El libro a comentar recoge las ponencias y comunicaciones presentadas al seminario que sobre Psic... more El libro a comentar recoge las ponencias y comunicaciones presentadas al seminario que sobre Psicología Ambiental se celebró en Orellana (Badajoz) en el mes de septiembre de 1992, con el fin de discutir en profundidad los aspectos teóricos, metodológicos y aplicados que en este momento constituyen los elementos de análisis y discusión de la disciplina. Los tópicos en torno a los que giró dicha discusión y que vertebran el libro fueron los seis siguientes:
reduces WWOX expression both in hetero and homozygous cases. There was a positive correlation bet... more reduces WWOX expression both in hetero and homozygous cases. There was a positive correlation between expression level of WWOX and marker of proliferation Ki67 (Rs = 0.5440; p < 0.0001), antiapoptotic gene Bcl2 (Rs = 0.7092; p < 0.0001) and JM-a isoform of ErbB4 mRNA level (Rs = 0.7102; p < 0.0001). Conclusions: Our results suggest that loss of heterozygosity (relatively frequent in GBM) along with promoter methylation may decrease the WWOX tumour suppressor expression. We also confirmed that WWOX is correlated with ErbB4 signalling pathway as well as with proliferation and apoptosis in glioblastoma multiforme. 739 Altered expression of miR-205 affects cell proliferation in human cervical cancer
En este trabajo se propone el estudio de la vida en las ciudades como campo de trabajo de la Psic... more En este trabajo se propone el estudio de la vida en las ciudades como campo de trabajo de la Psicología Social y Ambiental. La ciudad es tanto una estructura espacial como social, que incide sobre el comportamiento individual y social. Se sistematiza los modelos y aportaciones más relevantes para el estudio psicológico del hecho urbano. Igualmente, se revisan las primeras aportaciones de psicólogos y sociólogos sobre la ciudad. Unos y otros destacan los aspectos negativos de la vida urbana, particularmente a partir del éxito de las teorías de la sobrecarga. En un apartado posterior se señala la necesidad de que los psicólogos sociales trabajen en la definición de modelos de calidad de vida urbana. Se sugiere prestar atención a cuatro factores: Grado de control, nivel de seguridad en el escenario, programa de actividades sociales del lugar y satisfacción estética.
Oxaliplatin is a highly effective inducer of apoptosis in Mantle Cell Lymphoma cells Obrador Hevi... more Oxaliplatin is a highly effective inducer of apoptosis in Mantle Cell Lymphoma cells Obrador Hevia, Antònia, 1 Belayachi, Lamiae1,2; Ordinas, Carlos1; Rodríguez, José1; Villalonga, Priam1; Fernández de Mattos, Silvia1 1Cancer Cell Biology Group. Institut Universitari d'Investigació en Ciències de la Salut (IUNICS). Universitat de les Illes Balears. Illes Balears (Spain). ; 2Immunology and Biochemistry Laboratory Mohammed V Agdal University - Faculty of Sciences Rabat (Morocco). Mantle Cell Lymphoma (MCL) is an aggressive lymphoma subtype that accounts for 5-7 % of non Hodgkin’s lymphomas (NHL). The disease is mostly incurable because of the continuous pattern of relapse. The frontline treatment including consolidation with high dose radiochemotherapy followed by autologous stem cell transplantation (ASCT) in patients in first remission has improved the survival of this disease. However, the treatment stays generally highly toxic especially for patients over 65 years old. Previou...
Approximately one-third of vertebral fractures can be clinically diagnosed. To study the frequenc... more Approximately one-third of vertebral fractures can be clinically diagnosed. To study the frequency of vertebral fractures in postmenopausal women. We recruited 555 postmenopausal women from Santiago, Chile, aged 55-84 years, who manifested interest in their bone health. All were healthy by self-declaration and by general clinical and laboratory tests and had not taken any bone-active therapy. They all underwent a spine and femoral neck (FN) densitometry and a digital lateral spine X-ray from T4 to L4 was obtained. PTH, calcidiol, and other parameters of calcium metabolism were also measured. Overall, 142 of 478 patients with a complete study (29.7%) had at least one vertebral fracture. The proportion of women with fractures increased with age. A T score below -2.5 in the spine and hip was found in 32% and 14% of women, respectively. The proportion of women with spinal osteoporosis doubled between ages 55-70 and remained constant afterwards. In contrast, at the femoral neck, this pro...
The aim of this study was to assess lumbar spine bone density in a group of chilean postmenopausa... more The aim of this study was to assess lumbar spine bone density in a group of chilean postmenopausal females and to estimate the frequency of vertebral osteopenia in the national urban female population. A clinical assessment and lumbar spine bone density measurement were performed to 171 healthy women over 40 years of age and not receiving medications that modify bone turnover. Calcium ingestion was recalled in 77 of these. Fifty women (29.2%) had osteopenia, defined as a bone density of less than 0.92 g/cm2. Extrapolating this figure to the national urban population, an osteopenia frequency of 21.7% was estimated. Body mass index was 25.5 +/- 3.8 and 57% of the sample was overweight. Calcium ingestion was 740.3 +/- 331.7. These two parameters did not correlative with bone density. Women with osteopenia were older and had a longer postmenopausal lapse than those with normal bone density. The completion of further clinical an epidemiological studies is recommended to know the real mag...
The analysis of historical document images is not only interesting for the preservation of histor... more The analysis of historical document images is not only interesting for the preservation of historical heritage but also for the extraction of semantic knowledge. In this paper we present a word spotting approach to find keyword images in digital archives. Detected words allow ...
Vertebral fractures, osteoporosis and vitamin D levels in Chilean postmenopausal women Background... more Vertebral fractures, osteoporosis and vitamin D levels in Chilean postmenopausal women Background: Approximately one-third of vertebral fractures can be clinically diagnosed. Aim: To study the frequency of vertebral fractures in postmenopausal women. Patients and methods: We recruited 555 postmenopausal women from Santiago, Chile, aged 55-84 years, who manifested interest in their bone health. All were healthy by self-declaration and by general clinical and laboratory tests and had not taken any bone-active therapy. They all underwent a spine and femoral neck (FN) densitometry and a digital lateral spine X-ray from T4 to L4 was obtained. PTH, calcidiol, and other parameters of calcium metabolism were also measured. Results: Overall, 142 of 478 patients with a complete study (29.7%) had at least one vertebral fracture. The proportion of women with fractures increased with age. A T score below-2.5 in the spine and hip was found in 32% and 14% of women, respectively. The proportion of women with spinal opeoporosis doubled between ages 55-70 and remained constant afterwards. In contrast, at the femoral neck, this proportion increased progressively reaching 53.3% at age 80-85. However, 56% of patients with vertebral fractures did not have densitometric osteoporosis in any location. Calcidiol levels were 16.8±6.8 ng/mL. With a cutoff point of 17 ng/mL, 47.5% of the patients had hypovitaminosis D. There was no association between calcidiol levels and vertebral fractures or bone density at the spine or femoral neck. Patients with fractures differed from those without fractures in that they had significantly lower bone density at the spine and hip and were older (p <0.001). However they did not differ in weight, body mass index, or calcidiol levels. Conclusions: Thirty percent of postmenopausal women in this series had a vertebral fractures. Osteoporosis and vitamin D deficiency were also common. Most vertebral fractures were observed in women without osteoporosis by densitometric criteria (Rev Méd Chile 2007; 135: 31-6).
The effect of rapid thermal annealing in oxygen and nitrogen ambients on the properties of silico... more The effect of rapid thermal annealing in oxygen and nitrogen ambients on the properties of silicon oxide films of different stoichiometry was studied. The films were deposited on silicon wafers by plasma enhanced chemical vapour deposition (PECVD) from silane (SiH4) and nitrous oxide (N2O) at different N2O/SiH4 flow ratios. It was found that rapid thermal annealing significantly affects the thickness of deposited oxides and the total mechanical stress in the film. The density and the refractive index of the film hardly changed. The hydrogen content of the films has been discussed on the basis of Fourier transform infrared transmission spectroscopy, and is related to the changes in the film properties.
Enforced EGFR activation upon gene amplification and/or mutation is a common hallmark of malignan... more Enforced EGFR activation upon gene amplification and/or mutation is a common hallmark of malignant glioma. Small molecule EGFR tyrosine kinase inhibitors, such as erlotinib (Tarceva), have shown some activity in a subset of glioma patients in recent trials, although the reported data on the cellular basis of glioma cell responsiveness to these compounds have been contradictory. Here we have used a panel of human glioma cell lines, including cells with amplified or mutant EGFR, to further characterize the cellular effects of EGFR inhibition with erlotinib. Dose-response and cellular growth assays indicate that erlotinib reduces cell proliferation in all tested cell lines without inducing cytotoxic effects. Flow cytometric analyses confirm that EGFR inhibition does not induce apoptosis in glioma cells, leading to cell cycle arrest in G 1. Interestingly, erlotinib also prevents spontaneous multicellular tumour spheroid growth in U87MG cells and cooperates with sub-optimal doses of temozolomide (TMZ) to reduce multicellular tumour spheroid growth. This cooperation appears to be schedule-dependent, since pre-treatment with erlotinib protects against TMZ-induced cytotoxicity whereas concomitant treatment results in a cooperative effect. Cell cycle arrest in erlotinib-treated cells is associated with an inhibition of ERK and Akt signaling, resulting in cyclin D1 downregulation, an increase in p27 kip1 levels and pRB hypophosphorylation. Interestingly, EGFR inhibition also perturbs Rho GTPase signaling and cellular morphology, leading to Rho/ROCK-dependent formation of actin stress fibres and the inhibition of glioma cell motility and invasion.
The FOXO3 (Forkhead/winged helix box class O 3) transcription factor is a crucial regulator of ha... more The FOXO3 (Forkhead/winged helix box class O 3) transcription factor is a crucial regulator of haematopoietic cell fate that controls proliferation and apoptosis, among other processes. Despite the central role of FOXO3 as a tumour suppressor and phosphatidylinositol 3-kinase (PI3K)/AKT effector, little is known about its involvement in mantle cell lymphoma (MCL) biology. This study investigated the expression and activity of FOXO3 in MCL cell lines and in primary cultures. We analysed the expression of key FOXO regulators and targets, and studied the effect of modulators of FOXO function on cell viability and apoptosis. FOXO3 was constitutively inactivated in MCL cell lines, and showed cytoplasmic localization in patient-derived cells. PI3K and AKT, but not mammalian target of rapamycin (mTOR), inhibitors induced FOXO3 nuclear translocation and activation in correlation with their impact on MCL proliferation and survival. Moreover, FOXO3-defective cells were resistant to PI3K/AKT inhibitors. Reactivation of FOXO function with a nuclear export inhibitor had a profound effect on cell viability, consistent with FOXO3 nuclear accumulation. Interestingly, inhibition of FOXO3 nuclear export enhanced the effect of doxorubicin. Taken together, our results confirm that FOXO3 is a relevant regulator of proliferation and apoptosis in MCL, and suggest that reactivation of FOXO3 function might be a useful therapeutic strategy in MCL patients.
Background: Prostate cancer (PCa) is the second leading cause of cancer deaths in men in the Unit... more Background: Prostate cancer (PCa) is the second leading cause of cancer deaths in men in the United States. The prostate-specific antigen (PSA), often found at high levels in the serum of PCa patients, has been used as a marker for PCa detection and as a target of immunotherapy. The murine IgG1 monoclonal antibody AR47.47, specific for human PSA, has been shown to enhance antigen presentation by human dendritic cells and induce both CD4 and CD8 T-cell activation when complexed with PSA. In this study, we explored the properties of a novel mouse/human chimeric anti-PSA IgE containing the variable regions of AR47.47 as a potential therapy for PCa. Our goal was to take advantage of the unique properties of IgE in order to trigger immune activation against PCa. Methods: Binding characteristics of the antibody were determined by ELISA and flow cytometry. In vitro degranulation was determined by the release of β-hexosaminidase from effector cells. In vivo degranulation was monitored in human FcεRIα transgenic mice using the passive cutaneous anaphylaxis assay. These mice were also used for a vaccination study to determine the in vivo anti-cancer effects of this antibody. Significant differences in survival were determined using the Log Rank test. In vitro T-cell activation was studied using human dendritic cells and autologous T cells. Results: The anti-PSA IgE, expressed in murine myeloma cells, is properly assembled and secreted, and binds the antigen and FcεRI. In addition, this antibody is capable of triggering effector cell degranulation in vitro and in vivo when artificially cross-linked, but not in the presence of the natural soluble antigen, suggesting that such an interaction will not trigger systemic anaphylaxis. Importantly, the anti-PSA IgE combined with PSA also triggers immune activation in vitro and in vivo and significantly prolongs the survival of human FcεRIα transgenic mice challenged with PSA-expressing tumors in a prophylactic vaccination setting. Conclusions: The anti-PSA IgE exhibits the expected biological properties and is capable of triggering immune activation and anti-tumor protection. Further studies on this antibody as a potential PCa therapy are warranted.
Mantle cell lymphoma (MCL) is a well-defined lymphoid malignancy characterized by a rapid clinica... more Mantle cell lymphoma (MCL) is a well-defined lymphoid malignancy characterized by a rapid clinical evolution and poor response to current therapeutic protocols. The hallmark genetic alteration of MCL is the t(11;14)(q13;32) chromosomal translocation that leads to the overexpression of cyclin D1. Recently, new molecular alterations of major importance in the pathogenic mechanisms of this disease have been discovered, and have revealed the biological heterogeneity of MCL. The first section of our review discusses our current understanding of the molecular biology of this entity according to recent information from comparative genomic hybridization (CGH) and expression profiling studies, which are leading to the identification of several druggable targets. In the second section we revise new therapeutic strategies based on new drug families that target key molecular pathways of major relevance in this malignancy. We analyze emerging agents that are already producing significant results in different models of human cancers, including MCL. Based on the current knowledge and recent studies, we suggest that the encouraging results described here should provide a rationale platform for the design of new treatments that may overcome the resistance of this aggressive lymphoma to conventional therapy and improve patient prognosis.
El libro a comentar recoge las ponencias y comunicaciones presentadas al seminario que sobre Psic... more El libro a comentar recoge las ponencias y comunicaciones presentadas al seminario que sobre Psicología Ambiental se celebró en Orellana (Badajoz) en el mes de septiembre de 1992, con el fin de discutir en profundidad los aspectos teóricos, metodológicos y aplicados que en este momento constituyen los elementos de análisis y discusión de la disciplina. Los tópicos en torno a los que giró dicha discusión y que vertebran el libro fueron los seis siguientes:
reduces WWOX expression both in hetero and homozygous cases. There was a positive correlation bet... more reduces WWOX expression both in hetero and homozygous cases. There was a positive correlation between expression level of WWOX and marker of proliferation Ki67 (Rs = 0.5440; p < 0.0001), antiapoptotic gene Bcl2 (Rs = 0.7092; p < 0.0001) and JM-a isoform of ErbB4 mRNA level (Rs = 0.7102; p < 0.0001). Conclusions: Our results suggest that loss of heterozygosity (relatively frequent in GBM) along with promoter methylation may decrease the WWOX tumour suppressor expression. We also confirmed that WWOX is correlated with ErbB4 signalling pathway as well as with proliferation and apoptosis in glioblastoma multiforme. 739 Altered expression of miR-205 affects cell proliferation in human cervical cancer
En este trabajo se propone el estudio de la vida en las ciudades como campo de trabajo de la Psic... more En este trabajo se propone el estudio de la vida en las ciudades como campo de trabajo de la Psicología Social y Ambiental. La ciudad es tanto una estructura espacial como social, que incide sobre el comportamiento individual y social. Se sistematiza los modelos y aportaciones más relevantes para el estudio psicológico del hecho urbano. Igualmente, se revisan las primeras aportaciones de psicólogos y sociólogos sobre la ciudad. Unos y otros destacan los aspectos negativos de la vida urbana, particularmente a partir del éxito de las teorías de la sobrecarga. En un apartado posterior se señala la necesidad de que los psicólogos sociales trabajen en la definición de modelos de calidad de vida urbana. Se sugiere prestar atención a cuatro factores: Grado de control, nivel de seguridad en el escenario, programa de actividades sociales del lugar y satisfacción estética.
Oxaliplatin is a highly effective inducer of apoptosis in Mantle Cell Lymphoma cells Obrador Hevi... more Oxaliplatin is a highly effective inducer of apoptosis in Mantle Cell Lymphoma cells Obrador Hevia, Antònia, 1 Belayachi, Lamiae1,2; Ordinas, Carlos1; Rodríguez, José1; Villalonga, Priam1; Fernández de Mattos, Silvia1 1Cancer Cell Biology Group. Institut Universitari d'Investigació en Ciències de la Salut (IUNICS). Universitat de les Illes Balears. Illes Balears (Spain). ; 2Immunology and Biochemistry Laboratory Mohammed V Agdal University - Faculty of Sciences Rabat (Morocco). Mantle Cell Lymphoma (MCL) is an aggressive lymphoma subtype that accounts for 5-7 % of non Hodgkin’s lymphomas (NHL). The disease is mostly incurable because of the continuous pattern of relapse. The frontline treatment including consolidation with high dose radiochemotherapy followed by autologous stem cell transplantation (ASCT) in patients in first remission has improved the survival of this disease. However, the treatment stays generally highly toxic especially for patients over 65 years old. Previou...
Approximately one-third of vertebral fractures can be clinically diagnosed. To study the frequenc... more Approximately one-third of vertebral fractures can be clinically diagnosed. To study the frequency of vertebral fractures in postmenopausal women. We recruited 555 postmenopausal women from Santiago, Chile, aged 55-84 years, who manifested interest in their bone health. All were healthy by self-declaration and by general clinical and laboratory tests and had not taken any bone-active therapy. They all underwent a spine and femoral neck (FN) densitometry and a digital lateral spine X-ray from T4 to L4 was obtained. PTH, calcidiol, and other parameters of calcium metabolism were also measured. Overall, 142 of 478 patients with a complete study (29.7%) had at least one vertebral fracture. The proportion of women with fractures increased with age. A T score below -2.5 in the spine and hip was found in 32% and 14% of women, respectively. The proportion of women with spinal osteoporosis doubled between ages 55-70 and remained constant afterwards. In contrast, at the femoral neck, this pro...
The aim of this study was to assess lumbar spine bone density in a group of chilean postmenopausa... more The aim of this study was to assess lumbar spine bone density in a group of chilean postmenopausal females and to estimate the frequency of vertebral osteopenia in the national urban female population. A clinical assessment and lumbar spine bone density measurement were performed to 171 healthy women over 40 years of age and not receiving medications that modify bone turnover. Calcium ingestion was recalled in 77 of these. Fifty women (29.2%) had osteopenia, defined as a bone density of less than 0.92 g/cm2. Extrapolating this figure to the national urban population, an osteopenia frequency of 21.7% was estimated. Body mass index was 25.5 +/- 3.8 and 57% of the sample was overweight. Calcium ingestion was 740.3 +/- 331.7. These two parameters did not correlative with bone density. Women with osteopenia were older and had a longer postmenopausal lapse than those with normal bone density. The completion of further clinical an epidemiological studies is recommended to know the real mag...
The analysis of historical document images is not only interesting for the preservation of histor... more The analysis of historical document images is not only interesting for the preservation of historical heritage but also for the extraction of semantic knowledge. In this paper we present a word spotting approach to find keyword images in digital archives. Detected words allow ...
Vertebral fractures, osteoporosis and vitamin D levels in Chilean postmenopausal women Background... more Vertebral fractures, osteoporosis and vitamin D levels in Chilean postmenopausal women Background: Approximately one-third of vertebral fractures can be clinically diagnosed. Aim: To study the frequency of vertebral fractures in postmenopausal women. Patients and methods: We recruited 555 postmenopausal women from Santiago, Chile, aged 55-84 years, who manifested interest in their bone health. All were healthy by self-declaration and by general clinical and laboratory tests and had not taken any bone-active therapy. They all underwent a spine and femoral neck (FN) densitometry and a digital lateral spine X-ray from T4 to L4 was obtained. PTH, calcidiol, and other parameters of calcium metabolism were also measured. Results: Overall, 142 of 478 patients with a complete study (29.7%) had at least one vertebral fracture. The proportion of women with fractures increased with age. A T score below-2.5 in the spine and hip was found in 32% and 14% of women, respectively. The proportion of women with spinal opeoporosis doubled between ages 55-70 and remained constant afterwards. In contrast, at the femoral neck, this proportion increased progressively reaching 53.3% at age 80-85. However, 56% of patients with vertebral fractures did not have densitometric osteoporosis in any location. Calcidiol levels were 16.8±6.8 ng/mL. With a cutoff point of 17 ng/mL, 47.5% of the patients had hypovitaminosis D. There was no association between calcidiol levels and vertebral fractures or bone density at the spine or femoral neck. Patients with fractures differed from those without fractures in that they had significantly lower bone density at the spine and hip and were older (p <0.001). However they did not differ in weight, body mass index, or calcidiol levels. Conclusions: Thirty percent of postmenopausal women in this series had a vertebral fractures. Osteoporosis and vitamin D deficiency were also common. Most vertebral fractures were observed in women without osteoporosis by densitometric criteria (Rev Méd Chile 2007; 135: 31-6).
The effect of rapid thermal annealing in oxygen and nitrogen ambients on the properties of silico... more The effect of rapid thermal annealing in oxygen and nitrogen ambients on the properties of silicon oxide films of different stoichiometry was studied. The films were deposited on silicon wafers by plasma enhanced chemical vapour deposition (PECVD) from silane (SiH4) and nitrous oxide (N2O) at different N2O/SiH4 flow ratios. It was found that rapid thermal annealing significantly affects the thickness of deposited oxides and the total mechanical stress in the film. The density and the refractive index of the film hardly changed. The hydrogen content of the films has been discussed on the basis of Fourier transform infrared transmission spectroscopy, and is related to the changes in the film properties.
Enforced EGFR activation upon gene amplification and/or mutation is a common hallmark of malignan... more Enforced EGFR activation upon gene amplification and/or mutation is a common hallmark of malignant glioma. Small molecule EGFR tyrosine kinase inhibitors, such as erlotinib (Tarceva), have shown some activity in a subset of glioma patients in recent trials, although the reported data on the cellular basis of glioma cell responsiveness to these compounds have been contradictory. Here we have used a panel of human glioma cell lines, including cells with amplified or mutant EGFR, to further characterize the cellular effects of EGFR inhibition with erlotinib. Dose-response and cellular growth assays indicate that erlotinib reduces cell proliferation in all tested cell lines without inducing cytotoxic effects. Flow cytometric analyses confirm that EGFR inhibition does not induce apoptosis in glioma cells, leading to cell cycle arrest in G 1. Interestingly, erlotinib also prevents spontaneous multicellular tumour spheroid growth in U87MG cells and cooperates with sub-optimal doses of temozolomide (TMZ) to reduce multicellular tumour spheroid growth. This cooperation appears to be schedule-dependent, since pre-treatment with erlotinib protects against TMZ-induced cytotoxicity whereas concomitant treatment results in a cooperative effect. Cell cycle arrest in erlotinib-treated cells is associated with an inhibition of ERK and Akt signaling, resulting in cyclin D1 downregulation, an increase in p27 kip1 levels and pRB hypophosphorylation. Interestingly, EGFR inhibition also perturbs Rho GTPase signaling and cellular morphology, leading to Rho/ROCK-dependent formation of actin stress fibres and the inhibition of glioma cell motility and invasion.
The FOXO3 (Forkhead/winged helix box class O 3) transcription factor is a crucial regulator of ha... more The FOXO3 (Forkhead/winged helix box class O 3) transcription factor is a crucial regulator of haematopoietic cell fate that controls proliferation and apoptosis, among other processes. Despite the central role of FOXO3 as a tumour suppressor and phosphatidylinositol 3-kinase (PI3K)/AKT effector, little is known about its involvement in mantle cell lymphoma (MCL) biology. This study investigated the expression and activity of FOXO3 in MCL cell lines and in primary cultures. We analysed the expression of key FOXO regulators and targets, and studied the effect of modulators of FOXO function on cell viability and apoptosis. FOXO3 was constitutively inactivated in MCL cell lines, and showed cytoplasmic localization in patient-derived cells. PI3K and AKT, but not mammalian target of rapamycin (mTOR), inhibitors induced FOXO3 nuclear translocation and activation in correlation with their impact on MCL proliferation and survival. Moreover, FOXO3-defective cells were resistant to PI3K/AKT inhibitors. Reactivation of FOXO function with a nuclear export inhibitor had a profound effect on cell viability, consistent with FOXO3 nuclear accumulation. Interestingly, inhibition of FOXO3 nuclear export enhanced the effect of doxorubicin. Taken together, our results confirm that FOXO3 is a relevant regulator of proliferation and apoptosis in MCL, and suggest that reactivation of FOXO3 function might be a useful therapeutic strategy in MCL patients.
Background: Prostate cancer (PCa) is the second leading cause of cancer deaths in men in the Unit... more Background: Prostate cancer (PCa) is the second leading cause of cancer deaths in men in the United States. The prostate-specific antigen (PSA), often found at high levels in the serum of PCa patients, has been used as a marker for PCa detection and as a target of immunotherapy. The murine IgG1 monoclonal antibody AR47.47, specific for human PSA, has been shown to enhance antigen presentation by human dendritic cells and induce both CD4 and CD8 T-cell activation when complexed with PSA. In this study, we explored the properties of a novel mouse/human chimeric anti-PSA IgE containing the variable regions of AR47.47 as a potential therapy for PCa. Our goal was to take advantage of the unique properties of IgE in order to trigger immune activation against PCa. Methods: Binding characteristics of the antibody were determined by ELISA and flow cytometry. In vitro degranulation was determined by the release of β-hexosaminidase from effector cells. In vivo degranulation was monitored in human FcεRIα transgenic mice using the passive cutaneous anaphylaxis assay. These mice were also used for a vaccination study to determine the in vivo anti-cancer effects of this antibody. Significant differences in survival were determined using the Log Rank test. In vitro T-cell activation was studied using human dendritic cells and autologous T cells. Results: The anti-PSA IgE, expressed in murine myeloma cells, is properly assembled and secreted, and binds the antigen and FcεRI. In addition, this antibody is capable of triggering effector cell degranulation in vitro and in vivo when artificially cross-linked, but not in the presence of the natural soluble antigen, suggesting that such an interaction will not trigger systemic anaphylaxis. Importantly, the anti-PSA IgE combined with PSA also triggers immune activation in vitro and in vivo and significantly prolongs the survival of human FcεRIα transgenic mice challenged with PSA-expressing tumors in a prophylactic vaccination setting. Conclusions: The anti-PSA IgE exhibits the expected biological properties and is capable of triggering immune activation and anti-tumor protection. Further studies on this antibody as a potential PCa therapy are warranted.
Mantle cell lymphoma (MCL) is a well-defined lymphoid malignancy characterized by a rapid clinica... more Mantle cell lymphoma (MCL) is a well-defined lymphoid malignancy characterized by a rapid clinical evolution and poor response to current therapeutic protocols. The hallmark genetic alteration of MCL is the t(11;14)(q13;32) chromosomal translocation that leads to the overexpression of cyclin D1. Recently, new molecular alterations of major importance in the pathogenic mechanisms of this disease have been discovered, and have revealed the biological heterogeneity of MCL. The first section of our review discusses our current understanding of the molecular biology of this entity according to recent information from comparative genomic hybridization (CGH) and expression profiling studies, which are leading to the identification of several druggable targets. In the second section we revise new therapeutic strategies based on new drug families that target key molecular pathways of major relevance in this malignancy. We analyze emerging agents that are already producing significant results in different models of human cancers, including MCL. Based on the current knowledge and recent studies, we suggest that the encouraging results described here should provide a rationale platform for the design of new treatments that may overcome the resistance of this aggressive lymphoma to conventional therapy and improve patient prognosis.
Uploads
Papers by jose rodriguez