Frequency of human papillomavirus infection in patients with gastrointestinal cancer. / Frecuencia de infección por virus del papiloma humano en pacientes con cáncer del aparato digestivo.

INTRODUCTION AND AIM: Cancer is the result of the interaction of genetic and environmental factors. It has recently been related to viral infections, one of which is human papillomavirus. The aim of the present study was to describe the frequency of human papillomavirus infection in patients with digestive system cancers. MATERIALS AND METHODS: A prospective, multicenter, observational study was conducted on patients with gastrointestinal cancer at 2public healthcare institutes in Veracruz. Two tumor samples were taken, one for histologic study and the other for DNA determination of human papillomavirus and its genotypes. Anthropometric variables, risk factors, sexual habits, tumor location, and histologic type of the cancer were analyzed. Absolute and relative frequencies were determined using the SPSS version 24.0 program. RESULTS: Fifty-three patients were studied. They had gastrointestinal cancer located in: the colon (62.26%), stomach (18.87%), esophagus (7.55%), rectum (7.55%), and small bowel (3.77%). Human papillomavirus was identified in 11.32% of the patients, 66.7% of which corresponded to squamous cell carcinoma and 33.3% to adenocarcinoma. Only genotype 18 was identified. Mean patient age was 61.8±15.2 years, 56.60% of the patients were men, and 43.40% were women. A total of 15.8% of the patients had a family history of cancer and 31.6% had a personal history of the disease, 38.6% were tobacco smokers, and 61.4% consumed alcohol. Regarding sex, 5.3% of the patients said they were homosexual, 3.5% were bisexual, 29.8% engaged in oral sex, and 24.6% in anal sex. CONCLUSIONS: Our study showed that human papillomavirus infection was a risk factor for the development of gastrointestinal cancer, especially of squamous cell origin.

Non-Conjugated Chitosan-Based Nanoparticles to Proteic Antigens Elicit Similar Humoral Immune Responses to Those Obtained with Alum.

Biodegradables Chitosan-based Nanoparticles (CS NPs) have been extensively studied as delivery system for therapeutic molecules and as efficient carriers or adjuvants in experimental vaccination. Physicochemical association between CS NPs and antigens is a key step for the biological function as carrier devices. However, for the adjuvant CS NPs property, it is not well known if coupling with vaccine antigens is required or not to potentiate the immune response. To address this issue, in this work, we evaluated the potential adjuvant effect of CS NPs by simply mixing with two different antigens such as Bovine Serum Albumin (BSA) or E protein from Dengue Virus serotype 2 (E protein DENV2). Thus the CS NPs were prepared by ionic gelation with sodium tripolyphosphate, resulting particles among 68 and 188 nm of size. Immunization of 6­8 week old female BALB/c mice, were carried out by intraperitoneal route with a simple combination of CS NPs either with BSA (CS NPs-BSA) at 10 µg or with E protein DENV2 (CS NPs-Protein E) at 5 µg. Combinations with the above antigens with CS NPs elicited robust specific primary and secondary humoral responses comparable to alum, a well-known adjuvant. BSA-specific IgG titers were detectable by day 14 after priming with the CS NPs-BSA formulation, with titers that ranged from 102 to 103 EU ml-. After a second immunization, the anti-BSA titers ranged around 104 EU ml-. In contrast, in the group of mice immunized with the protein alone, BSA-specific serum IgG titers were undetectable at day 14 and 28. For the immunizations with the CS NPs-E protein formulation, we observed also a remarkable specific-antibody production in the primary response, with titers reaching 103 EU ml-. After the booster immunization the anti-E protein DENV2 antibodies titers reached peak values around 104 EU ml-. Interestingly, for both antigens, the combination with CS NPs polarized the immune response to a Th2-like profile, which is characterized mainly by the production of the IgG1 Isotype, confirming that CS NPs can enhance and modulate the humoral immune responses against different antigens independently of physicochemical conjugation. This could represent a simplification in the use of CS NPs as adjuvants in vaccination.

Evaluation of the safety and adjuvant effect of a detoxified listeriolysin O mutant on the humoral response to dengue virus antigens.

Listeriolysin O (LLO) has been proposed as a potential carrier or adjuvant molecule in the vaccination field. However, the cytotoxic and pro-apoptotic effects of LLO are the major limitations for this purpose. Here, we have performed a preclinical safety evaluation and characterized a new potential adjuvant application for a non-cytolytic LLO mutant (dtLLO) to enhance and modulate the immune response against the envelope (E) protein from dengue virus. In addition, we have studied the adjuvant effects of dtLLO on human immune cells and the role of membrane cholesterol for the binding and proinflammatory property of the toxoid. Our in-vivo results in the murine model confirmed that dtLLO is a safer molecule than wild-type LLO (wtLLO), with a significantly increased survival rate for mice challenged with dtLLO compared with mice challenged with wtLLO (P < 0·001). Histopathological analysis showed non-toxic effects in key target organs such as brain, heart, liver, spleen, kidney and lung after challenge with dtLLO. In vitro, dtLLO retained the capacity of binding to plasma membrane cholesterol on the surface of murine and human immune cells. Immunization of 6-8-week-old female BALB/c mice with a combination of dtLLO mixed with E protein elicited a robust specific humoral response with isotype diversification of immunoglobulin (Ig)G antibodies (IgG1 and IgG2a). Finally, we demonstrated that cholesterol and lipid raft integrity are required to induce a proinflammatory response by human cells. Taken together, these findings support a potential use of the dtLLO mutant as a safe and effective adjuvant molecule in vaccination.

Analysis of antibody response in human dengue patients from the Mexican coast using recombinant antigens.

This study was undertaken to evaluate the feasibility of using recombinant dengue proteins to discriminate between acute dengue infections versus uninfected dengue samples. Dengue virus proteins E, NS1, NS3, and NS4B were cloned as fusion proteins and expressed in Escherichia coli. Recombinant products were tested in 100 serum samples obtained from acute dengue fever cases collected from 3 states of Mexico where dengue is endemic. Sera from 75 healthy individuals living in nonendemic areas for dengue were used as a control group. In sera from the dengue patients group, antibody responses to E protein were demonstrated in 91% of cases and NS1 protein was recognized to various extents (99%) within the first 7 days of infection. The antibody responses to NS3 and NS4B were frequently of low magnitude. Consistent negative antibody responses to all proteins were found in sera from the control group. These data suggest that the glutathione-S-transferase (GST)-dengue fusion proteins may be feasible antigens for a sensitive and specific serological assay.