This document summarizes key aspects of mantle cell lymphoma (MCL) biology and pathogenesis. It discusses:
1) MCL is characterized by the t(11;14) translocation resulting in cyclin D1 overexpression. Prognosis is poor with median survival of 3-4 years, though survival has improved with new therapies.
2) MCL pathogenesis involves dysregulation of cell cycle control and DNA damage response pathways. Genetic alterations affect genes like ATM, p53, ARF-INK4a locus, MDM2, CDK4/cyclin D, and RB.
3) MCL demonstrates a spectrum of variants from classical to blastoid based on proliferation. Bi
This document summarizes HCV resistance to different antiviral treatments. It finds that:
1) HCV can develop resistance to IFN-α therapy, though the molecular mechanisms are unknown.
2) Ribavirin's antiviral effect is modest and transient, and long-term use does not select for resistance.
3) Specific antiviral inhibitors can select for viral variants bearing substitutions that reduce drug susceptibility; these variants preexist as minor populations and become selected under drug pressure.
AJS: a lethal weapon to combat with cancers Treatment of Human Cancers Using...gan-navi
This document describes a lentiviral vector called AJS2001 that can selectively silence the Cdc6 gene in cancer cells. Cdc6 is essential for initiating DNA replication, and silencing it blocks cancer cell proliferation. The vector was shown to inhibit growth of several cancer cell lines through Cdc6 knockdown, inducing senescence. Case studies are presented of cancer patients who recovered after treatment with injections of AJS2001 lentivirus, including patients with gastric carcinoma, brain and liver metastases from ovarian cancer, lung and larynx metastases from parotid carcinoma, and breast cancer.
This document discusses bioinformatics and the epigenome. It notes that the lab has over 100 people from diverse backgrounds including engineers, geneticists, and molecular biologists. It then discusses how epigenetic information like DNA methylation allows for cellular programming and differentiation of stem cells. The rest of the document discusses techniques for profiling the epigenome like MBD-Seq and integration of epigenomic data with other omics datasets to better understand gene regulation and phenotypes. It emphasizes that combining multiple sequencing techniques provides the best approach and that bioinformatics challenges include normalization and data visualization.
Isolation of genes differentially expressed during the defense response of Ca...CIAT
- The document describes research isolating genes differentially expressed in the cassava plant Manihot esculenta during defense response to attack by the whitefly Aleurotrachelus socialis.
- Researchers used subtractive cDNA libraries and microarray expression profiling to identify genes up- or down-regulated in a resistant cassava genotype compared to a susceptible one when infested with whiteflies.
- Over 550 genes were found to be significantly regulated during the cassava-whitefly interaction, including many involved in defense response, oxidative stress, and cell wall modification.
Analyzing ligand and small molecule binding activity of solubilized myszkaJohannesdedooper
This document describes a study that used biosensor technology to analyze the binding activity of solubilized G protein-coupled receptors (GPCRs). Specifically, it analyzed the binding of natural ligands and small molecules to the chemokine receptors CXCR4 and CCR5. Both receptors were solubilized from cell pellets and captured on an antibody surface for analysis. The solubilized receptors maintained high-affinity binding of chemokines and allowed characterization of binding kinetics for novel small molecule inhibitors of CCR5. This demonstrated that the solubilized receptors retained native binding properties, making them useful for biophysical studies and structural analysis.
This document discusses techniques for exploring protein-protein interactions within cells. It begins by defining the proteome and interactome. The proteome is the entire complement of proteins in a cell, while the interactome refers to the network of protein-protein interactions. The document then describes several techniques used to study the interactome, including affinity purification, immunoprecipitation, epitope tagging, and tandem affinity purification. These techniques allow researchers to purify a target protein along with any interacting protein partners in order to map out the social network of proteins within the cell.
1) Ab-XTEN fusions enable genetic fusion of antibody fragments to XTEN polymers for easy, specific drug conjugation and tunable pharmacokinetics. This allows for high drug loads and monovalent or multivalent formats.
2) Ab-XTEN-Drug conjugates specifically link cytotoxic drugs to Ab-XTEN fusions via cleavable linkers, offering many drug options for tumor-targeted delivery.
3) Preliminary studies show Ab-XTEN fusions maintain antigen binding, resist aggregation, and facilitate increased tumor uptake compared to antibody fragments alone.
A new effector pathway links ATM kinase with the DNA damage responseCostas Demonacos
The related kinases ATM (ataxia-telangiectasia mutated) and ATR (ataxia-telangiectasia and Rad3-related) phosphorylate a limited number of downstream protein targets in response to DNA damage. Here we report a new pathway in which ATM kinase signals the DNA damage response by targeting the transcriptional cofactor Strap. ATM phosphorylates Strap at a serine residue, stabilizing nuclear Strap and facilitating formation of a stress-responsive co-activator complex. Strap activity enhances p53 acetylation, and augments the response to DNA damage. Strap remains localized in the cytoplasm in cells derived from ataxia telangiectasia individuals with defective ATM, as well as in cells expressing a Strap mutant that cannot be phosphorylated by ATM. Targeting Strap to the nucleus reinstates protein stabilization and activates the DNA damage response. These results indicate that the nuclear accumulation of Strap is a critical regulator in the damage response, and argue that this function can be assigned to ATM through the DNA damage-dependent phosphorylation of Strap.
This document summarizes HCV resistance to different antiviral treatments. It finds that:
1) HCV can develop resistance to IFN-α therapy, though the molecular mechanisms are unknown.
2) Ribavirin's antiviral effect is modest and transient, and long-term use does not select for resistance.
3) Specific antiviral inhibitors can select for viral variants bearing substitutions that reduce drug susceptibility; these variants preexist as minor populations and become selected under drug pressure.
AJS: a lethal weapon to combat with cancers Treatment of Human Cancers Using...gan-navi
This document describes a lentiviral vector called AJS2001 that can selectively silence the Cdc6 gene in cancer cells. Cdc6 is essential for initiating DNA replication, and silencing it blocks cancer cell proliferation. The vector was shown to inhibit growth of several cancer cell lines through Cdc6 knockdown, inducing senescence. Case studies are presented of cancer patients who recovered after treatment with injections of AJS2001 lentivirus, including patients with gastric carcinoma, brain and liver metastases from ovarian cancer, lung and larynx metastases from parotid carcinoma, and breast cancer.
This document discusses bioinformatics and the epigenome. It notes that the lab has over 100 people from diverse backgrounds including engineers, geneticists, and molecular biologists. It then discusses how epigenetic information like DNA methylation allows for cellular programming and differentiation of stem cells. The rest of the document discusses techniques for profiling the epigenome like MBD-Seq and integration of epigenomic data with other omics datasets to better understand gene regulation and phenotypes. It emphasizes that combining multiple sequencing techniques provides the best approach and that bioinformatics challenges include normalization and data visualization.
Isolation of genes differentially expressed during the defense response of Ca...CIAT
- The document describes research isolating genes differentially expressed in the cassava plant Manihot esculenta during defense response to attack by the whitefly Aleurotrachelus socialis.
- Researchers used subtractive cDNA libraries and microarray expression profiling to identify genes up- or down-regulated in a resistant cassava genotype compared to a susceptible one when infested with whiteflies.
- Over 550 genes were found to be significantly regulated during the cassava-whitefly interaction, including many involved in defense response, oxidative stress, and cell wall modification.
Analyzing ligand and small molecule binding activity of solubilized myszkaJohannesdedooper
This document describes a study that used biosensor technology to analyze the binding activity of solubilized G protein-coupled receptors (GPCRs). Specifically, it analyzed the binding of natural ligands and small molecules to the chemokine receptors CXCR4 and CCR5. Both receptors were solubilized from cell pellets and captured on an antibody surface for analysis. The solubilized receptors maintained high-affinity binding of chemokines and allowed characterization of binding kinetics for novel small molecule inhibitors of CCR5. This demonstrated that the solubilized receptors retained native binding properties, making them useful for biophysical studies and structural analysis.
This document discusses techniques for exploring protein-protein interactions within cells. It begins by defining the proteome and interactome. The proteome is the entire complement of proteins in a cell, while the interactome refers to the network of protein-protein interactions. The document then describes several techniques used to study the interactome, including affinity purification, immunoprecipitation, epitope tagging, and tandem affinity purification. These techniques allow researchers to purify a target protein along with any interacting protein partners in order to map out the social network of proteins within the cell.
1) Ab-XTEN fusions enable genetic fusion of antibody fragments to XTEN polymers for easy, specific drug conjugation and tunable pharmacokinetics. This allows for high drug loads and monovalent or multivalent formats.
2) Ab-XTEN-Drug conjugates specifically link cytotoxic drugs to Ab-XTEN fusions via cleavable linkers, offering many drug options for tumor-targeted delivery.
3) Preliminary studies show Ab-XTEN fusions maintain antigen binding, resist aggregation, and facilitate increased tumor uptake compared to antibody fragments alone.
A new effector pathway links ATM kinase with the DNA damage responseCostas Demonacos
The related kinases ATM (ataxia-telangiectasia mutated) and ATR (ataxia-telangiectasia and Rad3-related) phosphorylate a limited number of downstream protein targets in response to DNA damage. Here we report a new pathway in which ATM kinase signals the DNA damage response by targeting the transcriptional cofactor Strap. ATM phosphorylates Strap at a serine residue, stabilizing nuclear Strap and facilitating formation of a stress-responsive co-activator complex. Strap activity enhances p53 acetylation, and augments the response to DNA damage. Strap remains localized in the cytoplasm in cells derived from ataxia telangiectasia individuals with defective ATM, as well as in cells expressing a Strap mutant that cannot be phosphorylated by ATM. Targeting Strap to the nucleus reinstates protein stabilization and activates the DNA damage response. These results indicate that the nuclear accumulation of Strap is a critical regulator in the damage response, and argue that this function can be assigned to ATM through the DNA damage-dependent phosphorylation of Strap.
This document describes a study using Denaturing Gradient Gel Electrophoresis (DGGE) to differentiate variants of the Infectious Salmon Anemia Virus (ISAv). DGGE allows detection of single point mutations by separating PCR-generated DNA fragments of the same length but different sequence. The study examines variants in segments 5 and 6 of the ISAv genome, which are important for pathogenicity. DGGE analysis of the variants showed distinct banding patterns, demonstrating the technique's ability to distinguish single nucleotide polymorphisms and its potential as a novel alternative for ISAv variant differentiation.
Analysis of mutant parasites that have a defect in adhésion - Conférence du 6e édition du Cours international « Atelier Paludisme » - MATTEI Denise - France - dmm@pasteur.fr
This document provides a bibliography of 10 publications that cite the use of SCHOTT Nexterion products. The publications cover a range of topics including:
1. Methods for distinguishing between types of lung cancer.
2. Analysis conditions for profiling mammalian tissue and cell extracts using antibody microarrays.
3. Isolating proteins from mammalian tissue for analysis on antibody microarrays.
4. Genes controlling metabolism in Corynebacterium glutamicum.
The bibliography lists the authors, year, title, journal, digital object identifier, and whether there is open/free access to the publication. The majority of citations do not provide open access to the full publication.
Carbonic Anhydrase IX: regulation and role in cancerMAASTRO clinic
Lecture by Prof. Silvia Pastorekova in the course: "Tumour Hypoxia: From Biology to Therapy III". For the complete e-Course see http://www.myhaikuclass.com/MaastroClinic/metoxia
This document summarizes research on rust effectors and rust resistance genes in flax. It discusses how 20 flax rust resistance genes have been cloned and encode receptor components of the plant immune system. Four flax rust avirulence genes have been identified that encode small secreted proteins expressed in haustoria. Recognition of these avirulence proteins occurs through direct interaction with the corresponding resistance proteins. The document also discusses how stem rust effectors are delivered into plant cells and the potential application of knowledge from flax to cereal rust diseases.
This document discusses how genetic information flows from DNA to proteins. It explains that DNA is transcribed into mRNA, which is then translated into proteins. Key points covered include:
1) The central dogma that genetic information flows from DNA to RNA to proteins.
2) Beadle and Tatum's "one gene, one enzyme" hypothesis helped establish that genes code for proteins.
3) Transcription involves using DNA as a template to make complementary mRNA strands in the nucleus, which are then processed and can leave the nucleus.
Downloadable slide decks are a great tool for self study and teaching purposes. They are non-certified resources available to enhance your knowledge.
Review a downloadable slide deck by Michael W. N. Deininger, MD, PhD, covering the most clinically relevant new data reported from Community Oncology Clinical Debates: Chronic Myelogenous Leukemia.
Target Audience
This educational activity has been designed to meet the unique learning needs of hematologists, medical oncologists, oncology fellows, and pathologists involved in the treatment of patients with chronic myelogenous leukemia (CML).
This program is designed to provide hematologists/oncologists with the latest clinical updates on the treatment of patients with CML in the frontline and relapsed settings. Key elements of this program will highlight many of the clinical challenges faced by physicians as they select appropriate therapeutic regimens for their patients. Assisting clinicians in gaining further perspective regarding the importance of response criteria, clinical monitoring of treatment failure/suboptimal response/disease resistance, timing for switching therapy to obtain maximum therapeutic benefit, the significance of BCR-ABL mutational analysis in patients and how this can assist in selecting therapy and designing individualized approaches to managing CML will be important discussion points throughout the symposium.
Slideshow is from the University of Michigan Medical School's M1 Patients and Populations: Medical Genetics Sequence.
View additional course materials on Open.Michigan:
openmi.ch/med-M1PatientsPopulations
The GeneArt® Gene Synthesis service consists of chemical synthesis, cloning, and sequence verification of virtually any desired genetic sequence. You will receive a bacterial stab and/or purified plasmid containing your synthesized gene—ready for downstream applications.
Whether you have limited cloning experience or simply want to save time, the GeneArt® Gene Synthesis service helps you move your ideas from the planning stage to the laboratory more quickly. Benefit from our experience in successfully producing over 180,000 constructs for customers as diverse as large pharmaceutical companies, biotechnology start-ups, and basic research institutions. The comparison shown in the figure below highlights the time and effort saved compared to traditional cloning. For more information visit:
https://www.invitrogen.com/site/us/en/home/Products-and-Services/Applications/Cloning/gene-synthesis.html?CID=genesynthesis-SS-12312
This study examined the relationship between lower leg muscle fatigue and changes in foot pronation in recreational runners. Three recreational runners had their foot biomechanics measured before and after a calf raise fatigue protocol using markers and video analysis. The results found minimal changes between the pre-and post-fatigue foot biomechanics, with coordinate location differences averaging around 1-2 mm. The fatigue protocol may not have been effective at inducing significant muscle fatigue, and the video measurement method lacked accuracy to detect small changes in pronation. More advanced equipment and protocols are needed to further study this relationship.
This document provides an overview of foot, ankle, and leg anatomy, evaluation, and common injuries for athletic trainers. It describes the bony, muscular, and ligamentous structures of the foot, ankle, and leg. Evaluation involves taking a thorough history, visual inspection, palpation, range of motion and special tests. Common foot injuries include bunions, turf toe, and stress fractures. Ankle injuries include sprains, syndesmosis sprains, and fractures. Leg injuries include compartment syndrome, Achilles tendon ruptures, muscle strains, and fractures.
Update on ACL reconstruction, with information on current direction of demineralized bone matrix (DBM) use in bone tunnels and biocartilage on chondral lesions
This document discusses the anatomy and kinematics of the knee joint. It begins by describing the three bones that make up the knee - the femur, tibia, and patella. It then discusses the anatomy of the femoral and tibial surfaces, as well as the patella. Next, it covers the ligaments that provide stability to the knee, including the medial and lateral collateral ligaments, anterior and posterior cruciate ligaments, and menisci. The document then discusses the blood supply and innervation of the knee. It concludes by explaining the different theories of knee kinematics, including rolling back of the femur, the four-bar linkage model, and screw home motion.
The document discusses injuries and treatments to the ACL, PCL, and MCL ligaments in the knee. It describes the anatomy of the knee and mechanisms of injury for each ligament, including being hit on the side of the knee or twisting motions. Treatment options are outlined depending on the severity of each ligament tear, ranging from RICE therapy for mild injuries to surgery and bracing for complete tears. The rehabilitation process after ACL surgery is also summarized, focusing on regaining strength and mobility over several months.
The document provides information on anterior cruciate ligament (ACL) injuries, including:
1. The ACL originates from the femur and inserts into the tibia, resisting anterior tibial translation and medial rotation. ACL injuries most commonly result from rapid changes in direction during sports.
2. Physical examination of ACL injuries involves tests like the Lachman test and anterior drawer test to assess knee stability. MRI is also used for diagnosis.
3. Treatment involves RICE initially, followed by either nonsurgical rehabilitation with bracing or surgical reconstruction using grafts like the patellar tendon. Reconstruction aims to restore stability and function to prevent further knee damage.
Susan O'Brien, M.D., Professor, Dept. of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center: Newest Strategies in the Treatment of CML/CLL presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center.
This document discusses various disease modifying treatments for multiple sclerosis. It begins by outlining the speaker's declarations of interests and background. It then examines the theoretical model of treating MS early and aggressively to prevent disability progression over time. Several graphs are presented showing patient data on inflammation, atrophy and disability levels with treatment. The rest of the document summarizes the mechanisms and efficacy data from clinical trials of various disease modifying therapies, including interferon beta, natalizumab, alemtuzumab, fingolimod, cladribine, ocrelizumab and others that are currently used or in development to treat multiple sclerosis. Safety issues are also discussed for many of the treatments.
Current Chemotherapy and the
Future of Targeted Therapies presented by Lee Krug, MD, of Memorial Sloan-Kettering Cancer Center at the Mesothelioma Applied Research Foundation's conference in New York, NY on September 28, 2012. www.curemeso.org
This document describes a study using Denaturing Gradient Gel Electrophoresis (DGGE) to differentiate variants of the Infectious Salmon Anemia Virus (ISAv). DGGE allows detection of single point mutations by separating PCR-generated DNA fragments of the same length but different sequence. The study examines variants in segments 5 and 6 of the ISAv genome, which are important for pathogenicity. DGGE analysis of the variants showed distinct banding patterns, demonstrating the technique's ability to distinguish single nucleotide polymorphisms and its potential as a novel alternative for ISAv variant differentiation.
Analysis of mutant parasites that have a defect in adhésion - Conférence du 6e édition du Cours international « Atelier Paludisme » - MATTEI Denise - France - dmm@pasteur.fr
This document provides a bibliography of 10 publications that cite the use of SCHOTT Nexterion products. The publications cover a range of topics including:
1. Methods for distinguishing between types of lung cancer.
2. Analysis conditions for profiling mammalian tissue and cell extracts using antibody microarrays.
3. Isolating proteins from mammalian tissue for analysis on antibody microarrays.
4. Genes controlling metabolism in Corynebacterium glutamicum.
The bibliography lists the authors, year, title, journal, digital object identifier, and whether there is open/free access to the publication. The majority of citations do not provide open access to the full publication.
Carbonic Anhydrase IX: regulation and role in cancerMAASTRO clinic
Lecture by Prof. Silvia Pastorekova in the course: "Tumour Hypoxia: From Biology to Therapy III". For the complete e-Course see http://www.myhaikuclass.com/MaastroClinic/metoxia
This document summarizes research on rust effectors and rust resistance genes in flax. It discusses how 20 flax rust resistance genes have been cloned and encode receptor components of the plant immune system. Four flax rust avirulence genes have been identified that encode small secreted proteins expressed in haustoria. Recognition of these avirulence proteins occurs through direct interaction with the corresponding resistance proteins. The document also discusses how stem rust effectors are delivered into plant cells and the potential application of knowledge from flax to cereal rust diseases.
This document discusses how genetic information flows from DNA to proteins. It explains that DNA is transcribed into mRNA, which is then translated into proteins. Key points covered include:
1) The central dogma that genetic information flows from DNA to RNA to proteins.
2) Beadle and Tatum's "one gene, one enzyme" hypothesis helped establish that genes code for proteins.
3) Transcription involves using DNA as a template to make complementary mRNA strands in the nucleus, which are then processed and can leave the nucleus.
Downloadable slide decks are a great tool for self study and teaching purposes. They are non-certified resources available to enhance your knowledge.
Review a downloadable slide deck by Michael W. N. Deininger, MD, PhD, covering the most clinically relevant new data reported from Community Oncology Clinical Debates: Chronic Myelogenous Leukemia.
Target Audience
This educational activity has been designed to meet the unique learning needs of hematologists, medical oncologists, oncology fellows, and pathologists involved in the treatment of patients with chronic myelogenous leukemia (CML).
This program is designed to provide hematologists/oncologists with the latest clinical updates on the treatment of patients with CML in the frontline and relapsed settings. Key elements of this program will highlight many of the clinical challenges faced by physicians as they select appropriate therapeutic regimens for their patients. Assisting clinicians in gaining further perspective regarding the importance of response criteria, clinical monitoring of treatment failure/suboptimal response/disease resistance, timing for switching therapy to obtain maximum therapeutic benefit, the significance of BCR-ABL mutational analysis in patients and how this can assist in selecting therapy and designing individualized approaches to managing CML will be important discussion points throughout the symposium.
Slideshow is from the University of Michigan Medical School's M1 Patients and Populations: Medical Genetics Sequence.
View additional course materials on Open.Michigan:
openmi.ch/med-M1PatientsPopulations
The GeneArt® Gene Synthesis service consists of chemical synthesis, cloning, and sequence verification of virtually any desired genetic sequence. You will receive a bacterial stab and/or purified plasmid containing your synthesized gene—ready for downstream applications.
Whether you have limited cloning experience or simply want to save time, the GeneArt® Gene Synthesis service helps you move your ideas from the planning stage to the laboratory more quickly. Benefit from our experience in successfully producing over 180,000 constructs for customers as diverse as large pharmaceutical companies, biotechnology start-ups, and basic research institutions. The comparison shown in the figure below highlights the time and effort saved compared to traditional cloning. For more information visit:
https://www.invitrogen.com/site/us/en/home/Products-and-Services/Applications/Cloning/gene-synthesis.html?CID=genesynthesis-SS-12312
This study examined the relationship between lower leg muscle fatigue and changes in foot pronation in recreational runners. Three recreational runners had their foot biomechanics measured before and after a calf raise fatigue protocol using markers and video analysis. The results found minimal changes between the pre-and post-fatigue foot biomechanics, with coordinate location differences averaging around 1-2 mm. The fatigue protocol may not have been effective at inducing significant muscle fatigue, and the video measurement method lacked accuracy to detect small changes in pronation. More advanced equipment and protocols are needed to further study this relationship.
This document provides an overview of foot, ankle, and leg anatomy, evaluation, and common injuries for athletic trainers. It describes the bony, muscular, and ligamentous structures of the foot, ankle, and leg. Evaluation involves taking a thorough history, visual inspection, palpation, range of motion and special tests. Common foot injuries include bunions, turf toe, and stress fractures. Ankle injuries include sprains, syndesmosis sprains, and fractures. Leg injuries include compartment syndrome, Achilles tendon ruptures, muscle strains, and fractures.
Update on ACL reconstruction, with information on current direction of demineralized bone matrix (DBM) use in bone tunnels and biocartilage on chondral lesions
This document discusses the anatomy and kinematics of the knee joint. It begins by describing the three bones that make up the knee - the femur, tibia, and patella. It then discusses the anatomy of the femoral and tibial surfaces, as well as the patella. Next, it covers the ligaments that provide stability to the knee, including the medial and lateral collateral ligaments, anterior and posterior cruciate ligaments, and menisci. The document then discusses the blood supply and innervation of the knee. It concludes by explaining the different theories of knee kinematics, including rolling back of the femur, the four-bar linkage model, and screw home motion.
The document discusses injuries and treatments to the ACL, PCL, and MCL ligaments in the knee. It describes the anatomy of the knee and mechanisms of injury for each ligament, including being hit on the side of the knee or twisting motions. Treatment options are outlined depending on the severity of each ligament tear, ranging from RICE therapy for mild injuries to surgery and bracing for complete tears. The rehabilitation process after ACL surgery is also summarized, focusing on regaining strength and mobility over several months.
The document provides information on anterior cruciate ligament (ACL) injuries, including:
1. The ACL originates from the femur and inserts into the tibia, resisting anterior tibial translation and medial rotation. ACL injuries most commonly result from rapid changes in direction during sports.
2. Physical examination of ACL injuries involves tests like the Lachman test and anterior drawer test to assess knee stability. MRI is also used for diagnosis.
3. Treatment involves RICE initially, followed by either nonsurgical rehabilitation with bracing or surgical reconstruction using grafts like the patellar tendon. Reconstruction aims to restore stability and function to prevent further knee damage.
Susan O'Brien, M.D., Professor, Dept. of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center: Newest Strategies in the Treatment of CML/CLL presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center.
This document discusses various disease modifying treatments for multiple sclerosis. It begins by outlining the speaker's declarations of interests and background. It then examines the theoretical model of treating MS early and aggressively to prevent disability progression over time. Several graphs are presented showing patient data on inflammation, atrophy and disability levels with treatment. The rest of the document summarizes the mechanisms and efficacy data from clinical trials of various disease modifying therapies, including interferon beta, natalizumab, alemtuzumab, fingolimod, cladribine, ocrelizumab and others that are currently used or in development to treat multiple sclerosis. Safety issues are also discussed for many of the treatments.
Current Chemotherapy and the
Future of Targeted Therapies presented by Lee Krug, MD, of Memorial Sloan-Kettering Cancer Center at the Mesothelioma Applied Research Foundation's conference in New York, NY on September 28, 2012. www.curemeso.org
Stereotactic radiosurgery (SRS) is an effective treatment option for brain tumors. SRS uses focused radiation beams directed at the tumor from multiple angles to deliver a high dose of radiation precisely to the tumor while minimizing exposure to surrounding normal brain tissue. SRS has been shown to control brain metastases and provide survival benefits compared to whole brain radiation therapy alone for certain patient groups. SRS has also shown good tumor control rates for benign brain tumors such as meningiomas and pituitary adenomas. Further research continues to optimize SRS techniques and fractionation schedules to maximize tumor control while minimizing side effects.
1) A phase 3 trial of abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive metastatic castration-resistant prostate cancer patients showed improved radiographic progression-free and overall survival for the abiraterone arm.
2) At the first interim analysis when 425 overall survival events occurred, the hazard ratio for overall survival was 0.66 with a p-value of 0.0034, crossing the pre-specified boundary for statistical significance.
3) Secondary endpoints including time to opiate use, chemotherapy initiation, performance status deterioration, and prostate specific antigen progression were also all significantly prolonged in the abiraterone arm.
1. The document discusses DNA replication and the cell cycle checkpoint processes that ensure DNA is properly replicated. It specifically focuses on proteins involved like CHK1 and CHK2 kinases.
2. CHK1 plays a key role in the G2/M checkpoint and inhibition of CHK1 can sensitize tumors to treatments like radiation and chemotherapy.
3. The document includes figures and diagrams illustrating concepts like the relationship between origin firing and fork velocity, and how DNA damage checkpoints work at the single cell level.
1) The document describes experiments to modify the DNA of the SecA gene through site-directed mutagenesis.
2) Two types of mutations are introduced: an amino acid substitution (T624C) and an LBT insertion at position G151.
3) The mutations are generated using PCR-based methods like sdmPCR and round-the-horn PCR and subsequently transformed into E. coli for protein expression analysis.
Pfizer at Lehman Brothers Global Health Care Conferencefinance5
Martin Mackay, president of Pfizer's Global Research and Development division, outlines Pfizer's 5-point plan to aggressively deliver their phase 2 and 3 pipelines. The plan includes prioritizing their portfolio, becoming a top biotherapeutics company, dramatically raising productivity, and pursuing external science. Pfizer has a rich pipeline of 85 new molecular entities in development across 10 therapeutic areas. Their goal is to rebuild their phase 3 portfolio with 15-20 phase 3 starts per year between 2008-2009. Pfizer expects 15-20 regulatory submissions between 2010-2012. Several investigational drugs, including axitinib and CP-690550, show promising results.
This document summarizes a presentation on using micro and nanotechnologies for cancer diagnostics and therapy. It discusses using various technologies like microarrays, comparative genomic hybridization, and integration of genome and transcriptome data to analyze cancer at multiple levels. In particular, it focuses on using these techniques to study neuroblastoma and identify genetic signatures that can predict patient outcomes and survival. Signatures identified include miRNA profiles and their interactions with mRNA that are associated with poor survival in neuroblastoma patients.
Microsampling techniques like dried blood spots (DBS) allow for small volume samples that are stable at ambient temperatures and easy to ship. A new automated online card extraction LC/MS system from Agilent allows for reproducible, sensitive DBS analysis in about an hour, comparable to offline methods that take around five hours. The system uses robotic grippers to clamp DBS cards, extract samples, and introduce them to an LC/MS workflow via switching valves. It was shown to quantitate clozapine and related compounds down to 0.5 ng/mL in blood across a wide linear range over four orders of magnitude, with accuracy and precision similar to offline DBS methods.
The DTExtm method allows simultaneous analysis of changes in gene expression levels of 145 ADME-associated genes using a microarray. Total RNA is converted to cDNA and labeled before being hybridized to the DTExtm microarray. The method can survey basal gene expression levels and coordinated changes in expression levels caused by drug treatment in various cell lines and tissues. Rifampicin treatment of human hepatocytes showed induction of genes such as CYP3A4, UGT1A1, and ABCB1 in a coordinated manner mediated by PXR activation. Benzoflavone treatment also coordinately induced CYP1A2, UGT1A1, and ABCC2 through AHR activation. DTE
1. Hematopoietic stem cell transplantation (HSCT) can provide long-term remission for some CML patients, but it carries risks of mortality and morbidity.
2. HSCT is best considered after failure of tyrosine kinase inhibitor (TKI) therapy or for accelerated/blast phase disease.
3. Directly after diagnosis, HSCT may be too risky due to transplant-related risks outweighing potential benefits. In blast crisis phase, HSCT may be too late due to disease progression.
Melanoma arises from neural crest cells that migrate and produce the pigment melanin. It can present in skin or mucosal surfaces and commonly spreads from radial to vertical growth phases as it invades deeper tissues. Treatment depends on tumor stage and characteristics as well as mutation status, and may involve surgery, radiation, immunotherapy, targeted therapy, or chemotherapy.
The VERSA platform isolates circulating tumor cells from blood samples using paramagnetic particles coated with tumor-specific antibodies. Initial results show it can isolate renal cell carcinoma and prostate cancer cells from blood with 50-70% efficiency. CTCs isolated from patient blood samples expressed tumor antigens and were sufficient for molecular analysis. Significant heterogeneity was seen in MHC expression among CTC populations, which could have implications for immunotherapy responses. Prospective clinical trials are needed to validate the utility of using CTC analysis as a biomarker.
This document discusses white foods and their nutritional value. It summarizes that while colorful foods contain many nutrients, white foods should not be avoided and contain important nutrition as well. Examples of healthy white foods provided are potatoes, cauliflower, beans, mushrooms, and onions. The document then provides recipes for a potato soup, white bean spread, and kasha pilaf with mushrooms to showcase nutritious white food options.
This document summarizes a nutrition discussion and cooking demonstration that featured three healthy appetizer recipes: Cranberry Chicken Salad Cups made with wonton skins, Mini Spanakopitas which are low-fat Greek spinach pies, and Garbanzo Guacamole which combines beans and avocado. The demonstration emphasized making party foods that are both tasty and healthy by using ingredients like egg whites instead of whole eggs, baking wonton skins instead of frying, and reducing fat and calories in the recipes. Detailed instructions and nutrition information are provided for each of the three appetizer recipes.
This document provides recipes for two savory side dishes - a Savory Bread Pudding with Swiss Chard and a Wild Rice Pilaf with Cranberries and Pecans. The bread pudding uses stale bread, Swiss chard, cheese, herbs and eggs baked into a creamy dish. The pilaf combines wild rice, stock, shallots, dried fruits and toasted pecans for a flavorful grain side. Instructions for preparing both dishes are included.
A chef from Whole Foods Market demonstrated how to use various whole grains like brown rice, wheat berries, and pearled barley in meals. She shared recipes for breakfast porridge made with brown rice, a wheat berry and apricot salad, and a barley pilaf. Whole grains provide more fiber and nutrients than processed grains and have a nutty taste and chewy texture. The chef provided tips for incorporating more whole grains into meals easily.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
The document provides recipes for Southwest Stew, Babaganoush, and Chocolate Haystacks to serve at a Super Bowl party. The Southwest Stew is a hearty vegetarian chili-like dish made with tomatoes, vegetables, chickpeas and spinach. Babaganoush is a roasted eggplant dip made with tahini, lemon juice and olive oil. Chocolate Haystacks are a fiber-rich dessert made by coating a high-fiber cereal with dark chocolate and peanut butter, then adding dried fruit. The recipes allow for preparations in advance so the host is not busy during the game.
Evelyn Margolin from Whole Foods Market in Ridgewood visited a cooking studio to demonstrate how to make traditional Passover Seder menu items vegan. She used recipes from Vegan Holiday Kitchen to modify dishes like matzo ball soup, vegetable kugel, and coconut almond macaroons to eliminate animal products and comply with Kosher for Passover restrictions. The matzo balls were made with quinoa flakes instead of eggs. The vegetable kugel contained mushrooms for texture and potato starch instead of eggs. Coconut almond macaroons used potato starch instead of egg whites for leavening. The dishes were flavorful and satisfying for the vegan Passover Seder.
This document provides a recipe for Irish soda bread along with context about the cultural history and variations of Irish soda bread. It discusses how there is no single authentic recipe as versions vary between Ireland and America. The winner of a soda bread baking contest was John Napoli's entry using his great-grandmother's recipe passed down to him. The document also provides the full recipe for Great-Grandma Henrehan's Irish soda bread and a strawberry rhubarb compote recipe to serve alongside.
This document provides recipes for two immune-boosting soups - Greek Avgolemono Soup and Shiitake Hot and Sour Soup - that can help protect against colds and flu. It discusses how foods like vitamin C, zinc, garlic and ginger have immune-boosting properties. The soups contain ingredients like chicken broth, eggs, tofu and vegetables that are nourishing and may help ease symptoms. Directions are included for making both easy and flavorful soup recipes.
This document announces an interactive evening event about multiple myeloma featuring speaker Dr. David H. Vesole. The event will be held on February 28, 2013 from 6-7:30 PM at Gilda's Club Northern New Jersey and will include a presentation on myeloma disease management and treatment options, followed by a question and answer session and stories from myeloma survivors. Pre-registration is required by February 26th.
Sudheer Mechineni, Head of Application Frameworks, Standard Chartered Bank
Discover how Standard Chartered Bank harnessed the power of Neo4j to transform complex data access challenges into a dynamic, scalable graph database solution. This keynote will cover their journey from initial adoption to deploying a fully automated, enterprise-grade causal cluster, highlighting key strategies for modelling organisational changes and ensuring robust disaster recovery. Learn how these innovations have not only enhanced Standard Chartered Bank’s data infrastructure but also positioned them as pioneers in the banking sector’s adoption of graph technology.
A tale of scale & speed: How the US Navy is enabling software delivery from l...sonjaschweigert1
Rapid and secure feature delivery is a goal across every application team and every branch of the DoD. The Navy’s DevSecOps platform, Party Barge, has achieved:
- Reduction in onboarding time from 5 weeks to 1 day
- Improved developer experience and productivity through actionable findings and reduction of false positives
- Maintenance of superior security standards and inherent policy enforcement with Authorization to Operate (ATO)
Development teams can ship efficiently and ensure applications are cyber ready for Navy Authorizing Officials (AOs). In this webinar, Sigma Defense and Anchore will give attendees a look behind the scenes and demo secure pipeline automation and security artifacts that speed up application ATO and time to production.
We will cover:
- How to remove silos in DevSecOps
- How to build efficient development pipeline roles and component templates
- How to deliver security artifacts that matter for ATO’s (SBOMs, vulnerability reports, and policy evidence)
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How to Get CNIC Information System with Paksim Ga.pptxdanishmna97
Pakdata Cf is a groundbreaking system designed to streamline and facilitate access to CNIC information. This innovative platform leverages advanced technology to provide users with efficient and secure access to their CNIC details.
Observability Concepts EVERY Developer Should Know -- DeveloperWeek Europe.pdfPaige Cruz
Monitoring and observability aren’t traditionally found in software curriculums and many of us cobble this knowledge together from whatever vendor or ecosystem we were first introduced to and whatever is a part of your current company’s observability stack.
While the dev and ops silo continues to crumble….many organizations still relegate monitoring & observability as the purview of ops, infra and SRE teams. This is a mistake - achieving a highly observable system requires collaboration up and down the stack.
I, a former op, would like to extend an invitation to all application developers to join the observability party will share these foundational concepts to build on:
Let's Integrate MuleSoft RPA, COMPOSER, APM with AWS IDP along with Slackshyamraj55
Discover the seamless integration of RPA (Robotic Process Automation), COMPOSER, and APM with AWS IDP enhanced with Slack notifications. Explore how these technologies converge to streamline workflows, optimize performance, and ensure secure access, all while leveraging the power of AWS IDP and real-time communication via Slack notifications.
Essentials of Automations: The Art of Triggers and Actions in FMESafe Software
In this second installment of our Essentials of Automations webinar series, we’ll explore the landscape of triggers and actions, guiding you through the nuances of authoring and adapting workspaces for seamless automations. Gain an understanding of the full spectrum of triggers and actions available in FME, empowering you to enhance your workspaces for efficient automation.
We’ll kick things off by showcasing the most commonly used event-based triggers, introducing you to various automation workflows like manual triggers, schedules, directory watchers, and more. Plus, see how these elements play out in real scenarios.
Whether you’re tweaking your current setup or building from the ground up, this session will arm you with the tools and insights needed to transform your FME usage into a powerhouse of productivity. Join us to discover effective strategies that simplify complex processes, enhancing your productivity and transforming your data management practices with FME. Let’s turn complexity into clarity and make your workspaces work wonders!
Cosa hanno in comune un mattoncino Lego e la backdoor XZ?Speck&Tech
ABSTRACT: A prima vista, un mattoncino Lego e la backdoor XZ potrebbero avere in comune il fatto di essere entrambi blocchi di costruzione, o dipendenze di progetti creativi e software. La realtà è che un mattoncino Lego e il caso della backdoor XZ hanno molto di più di tutto ciò in comune.
Partecipate alla presentazione per immergervi in una storia di interoperabilità, standard e formati aperti, per poi discutere del ruolo importante che i contributori hanno in una comunità open source sostenibile.
BIO: Sostenitrice del software libero e dei formati standard e aperti. È stata un membro attivo dei progetti Fedora e openSUSE e ha co-fondato l'Associazione LibreItalia dove è stata coinvolta in diversi eventi, migrazioni e formazione relativi a LibreOffice. In precedenza ha lavorato a migrazioni e corsi di formazione su LibreOffice per diverse amministrazioni pubbliche e privati. Da gennaio 2020 lavora in SUSE come Software Release Engineer per Uyuni e SUSE Manager e quando non segue la sua passione per i computer e per Geeko coltiva la sua curiosità per l'astronomia (da cui deriva il suo nickname deneb_alpha).
GraphSummit Singapore | The Future of Agility: Supercharging Digital Transfor...Neo4j
Leonard Jayamohan, Partner & Generative AI Lead, Deloitte
This keynote will reveal how Deloitte leverages Neo4j’s graph power for groundbreaking digital twin solutions, achieving a staggering 100x performance boost. Discover the essential role knowledge graphs play in successful generative AI implementations. Plus, get an exclusive look at an innovative Neo4j + Generative AI solution Deloitte is developing in-house.
Why You Should Replace Windows 11 with Nitrux Linux 3.5.0 for enhanced perfor...SOFTTECHHUB
The choice of an operating system plays a pivotal role in shaping our computing experience. For decades, Microsoft's Windows has dominated the market, offering a familiar and widely adopted platform for personal and professional use. However, as technological advancements continue to push the boundaries of innovation, alternative operating systems have emerged, challenging the status quo and offering users a fresh perspective on computing.
One such alternative that has garnered significant attention and acclaim is Nitrux Linux 3.5.0, a sleek, powerful, and user-friendly Linux distribution that promises to redefine the way we interact with our devices. With its focus on performance, security, and customization, Nitrux Linux presents a compelling case for those seeking to break free from the constraints of proprietary software and embrace the freedom and flexibility of open-source computing.
20 Comprehensive Checklist of Designing and Developing a WebsitePixlogix Infotech
Dive into the world of Website Designing and Developing with Pixlogix! Looking to create a stunning online presence? Look no further! Our comprehensive checklist covers everything you need to know to craft a website that stands out. From user-friendly design to seamless functionality, we've got you covered. Don't miss out on this invaluable resource! Check out our checklist now at Pixlogix and start your journey towards a captivating online presence today.
Generative AI Deep Dive: Advancing from Proof of Concept to ProductionAggregage
Join Maher Hanafi, VP of Engineering at Betterworks, in this new session where he'll share a practical framework to transform Gen AI prototypes into impactful products! He'll delve into the complexities of data collection and management, model selection and optimization, and ensuring security, scalability, and responsible use.
TrustArc Webinar - 2024 Global Privacy SurveyTrustArc
How does your privacy program stack up against your peers? What challenges are privacy teams tackling and prioritizing in 2024?
In the fifth annual Global Privacy Benchmarks Survey, we asked over 1,800 global privacy professionals and business executives to share their perspectives on the current state of privacy inside and outside of their organizations. This year’s report focused on emerging areas of importance for privacy and compliance professionals, including considerations and implications of Artificial Intelligence (AI) technologies, building brand trust, and different approaches for achieving higher privacy competence scores.
See how organizational priorities and strategic approaches to data security and privacy are evolving around the globe.
This webinar will review:
- The top 10 privacy insights from the fifth annual Global Privacy Benchmarks Survey
- The top challenges for privacy leaders, practitioners, and organizations in 2024
- Key themes to consider in developing and maintaining your privacy program
Removing Uninteresting Bytes in Software FuzzingAftab Hussain
Imagine a world where software fuzzing, the process of mutating bytes in test seeds to uncover hidden and erroneous program behaviors, becomes faster and more effective. A lot depends on the initial seeds, which can significantly dictate the trajectory of a fuzzing campaign, particularly in terms of how long it takes to uncover interesting behaviour in your code. We introduce DIAR, a technique designed to speedup fuzzing campaigns by pinpointing and eliminating those uninteresting bytes in the seeds. Picture this: instead of wasting valuable resources on meaningless mutations in large, bloated seeds, DIAR removes the unnecessary bytes, streamlining the entire process.
In this work, we equipped AFL, a popular fuzzer, with DIAR and examined two critical Linux libraries -- Libxml's xmllint, a tool for parsing xml documents, and Binutil's readelf, an essential debugging and security analysis command-line tool used to display detailed information about ELF (Executable and Linkable Format). Our preliminary results show that AFL+DIAR does not only discover new paths more quickly but also achieves higher coverage overall. This work thus showcases how starting with lean and optimized seeds can lead to faster, more comprehensive fuzzing campaigns -- and DIAR helps you find such seeds.
- These are slides of the talk given at IEEE International Conference on Software Testing Verification and Validation Workshop, ICSTW 2022.
Building RAG with self-deployed Milvus vector database and Snowpark Container...Zilliz
This talk will give hands-on advice on building RAG applications with an open-source Milvus database deployed as a docker container. We will also introduce the integration of Milvus with Snowpark Container Services.
Building RAG with self-deployed Milvus vector database and Snowpark Container...
Dr. Campo MCL
1. Biology and Pathology of
Mantle Cell Lymphoma
Elias Campo
Hospital Clinic, University of Barcelona
2. Mantle Cell Lymphoma
1.0
0.8
Probability
0.6
Cyclin D1 0.4
0.2
0.0
0 2 4 6 8
Years
Complete Response 25% (6-50%)
14 der(14) 11 der(11) Duration of CR 1.5 yrs (0.5-2.5 yrs)
Median Survival 3-4 years
IGH/CCND1
3. Improvement in Survival of Patients
with non-blastoid MCL
1996 to 2004
1975 to 1986
• New diagnostic tools and management measures
• Application of new therapeutic regimens
Herrmann, A. et al. J Clin Oncol; 27:511-518 2009
4. MCL Pathogenesis
• Cell Cycle Dysregulation
• Dysruption of DNA damage
response pathway
• Cell survival pathways
12. Molecular Pathogenesis in MCL
Early Classical Blastoid
Naive B
MCL MCL MCL
lymphocyte
t(11;14) ATM p16/CDK4/Rb Bcl-2/other
ARF/MdM2/p53
Cyclin D1 CHK2
Increased High Cell
Rb p27 Genomic Proliferation Survival
Instability
Jares P et al Nat Rev Cancer 2007
13. IGH Somatic Hypermutations in 807 MCL
Highly mutated 111 (13%)
Minimally/borderline mutated 458 (57%)
Truly Unmutated 238 (30%)
Hadzidimitriou A et al Blood 2011
14. MCL: From Naive to an Antigen Selected Cell ?
UnMutated-MCL
T Cell-Independent Response
Naïve Boderline Mutated-MCL
V D J cμ cγ
Antigen Selection
Ig Somatic Mutations
Class Switch
HyperMutated-MCL
23. MCL with Indolent Clinical Behavior
OS from diagnosis OS from treatment
Martin P et al JCO 2009
24. Conventional vs Indolent MCL
Clinical Characteristics
Clinical data Conventional Indolent
MCL (15) MCL (12)
Chemotherapy 15 0
Median Follow-up 15 m (0.5 - 79) 70 m (25-121)
5-year Overall Survival 49% 100%*
ECOG≥2 70% 0+
Intermediate/High MIPI 46% 0+
Lymphadenopathy (>1cm) 15/15 2/12+
Lymphocytosis (≥5x109/L) 9/11 4/9
+ p <0.05
* p=0.002 Fernandez V et al Cancer Res 2010
25. iMCL and cMCL Have a Distinct Gene Expression Signature
Supervised analysis
Indolent and
conventional MCL
LGALS3BP
CSNK1E
SOX11
KIAA1909
FARP1
PON2
CNN3
DBN1
HDGFRP3
CDK2AP1
HMGB3
SETMAR
CNR1
RNGTT
Fernandez V et al Cancer Res 2010
27. Can SOX11 expression recognize a subtype of MCL with
different clinicopathological features and outcome?
Clinical data SOX11 - SOX11 +
(n = 15) (n = 97)
High MIPI 33% 46%
Lymphn nodes (>1cm) 53% 99% *
Splenomegaly 92% 48%*
WBC ≥ 10x109/L 57% 18%*
Lymphocytosis (≥5x109/L) 83% 24% *
Ki67 high >50% 20% 28%
Adriamycin-Regimens 67% 72%
Complete Response 40% 54%
5-year OS (%) 78% 36%*
+ p <0.01 Fernandez V et al Cancer Res 2010
28. Overall Survival in MCL patients according to SOX11 Expression
1
SOX11 negative (N=15; dead: 4)
.8
.6
Sox11 -
.4
PROBABILITY
SOX11 positive (N=97; dead: 68)
.2 Sox11 +
0
0 2 4 6 8 10 12 14 16
YEARS
P< 0.001
Fernandez V et al Cancer Res 2010
33. Conclusions
- MCL pathogenesis integrates alterations in cell cycle, DNA damage
response and survival pathways that may be targeted by new
therapies
- Antigen selection may play a role in the pathogenesis of at least a
subgroup of MCL
- Cyclin D1 negative MCL can be recognized by SOX11 expression
and seem to have similar clinical and genetic characteristics to
conventional MCL.
- Some MCL have an indolent clinical course and may benefit of a
more conservative clinical management. A subset of them seems to
correspond to a different biological subtype.
- We may recognize early steps in MCL lymphomagenesis that
should be managed with caution.
34. Acknowledgments
Hospital Clínic-University National Institute of Health
of Barcelona Bethesda
Adrian Wiestner
Silvia Bea Wyndham Wilson
Cristina Royo Elaine Jaffe
Alba Navarro
Guillem Clot
Alejandra Martinez Institute of Pathology-Würzburg
Eva Giné Elena Hartmann
Gonzalo Gutierrez Andreas Rosenwald
Verònica Fernàndez
Dolors Colomer
Abteilung für Klinische-Pathologie-
Neus Villamor
Stuttgart
Pedro Jares
German Ott
Armando Lopez-Guillermo
University Hospital
Schleswig-Holstein-Kiel
Chistiane Pott Addenbrooke’s Hospital-Cambridge
Itziar Salverria Nicola Trim
Reiner Siebert
Wendy Erber
University Hospital Munich-
Grosshadern-Munich S. Orsola-Malpighi Hospital-Bologna
Martin Dreyling Claudio Agostinelli
Stefano A Pileri