A systematic analysis of experimental immunotherapies on tumors differing in size and duration of growth

We conducted a systematic analysis to determine the reason for the apparent disparity of success of immunotherapy between clinical and experimental cancers. To do this, we performed a search of PubMed using the keywords “immunotherapy” AND “cancer” for the years of 1980 and 2010. The midspread of experimental tumors used in all the relevant literature published in 2010 were between 0.5–121 mm3 in volume or had grown for four to eight days. Few studies reported large tumors that could be considered representative of clinical tumors, in terms of size and duration of growth. The predominant effect of cancer immunotherapies was slowed or delayed outgrowth. Regression of tumors larger than 200 mm3 was observed only after passive antibody or adoptive T cell therapy. The effectiveness of other types of immunotherapy was generally scattered. By comparison, very few publications retrieved by the 1980 search could meet our selection criteria; all of these used tumors smaller than 100 mm3, and none reported regression. In the entire year of 2010, only 13 used tumors larger than 400 mm3, and nine of these reported tumor regression. Together, these results indicate that most recent studies, using many diverse approaches, still treat small tumors only to report slowed or delayed growth. Nevertheless, a few recent studies indicate effective therapy against large tumors when using passive antibody or adoptive T cell therapy. For the future, we aspire to witness the increased use of experimental studies treating tumors that model clinical cancers in terms of size and duration of growth

The rise of noncommunicable diseases in Latin America and the Caribbean: challenges for public health policies

The health landscape in Latin America and the Caribbean is changing quickly. The region is undergoing a demographic and epidemiological transition in which health problems are highly concentrated on noncommunicable diseases (NCDs). In light of this, the region faces two main challenges: (1) develop cost-effective policies to prevent NCD risk factors, and (2) increase access to quality healthcare in a scenario in which a large share of the labor force is employed in the informal sector. This paper describes both alternative interventions to expand health insurance coverage and their trade-off with labor informality and moral hazard problems. The paper also focuses on obesity as a case example of an NCD, and emphasizes how lack of knowledge along with self-control problems would lead people to make suboptimal decisions related to food consumption, which may later manifest in obesity problems.Fil: Anauati, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; ArgentinaFil: Galiani, Sebastian. University of Maryland; Estados UnidosFil: Weinschelbaum, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de San Andrés; Argentin

Comparison of the effect of orally administered soluble β-(1-3),(1-6)-D-glucan and of G-CSF on the recovery of murine hematopoiesis

beta-Glucans are branched fungal polysaccharide compounds with pleiotropic activating effects on cells of the immune and the hematopoietic system. In this study, the hematopoiesis-promoting effect of an orally administered soluble beta-(1-3),(1-6)-D-glucan and of intravenously (i.v.) injected recombinant human granulocyte colony-stimulating factor (G-CSF/filgrastim) was tested in cyclophosphamide (CY)-conditioned mice. Both agents were administered for 5 consecutive days following treatment with CY. When G-CSF and the carbohydrate compound were co-administered, a small but non-significant increase of granulopoiesis compared to G-CSF alone was detected. beta-Glucan alone failed to augment granulopoiesis in the peripheral blood of CY-treated mice. However, both G-CSF and beta-glucan significantly enhanced the recovery of monocytes in the peripheral blood of leukopenic mice when orally administered as single agents. In conclusion, the present study provides further evidence of a stimulatory function of orally administered beta-glucans on monocyte production and shows a weak additive effect on granulopoiesis when co-administered with G-CSF into leukopenic mice

Oral administration of a soluble 1-3, 1-6 beta-glucan during prophylactic survivin peptide vaccination diminishes growth of a B cell lymphoma in mice

beta-glucans are biological response modifiers with activatory effects on macrophages, dendritic cells (DC), granulocytes and NK-cells. In this study, we investigated the effect of a soluble yeast-derived beta- (1-3), (1-6)-D-glucan on prophylactic peptide vaccination against the B cell lymphoma A20 in syngeneic Balb/c mice. We found that repeated immunizations with two MHC class I-restricted peptides derived from the tumor antigen survivin combined with oral co-administration of beta-glucan could significantly diminish intradermal tumor growth, whereas peptide vaccination alone failed to control tumor growth. beta-glucan as single agent induced only a weak but non-significant growth inhibitory effect. To determine whether the tumor inhibitory effect of the combined treatment was associated with the induction of a tumor specific immune response we quantified splenic DC and macrophages, analyzed the maturation of DC and measured the frequency of peptide-specific CD8(+) and CD4(+) T cells. Treated mice showed significantly increased numbers of splenic macrophages and mature DC compared to untreated tumor bearing mice. After restimulation with both peptides in vitro elevated levels of interferon (IFN)-gamma-secreting CD8(+) T cells were found in two of four tested mice following treatment and one of four mice showed a strong increase of interleukin (IL)-4-secreting CD4(+) T cells. Our data reveal a beneficial effect of beta- (1-3), (1-6)-D-glucan in tumor growth inhibition by tumor specific peptide vaccination which may rely on a function of the polymeric sugar as immunological adjuvant