Interaction Networks Help to Infer the Vulnerability of the Saproxylic Beetle Communities That Inhabit Tree Hollows in Mediterranean Forests.

Insect communities are facing contrasting responses due to global change. However, knowledge on impacts of communities' reorganizations is scarce. Network approaches could help to envision community changes in different environmental scenarios. Saproxylic beetles were selected to examine long-term variations in insect interaction/diversity patterns and their vulnerability to global change. We evaluated interannual differences in network patterns in the tree hollow-saproxylic beetle interaction using absolute samplings over an 11-year interval in three Mediterranean woodland types. We explored saproxylic communities' vulnerability to microhabitat loss via simulated extinctions and by recreating threat scenarios based on decreasing microhabitat suitability. Although temporal diversity patterns varied between woodland types, network descriptors showed an interaction decline. The temporal beta-diversity of interactions depended more on interaction than on species turnover. Interaction and diversity temporal shifts promoted less specialized and more vulnerable networks, which is particularly worrisome in the riparian woodland. Network procedures evidenced that saproxylic communities are more vulnerable today than 11 years ago irrespective of whether species richness increased or decreased, and the situation could worsen in the future depending on tree hollow suitability. Network approaches were useful for predicting saproxylic communities' vulnerability across temporal scenarios and, thus, for providing valuable information for management and conservation programs.

Sex specificity of dispersal behaviour and flight morphology varies among tree hollow beetle species.

BACKGROUND: Flight performance and dispersal behaviour can differ between sexes, resulting in sex-biased dispersal. The primary sex ratio of populations may also explain dispersal bias between sexes, as this bias may evolve with the primary sex ratio to reduce intrasexual competition. Although dispersal bias between sexes is relevant to population dynamics, there are few studies on sex-biased dispersal in insects. We studied the flight performance and dispersal behaviour of seven saproxylic beetle species associated with tree hollows from a sex perspective. We also analysed the possible coevolution of flight performance with the primary sex ratio. METHODS: Wing loading and wing aspect ratio were used as measures of the flight performance of species and sexes. Dispersal behaviour was explored by analysing the frequency of each sex in interception traps versus the primary sex ratio obtained by tree hollow emergence traps using contingency tables and posthoc standardized residuals. A more active flight behaviour was expected for the sex with higher capture frequency in the interception traps. To explore the causes of flight performance bias between sexes, we searched for possible correlations between wing loading or wing aspect ratio and primary sex ratio using Pearson's correlation coefficient. RESULTS: Wing loading and wing aspect ratio differed between species and sexes, with flight performance being higher in males than in females for four of the seven species analysed. Dispersal behaviour and flight performance matched in the case of Elater ferrugineus; males showed higher flight performance and were the most collected sex in the interception traps (more active flyers). In contrast, the higher flight activity of Cetonia carthami aurataeformis females was not correlated with a higher flight performance than that of males. Moreover, we found that a bias in the primary sex ratio towards females is often correlated with a decrease in female flight performance. CONCLUSIONS: We stress that flight performance and dispersal behaviour of sexes do not always go hand in hand. Moreover, the relationship between the sex ratio and flight performance bias between sexes is not driven by competition within the most abundant sex. The inclusion of a sex perspective in insect dispersal studies would be useful to detect dispersal bias between sexes and its causes and would allow for further analysis of its effects on population dynamics.

Author Correction: Contrasting functional structure of saproxylic beetle assemblages associated to different microhabitats.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Contrasting functional structure of saproxylic beetle assemblages associated to different microhabitats.

Saproxylic beetles depend on diverse microhabitats that are exploited by different species assemblages. We focused on anlyse the functional trait patterns and functional diversity components of two main assemblages that were collected with window traps (WTs) and hollow emergence traps (HETs) respectively, between three protected areas of the Iberian Peninsula. For that we measured phenological, physiological, morphological, and ecological traits. Results showed that the main microhabitats exploited by each assemblage (WT and HET) constrain most of the morphological traits and trophic guilds. In addition, relative elytra length and predator guild, together with adult activity period, responded to differences at the habitat level (among study areas). HET assemblages were less taxonomically diverse but more functionally diverse than those of WTs, enhancing the functional relevance of tree hollows. Additionally, niche filtering dominated WT assemblages, which were characterised by a narrower functional space and a higher redundancy. In contrast, in the HET assemblages the coexistence of functionally dissimilar species is driven by the niche heterogeneity. HET and WT assemblages differed in the functional space occupied by each within areas, but both assemblages reflected coincident patterns among areas that pointed to a reduction of functional space with management.

Saproxylic Cetoniidae (Coleoptera: Scarabaeoidea): A 'Females' World' or a Question of Dependence on Deadwood?

We explored the dependence of some Cetoniidae species on saproxylic environments and microhabitats in a Mediterranean oak forest by analyzing species collected using different kinds of traps-log emergence, hollow emergence, and interception traps-and the sex ratio of the species in each trap. Comparing the sex ratio of the species collected via emergence versus interception was useful to unravel the degree of dependence on saproxylic microhabitats. Among the species studied, Cetonia aurataeformis Curti, 1913 (Coleoptera: Cetoniidae) was the only obligate tree hollow inhabitant. Special attention should thus be paid to the maintenance of tree hollows for the species' conservation in Mediterranean forests. A gradient of dependence on tree hollows was established from the more dependent Protaetia (Potosia) cuprea (Fabricius, 1775) (Coleoptera: Cetoniidae) and Protaetia (Potosia) opaca (Fabricius, 1787) (Coleoptera: Cetoniidae) to the less dependent Protaetia (Netocia) morio (Fabricius, 1781) (Coleoptera: Cetoniidae). All the latter species can be considered facultatively dependent, to varying degrees, on tree hollows. By contrast, the saproxylic affinity of Protaetia (Netocia) oblonga (Gory and Percheron, 1833) (Coleoptera: Cetoniidae), Tropinota squalida (Scopoli, 1783) (Coleoptera: Cetoniidae) and Oxythyrea funesta (Poda, 1761) (Coleoptera: Cetoniidae) was doubtful. Generally, the sex ratio of the studied species was female-biased. A possible explanation may be local male competition for females, suggesting the Cetoniinae is a female world. However, the range of difference in the female-biased sex ratio among species suggests it is important to explore other possible causes, such as differences in dispersal abilities.

Unraveling Saproxylic Insect Interactions in Tree Hollows from Iberian Mediterranean Forest.

Tree hollows are complex microhabitats in which a variety of abiotic and biotic factors shape the community assembly of saproxylic insects. Detecting non-random species co-occurrence patterns is a fundamental goal in ecology in order to understand the assembly mechanisms of communities. We study association patterns of species of Coleoptera and Diptera (Syrphidae), belonging to different trophic guilds, on 72 tree hollows at a local and regional scale in three protected areas in Mediterranean forests using a fixed-fixed null model. Our matrix-level analysis shows a tendency for segregation in species association (species exclusion) at the regional and site levels. However, the high complexity of tree-hollow habitats, offering different resources for a more or less specialized fauna, makes it difficult to prove competition interactions. Indeed, pairwise analysis shows a dominance of non-random aggregation patterns (species coexistence) at the local and regional levels. Both aggregation and segregation of non-random patterns were more common among species from different trophic guilds than within the same guilds, with predators being a common denominator for a high percentage of the inter-guild pairs. Our results suggest that predation and facilitation interactions, together with habitat segregation, are the main factors shaping tree-hollow assemblages, while competition seems to be less important. We conclude that species interactions take an important part of the process of assemblage structuration and special attention should be paid to 'ecosystem engineers' and threatened species in the conservation of tree hollow assemblages.

'Mate' Intake, Hormone-Based Risk Factors and Breast Cancer: a Case-Control Study

Previous reports on the inverse association between 'mate' intake (infusion of Ilex Paraguariensis herb) and breast cancer (BC) risk led us to consider two main roles for the infusion: as a substantial antioxidant contributor and as a hormone regulator, particularly through anti-aromatase capacities. Since menstrual-reproductive risk factors for BC reflect women's estrogenic exposure during the reproductive lifespan, and considering that 'mate' intake exerts putative stronger protection among high antioxidant contributors, we attempted to analyze interactions among the infusion, hormon-linked reproductive factors and BC risk, which have hitherto remained unexplored. We analyzed a database of 572 BC incident cases and 889 controls. Women were interviewed with a specific questionnaire featuring socio-demographic, lifestyle and reproductive variables (age at menarche, 1st live birth and menopause; number of live births; breastfeeding months), and a food frequency questionnaire, focusing on 'mate' intake (consumer status, daily intake, age at start, age at quit, duration of habit). Odds ratios (OR) and their 95% confidence Intervals were calculated through unconditional logistic regression, adjusting for relevant potential confounders. 'Mate' intake showed strong inverse associations with some high-risk hormone-related factors: early menarche, nulliparity, low breastfeeding, long reproductive years and high number of ovulatory cycles. Moreover, all subsets of high dietary energy demonstrated even stronger associations. In conclusion, regarding exposure to known hormone risk factors, we found strong inverse associations between high 'mate' intake and BC, which were greater among those consuming higher calorific diets. Our analyses support possible combined antioxidant and antiestrogenic effects for 'mate' infusions.

Checklist and identification key of Anomalini (Coleoptera, Scarabaeidae, Rutelinae) of Costa Rica.

A checklist and identification key for the species of the tribe Anomalini in Costa Rica are presented. The Anomalini species are important economically, as they have larvae that are or can become agricultural pests, as well as ecologically, having potential as bioindicators. In spite of their importance and richness, identification tools for the group in the Neotropics remain scarce. The Costa Rican fauna comprises six genera (Anomala, Anomalorhina, Callistethus, Epectinaspis, Moroniella, and Strigoderma) and a total of 120 species. Anomala contusa Filippini, Micó, Galante, 2015 is proposed as a synonym of Anomala inbio (Ramírez-Ponce, Bitar, Curoe 2014); Anomala limonnom. n. is proposed as a new name for Anomala inbio Filippini, Galante, Micó, 2015, a homonym of Anomala inbio (Ramírez-Ponce, Bitar, Curoe, 2014); Anomala cinaediasnom. n. is proposed as a new name for Anomala chloropyga Ohaus, 1897, a homonym of Anomala chloropyga Burmeister, 1844; and Anomala chrysomelina is moved to the genus Callistethus.

ResumenPresentamos el listado y la clave de identificación de las especies de la tribu Anomalini de Costa Rica. Las especies de Anomalini son importantes económica, con larvas que son o pueden ser plagas agrícolas, y ecológicamente, con un potencial como bioindicadores. A pesar de su importancia y riqueza, los instrumentos de identificación para el grupo para el Neoptrópico son todavía escasos. La fauna de Costa Rica está compuesta por seis géneros (Anomala, Anomalorhina, Callistethus, Epectinaspis, Moroniella y Strigoderma) y un total de 120 especies. Anomala contusa Filippini, Micó, Galante, 2015 se propone como sinónimo de Anomala inbio (Ramírez-Ponce, Bitar, Curoe, 2014); Anomala limon se propone como nuevo nombre de Anomala inbio Filippini, Galante, Micó, 2015, homónimo de Anomala inbio (Ramírez-Ponce, Bitar, Curoe, 2014); Anomala cinaedias se propone como nuevo nombre de Anomala chloropyga Ohaus, 1897, homónimo de Anomala chloropyga Burmeister, 1844; Anomala chrysomelina se mueve al género Callistethus.

Description of six new species of Anomalini from Costa Rica (Coleoptera: Scarabaeidae: Rutelinae).

Four new species of Anomala Samouelle and two new species of Callistethus Blanchard (Coleoptera: Scarabaeidae: Rutelinae: Anomalini) from Costa Rica are described: A. aglaos new species, A. estrella new species, A. inbio new species, A. pincelada new species, C. ruteloides new species, and C. yalizo new species. A distribution map of each species is given and the male genitalia (aedeagus and endophallus) of the species described and similar species are illustrated.

Association patterns in saproxylic insect networks in three Iberian Mediterranean woodlands and their resistance to microhabitat loss.

The assessment of the relationship between species diversity, species interactions and environmental characteristics is indispensable for understanding network architecture and ecological distribution in complex networks. Saproxylic insect communities inhabiting tree hollow microhabitats within Mediterranean woodlands are highly dependent on woodland configuration and on microhabitat supply they harbor, so can be studied under the network analysis perspective. We assessed the differences in interacting patterns according to woodland site, and analysed the importance of functional species in modelling network architecture. We then evaluated their implications for saproxylic assemblages' persistence, through simulations of three possible scenarios of loss of tree hollow microhabitat. Tree hollow-saproxylic insect networks per woodland site presented a significant nested pattern. Those woodlands with higher complexity of tree individuals and tree hollow microhabitats also housed higher species/interactions diversity and complexity of saproxylic networks, and exhibited a higher degree of nestedness, suggesting that a higher woodland complexity positively influences saproxylic diversity and interaction complexity, thus determining higher degree of nestedness. Moreover, the number of insects acting as key interconnectors (nodes falling into the core region, using core/periphery tests) was similar among woodland sites, but the species identity varied on each. Such differences in insect core composition among woodland sites suggest the functional role they depict at woodland scale. Tree hollows acting as core corresponded with large tree hollows near the ground and simultaneously housing various breeding microsites, whereas core insects were species mediating relevant ecological interactions within saproxylic communities, e.g. predation, competitive or facilitation interactions. Differences in network patterns and tree hollow characteristics among woodland sites clearly defined different sensitivity to microhabitat loss, and higher saproxylic diversity and woodland complexity showed positive relation with robustness. These results highlight that woodland complexity goes hand in hand with biotic and ecological complexity of saproxylic networks, and together exhibited positive effects on network robustness.

Redescription of Anomala eucoma Bates, 1888 and a description of three new species from Costa Rica (Coleoptera: Scarabaeidae: Rutelinae).

Anomala eucoma Bates, 1888 is redescribed and a lectotype from Guatemala is designated. Three new species from Costa Rica, A. flavacoma new species, A. megaparamera new species, and A. pseudoeucoma new species, are described, and a distribution map is given. The internal sac (endophallus) of the species covered is illustrated, and its use in separating closely related species in this region is discussed. An identification key for morphologically similar species from the Neotropical region is provided.

Breaking down complex Saproxylic communities: understanding sub-networks structure and implications to network robustness.

Saproxylic insect communities inhabiting tree hollow microhabitats correspond with large food webs which simultaneously are constituted by multiple types of plant-animal and animal-animal interactions, according to the use of trophic resources (wood- and insect-dependent sub-networks), or to trophic habits or interaction types (xylophagous, saprophagous, xylomycetophagous, predators and commensals). We quantitatively assessed which properties of specialised networks were present in a complex networks involving different interacting types such as saproxylic community, and how they can be organised in trophic food webs. The architecture, interacting patterns and food web composition were evaluated along sub-networks, analysing their implications to network robustness from random and directed extinction simulations. A structure of large and cohesive modules with weakly connected nodes was observed throughout saproxylic sub-networks, composing the main food webs constituting this community. Insect-dependent sub-networks were more modular than wood-dependent sub-networks. Wood-dependent sub-networks presented higher species degree, connectance, links, linkage density, interaction strength, and were less specialised and more aggregated than insect-dependent sub-networks. These attributes defined high network robustness in wood-dependent sub-networks. Finally, our results emphasise the relevance of modularity, differences among interacting types and interrelations among them in modelling the structure of saproxylic communities and in determining their stability.

Addition of an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy improves survival in advanced malignancies.

Studies have shown that cancer requires two conditions for tumor progression: cancer cell proliferation and an environment permissive to and conditioned by malignancy. Chemotherapy aims to control the number and proliferation of cancer cells, but it does not effectively control the two best-known conditions of the tumor-permissive environment: neoangiogenesis and tolerogenic immunity. Many malignant diseases exhibit poor outcomes after treatment with chemotherapy. Therefore, we investigated the potential benefits of adding an induction regimen of antiangiogenesis and antitumor immunity to chemotherapy in poor outcome disease. In a prospective, randomized trial, we included patients with advanced, unresectable pancreatic adenocarcinomas, non-small cell lung cancer, or prostate cancer. Two groups of each primary condition were compared: group 1 (G1), n = 30, was treated with the standard chemotherapy and used as a control, and group 2 (G2), n = 30, was treated with chemotherapy plus an induction regimen of antiangiogenesis and antitumor immunity. This induction regimen included a low dose of metronomic cyclophosphamide, a high dose of Cox-2 inhibitor, granulocyte colony-stimulating factor, a sulfhydryl (SH) donor, and a hemoderivative that contained autologous tumor antigens released from patient tumors into the blood. After treatment, the G2 group demonstrated significantly longer survival, lower blood level of neoangiogenesis and immune-tolerance mediators, and higher blood levels of antiangiogenesis and antitumor immunity mediators compared with the G1 group. Toxicity and quality of life were not significantly different between the groups. In conclusion, in several advanced malignancies of different primary localizations, an increase in survival was observed by adding an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy.

Sampling scarab beetles in tropical forests: the effect of light source and night sampling periods.

Light traps have been used widely to sample insect abundance and diversity, but their performance for sampling scarab beetles in tropical forests based on light source type and sampling hours throughout the night has not been evaluated. The efficiency of mercury-vapour lamps, cool white light and ultraviolet light sources in attracting Dynastinae, Melolonthinae and Rutelinae scarab beetles, and the most adequate period of the night to carry out the sampling was tested in different forest areas of Costa Rica. Our results showed that light source wavelengths and hours of sampling influenced scarab beetle catches. No significant differences were observed in trap performance between the ultraviolet light and mercury-vapour traps, whereas these two methods caught significantly more species richness and abundance than cool white light traps. Species composition also varied between methods. Large differences appear between catches in the sampling period, with the first five hours of the night being more effective than the last five hours. Because of their high efficiency and logistic advantages, we recommend ultraviolet light traps deployed during the first hours of the night as the best sampling method for biodiversity studies of those scarab beetles in tropical forests.

The effect of the landscape matrix on the distribution of dung and carrion beetles in a fragmented tropical rain forest.

Understanding the response of species to anthropogenic landscape modification is essential to design effective conservation programs. Recently, insects have been used in empirical studies to evaluate the impact of habitat modification and landscape fragmentation on biological diversity because they are often affected rapidly by changes in land use. In this study, the use of the landscape matrix by dung and carrion beetles in a fragmented tropical rain forest in the Los Tuxtlas Biosphere Reserve was analyzed. Fragments of tropical rain forest, forest-pasture edges, pastures, isolated trees, living fences (trees connected with barbed wire) and barbed wire fences were studied both near and far from forest fragments. Forest fragments had the highest abundance values, but pastures had the highest dung and carrion beetle biomass. Habitat specificity was high for the beetles in the most dissimilar habitats. Forest fragments and forest-pasture edges had and shared the highest number of species, but they shared only two species with pastures, barbed wire fences and isolated trees. Only one forest species was found within living fences far from the forest fragments. However, approximately 37% of the forest species were caught within living fences near the forest fragments. Therefore, forest-pasture edges function as hard edges and prevent movement among forest fragments, but living fences seem to act as continuous habitat corridors when connected to forest fragments, allowing forest beetles to move between the fragments. Further studies are necessary to determine the minimum width of living fences necessary to provide good corridors for these beetles and other species.

Freshwater fish's spatial patterns in isolated water springs in North-eastern Mexico.

The Media Luna lake-spring was selected as representative of all thermal or no thermal springs in the zone of Valley of Rioverde, a semi-arid vegetation in the North-eastern of Mexico. This system is inhabited by 11 fish species, of which six are native. Four of the native species are endemic to the region and threatened due to touristic pressure and to the introduction of exotic species. The objectives were to determine the characteristics that influence the spatial distribution of the fish species, to analyze their spatial distribution patterns, and to describe the relationships between the different species. The general aim was to establish some basis for the conservation of these fish communities and their habitat. Several sessions were initiated in 1992 through direct observation. Later, between 1998 and 1999 five systematically seasonal sampling sessions were conducted (54 subaquatic transects/session). Finally, the data was updated by sampling in summer 2002 and winter 2006. Through the analysis was performed only for endemics of the region, like Ataeniobius toweri Meek, Cualac tessellatus Miller, Cichlasoma bartoni Bean and C. labridens Pellegrin, in at least one life stage, showed correlation with habitat variables or with other species. For these species, patterns of spatial aggregation and association with other species were observed. These results show a certain degree of specialization of endemic species to some microhabitat characteristics, as well as a significant interaction with other native species which they coexist. In addition, some significant relations between endemic and alien species suggest an antagonist relation. Management actions focused in the touristic use of the spring represent the main threat for these species, followed by an adequate management of exotic species. This study provides basis for future responsible management of these wetlands, where tourism and conservation can be combined.

Freshwater fish’s spatial patterns in isolated water springs in North-eastern Mexico

The Media Luna lake-spring was selected as representative of all thermal or no thermal springs in the zone of Valley of Rioverde, a semi-arid vegetation in the North-eastern of Mexico. This system is inhabited by 11 fish species, of which six are native. Four of the native species are endemic to the region and threatened due to touristic pressure and to the introduction of exotic species. The objectives were to determine the characteristics that influence the spatial distribution of the fish species, to analyze their spatial distribution patterns, and to describe the relationships between the different species. The general aim was to establish some basis for the conservation of these fish communities and their habitat. Several sessions were initiated in 1992 through direct observation. Later, between 1998 and 1999 five systematically seasonal sampling sessions were conducted (54 subaquatic transects/session). Finally, the data was updated by sampling in summer 2002 and winter 2006. Through the analysis was performed only for endemics of the region, like Ataeniobius toweri Meek, Cualac tessellatus Miller, Cichlasoma bartoni Bean and C. labridens Pellegrin, in at least one life stage, showed correlation with habitat variables or with other species. For these species, patterns of spatial aggregation and association with other species were observed. These results show a certain degree of specialization of endemic species to some microhabitat characteristics, as well as a significant interaction with other native species which they coexist. In addition, some significant relations between endemic and alien species suggest an antagonist relation. Management actions focused in the touristic use of the spring represent the main threat for these species, followed by an adequate management of exotic species. This study provides basis for future responsible management of these wetlands, where tourism and conservation can be combined. Rev. Biol. Trop. 58 (1): 413- 426. Epub 2010 March 01.

Este estudio se enfocó en los peces de un sistema dulceacuícola en el noreste de México, donde habitan seis especies nativas (cuatro endémicas amenazadas) y cinco exóticas. El objetivo fue establecer los patrones que determinan la distribución espacial, así como las interrelaciones de las especies. Los datos se basan en sesiones de observación directa desde 1992; entre 1998 y 1999 se llevó a cabo un muestreo sistematizado mediante transectos subacuáticos en cinco sesiones estacionales (54 transectos/ sesión), con sesiones adicionales en 2002 y 2006. Sólo las especies endémicas de la región: Ataeniobius toweri, Cualac tessellatus, Cichlasoma bartoni y C. labridens, en al menos un estadio de vida, mostraron correlación significativa con variables del hábitat o con otras especies. También mostraron patrones de agregación y asociación con otras especies nativas o introducidas. Existe especialización de los endémicos a las condiciones de su microhábitat, así como interacciones significativas con otras especies. Acciones inadecuadas para promover el turismo representaron la mayor amenaza por destrucción del hábitat, endémicos tales como A, toweri y C. bartoni enfrentan solapamiento con especies introducidas, sobre todo en sus sitios de crianza. Este estudio aporta bases para un manejo responsable de estos humedales, donde turismo y conservación pueden combinarse.

Randomized phase II clinical trial of chemo-immunotherapy in advanced nonsmall cell lung cancer.

The purpose of this study was to compare chemotherapy-naive patients with stage IV nonsmall cell lung cancer patients treated with chemotherapy or chemoimmunotherapy. We tested doxetacel plus cisplatinum as chemotherapy protocol. An immunomodulatory adjuvant system was added as chemoimmunotherapy to the previously mentioned protocol. This system contains three well-known and complementary conditioners of protective immune-responses: cyclophosphamide low-dose, granulocyte macrophage-colony stimulant factor and magnesium silicate granuloma. Eighty-eight patients were randomly assigned to receive every 3-weeks one of the treatments under comparison. Patients received four cycles of treatment unless disease progression or unacceptable toxicity was documented. The maximum follow-up was one year. In each arm, tumor response (rate,duration), median survival time, 1-year overall survival, safety, and immunity modifications were assessed. Immunity was evaluated by submitting peripheral blood mononuclear cells to laboratory tests for nonspecific immunity: a) phytohemaglutinin-induced lymphocyte proliferation, b) prevalence of T-Regulatory (CD4+CD25+) cells and for specific immunity: a) lymphocyte proliferation induced by tumor-associated antigens (TAA) contained in a previously described autologous thermostable hemoderivative. The difference (chemotherapy vs. chemoimmunotherapy) in response rate induced by the two treatments (39.0% and 35.0%) was not statistically significant. However, the response duration (22 and 31 weeks), the median survival time (32 and 44 weeks) and 1-year survival (33.3% and 39.1%) were statistically higher with chemoimmunotherapy. No difference in toxicity between both arms was demonstrated. A switch in the laboratory immunity profile, nonspecific and specific, was associated with the chemoimmunotherapy treatment: increase of proliferative lymphocyte response, decrease of tolerogenic T-regulatory cells and eliciting TAA-sensitization.

Advanced breast cancer: anti-progressive immunotherapy using a thermostable autologous hemoderivative.

INTRODUCTION: Advanced breast cancer patients, acquired-chemotherapy resistant and in progression, are therapeutically terminal. We tested a recently described medical procedure using a thermostable autohemoderivative purported to inhibit tumor growth possibly through an immunological mechanism of action. PATIENTS AND METHODS: Metastatic breast cancer patients, chemotherapy-resistant, high CEA and CA 15-3 plasma levels of tumor markers, in progression, were 2-group randomized. Group 1 received the test procedure and Group 2 adequate measures to be comparable control. From 121 included patients, 108 could be evaluated. During 8-month follow-up period, tumor growth, number of cases attaining clinical non-progressive status and mortality were monthly assessed. Immunologic effect was assessed by delayed type hypersensitivity test and lymphocyte proliferation assay. Responding-tumors histopathologies were studied. The proteome of the autologous immunogen was characterized by 2-D electrophoresis. RESULTS AND DISCUSSION: In a significant number of cases, the test procedure promoted inhibition of tumor growth, non-progressive disease status, and lower cumulative mortality. These clinical results were associated with polyvalent immunization against several tested antigens: the hemoderivative used for treatment, the blood tumor markers and the derivative obtained from a regulatory lymphocyte population (CD4+CD25+). Interference with this regulatory activity could explain the selective autoimmunity suggested by the histopathology findings in responding tumors. The thermostability could be an essential property of the immunogen hemoderivative. CONCLUSION: The thermostable autohemoderivative tested is antigenically polyvalent and promoted a polytargeted immune response associated to a tumor anti-progressive effect, consequently, acting as an autohemoderivative cancer vaccine.