Elba Vazquez - Academia.edu (original) (raw)
Papers by Elba Vazquez
Cancer Epidemiology, Biomarkers & Prevention
Purpose: Long non-coding RNAs (lncRNAs) regulate several biochemical pathways and contribute to t... more Purpose: Long non-coding RNAs (lncRNAs) regulate several biochemical pathways and contribute to the pathophysiology of cancer. In previous analyses, we identified 27 lncRNAs whose expression respond to hormone therapy in prostate cancer patients. Furthermore, in castration-resistant prostate cancer (CRPC), their levels were restored to those observed in therapy-naïve primary tumors. Nevertheless, lncRNAs contribution in tumorigenesis is still not understood. Since one mechanism of action of lncRNAs is acting as sponges of miRNAs, our main goal was to identify lncRNA-miRNA-mRNA networks altered during prostate cancer progression. Methods: We performed a bioinformatics-based analysis using public datasets comprising 40 primary prostate tumors (11 paired pre- and post-androgen deprivation therapy (ADT) and 29 pre-ADT) and 8 CRPC. We used miRNet (a miRNA-centric network visual analytics platform) to seek miRNAs that target both lncRNAs and mRNAs, and constructed ceRNA networks. Results:...
Cancer Research
Eighty percent of prostate cancers (PCa) metastasize to bone, showing a significant source of pat... more Eighty percent of prostate cancers (PCa) metastasize to bone, showing a significant source of patient morbidity. PCa stem-like cells (PCSCs) are capable to quiescently outlast retaining the ability to proliferate and regenerate, consequently remaining able to develop therapy-resistant tumors and metastatic lesions. We have previously reported that the overexpression of heme oxygenase 1 (HO-1), the rate limiting enzyme in heme degradation, leads to a less aggressive PCa phenotype. However, its effect on metastasis-stemness (MS) remains unknown. In this work, we address the biological significance of HO-1 in association with relevant MS genes for PCa progression. Clonogenic assays performed in PCa cells (PC3 and C4-2B) to assess colony formation, evidenced a reduction on the stem-like properties of tumor cells treated with hemin (FDA approved drug and specific HO-1 inducer). RNA-seq analysis to identify MS genes that could be modulated by HO-1 induction, revealed 32 MS-genes that were...
Table S1: Genesets enriched in PC3.pGIPZ xenografts. Table S2: Genesets enriched in PC3.shCtBP1 x... more Table S1: Genesets enriched in PC3.pGIPZ xenografts. Table S2: Genesets enriched in PC3.shCtBP1 xenografts. Supplemental Figure 1: (A) Crystal violet stained NIH3T3 cells foci transfected with pcDNA3.CtBP1 or beta-gal expression vectors. (B) CtBP1 RT-qPCR from PC3.CtBP1, PC3.shCtBP1 and PC3.pGIPZ stable cells using specific CtBP1 and Actin beta primers. Fold induction was calculated normalizing data to Actin beta and control. Bars represent the average and standard deviation of one representative experiment.***p < 0.001. Supplemental Figure 2: Box plots for (A) triglycerides, (B) glycemia and (C) estradiol serum levels for CD or HFD fed mice were shown. Boxes represent the interquartile range, the horizontal line within each box represents the median, and the upper and lower whiskers represent the standard deviation of one independent experiment. (D-E) Representative photograph of H&E staining from kidney and liver of mice fed with CD or HFD (Magnification 400x & 250x respectivel...
Purpose:Advances in prostate cancer lag behind other tumor types partly due to the paucity of mod... more Purpose:Advances in prostate cancer lag behind other tumor types partly due to the paucity of models reflecting key milestones in prostate cancer progression. Therefore, we develop clinically relevant prostate cancer models.Experimental Design:Since 1996, we have generated clinically annotated patient-derived xenografts (PDXs; the MDA PCa PDX series) linked to specific phenotypes reflecting all aspects of clinical prostate cancer.Results:We studied two cell line–derived xenografts and the first 80 PDXs derived from 47 human prostate cancer donors. Of these, 47 PDXs derived from 22 donors are working models and can be expanded either as cell lines (MDA PCa 2a and 2b) or PDXs. The histopathologic, genomic, and molecular characteristics (androgen receptor, ERG, and PTEN loss) maintain fidelity with the human tumor and correlate with published findings. PDX growth response to mouse castration and targeted therapy illustrate their clinical utility. Comparative genomic hybridization and s...
Purpose: Clinical and epidemiologic data suggest that obesity is associated with more aggressive ... more Purpose: Clinical and epidemiologic data suggest that obesity is associated with more aggressive forms of prostate cancer, poor prognosis, and increased mortality. C-terminal–binding protein 1 (CtBP1) is a transcription repressor of tumor suppressor genes and is activated by NADH binding. High calorie intake decreases intracellular NAD+/NADH ratio. The aim of this work was to assess the effect of high-fat diet (HFD) and CtBP1 expression modulation over prostate xenograft growth.Experimental Design: We developed a metabolic syndrome-like disease in vivo model by feeding male nude mice with HFD during 16 weeks. Control diet (CD)–fed animals were maintained at the same conditions. Mice were inoculated with PC3 cells stable transfected with shCtBP1 or control plasmids. Genome-wide expression profiles and Gene Set Enrichment Analysis (GSEA) were performed from PC3.shCtBP1 versus PC3.pGIPZ HFD-fed mice tumors.Results: No significant differences were observed in tumor growth on CD-fed mice...
Purpose: To study Wnt/β-catenin in castrate-resistant prostate cancer (CRPC) and understand its f... more Purpose: To study Wnt/β-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the β-catenin–androgen receptor (AR) interaction.Experimental Design: We carried out β-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of β-catenin–mediated transcription), and sequenced the β-catenin gene in MDA prostate cancer 118a, MDA prostate cancer 118b, MDA prostate cancer 2b, and PC-3 prostate cancer cells. We knocked down β-catenin in AR-negative MDA prostate cancer 118b cells and carried out comparative gene-array analysis. We also immunohistochemically analyzed β-catenin and AR in 27 bone metastases of human CRPCs.Results: β-Catenin nuclear accumulation and TOP-flash reporter activity were high in MDA prostate cancer 118b but not in MDA prostate cancer 2b or PC-3 cells. MDA prostate cancer 118a and MDA prostate cancer 118b cells carry a mutated β-catenin at codon 32 (D32G). Ten genes were expressed differently (fa...
Supplementary Methods, Figures 1-3 from Transcriptional Autoregulation by BRCA1
Legend of Supplementary Figures
PDF file - 88K, Table S1. Primers used to delineate the 'galectin signature' of prostate ... more PDF file - 88K, Table S1. Primers used to delineate the 'galectin signature' of prostate cancer cells Table S2. Primers used to determine angiogenesis-related genes
PDF file - 123K, Figure S1. Gal-1 mRNA expression and PSA mRNA expression in hormone-responsive (... more PDF file - 123K, Figure S1. Gal-1 mRNA expression and PSA mRNA expression in hormone-responsive (HR) and castration-resistant (CR) LNCaP cells Figure S2: Immunoreactivity of anti-galectin antibodies
Galectins, a family of glycan-binding proteins, influence tumor progression by modulating interac... more Galectins, a family of glycan-binding proteins, influence tumor progression by modulating interactions between tumor, endothelial, stromal, and immune cells. Despite considerable progress in identifying the roles of individual galectins in tumor biology, an integrated portrait of the galectin network in different tumor microenvironments is still missing. We undertook this study to analyze the “galectin signature” of the human prostate cancer microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. In examining androgen-responsive and castration-resistant prostate cancer cells and primary tumors representing different stages of the disease, we found that galectin-1 (Gal-1) was the most abundantly expressed galectin in prostate cancer tissue and was markedly upregulated during disease progression. In contrast, all other galectins were expressed at lower levels: Gal-3, -4, -9, and -12 were downregulated during disease evol...
Cancer Research, 2021
Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable.... more Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The intricacy of metabolic pathways associated with PCa progression spurred us to develop a metabolism-centric analysis. Using PCa patient-derived xenografts (PDXs) we assessed the metabolic changes after castration of tumor-bearing mice. We found that relapsed tumors had a significant increase in fatty acids and ketone body content compared with baseline. We confirmed that critical ketogenic/ketolytic enzymes (ACAT1, OXCT1, BDH1) were significantly augmented after castrate-resistant progression. Further, these enzymes are increased in the human donor tissue after progressing to ADT. Increased ACAT1 and OXCT1 was also observed for a subset of PCa patients that relapsed with low AR and ERG expression. These factors were associated with decreased biochemical relapse and progression free survival. In summary, our studies reveal the key metabolites fueling castration resistant progression i...
Cancer Research, 2018
Prostate cancer (PCa) is a complex and progressive disease. Under the selective pressure of medic... more Prostate cancer (PCa) is a complex and progressive disease. Under the selective pressure of medical and drug treatment, PCa cells are able to acquire molecular changes that allow them to survive in androgen-deprived conditions and finally cause their host’s death. Inflammation fosters multiple hallmarks of cancer. However, the molecular mechanisms that prime the pathogenesis of cancer-related inflammation are yet to be deciphered. In this context, heme-oxygenase 1 (HO-1), the rate-limiting enzyme in heme degradation, emerges as a potential target in PCa, maintaining homeostasis and counteracting oxidative and inflammatory damage. We have previously documented HO-1 nuclear expression in human primary prostate carcinomas. In PCa cell lines we confirmed that HO-1 overexpression inhibits cell proliferation, migration, and invasion. It also impairs tumor growth in vivo and downregulates the expression of target genes associated with inflammation. Considering the crosstalk between inflamm...
Cancer Research, 2015
Concomitant tumor resistance (CR) is the phenomenon according to which a tumor-bearing host inhib... more Concomitant tumor resistance (CR) is the phenomenon according to which a tumor-bearing host inhibits the growth of secondary tumor implants. Ehrlich first described it in 1906, but this phenomenon remained forgotten for about 60 years. After its renascence, some groups have demonstrated that both immunogenic and non-immunogenic tumors can induce CR in different animal models. Metastases could be considered as secondary tumor implants developed spontaneously during the primary tumor growth, thus CR could be relevant for cancer progression. Clinical and experimental evidence suggest that the removal of human and murine tumors might be followed by an abrupt increase in metastatic growth, hence the primary tumor could exert a controlling action on its metastases. In previous papers we demonstrated that, in mice, two temporally separate peaks of CR can be detected during murine T-lymphoma (LB) primary tumor growth. The second peak of CR is mediated by most large-sized immunogenic and non...
Cancer Research, 2015
Prostate cancer (PCa) is the second leading cause of cancer death in men in the United States, an... more Prostate cancer (PCa) is the second leading cause of cancer death in men in the United States, and inflammation is recognized as a risk factor. In this regard we have previously shown that Heme Oxygenase-1 (HO-1) over-expression plays a critical role in prostate tumor cells per se by impairing cell proliferation, invasion and migration in vitro and tumor growth in vivo. In the present study, we aimed to assess the role of stromal HO-1 in PCa. The stroma was conditioned by subcutaneously (s.c.) injecting C57BL/6 mice with 200μl of hemin (30μM; HO-1 pharmacological inducer) or its vehicle PBS on days 8, 5 and 1 prior to tumor challenge. TRAMP-C1 cells (T-C1; 2×106 isogenic murine PCa cells) were s.c. injected on the same flank in Matrigel®. Hemin pre-treated animals showed a significant increase in tumor latency (12-day delay when compared to control mice; Mantel-Cox test, P<0.01) and a significant decrease in tumor growth rate (Student t test, P <0.05). In vitro lymphocyte prol...
ABSTRACTSARS-CoV-2 infection causes a multisystemic disease that affects numerous organs beyond t... more ABSTRACTSARS-CoV-2 infection causes a multisystemic disease that affects numerous organs beyond the respiratory system. Thus, it is well known that COVID-19 is associated with a wide range of hematological disorders; however, it remains unclear how the SARS-CoV-2 virus is able to navigate from tissue to tissue. In this work, we performed a comprehensive analysis of the pleiotropic effects of a prototypical coronavirus in its natural host, the validated preclinical model of murine hepatitis virus (MHV). Throughout this study we compared our results with the real-world data from COVID-19 patients (including autopsies). Thus, the presence of viral RNA was only detected in less than 25% of the human serum samples, whereas all had multiple positive nasal swabs for SARS-CoV-2. Notably, we found viral RNA not only in lungs, but also in heart and kidney of deceased COVID-19 patients. Subsequently, we investigated the association between viral organotropism and clinical manifestations employ...
S1A. Cross-cancer alteration summary for BRCA1, HMOX1, NFE2L2 (9 studies / 3 genes). S1B. mRNA co... more S1A. Cross-cancer alteration summary for BRCA1, HMOX1, NFE2L2 (9 studies / 3 genes). S1B. mRNA co-expression of gene pairs BRCA1/NRF2 and HO-1/NRF2 in 109 samples (Broad/Cornell, Nature Genetics 2012) and 56 samples (Broad/Cornell, Cell 2013), respectively. Perason's correlation and Spearman's correlation scores are shown. S1C. mRNA co-expression of gene pairs HO-1/NRF2 in 103 samples (MSKCC, Cancer Cell 2010). Perason's correlation and Spearman's correlation scores are shown. S1D. mRNA co-expression of gene pairs HO-1/NRF2 in 103 samples (MSKCC, Cancer Cell 2010), given by mRNA expression Z-scores vs Normals.Perason's correlation and Spearman's correlation scores are shown. S1E. mRNA co-expression of gene pairs HO-1/BRCA1 in 103 samples (MSKCC, Cancer Cell 2010), given by mRNA expression outliers. Perason's correlation and Spearman's correlation scores are shown.
PDXs derived from mixed adeno- and neuroendocrine human prostate carcinoma recapitulating only on... more PDXs derived from mixed adeno- and neuroendocrine human prostate carcinoma recapitulating only one morphologic component
Clinical information and pathologic diagnosis of one human donor for 2 cell lines and of 47 human... more Clinical information and pathologic diagnosis of one human donor for 2 cell lines and of 47 human donors for 80 PDXs
Cancer Epidemiology, Biomarkers & Prevention
Purpose: Long non-coding RNAs (lncRNAs) regulate several biochemical pathways and contribute to t... more Purpose: Long non-coding RNAs (lncRNAs) regulate several biochemical pathways and contribute to the pathophysiology of cancer. In previous analyses, we identified 27 lncRNAs whose expression respond to hormone therapy in prostate cancer patients. Furthermore, in castration-resistant prostate cancer (CRPC), their levels were restored to those observed in therapy-naïve primary tumors. Nevertheless, lncRNAs contribution in tumorigenesis is still not understood. Since one mechanism of action of lncRNAs is acting as sponges of miRNAs, our main goal was to identify lncRNA-miRNA-mRNA networks altered during prostate cancer progression. Methods: We performed a bioinformatics-based analysis using public datasets comprising 40 primary prostate tumors (11 paired pre- and post-androgen deprivation therapy (ADT) and 29 pre-ADT) and 8 CRPC. We used miRNet (a miRNA-centric network visual analytics platform) to seek miRNAs that target both lncRNAs and mRNAs, and constructed ceRNA networks. Results:...
Cancer Research
Eighty percent of prostate cancers (PCa) metastasize to bone, showing a significant source of pat... more Eighty percent of prostate cancers (PCa) metastasize to bone, showing a significant source of patient morbidity. PCa stem-like cells (PCSCs) are capable to quiescently outlast retaining the ability to proliferate and regenerate, consequently remaining able to develop therapy-resistant tumors and metastatic lesions. We have previously reported that the overexpression of heme oxygenase 1 (HO-1), the rate limiting enzyme in heme degradation, leads to a less aggressive PCa phenotype. However, its effect on metastasis-stemness (MS) remains unknown. In this work, we address the biological significance of HO-1 in association with relevant MS genes for PCa progression. Clonogenic assays performed in PCa cells (PC3 and C4-2B) to assess colony formation, evidenced a reduction on the stem-like properties of tumor cells treated with hemin (FDA approved drug and specific HO-1 inducer). RNA-seq analysis to identify MS genes that could be modulated by HO-1 induction, revealed 32 MS-genes that were...
Table S1: Genesets enriched in PC3.pGIPZ xenografts. Table S2: Genesets enriched in PC3.shCtBP1 x... more Table S1: Genesets enriched in PC3.pGIPZ xenografts. Table S2: Genesets enriched in PC3.shCtBP1 xenografts. Supplemental Figure 1: (A) Crystal violet stained NIH3T3 cells foci transfected with pcDNA3.CtBP1 or beta-gal expression vectors. (B) CtBP1 RT-qPCR from PC3.CtBP1, PC3.shCtBP1 and PC3.pGIPZ stable cells using specific CtBP1 and Actin beta primers. Fold induction was calculated normalizing data to Actin beta and control. Bars represent the average and standard deviation of one representative experiment.***p < 0.001. Supplemental Figure 2: Box plots for (A) triglycerides, (B) glycemia and (C) estradiol serum levels for CD or HFD fed mice were shown. Boxes represent the interquartile range, the horizontal line within each box represents the median, and the upper and lower whiskers represent the standard deviation of one independent experiment. (D-E) Representative photograph of H&E staining from kidney and liver of mice fed with CD or HFD (Magnification 400x & 250x respectivel...
Purpose:Advances in prostate cancer lag behind other tumor types partly due to the paucity of mod... more Purpose:Advances in prostate cancer lag behind other tumor types partly due to the paucity of models reflecting key milestones in prostate cancer progression. Therefore, we develop clinically relevant prostate cancer models.Experimental Design:Since 1996, we have generated clinically annotated patient-derived xenografts (PDXs; the MDA PCa PDX series) linked to specific phenotypes reflecting all aspects of clinical prostate cancer.Results:We studied two cell line–derived xenografts and the first 80 PDXs derived from 47 human prostate cancer donors. Of these, 47 PDXs derived from 22 donors are working models and can be expanded either as cell lines (MDA PCa 2a and 2b) or PDXs. The histopathologic, genomic, and molecular characteristics (androgen receptor, ERG, and PTEN loss) maintain fidelity with the human tumor and correlate with published findings. PDX growth response to mouse castration and targeted therapy illustrate their clinical utility. Comparative genomic hybridization and s...
Purpose: Clinical and epidemiologic data suggest that obesity is associated with more aggressive ... more Purpose: Clinical and epidemiologic data suggest that obesity is associated with more aggressive forms of prostate cancer, poor prognosis, and increased mortality. C-terminal–binding protein 1 (CtBP1) is a transcription repressor of tumor suppressor genes and is activated by NADH binding. High calorie intake decreases intracellular NAD+/NADH ratio. The aim of this work was to assess the effect of high-fat diet (HFD) and CtBP1 expression modulation over prostate xenograft growth.Experimental Design: We developed a metabolic syndrome-like disease in vivo model by feeding male nude mice with HFD during 16 weeks. Control diet (CD)–fed animals were maintained at the same conditions. Mice were inoculated with PC3 cells stable transfected with shCtBP1 or control plasmids. Genome-wide expression profiles and Gene Set Enrichment Analysis (GSEA) were performed from PC3.shCtBP1 versus PC3.pGIPZ HFD-fed mice tumors.Results: No significant differences were observed in tumor growth on CD-fed mice...
Purpose: To study Wnt/β-catenin in castrate-resistant prostate cancer (CRPC) and understand its f... more Purpose: To study Wnt/β-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the β-catenin–androgen receptor (AR) interaction.Experimental Design: We carried out β-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of β-catenin–mediated transcription), and sequenced the β-catenin gene in MDA prostate cancer 118a, MDA prostate cancer 118b, MDA prostate cancer 2b, and PC-3 prostate cancer cells. We knocked down β-catenin in AR-negative MDA prostate cancer 118b cells and carried out comparative gene-array analysis. We also immunohistochemically analyzed β-catenin and AR in 27 bone metastases of human CRPCs.Results: β-Catenin nuclear accumulation and TOP-flash reporter activity were high in MDA prostate cancer 118b but not in MDA prostate cancer 2b or PC-3 cells. MDA prostate cancer 118a and MDA prostate cancer 118b cells carry a mutated β-catenin at codon 32 (D32G). Ten genes were expressed differently (fa...
Supplementary Methods, Figures 1-3 from Transcriptional Autoregulation by BRCA1
Legend of Supplementary Figures
PDF file - 88K, Table S1. Primers used to delineate the 'galectin signature' of prostate ... more PDF file - 88K, Table S1. Primers used to delineate the 'galectin signature' of prostate cancer cells Table S2. Primers used to determine angiogenesis-related genes
PDF file - 123K, Figure S1. Gal-1 mRNA expression and PSA mRNA expression in hormone-responsive (... more PDF file - 123K, Figure S1. Gal-1 mRNA expression and PSA mRNA expression in hormone-responsive (HR) and castration-resistant (CR) LNCaP cells Figure S2: Immunoreactivity of anti-galectin antibodies
Galectins, a family of glycan-binding proteins, influence tumor progression by modulating interac... more Galectins, a family of glycan-binding proteins, influence tumor progression by modulating interactions between tumor, endothelial, stromal, and immune cells. Despite considerable progress in identifying the roles of individual galectins in tumor biology, an integrated portrait of the galectin network in different tumor microenvironments is still missing. We undertook this study to analyze the “galectin signature” of the human prostate cancer microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. In examining androgen-responsive and castration-resistant prostate cancer cells and primary tumors representing different stages of the disease, we found that galectin-1 (Gal-1) was the most abundantly expressed galectin in prostate cancer tissue and was markedly upregulated during disease progression. In contrast, all other galectins were expressed at lower levels: Gal-3, -4, -9, and -12 were downregulated during disease evol...
Cancer Research, 2021
Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable.... more Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The intricacy of metabolic pathways associated with PCa progression spurred us to develop a metabolism-centric analysis. Using PCa patient-derived xenografts (PDXs) we assessed the metabolic changes after castration of tumor-bearing mice. We found that relapsed tumors had a significant increase in fatty acids and ketone body content compared with baseline. We confirmed that critical ketogenic/ketolytic enzymes (ACAT1, OXCT1, BDH1) were significantly augmented after castrate-resistant progression. Further, these enzymes are increased in the human donor tissue after progressing to ADT. Increased ACAT1 and OXCT1 was also observed for a subset of PCa patients that relapsed with low AR and ERG expression. These factors were associated with decreased biochemical relapse and progression free survival. In summary, our studies reveal the key metabolites fueling castration resistant progression i...
Cancer Research, 2018
Prostate cancer (PCa) is a complex and progressive disease. Under the selective pressure of medic... more Prostate cancer (PCa) is a complex and progressive disease. Under the selective pressure of medical and drug treatment, PCa cells are able to acquire molecular changes that allow them to survive in androgen-deprived conditions and finally cause their host’s death. Inflammation fosters multiple hallmarks of cancer. However, the molecular mechanisms that prime the pathogenesis of cancer-related inflammation are yet to be deciphered. In this context, heme-oxygenase 1 (HO-1), the rate-limiting enzyme in heme degradation, emerges as a potential target in PCa, maintaining homeostasis and counteracting oxidative and inflammatory damage. We have previously documented HO-1 nuclear expression in human primary prostate carcinomas. In PCa cell lines we confirmed that HO-1 overexpression inhibits cell proliferation, migration, and invasion. It also impairs tumor growth in vivo and downregulates the expression of target genes associated with inflammation. Considering the crosstalk between inflamm...
Cancer Research, 2015
Concomitant tumor resistance (CR) is the phenomenon according to which a tumor-bearing host inhib... more Concomitant tumor resistance (CR) is the phenomenon according to which a tumor-bearing host inhibits the growth of secondary tumor implants. Ehrlich first described it in 1906, but this phenomenon remained forgotten for about 60 years. After its renascence, some groups have demonstrated that both immunogenic and non-immunogenic tumors can induce CR in different animal models. Metastases could be considered as secondary tumor implants developed spontaneously during the primary tumor growth, thus CR could be relevant for cancer progression. Clinical and experimental evidence suggest that the removal of human and murine tumors might be followed by an abrupt increase in metastatic growth, hence the primary tumor could exert a controlling action on its metastases. In previous papers we demonstrated that, in mice, two temporally separate peaks of CR can be detected during murine T-lymphoma (LB) primary tumor growth. The second peak of CR is mediated by most large-sized immunogenic and non...
Cancer Research, 2015
Prostate cancer (PCa) is the second leading cause of cancer death in men in the United States, an... more Prostate cancer (PCa) is the second leading cause of cancer death in men in the United States, and inflammation is recognized as a risk factor. In this regard we have previously shown that Heme Oxygenase-1 (HO-1) over-expression plays a critical role in prostate tumor cells per se by impairing cell proliferation, invasion and migration in vitro and tumor growth in vivo. In the present study, we aimed to assess the role of stromal HO-1 in PCa. The stroma was conditioned by subcutaneously (s.c.) injecting C57BL/6 mice with 200μl of hemin (30μM; HO-1 pharmacological inducer) or its vehicle PBS on days 8, 5 and 1 prior to tumor challenge. TRAMP-C1 cells (T-C1; 2×106 isogenic murine PCa cells) were s.c. injected on the same flank in Matrigel®. Hemin pre-treated animals showed a significant increase in tumor latency (12-day delay when compared to control mice; Mantel-Cox test, P<0.01) and a significant decrease in tumor growth rate (Student t test, P <0.05). In vitro lymphocyte prol...
ABSTRACTSARS-CoV-2 infection causes a multisystemic disease that affects numerous organs beyond t... more ABSTRACTSARS-CoV-2 infection causes a multisystemic disease that affects numerous organs beyond the respiratory system. Thus, it is well known that COVID-19 is associated with a wide range of hematological disorders; however, it remains unclear how the SARS-CoV-2 virus is able to navigate from tissue to tissue. In this work, we performed a comprehensive analysis of the pleiotropic effects of a prototypical coronavirus in its natural host, the validated preclinical model of murine hepatitis virus (MHV). Throughout this study we compared our results with the real-world data from COVID-19 patients (including autopsies). Thus, the presence of viral RNA was only detected in less than 25% of the human serum samples, whereas all had multiple positive nasal swabs for SARS-CoV-2. Notably, we found viral RNA not only in lungs, but also in heart and kidney of deceased COVID-19 patients. Subsequently, we investigated the association between viral organotropism and clinical manifestations employ...
S1A. Cross-cancer alteration summary for BRCA1, HMOX1, NFE2L2 (9 studies / 3 genes). S1B. mRNA co... more S1A. Cross-cancer alteration summary for BRCA1, HMOX1, NFE2L2 (9 studies / 3 genes). S1B. mRNA co-expression of gene pairs BRCA1/NRF2 and HO-1/NRF2 in 109 samples (Broad/Cornell, Nature Genetics 2012) and 56 samples (Broad/Cornell, Cell 2013), respectively. Perason's correlation and Spearman's correlation scores are shown. S1C. mRNA co-expression of gene pairs HO-1/NRF2 in 103 samples (MSKCC, Cancer Cell 2010). Perason's correlation and Spearman's correlation scores are shown. S1D. mRNA co-expression of gene pairs HO-1/NRF2 in 103 samples (MSKCC, Cancer Cell 2010), given by mRNA expression Z-scores vs Normals.Perason's correlation and Spearman's correlation scores are shown. S1E. mRNA co-expression of gene pairs HO-1/BRCA1 in 103 samples (MSKCC, Cancer Cell 2010), given by mRNA expression outliers. Perason's correlation and Spearman's correlation scores are shown.
PDXs derived from mixed adeno- and neuroendocrine human prostate carcinoma recapitulating only on... more PDXs derived from mixed adeno- and neuroendocrine human prostate carcinoma recapitulating only one morphologic component
Clinical information and pathologic diagnosis of one human donor for 2 cell lines and of 47 human... more Clinical information and pathologic diagnosis of one human donor for 2 cell lines and of 47 human donors for 80 PDXs