Enhancing dendritic cell immunotherapy for melanoma using a simple mathematical model

ABSTRACT Background: The immunotherapy using dendritic cells (DCs) against different varieties of cancer is an approach that has been previously explored which induces a specific immune response. This work presents a mathematical model of DCs immunotherapy for melanoma in mice based on work by Experimental Immunotherapy Laboratory of the Medicine Faculty in the Universidad Autonoma de Mexico (UNAM). Method: The model is a five delay differential equation (DDEs) which represents a simplified view of the immunotherapy mechanisms. The mathematical model takes into account the interactions between tumor cells, dendritic cells, naive cytotoxic T lymphocytes cells (inactivated cytotoxic cells), effector cells (cytotoxic T activated cytotoxic cells) and transforming growth factor β cytokine (TGF − β). The model is validated comparing the computer simulation results with biological trial results of the immunotherapy developed by the research group of UNAM. Results: The results of the growth of tumor cells obtained by the control immunotherapy simulation show a similar amount of tumor cell population than the biological data of the control immunotherapy. Moreover, comparing the increase of tumor cells obtained from the immunotherapy simulation and the biological data of the immunotherapy applied by the UNAM researchers obtained errors of approximately 10 %. This allowed us to use the model as a framework to test hypothetical treatments. The numerical simulations suggest that by using more doses of DCs and changing the infusion time, the tumor growth decays compared with the current immunotherapy. In addition, a local sensitivity analysis is performed; the results show that the delay in time “τ ”, the maximal growth rate of tumor “r” and the maximal efficiency of tumor cytotoxic cells rate “aT” are the most sensitive model parameters. Conclusion: By using this mathematical model it is possible to simulate the growth of the tumor cells with or without immunotherapy using the infusion protocol of the UNAM researchers, to obtain a good approximation of the biological trials data. It is worth mentioning that by manipulating the different parameters of the model the effectiveness of the immunotherapy may increase. This last suggests that different protocols could be implemented by the Immunotherapy Laboratory of UNAM in order to improve their results

Clinical trial evaluating the effectiveness of biocompound IMMUNEPOTENT CRP in the third-molar extraction

ABSTRACT A controlled, parallel, randomized and comparative trial was carried out to evaluate the antiinflammatory efficacy of IMMUNEPOTENT CRP versus ibuprofen in patients after third-molar surgery over seven days. The anti-inflammatory efficacy of IMMUNEPOTENT CRP was evaluated using the method of Amin and Laskin, and the analysis of cytokine production (IL-2, IL-4, IL-6, IL-10, TNF-a, INF-g) in saliva was done by flow cytometry. The swelling process after surgery was significant (p < 0.05) and the treatments with IMMUNEPOTENT CRP or ibuprofen controlled this process properly; no difference between the groups was found (p < 0.05). Both treatments were shown to modulate the cytokine production. These results demonstrate the anti-inflammatory activity of the natural compound IMMUNEPOTENT CRP and suggest it could be used in clinical dental practice

Runoff response of a small agricultural basin in the argentine Pampas considering connectivity aspects

Our manuscript analyses the surface runoff variability, and its controlling factors in a small basin with gentle slopes, at the headwaters of a flat catchment, to improve the knowledge of the hydrology of plain areas under agriculture. We study runoff, rainfall and antecedent conditions in the argentine Pampas region. We use correlations, regressions and quantitative and qualitative descriptive information of the system: erosion signs, ground cover by crops, groundwater depth data and temporal changes in the drainage network, to discuss and understand the complexity of the runoff process by frameworks to study (dis)connectivity. The analysis of 56 events evidenced a nonlinear rainfall–runoff relationship. In contrast with other works, we identified clear upper limit events, under which hydrological responses emerge, as a result of combinations of antecedent wetness, rainfall erosivity, ground cover and preferential drainage paths. We separated the nonlinear rainfall–runoff response in three linear relationships according to differences in antecedent wetness conditions. We found differences in runoff responses under wet and dry antecedent conditions, but complex responses under medium antecedent conditions. The analyses of the inputs, the structural and the functional elements of the (dis)connectivity frameworks, were key in the understanding of the temporal changes of runoff, and its complex responses. Temporal coincidences of connectivity components and their feedbacks appear to be strongly associated with the runoff dynamics. High-magnitude hydrological responses occur with complete coincidences, while partial coincidences between the components reduce connectivity and low magnitude and/or heterogeneous responses prevail. Thus, these analyses suggest that runoff is controlled by (dis)connectivity in this basin with gentle slopes. Our work contributes to the understanding of the process of surface runoff in the context of humid flatlands under agricultural land use, by the identification of the complex combinations of factors which regulate/control the (dis)connectivity that helps to interpret the nonlinearities of runoff.Fil: Ares, María Guadalupe. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff". - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff". - Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff"; ArgentinaFil: Varni, Marcelo Raúl. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff". - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff". - Universidad Nacional del Centro de la Provincia de Buenos Aires. Instituto de Hidrología de Llanuras "Dr. Eduardo Jorge Usunoff"; ArgentinaFil: Chagas, Celio Ignacio. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Ingenieria Agricola y Uso de la Tierra. Cátedra de Manejo y Conservación de Suelo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Detection of dengue virus serotype 2 in aedes aegypti in Quintana Roo, Mexico, 2011

Abstract. In October 2011, the State Health Department announced that several laboratory-confirmed cases of dengue had occurred among residents in two neighborhoods of Benito Juarez, Quintana Roo State, Mexico. To identify the dengue virus serotype(s) temporally and spatially associated with the cases, entomologic-based virus surveillance was initiated in October 2011 in both neighborhoods. Adult mosquitoes were collected from 88 houses by CDCbackpack aspirator, and all female Aedes aegypti L. (n = 419) were individually homogenized and assayed in pools of as many as 10 by reverse transcriptionpolymerase chain reaction (RT-PCR) using dengue virus-specific primers. Five (12%) of 41 pools were positive for dengue virus RNA. The individual mosquitoes that comprised the pools were analyzed separately by RT-PCR using dengue virus serotype-specific primers. Six mosquitoes were positive for dengue virus serotype-2 (DENV-2) RNA, three of which were collected in the same house. The mean number of female Ae. aegypti collected in each house was 4.76 ± 6.19. The overall dengue virus-infection rate in female Ae. aegypti was 1.4%. Interestingly, most (60%) of mosquito females were collected only from 15 (17%) houses. In summary, we provide evidence of recent DENV-2 transmission in Quintana Roo State

Soluciones creativas de intervención

En este proyecto se trabajó con empresas socialmente responsables en la creación de vínculos con comunidades, organización y otros ámbitos de la sociedad para mejorar su entorno. Esto se logró a través de la creación de estrategias de comunicación e intervención social, con lo cual la empresa logra obtener un beneficio de posicionamiento y, a la vez, produce un beneficio social tangible

Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC): a dose-finding study and pharmacogenomic analysis

A dose-finding study was performed to evaluate the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD) and the recommended dose (RD) of escalating the doses of capecitabine and fixed doses of irinotecan and oxaliplatin on a biweekly schedule for metastatic colorectal cancer patients (mCRC). A pharmacogenomic analysis was performed to investigate the association between SNPs and treatment outcome. METHODS: Eighty-seven chemotherapy-naive mCRC patients were recruited through a two-step study design; 27 were included in the dose-finding study and 60 in the pharmacogenomic analysis. Oxaliplatin (85 mg m(-2)) and CPT-11 (150 mg m(-2)), both on day 1, and capecitabine doses ranging from 850 to 1500 mg m(-2) bid on days 1-7 were explored. Peripheral blood samples were used to genotype 13 SNPs in 10 genes related to drug metabolism or efficacy. Univariate and multivariate Cox analysis was performed to examine associations between SNPs, ORR and PFS. RESULTS: The capecitabine RD was 1000 mg m(-2) bid. Diarrhoea and neutropenia were the DLTs. After a median follow-up of 52.5 months, the median PFS and OS were 12 (95% CI; 10.6-13.4) and 27 months (95% CI; 17.2-36.8), respectively.The GSTP1-G genotype, the Kohne low-risk category and use of a consolidation approach strongly correlated with decreased risk of progression. Patients with all favourable variables showed a median PFS of 42 months vs 3.4 months in the group with all adverse factors. A superior clinical response was obtained in patients with one GSTP1-G allele as compared with GSTP1-AA carriers (P=0.004). CONCLUSION: First-line therapy with oxaliplatin, irinotecan and capecitabine is efficient and well-tolerated. The GSTP1 polymorphism A>G status was significantly associated with ORR and PFS in mCRC treated with this triplet therapy