Alteration of BRCA1 expression affects alcohol-induced transcription of RNA P...Juan Diego Villegas
The document discusses a study that investigated the role of alcohol in RNA Polymerase III (Pol III) transcription. The study found that ethanol induces deregulation of Pol III gene transcription via estrogen receptors in breast cancer cells. It also found that overexpression of the BRCA1 gene, which repairs DNA and prevents uncontrolled cell proliferation, reduces ethanol-induced tRNA and 5S rRNA transcription. This suggests that alcohol intake promotes cell transformation and tumor formation by altering Pol III transcription, and that BRCA1 plays a role in regulating this effect of alcohol.
The document describes an analysis of RNA-seq data from 21 breast cancer samples representing 3 subtypes (TNBC, ER+, HER2+) profiled in 3 different mouse PDX models. The goals were to identify transcriptional differences between cancer subtypes and mouse models in order to select biomarker candidate genes. An overview of the RNA-seq analysis pipeline is provided, including mapping, quantification, normalization, and downstream analyses like PCA, factor regression, and tumor-stroma association studies.
Whole Transcriptome Profiling of Cancer Tumors in Mouse PDX ModelsTom Koch
This document describes an analysis of RNA sequencing data from patient-derived breast cancer xenograft models. The analysis identified gene expression differences between triple negative and estrogen receptor positive breast cancer subtypes. Factor regression analysis was also used to identify genes influenced by tumor type and mouse strain. Some long non-coding RNAs and genes like CXorf61 were found to be potential biomarkers for triple negative breast cancer.
The document discusses two studies: 1) A study showing that the RNF20 protein is required for amplification of MLL-rearranged leukemia. 2) A study describing how multiple RNA binding proteins cooperatively control genetic splicing codes.
Diagnostic value of comparative analysis of the gene p53 promoter and the car...Milan Gilić
diagnostic value of comparative analysis of the gene p53 promoter and the carboxyl part of the ubiquitin in searching the global error(s) in the syntax of the protein and DNA sequences
Arpin downregulation is associated with poor prognosis in pancreatic ductal a...MarianaBarona
This document discusses pancreatic ductal adenocarcinoma (PDAC) and the protein Arpin. PDAC is a form of pancreatic cancer with a low 5-year survival rate. Arpin inhibits the Arp2/3 complex, which generates branched actin networks involved in cell motility and migration. The study examined Arpin expression in PDAC tissues using immunohistochemistry and western blot. Results showed Arpin was diminished in PDAC tissues. Low Arpin expression correlated with higher tumor stage and poorer prognosis. As Arpin inhibits Arp2/3, lower Arpin allows increased Arp2/3 activation and cell migration, supporting rapid PDAC metastasis.
This review proposes a new targeted cancer therapeutic called an intracellular caspase-modulating chimeric antigen receptor (iCCAR) that functions inside malignant cells. The iCCAR would contain an antibody-based single-chain variable fragment (scFv) domain targeting a specific epitope in a mutant protein expressed by cancer cells. Upon binding this epitope, the iCCAR would directly induce apoptosis. Two possible configurations for achieving this controlled apoptosis are described. The review focuses on an approach using an scFv to control a constitutively active apoptosis effector embedded within via an intein. The goal is to develop a therapeutic that can target cancer cells more specifically than current CAR-T cell therapies, reducing the risk of serious adverse events
Seminario biologia molecular. MicroRNA 197-3p y daño endotelial en la enferme...VALEVEROVILLADAORTIZ
En esta exposición se hace referencia a un artículo en el que se estudió la relación entre el MicroRNA 197-3p y el daño en células endoteliales de arteria coronaria en niños con enfermedad de Kawasaki.
Alteration of BRCA1 expression affects alcohol-induced transcription of RNA P...Juan Diego Villegas
The document discusses a study that investigated the role of alcohol in RNA Polymerase III (Pol III) transcription. The study found that ethanol induces deregulation of Pol III gene transcription via estrogen receptors in breast cancer cells. It also found that overexpression of the BRCA1 gene, which repairs DNA and prevents uncontrolled cell proliferation, reduces ethanol-induced tRNA and 5S rRNA transcription. This suggests that alcohol intake promotes cell transformation and tumor formation by altering Pol III transcription, and that BRCA1 plays a role in regulating this effect of alcohol.
The document describes an analysis of RNA-seq data from 21 breast cancer samples representing 3 subtypes (TNBC, ER+, HER2+) profiled in 3 different mouse PDX models. The goals were to identify transcriptional differences between cancer subtypes and mouse models in order to select biomarker candidate genes. An overview of the RNA-seq analysis pipeline is provided, including mapping, quantification, normalization, and downstream analyses like PCA, factor regression, and tumor-stroma association studies.
Whole Transcriptome Profiling of Cancer Tumors in Mouse PDX ModelsTom Koch
This document describes an analysis of RNA sequencing data from patient-derived breast cancer xenograft models. The analysis identified gene expression differences between triple negative and estrogen receptor positive breast cancer subtypes. Factor regression analysis was also used to identify genes influenced by tumor type and mouse strain. Some long non-coding RNAs and genes like CXorf61 were found to be potential biomarkers for triple negative breast cancer.
The document discusses two studies: 1) A study showing that the RNF20 protein is required for amplification of MLL-rearranged leukemia. 2) A study describing how multiple RNA binding proteins cooperatively control genetic splicing codes.
Diagnostic value of comparative analysis of the gene p53 promoter and the car...Milan Gilić
diagnostic value of comparative analysis of the gene p53 promoter and the carboxyl part of the ubiquitin in searching the global error(s) in the syntax of the protein and DNA sequences
Arpin downregulation is associated with poor prognosis in pancreatic ductal a...MarianaBarona
This document discusses pancreatic ductal adenocarcinoma (PDAC) and the protein Arpin. PDAC is a form of pancreatic cancer with a low 5-year survival rate. Arpin inhibits the Arp2/3 complex, which generates branched actin networks involved in cell motility and migration. The study examined Arpin expression in PDAC tissues using immunohistochemistry and western blot. Results showed Arpin was diminished in PDAC tissues. Low Arpin expression correlated with higher tumor stage and poorer prognosis. As Arpin inhibits Arp2/3, lower Arpin allows increased Arp2/3 activation and cell migration, supporting rapid PDAC metastasis.
This review proposes a new targeted cancer therapeutic called an intracellular caspase-modulating chimeric antigen receptor (iCCAR) that functions inside malignant cells. The iCCAR would contain an antibody-based single-chain variable fragment (scFv) domain targeting a specific epitope in a mutant protein expressed by cancer cells. Upon binding this epitope, the iCCAR would directly induce apoptosis. Two possible configurations for achieving this controlled apoptosis are described. The review focuses on an approach using an scFv to control a constitutively active apoptosis effector embedded within via an intein. The goal is to develop a therapeutic that can target cancer cells more specifically than current CAR-T cell therapies, reducing the risk of serious adverse events
Seminario biologia molecular. MicroRNA 197-3p y daño endotelial en la enferme...VALEVEROVILLADAORTIZ
En esta exposición se hace referencia a un artículo en el que se estudió la relación entre el MicroRNA 197-3p y el daño en células endoteliales de arteria coronaria en niños con enfermedad de Kawasaki.
This study found that overexpression of vascular endothelial growth factor (VEGF) by estrogen-dependent MCF-7 breast cancer cells promoted estrogen-independent tumor growth in mice. MCF-7 cells were engineered to overexpress VEGF121 or VEGF165. When implanted in ovariectomized mice, the VEGF-overexpressing MCF-7 tumors grew similarly to, or greater than, parental MCF-7 tumors in mice supplemented with estrogen. Overexpression of VEGF stimulated angiogenesis and proliferation in the MCF-7 tumors through both autocrine and paracrine mechanisms, allowing the tumors to grow independently of estrogen. This suggests that upregulation of VEGF contributes to breast cancers acquiring estrogen-independent growth.
This document summarizes three scientific articles:
1) The first article describes fabricating a nickel oxide/graphene nanocomposite to non-enzymatically detect cholesterol concentrations between 2-40 mM with high sensitivity and a low detection limit of 0.13 mM.
2) The second article discusses using a porous covalent triazine polymer as a pH-responsive nanocarrier for cancer therapy and imaging, which exhibited higher cytotoxic effects on cancer cells than free drugs and induced strong senescence at lower concentrations.
3) The third article examines using a PAMAM/5-fluorouracil drug conjugate to target cervical cancer oncoproteins E6 and E7, which molecular docking analysis revealed could
This document describes an online tool called IDEp that provides various bioinformatics analysis methods for high-throughput sequencing data including dimensionality reduction techniques like PCA and t-SNE, differential expression analysis, enrichment analysis, pathway analysis, protein-protein interaction networks, biclustering, and more. It was created by Prof. Xijin Ge and colleagues at South Dakota State University.
1) The document describes a Markov Chain model built to predict gene expression signatures associated with epithelial and mesenchymal cells based on data from 1165 breast cancer patients.
2) The model incorporates the known TGFB-induced EMT pathway and regulatory relationships between molecules to recursively predict expression likelihood.
3) Expression patterns are mapped to epithelial and mesenchymal cell types based on the expression level of the CDH1 gene, which plays a key role in cell phenotype and the initiation of EMT.
This document discusses cancer gene therapy. It explains that gene therapy involves introducing genetic material into cells to replace missing or defective genes that may cause cancer. There are two main approaches - ex vivo gene therapy, where genes are introduced into cells removed from the body and cultured before being returned, and in vivo gene therapy where genes are directly delivered to target cells and tissues in the body. Various gene delivery methods and vector systems are described. Examples of specific cancer types and genes targeted for therapy are provided, such as introducing the Hs-tk gene for ovarian cancer treatment. The goals and applications of cancer gene therapy are to alter the immunogenicity of tumors, genetically modify immune cells, introduce suicide or sensitivity genes, and replace tumor suppressor
This document discusses the identification of Necdin as a novel STAT3 target gene that is downregulated in human cancer. The researchers used microarray analysis to compare gene expression profiles between cells with constitutively active STAT3 and normal cells. They identified differentially expressed genes between cells expressing oncogenic v-Src or constitutively active STAT3-C. Genes common to both lists were most likely directly regulated by STAT3. Computational analysis identified Necdin, a negative growth regulator, as downregulated in cells with active STAT3. Experiments confirmed STAT3 directly binds to and regulates the Necdin promoter, and Necdin expression inversely correlates with STAT3 activity in cancer cell lines. This suggests STAT
Three genes - COX2, HB-EGF, and ST6GALNAC5 - are linked to the spread of breast cancer, with COX2 and HB-EGF priming breast cancer cells to enter the brain and lungs, and ST6GALNAC5 causing a reaction creating a coating enhancing cancer cells' ability to breach the blood-brain barrier. Researchers believe new treatments could be developed to disrupt ST6GALNAC5's interaction with cancer cells.
This document describes a new cell-based diagnostic technique called Cellular Multiplex that can simultaneously detect protein expression, mRNA expression, and cell cycle analysis from breast cancer biopsies. In a preliminary study of 16 breast tumors and 5 normal tissues, the technique identified heterogeneity in biomarker expression between tumors. It also established normal biomarker expression levels and cell cycle distributions in normal breast tissue. The approach has potential to provide a more comprehensive view of the tumor environment and limit inaccuracies of current methods, which could lead to better patient outcomes.
The document summarizes research on DNA repair mechanisms and their link to certain cancers. It discusses how mutations in BRCA1 and BRCA2 genes can increase risks of aggressive uterine cancer and metastatic prostate cancer by impairing homologous recombination DNA repair. Early detection of DNA repair mutations can help identify risk and allow preventative measures like hysterectomy or personalized therapies to reduce cancer development and improve patient outcomes.
VectorBase contains mitochondrial DNA sequence information for Anopheline mosquitoes and two subfamilies of ticks. The sections provide compiled mtDNA sequences submitted to EMBL by various authors. Users can view lists of Anopheles gambiae mitochondrial genes and orthologs of genes from multiple species, including gene accession numbers linked to GenBank entries and sequence coordinates. Lists of Anopheles species and their mitochondrial genes are also available.
Ki-67 for further classification of triple negative breast cancerSenology.org
Triple negative breast cancer (TNBC) has a poor prognosis due to its aggressive nature and lack of targeted treatments. Research found that TNBC tumors with high levels of the Ki-67 protein were associated with more aggressive clinical features despite having a higher rate of complete pathological response (pCR) to treatment. The study suggests that Ki-67 levels can be used to further classify TNBC into two subtypes with different prognoses, and that TNBC patients with residual disease and high Ki-67 after treatment should receive additional postoperative treatments like platinum-based chemotherapy or clinical trials to improve outcomes. These high-risk patients should also receive more frequent follow-ups in the first three years to watch for any recurrence.
A New Generation Of Mechanism-Based Biomarkers For The ClinicJoaquin Dopazo
The document discusses moving from single gene biomarkers to more functional, modular biomarkers for disease. It argues that most diseases are caused by combinations of variants affecting functional modules rather than single genes. The document proposes analyzing genomic data like SNPs and gene expression in the context of protein interaction networks and gene ontologies to better capture disease mechanisms and identify more informative biomarkers. Examples show how this approach can prioritize genes interacting with known disease genes and find enriched functional groups associated with diseases.
Digging into thousands of variants to find disease genes in Mendelian and com...Joaquin Dopazo
This document summarizes a presentation about using genomic technologies to enable precision medicine. It discusses:
1) Precision medicine requires a better understanding of phenotype-genotype relationships and incorporating genomics into diagnostics and treatment.
2) Exome sequencing has been used to study a variety of rare and common diseases, generating a knowledge database.
3) Analysis pipelines involve initial processing, variant calling, knowledge-based prioritization using databases, and heuristic filtering to generate candidate genes.
4) Local population databases can improve gene prioritization by providing more accurate frequency filters of common variants.
This document discusses the modular nature of human genetic diseases and how disease genes often reside in the same biological module or pathway. It then discusses how most personalized treatments are based on single-gene biomarkers, with some exceptions like MammaPrint which uses a multigenic biomarker. The rest of the document discusses challenges in defining functional modules and modeling their behavior, and how this could lead to more realistic "actionable pathway models" and a transition to true precision medicine.
This document summarizes a study analyzing gene expression of anergic and suppressive T cells to identify new factors involved in regulatory T cell (Treg) biology. The researchers undertook gene expression analysis of Tregs isolated from peripheral blood before and after expansion in vitro, as well as a Jurkat T cell line stably transfected with the FOXP3 gene. Their initial microarray data showed that FOXP3 acts as a transcriptional regulator, shutting down pathways associated with T cell activation. They also identified individual genes upregulated in response to FOXP3 expression, which could serve as candidate biomarkers for better understanding and identifying Treg cells. The goal is to gain more insight into Treg identification and function by comparing gene expression in
This document describes research developing 3D models of breast cancer using PEG-fibrinogen hydrogels to encapsulate cancer cells. Three breast cancer cell lines (MCF-7, MDA-MB-231, SK-BR-3) representing different molecular subtypes were cultured in the hydrogels. Over time, colony area, diameter and circularity changed differently depending on the cell line. Immunofluorescence staining showed differences in protein and integrin expression between 2D and 3D cultures. The 3D models provide a more accurate representation of cancer growth compared to standard 2D cultures and could improve cancer screening.
1. The document presents a computational model that analyzes gene expression profiles of breast cancer patients to identify intermediate epithelial-mesenchymal transition (EMT) states.
2. The model evaluates patient data and finds some quasi-epithelial and quasi-mesenchymal gene expression patterns with high stability scores, indicating possible intermediate EMT stages.
3. The results confirm previous studies showing that induction of EMT in mammary epithelial cells leads to expression of stem cell markers and properties through acquisition of mesenchymal traits.
A germline mutation in the brca1 3'utr predicts stage iv breast cancerDavid W. Salzman
1) A variant in the 3' untranslated region (3'UTR) of the BRCA1 gene was found to predict increased risk of stage IV breast cancer.
2) In vitro luciferase assays showed the variant reduced BRCA1 expression and altered response to stimuli compared to the normal 3'UTR.
3) Analysis of breast tumor tissue found reduced BRCA1 expression in patients with the variant, and patients with the variant had a 4-fold increased risk of stage IV disease.
Gene expression profiling in breast carcinomaghoshparthanrs
This document discusses gene expression profiling in breast cancer and its use in classifying tumor subtypes. It describes how gene expression profiling analyzes thousands of genes simultaneously to more accurately classify tumors. Breast cancer is classified into clinical subtypes based on receptor expression, including luminal, HER2-enriched, and basal subtypes. Gene signatures can provide prognostic information to help guide treatment decisions for early-stage breast cancer patients. Tests like Oncotype DX and Mammaprint analyze gene expression from tumor samples to predict the risk of recurrence.
This meta-analysis examined the effectiveness of platinum-based chemotherapy compared to non-platinum chemotherapy for treating triple negative breast cancer. Data from over 1000 patients across numerous studies was analyzed. The results showed that platinum-based chemotherapy had significantly higher rates of pathological complete response and objective response compared to non-platinum chemotherapy. Specifically, platinum regimens led to higher levels of cancer cell death. Therefore, platinum-based chemotherapy appears to be more effective at treating triple negative breast cancer than non-platinum alternatives.
This study found that overexpression of vascular endothelial growth factor (VEGF) by estrogen-dependent MCF-7 breast cancer cells promoted estrogen-independent tumor growth in mice. MCF-7 cells were engineered to overexpress VEGF121 or VEGF165. When implanted in ovariectomized mice, the VEGF-overexpressing MCF-7 tumors grew similarly to, or greater than, parental MCF-7 tumors in mice supplemented with estrogen. Overexpression of VEGF stimulated angiogenesis and proliferation in the MCF-7 tumors through both autocrine and paracrine mechanisms, allowing the tumors to grow independently of estrogen. This suggests that upregulation of VEGF contributes to breast cancers acquiring estrogen-independent growth.
This document summarizes three scientific articles:
1) The first article describes fabricating a nickel oxide/graphene nanocomposite to non-enzymatically detect cholesterol concentrations between 2-40 mM with high sensitivity and a low detection limit of 0.13 mM.
2) The second article discusses using a porous covalent triazine polymer as a pH-responsive nanocarrier for cancer therapy and imaging, which exhibited higher cytotoxic effects on cancer cells than free drugs and induced strong senescence at lower concentrations.
3) The third article examines using a PAMAM/5-fluorouracil drug conjugate to target cervical cancer oncoproteins E6 and E7, which molecular docking analysis revealed could
This document describes an online tool called IDEp that provides various bioinformatics analysis methods for high-throughput sequencing data including dimensionality reduction techniques like PCA and t-SNE, differential expression analysis, enrichment analysis, pathway analysis, protein-protein interaction networks, biclustering, and more. It was created by Prof. Xijin Ge and colleagues at South Dakota State University.
1) The document describes a Markov Chain model built to predict gene expression signatures associated with epithelial and mesenchymal cells based on data from 1165 breast cancer patients.
2) The model incorporates the known TGFB-induced EMT pathway and regulatory relationships between molecules to recursively predict expression likelihood.
3) Expression patterns are mapped to epithelial and mesenchymal cell types based on the expression level of the CDH1 gene, which plays a key role in cell phenotype and the initiation of EMT.
This document discusses cancer gene therapy. It explains that gene therapy involves introducing genetic material into cells to replace missing or defective genes that may cause cancer. There are two main approaches - ex vivo gene therapy, where genes are introduced into cells removed from the body and cultured before being returned, and in vivo gene therapy where genes are directly delivered to target cells and tissues in the body. Various gene delivery methods and vector systems are described. Examples of specific cancer types and genes targeted for therapy are provided, such as introducing the Hs-tk gene for ovarian cancer treatment. The goals and applications of cancer gene therapy are to alter the immunogenicity of tumors, genetically modify immune cells, introduce suicide or sensitivity genes, and replace tumor suppressor
This document discusses the identification of Necdin as a novel STAT3 target gene that is downregulated in human cancer. The researchers used microarray analysis to compare gene expression profiles between cells with constitutively active STAT3 and normal cells. They identified differentially expressed genes between cells expressing oncogenic v-Src or constitutively active STAT3-C. Genes common to both lists were most likely directly regulated by STAT3. Computational analysis identified Necdin, a negative growth regulator, as downregulated in cells with active STAT3. Experiments confirmed STAT3 directly binds to and regulates the Necdin promoter, and Necdin expression inversely correlates with STAT3 activity in cancer cell lines. This suggests STAT
Three genes - COX2, HB-EGF, and ST6GALNAC5 - are linked to the spread of breast cancer, with COX2 and HB-EGF priming breast cancer cells to enter the brain and lungs, and ST6GALNAC5 causing a reaction creating a coating enhancing cancer cells' ability to breach the blood-brain barrier. Researchers believe new treatments could be developed to disrupt ST6GALNAC5's interaction with cancer cells.
This document describes a new cell-based diagnostic technique called Cellular Multiplex that can simultaneously detect protein expression, mRNA expression, and cell cycle analysis from breast cancer biopsies. In a preliminary study of 16 breast tumors and 5 normal tissues, the technique identified heterogeneity in biomarker expression between tumors. It also established normal biomarker expression levels and cell cycle distributions in normal breast tissue. The approach has potential to provide a more comprehensive view of the tumor environment and limit inaccuracies of current methods, which could lead to better patient outcomes.
The document summarizes research on DNA repair mechanisms and their link to certain cancers. It discusses how mutations in BRCA1 and BRCA2 genes can increase risks of aggressive uterine cancer and metastatic prostate cancer by impairing homologous recombination DNA repair. Early detection of DNA repair mutations can help identify risk and allow preventative measures like hysterectomy or personalized therapies to reduce cancer development and improve patient outcomes.
VectorBase contains mitochondrial DNA sequence information for Anopheline mosquitoes and two subfamilies of ticks. The sections provide compiled mtDNA sequences submitted to EMBL by various authors. Users can view lists of Anopheles gambiae mitochondrial genes and orthologs of genes from multiple species, including gene accession numbers linked to GenBank entries and sequence coordinates. Lists of Anopheles species and their mitochondrial genes are also available.
Ki-67 for further classification of triple negative breast cancerSenology.org
Triple negative breast cancer (TNBC) has a poor prognosis due to its aggressive nature and lack of targeted treatments. Research found that TNBC tumors with high levels of the Ki-67 protein were associated with more aggressive clinical features despite having a higher rate of complete pathological response (pCR) to treatment. The study suggests that Ki-67 levels can be used to further classify TNBC into two subtypes with different prognoses, and that TNBC patients with residual disease and high Ki-67 after treatment should receive additional postoperative treatments like platinum-based chemotherapy or clinical trials to improve outcomes. These high-risk patients should also receive more frequent follow-ups in the first three years to watch for any recurrence.
A New Generation Of Mechanism-Based Biomarkers For The ClinicJoaquin Dopazo
The document discusses moving from single gene biomarkers to more functional, modular biomarkers for disease. It argues that most diseases are caused by combinations of variants affecting functional modules rather than single genes. The document proposes analyzing genomic data like SNPs and gene expression in the context of protein interaction networks and gene ontologies to better capture disease mechanisms and identify more informative biomarkers. Examples show how this approach can prioritize genes interacting with known disease genes and find enriched functional groups associated with diseases.
Digging into thousands of variants to find disease genes in Mendelian and com...Joaquin Dopazo
This document summarizes a presentation about using genomic technologies to enable precision medicine. It discusses:
1) Precision medicine requires a better understanding of phenotype-genotype relationships and incorporating genomics into diagnostics and treatment.
2) Exome sequencing has been used to study a variety of rare and common diseases, generating a knowledge database.
3) Analysis pipelines involve initial processing, variant calling, knowledge-based prioritization using databases, and heuristic filtering to generate candidate genes.
4) Local population databases can improve gene prioritization by providing more accurate frequency filters of common variants.
This document discusses the modular nature of human genetic diseases and how disease genes often reside in the same biological module or pathway. It then discusses how most personalized treatments are based on single-gene biomarkers, with some exceptions like MammaPrint which uses a multigenic biomarker. The rest of the document discusses challenges in defining functional modules and modeling their behavior, and how this could lead to more realistic "actionable pathway models" and a transition to true precision medicine.
This document summarizes a study analyzing gene expression of anergic and suppressive T cells to identify new factors involved in regulatory T cell (Treg) biology. The researchers undertook gene expression analysis of Tregs isolated from peripheral blood before and after expansion in vitro, as well as a Jurkat T cell line stably transfected with the FOXP3 gene. Their initial microarray data showed that FOXP3 acts as a transcriptional regulator, shutting down pathways associated with T cell activation. They also identified individual genes upregulated in response to FOXP3 expression, which could serve as candidate biomarkers for better understanding and identifying Treg cells. The goal is to gain more insight into Treg identification and function by comparing gene expression in
This document describes research developing 3D models of breast cancer using PEG-fibrinogen hydrogels to encapsulate cancer cells. Three breast cancer cell lines (MCF-7, MDA-MB-231, SK-BR-3) representing different molecular subtypes were cultured in the hydrogels. Over time, colony area, diameter and circularity changed differently depending on the cell line. Immunofluorescence staining showed differences in protein and integrin expression between 2D and 3D cultures. The 3D models provide a more accurate representation of cancer growth compared to standard 2D cultures and could improve cancer screening.
1. The document presents a computational model that analyzes gene expression profiles of breast cancer patients to identify intermediate epithelial-mesenchymal transition (EMT) states.
2. The model evaluates patient data and finds some quasi-epithelial and quasi-mesenchymal gene expression patterns with high stability scores, indicating possible intermediate EMT stages.
3. The results confirm previous studies showing that induction of EMT in mammary epithelial cells leads to expression of stem cell markers and properties through acquisition of mesenchymal traits.
A germline mutation in the brca1 3'utr predicts stage iv breast cancerDavid W. Salzman
1) A variant in the 3' untranslated region (3'UTR) of the BRCA1 gene was found to predict increased risk of stage IV breast cancer.
2) In vitro luciferase assays showed the variant reduced BRCA1 expression and altered response to stimuli compared to the normal 3'UTR.
3) Analysis of breast tumor tissue found reduced BRCA1 expression in patients with the variant, and patients with the variant had a 4-fold increased risk of stage IV disease.
Gene expression profiling in breast carcinomaghoshparthanrs
This document discusses gene expression profiling in breast cancer and its use in classifying tumor subtypes. It describes how gene expression profiling analyzes thousands of genes simultaneously to more accurately classify tumors. Breast cancer is classified into clinical subtypes based on receptor expression, including luminal, HER2-enriched, and basal subtypes. Gene signatures can provide prognostic information to help guide treatment decisions for early-stage breast cancer patients. Tests like Oncotype DX and Mammaprint analyze gene expression from tumor samples to predict the risk of recurrence.
This meta-analysis examined the effectiveness of platinum-based chemotherapy compared to non-platinum chemotherapy for treating triple negative breast cancer. Data from over 1000 patients across numerous studies was analyzed. The results showed that platinum-based chemotherapy had significantly higher rates of pathological complete response and objective response compared to non-platinum chemotherapy. Specifically, platinum regimens led to higher levels of cancer cell death. Therefore, platinum-based chemotherapy appears to be more effective at treating triple negative breast cancer than non-platinum alternatives.
Expression of bmp2 in epithelial ovarian cancer.Evert Cotes
This study aimed to determine the expression levels of bone morphogenetic protein-2 (BMP-2) and its receptors (BMPRIA, BMPRIB, BMPRII) in epithelial ovarian cancer, benign ovarian tumors, and normal ovarian tissue. The researchers found that mRNA and protein levels of BMP-2, BMPRIB, and BMPRII were significantly lower in ovarian cancer tissue compared to benign ovarian tumors or normal tissue, but BMPRIA levels did not differ. Lower expression of these proteins was associated with poorer five-year survival rates in ovarian cancer patients.
A 3′-untranslated region KRAS variant and triple-negative breast cancer: a ca...UCLA
The KRAS-variant might be a genetic marker for development of triple negative breast cancer in premenopausal women, and altered gene and miRNA expression signatures should enable molecular and biological stratification of patients with this subgroup of
breast cancer.
As an uncommon malignant tumor, hypopharyngeal cancer accounts for 3–5% of head and neck tumors [1]. Most pathological types of hypopharyngeal cancer are squamous cell carcinoma. Due to the occult anatomical location of hypopharyngeal cancer and poor surgical effect, local recurrence or distant metastasis often occurs in patients with hypopharyngeal cancer following surgery.
Breast cancer is the most common female malignancy and is
responsible for about 14% of cancer-related deaths in women
[1]. Triple-negative breast cancer (TNBC), characterized by the
absence of expression of Estrogen Receptor (ER), Progesterone
Receptor (PR), and human epidermal growth factor receptor 2
(HER2), is the most aggressive and deadly subtype of breast cancer
This document provides a review of BRCA1 and BRCA2 mutations found globally in breast cancer patients. It discusses the structure and role of BRCA1 and BRCA2 genes/proteins in DNA repair. The review summarizes common polymorphisms and the most frequent mutations identified in different populations worldwide. It aims to provide quick access to high-risk alterations that can help with BRCA screening programs. The review covers mutations in BRCA1 exon 11, which harbors the most common mutations, as well as BRCA2 mutations commonly found in exons 10-11.
This document summarizes a study examining molecular profiling of breast cancer in African American females. Gene expression profiling was performed on 53 early-stage or locally advanced breast cancer patients using the MammaPrint, BluePrint, and TargetPrint tests. Preliminary results found that African American women were often classified as high risk by MammaPrint, and molecular subtyping confirmed biological heterogeneity in triple negative and hormone receptor-positive tumors. Further follow up is needed to determine correlations between gene expression profiling results and patient outcomes.
Correlation of Estrogen and Progesterone Receptor expression in Breast Canceriosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
This document summarizes a research article that studied the role of the heparan sulfate sulfotransferase 3-OST3A in breast cancer. The key findings were:
1) 3-OST3A expression was epigenetically repressed in most breast cancer cell lines through DNA methylation and histone modifications, except in HER2+ SKBR3 cells.
2) Gain and loss of function experiments showed 3-OST3A had profound effects on cell behavior, acting as a tumor suppressor in luminal MCF-7 and triple negative MDA-MB-231 cells but as an oncogene in HER2+ SKBR3 cells.
3) In a clinical study
The document describes a project to develop a nanoparticle-based molecular probe targeted to HER1-overexpressing breast cancer cells for diagnosis. The probe would use quantum dot nanoparticles conjugated to an anti-EGFR single chain antibody for multi-modal MRI and fluorescence imaging of breast cancer in mouse models. The objectives are to develop Gd3+- and 64Cu-labeled quantum dots coated with the targeting antibody, characterize their targeting ability and toxicity, and use them for MRI and fluorescence imaging of breast cancer xenografts in mice.
1) HER2 positive breast cancer accounts for around 15-20% of cases and has a poorer prognosis than other subtypes without HER2 targeted therapy.
2) Multiple HER2 targeted agents are available including trastuzumab, lapatinib, pertuzumab, T-DM1, neratinib, and tucatinib which inhibit HER2 signaling through different mechanisms such as antibody binding or tyrosine kinase inhibition.
3) Combining HER2 targeted therapies such as trastuzumab with chemotherapy improves outcomes for patients with metastatic HER2 positive breast cancer compared to chemotherapy alone.
Rare events or not i want to know about themMehis Pold
The document discusses rare genomic variants called inversions and deletions/insertions (delins) that can affect gene start sites. The author shows that their tool, Garage Genomics (GG), more sensitively detects variants causing start loss compared to the popular tool Variant Effect Predictor (VEP). Analyzing real disease variants from databases, GG resolved previously unexplained cases for important disease genes like MLH1, SLC25A13, WRN, and GSTM1 by correctly annotating start-lost variants that VEP missed. While individually rare, resolving such variants can provide new diagnostic insights, demonstrating the value of continued software improvements in clinical genomics.
Exon 20 of ALK is the hotspot of breakpoints on ALK-gene giving rise to ALK-fusions with a number of genes. The ALK-partners in ALK-fusions are unrelated to ALK but can be closely related to one another, structurally and functionally.
Hidden value in medical genetics databases. Splice the silence!Mehis Pold
Silent mutations in medical genetics databases like ClinVar contain extra value if analyzed with the most current genomics tools. In most cases the silent mutations are of low priority in big data genomics analysis, unless additional value like them being found at functionally important DNA sequences accompanies them. This presentation describes a method to add value to the silent mutations in human exome. Specifically, mapping variants, including silent variants to the known exon-intron boundaries identifies the silent mutations whose potential as pathogenic would otherwise be a lot more unclear.
Silent mutations that occur at the +1 position of splice acceptor sites can impact splicing even though they do not change the encoded amino acid. The author analyzed the Catalogue of Somatic Mutations in Cancer and found 124 variants annotated as silent mutations that actually occur at conserved splice acceptor sites, which may have pathogenic effects by altering splicing. Next-generation sequencing analysis pipelines should include splice site mapping to avoid missing potentially important clues from variants affecting splicing.
Development of multivariate classifiers in cancerMehis Pold
Short presentation about development of multivariate classifiers to predict chemotherapy treatment responses in breast cancer. The steps of workflow are briefly described and the results indicate that expression data on micro-RNA in breast cancer alone are not sufficient to predict treatment responses.
Higher order of endometriosis gene-expression, chromosome 1q significantly contributes to endometriosis specific gene-expression, meta-analysis of three (3)independent endometriosis studies
Why Does FDA Need Standards For In Vitro Diagnostic DevicesMehis Pold
FDA standards for in vitro diagnostic devices (IVDs) are necessary to ensure their quality, safety, and effectiveness. Title 21 of the Code of Federal Regulations Part 820 contains quality system regulations that IVD manufacturers must comply with. These regulations require that IVD design, production, and distribution be carried out in a controlled and documented manner. While the regulations provide clarity for approval processes, novel IVD technologies may require pre-submission engagement with FDA to determine regulatory pathways. Overall, following IVD standards and engaging in dialogue with FDA can help manufacturers successfully achieve regulatory approval.