 enhance the therapeutic efficacy of anti-PD-1 immunotherapy in preclinical model of HPV oral cancer.

Background: The US is experiencing an epidemic of HPV oropharyngeal cancers (OPC), the rates and burden of which now exceed that for cervical cancer. Immunotherapy targeting programmed death 1 (PD-1) on tumor-infiltrating lymphocytes and/or its ligand PD-L1 on tumor cells, which was effective in several cancers has however, showed efficacy in only less than 15% of patients.

Methods: We used a preclinical HPV oral tumor model, mEER, consisting of mouse tonsil derived epithelial cells expressing HPV-16 E6 and E7 genes, along with the H-ras oncogene to test strategies for enhancing the efficacy of anti-PD-1 therapy.

Relationship Between the History of Abuse in the Childhood and Abusive Behaviour Towards Children. Itagüí, Colombia, 2012-2013.

Introduction: One of the experiences that represent the biggest risk for any society is child abuse. Despite the consequences of this form of violence, it tends to be a hidden and little understood phenomenon. The reason why parents mistreat their children has been one of the issues that has raised the most interest in the investigation of this phenomenon.

Mucosal HPV E6/E7 Peptide Vaccination in Combination with Immune Checkpoint Modulation Induces Regression of HPV Oral Cancers.

High-risk human papillomavirus (HPV)-associated squamous cell carcinomas of the oropharynx (SCCOP) are among the fastest growing cancers. After standard-of-care treatment, however, patients with HPV SCCOP have better overall and disease-specific survival than patients with HPV SCCOP, suggesting the importance of HPV-specific immunity. We reasoned that therapeutic vaccination targeting the HPV-16 E6 and E7 oncogenes could elicit high-affinity, high-frequency tumor antigen-specific T-cell responses, which could then be augmented and shielded from suppression in the tumor microenvironment by immune checkpoint modulation.

Mental disorders and drug use in victims of the armed conflict in three cities in Colombia.

Introduction: Violence in its different forms increases the risk of mental disorders and the use of drugs. Objectives: To assess the prevalence of mental disorders, and the use and abuse of drugs, as well as associated factors in victims of forced displacement in three cities in Colombia. Materials and methods: We conducted a prevalence study with 1.

[Sexual Abuse and Neglect Situations as Risk Factors for Adolescent Pregnancy].

Background: In Colombia, one out of five women between the ages of 15 and 19 years have been pregnant. Almost two-thirds (64%) of these pregnancies were unplanned.

Objectives: To examine the socio-demographic, psychosocial and clinical risk factors associated with adolescent pregnancy.

Socio-demographic patterns of posttraumatic stress disorder in Medellin, Colombia and the context of lifetime trauma exposure.

Colombia, South America is currently transitioning to post-conflict status following 6 decades of armed conflict. The population has experienced extensive exposures to potentially traumatic events throughout the lifespan. Sources of trauma exposure include the prolonged armed insurgency, narco-trafficking violence, urban gang violence, violent actions of criminal bands, intra-familial violence, gender-based violence, and sex trafficking.

Spatial Analysis of Dengue Seroprevalence and Modeling of Transmission Risk Factors in a Dengue Hyperendemic City of Venezuela.

Background: Dengue virus (DENV) transmission is spatially heterogeneous. Hence, to stratify dengue prevalence in space may be an efficacious strategy to target surveillance and control efforts in a cost-effective manner particularly in Venezuela where dengue is hyperendemic and public health resources are scarce. Here, we determine hot spots of dengue seroprevalence and the risk factors associated with these clusters using local spatial statistics and a regression modeling approach.

Multicountry prospective clinical evaluation of two enzyme-linked immunosorbent assays and two rapid diagnostic tests for diagnosing dengue fever.

We evaluated four dengue diagnostic devices from Alere, including the SD Bioline Dengue Duo (nonstructural [NS] 1 Ag and IgG/IgM), the Panbio Dengue Duo Cassette (IgM/IgG) rapid diagnostic tests (RDTs), and the Panbio dengue IgM and IgG capture enzyme-linked immunosorbent assays (ELISAs) in a prospective, controlled, multicenter study in Peru, Venezuela, Cambodia, and the United States, using samples from 1,021 febrile individuals. Archived, well-characterized samples from an additional 135 febrile individuals from Thailand were also used. Reference testing was performed on all samples using an algorithm involving virus isolation, in-house IgM and IgG capture ELISAs, and plaque reduction neutralization tests (PRNT) to determine the infection status of the individual.

Dengue seroprevalence and risk factors for past and recent viral transmission in Venezuela: a comprehensive community-based study.

Dengue transmission in Venezuela has become perennial and a major public health problem. The increase in frequency and magnitude of recent epidemics prompted a comprehensive community-based cross-sectional study of 2,014 individuals in high-incidence neighborhoods of Maracay, Venezuela. We found a high seroprevalence (77.

Sentinel surveillance of influenza-like illness in two hospitals in Maracay, Venezuela: 2006-2010.

Background: Limited information exists on the epidemiology of acute febrile respiratory illnesses in tropical South American countries such as Venezuela. The objective of the present study was to examine the epidemiology of influenza-like illness (ILI) in two hospitals in Maracay, Venezuela.

Methodology/principal Findings: We performed a prospective surveillance study of persons with ILI who presented for care at two hospitals in Maracay, Venezuela, from October 2006 to December 2010.

A three-component biomarker panel for prediction of dengue hemorrhagic fever.

Dengue virus infections are a major cause of morbidity in tropical countries. Early detection of dengue hemorrhagic fever (DHF) may help identify individuals that would benefit from intensive therapy. Predictive modeling was performed using 11 laboratory values of 51 individuals (38 DF and 13 DHF) obtained on initial presentation using logistic regression.

Dengue virus infections in a cohort of schoolchildren from Maracay, Venezuela: a 2-year prospective study.

In 2001, we began a prospective longitudinal study in a cohort of schoolchildren 5-13 years of age residing in Maracay, Venezuela, to determine the cumulative incidence of dengue virus (DENV) infections by virus serotype. This report presents serological data from 710 schoolchildren who were tested during the first 2 years of the study. Serological evaluations were conducted by plaque reduction neutralization test (PRNT).

[Laboratory diagnosis of dengue virus infections in Aragua State, Venezuela: October 1997-December 1998].

The efficacy of a proactive dengue surveillance system to predict epidemics depends on the laboratory diagnostic capacity for an early detection of virus circulation. This study shows the results of the dengue virologic and serologic surveillance accomplished in Aragua State (Venezuela) from October 1997 to December 1998. Five hundred and forty seven sera from suspected dengue patients were tested using the techniques of Virus Isolation and Immunofluorescence Serotyping (VIIS), Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), Anti-dengue IgM Capture Enzyme Immunoassay (MAC-ELISA) and Haemagglutination Inhibition test (HI).