Mortalidad y comportamiento de búsqueda de pareja en Pomacea canaliculata (Caenogastropoda: Ampullariidae)

Pomacea canaliculata es un caracol dulceacuícola de origen sudamericano conocido como plaga de cultivos acuáticos y generador de cambios ecosistémicos en humedales naturales. Esto lo ha convertido en una especie modelo para estudios ecológicos. Sin embargo, aspectos fundamentales de su biología, como los factores que afectan su supervivencia permanecen poco explorados. Estudios recientes sugieren que los machos podrían mantener niveles altos de actividad para buscar pareja aun en condiciones de ayuno, poniendo en juego su supervivencia. Los objetivos del presente trabajo fueron analizar la supervivencia de P. canaliculata ante la presencia de un congénere del mismo o de distinto sexo, y buscar cambios en los patrones de actividad relacionados a la búsqueda de pareja que pudiesen mermar su supervivencia. Se registró una menor supervivencia en los machos, sin poder demostrar que ésta sea afectada por el sexo del congénere con quien compartían acuario. No se observaron cambios de actividad, medidos como la velocidad media, velocidad máxima o superficie explorada, en función del sexo de la pareja asignada al caracol experimental. La menor supervivencia en machos no se relaciona con mayores niveles de actividad y probablemente obedezca a diferencias fisiológicas entre sexos. La ausencia de diferencias de comportamiento en relación al sexo de la pareja parece explicarse por un inesperado estado de reposo post-reproductivo. Este estudio puede considerarse como una descripción de los niveles de actividad normales y estudios de una escalatemporal más amplia podrían requerirse para detectar si el comportamiento sexual puede alterar la supervivencia de esta especie.Pomacea canaliculata is a South American freshwater snail which is well known as a pest of aquatic crops and a driver of ecosystem changes in natural wetlands. This has made it a model for ecological studies. However, fundamental aspects of their biology, such as the factors that affect their survival, remain little explored. Recent studies suggest that males may maintain high levels of mate-searching activity even under fasting conditions, jeopardizing their survival. The aims of this study were to analyse the survival of P. canaliculata snails in presence of a congener of the same or different sex and to look for changes in the activity patterns related to the search for a mate that could reduce its survival. A lower survival was recorded in males, without being able to demonstrate that this is affected by the sex of the congener with whom they shared an aquarium. No differences in activity (mean speed, maximum speed or explored surface) were observed depending on the sex of the pair assigned to the experimental snail. The lower survival of males is not related to higher levels of activity and is probably due to physiological differences between the sexes. The absence of behavioural differences in relation to the sex of the couple seems to be explained by an unexpected state of post-reproductive arrest. This study can be considered as a description of normal activity levels and studies of a broader time scale may be necessary to detect whether sexual behaviour can alter their survival.Fil: Osinaga, Milagros Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; ArgentinaFil: Tamburi, Nicolas Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina. Universidad Nacional del Sur. Departamento de Matemática; ArgentinaFil: Martín, Pablo Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentin

Prevalence of EGFR Mutations in Lung Cancer in Uruguayan Population

Background. Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice represents a milestone for personalized therapy of the non-small-cell lung cancer (NSCLC). However, the genetic testing of EGFR mutations has not yet become a routine clinical practice in developing countries. In view of different prevalence of such mutations among different ethnicities and geographic regions, as well as the limited existing data from Latin America, our aim was to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients from Uruguay. Methods. We examined EGFR mutations in exons 18 through 21 in 289 NSCLC Uruguayan patients by PCR-direct sequencing. Results. EGFR mutations were detected in 53 of the 289 (18.3%) patients, more frequently in women (23.4%) than in men (14.5%). The distribution by exon was similar to that generally reported in the literature. Conclusions. This first epidemiological study of EGFR mutations in Uruguay reveals a wide spectrum of mutations and an overall prevalence of 18.3%. The background ethnic structure of the Uruguayan population could play an important role in explaining our findings

Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease

Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1(+) cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4(+)CD25(+) Foxp3(+) regulatory T (T(reg)) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T(reg) cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease.Fil: D'alotto Moreno, Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Martínez Allo, Verónica Candela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Dergan Dylon, Leonardo Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Stupirski, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Mazal, Daniel. Centro Hospitalario Pereira Rossell. Servicio de Anatomía Patologica,; UruguayFil: Osinaga, Eduardo. Universidad de la Republica; UruguayFil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Sundblad, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Salatino, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin

Re-HEDP : pharmacokinetic characterization, clinical and dosimetric evaluation in osseous metastatic patients with two levels of radiopharmaceutical dose

BACKGROUND: A study for pain relief therapy with (188)Re-HEDP was done in patients with bone metastases secondary to breast and prostate cancer. MATERIALS AND METHODS: Patients received 1.3 or 2.2 GBq, in single or multiple doses. Platelets, white and red cells were evaluated during 11 weeks. Pharmacokinetic characterization was done from blood and urine samples for 5 patients along 24 hours. Urinary excretion was evaluated in other 16 patients during 6 hours. Bone uptake was estimated as remaining activity in whole body. Scintigraphic images were acquired at 2 and 24 hs post-administration. Absorbed dose in bone marrow was estimated with Mirdose3. Analgesics intake and pain score were daily recorded. Tumour markers (PSA, and Tn-structure) were monitored in 9 patients during 4 to 6 months. Single doses of low activity (1.3 GBq) were given to twelve patients. Nine patients received multiple doses. RESULTS: All except one patient had normal levels of platelets, white and red cells. Remaining dose in blood at 2 hours was 9%. Urinary elimination was 58%. Bone uptake at 24 hours was 43% (mean value; n = 5). No changes of the haematological parameters were detected along follow-up period. Pain relief was evidenced by decrease or supression of opioid analgesic and by subjective index. PSA showed a decrease in prostate cancer patients (n = 4). Tn-structure showed a significant increase after 4 to 8 months. CONCLUSION: Single or multiple dose scheme could be safely used, with administered activity of (188)Re-HEDP up to 60 mCi, with low bone marrow absorbed doses

Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives

Aberrant glycosylation is a hallmark of cancer and can lead to changes that influence tumor behavior. Glycans can serve as a source of novel clinical biomarker developments, providing a set of specific targets for therapeutic intervention. Different mechanisms of aberrant glycosylation lead to the formation of tumor-associated carbohydrate antigens (TACAs) suitable for selective cancer-targeting therapy. The best characterized TACAs are truncated O-glycans (Tn, TF, and sialyl-Tn antigens), gangliosides (GD2, GD3, GM2, GM3, fucosyl-GM1), globo-serie glycans (Globo-H, SSEA-3, SSEA-4), Lewis antigens, and polysialic acid. In this review, we analyze strategies for cancer immunotherapy targeting TACAs, including different antibody developments, the production of vaccines, and the generation of CAR-T cells. Some approaches have been approved for clinical use, such as anti-GD2 antibodies. Moreover, in terms of the antitumor mechanisms against different TACAs, we show results of selected clinical trials, considering the horizons that have opened up as a result of recent developments in technologies used for cancer control

Molecular basis of incomplete O-glycan synthesis in MCF-7 breast cancer cells: putative role of MUC6 in Tn antigen expression.

International audienceAn incomplete elongation of O-glycan saccharide chains in mucins have been found in epithelial cancers, leading to the expression of shorter carbohydrate structures, such as the Tn antigen (GalNAc-O-Ser/Thr). This antigen is one of the most specific human cancer-associated structures and is capable of inducing effective immune responses against cancer cells. We aimed to investigate the causes of the expression of Tn antigen in the Tn-rich MCF-7 breast cancer cell line focusing on the first step of the O-glycosylation process. Interestingly, amino acid sequences derived from "non-mammary" apomucins (MUC5B and MUC6) were very good acceptor substrates for ppGalNAc-Ts, which are the enzymes catalyzing the Tn antigen synthesis. MUC6 peptide glycosylation with MCF-7 microsome extracts as source of ppGalNAc-T activity yielded 95% conversion of the peptide into MUC6-Tn. In addition, the MUC6-Tn glycopeptide was a poor acceptor substrate for core 1 beta3Gal-T, the next enzyme involved in the saccharide chain biosynthesis, yielding only 5% conversion of MUC6-Tn into MUC6-TF. These results indicate that non-mammary apomucin expression could be responsible, at least in part, for Tn antigen expression in MCF-7 breast cancer cells due to a combined action on glycosyltransferases: an increase of ppGalNAc-T activity and a decrease of core 1 beta3Gal-T activity. Our hypothesis is supported by experiments in vivo showing that (a) native MUC6 glycoproteins express the Tn antigen in MCF-7 cells and (b) Tn antigen expression is increased after transfection with a construct encoding for a MUC6 recombinant protein into the low Tn-expressing breast cancer cell T47D. These results open new horizons in breast cancer glycoimmunology, stressing the potential role of non-mammary apomucins

Crystallization and Preliminary Crystallographic Analysis of a Tetrameric Isolectin from Vicia villosa, Specific for the Tn Antigen

International audienceIsolectin B4 isolated from Vicia villosa seeds is specific for the Tn antigen, a carcinoma-associated molecular marker. Crystals of the isolectin grown in the presence of carbohydrate are tetragonal, space group P 41 (or P43), with a = 91·3 Å, c = 151·7 Å and one tetramer in the asymmetric unit. The crystals diffract X-rays to 2·8 Å resolution and are suitable for high-resolution structural analysis

A Tn antigen binding lectin from Myrsine coriacea displays toxicity in human cancer cell lines.

International audienceThe Tn antigen (GalNAc-O-Ser/Thr) is one of the most specific human cancer-associated structures. In the present study we characterize the biochemical and functional properties of the Myrsine coriacea lectin (McL). We show that McL is an unusual high molecular weight highly glycosylated protein, which displays a strong Tn binding activity. The lectin exhibits in vitro inhibition of proliferation in the six cancer cell lines evaluated, in a dose-dependent manner (the strongest activity being against HT-29 and HeLa cells), whereas it does not exhibit toxicity against normal lymphocytes. McL could be exploited in the design of potential new tools for the diagnosis or treatment of cancer