Acquired Resistance to Targeted Therapy in EGFR and ALK-Positive Lung Cancer:...H. Jack West
This is a presentation I did for a meeting on new general management of acquired resistance in 2014, including the concept of local therapy for limited progression, and new treatment approaches and new agents for this setting. It features discussion of several of the most important trials.
Best of ASCO Metastatic Non-Small Cell Lung CancerH. Jack West
Dr. Jack West's presentation on highlights in advanced non-small cell lung cancer from ASCO 2014, focusing on new agents ramucirumab and necitumumab for broad NSCLC populations, crizotinib and ceritinib for ALK-positive NSCLC, EGFR inhibitor-options of afatinib and bevacizumab added to erlotinib for first line treatment of EGFR mutation-positive NSCLC, and AZD9291 or CO1686 for EGFR mutation-positive patients with acquired resistance.
Co-Chairs Roy S. Herbst, MD, PhD, and Lecia V. Sequist, MD, MPH, prepared useful Practice Aids pertaining to EGFR-mutated lung cancer for this CME activity titled “New Milestones and Changing Standards of Care in EGFR-Mutated NSCLC: Expanding the Benefits of Genomic Testing and EGFR-Targeted Therapy to Early-Stage Lung Cancer.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at http://bit.ly/36aVo39. CME credit will be available until March 8, 2022.
Acquired Resistance to Targeted Therapy in EGFR and ALK-Positive Lung Cancer:...H. Jack West
This is a presentation I did for a meeting on new general management of acquired resistance in 2014, including the concept of local therapy for limited progression, and new treatment approaches and new agents for this setting. It features discussion of several of the most important trials.
Best of ASCO Metastatic Non-Small Cell Lung CancerH. Jack West
Dr. Jack West's presentation on highlights in advanced non-small cell lung cancer from ASCO 2014, focusing on new agents ramucirumab and necitumumab for broad NSCLC populations, crizotinib and ceritinib for ALK-positive NSCLC, EGFR inhibitor-options of afatinib and bevacizumab added to erlotinib for first line treatment of EGFR mutation-positive NSCLC, and AZD9291 or CO1686 for EGFR mutation-positive patients with acquired resistance.
Co-Chairs Roy S. Herbst, MD, PhD, and Lecia V. Sequist, MD, MPH, prepared useful Practice Aids pertaining to EGFR-mutated lung cancer for this CME activity titled “New Milestones and Changing Standards of Care in EGFR-Mutated NSCLC: Expanding the Benefits of Genomic Testing and EGFR-Targeted Therapy to Early-Stage Lung Cancer.” For the full presentation, downloadable Practice Aids, and complete CME information, and to apply for credit, please visit us at http://bit.ly/36aVo39. CME credit will be available until March 8, 2022.
West egfr mutation acquired resistanceH. Jack West
Review by Dr. H. Jack West of current understanding of mechanisms behind and emerging treatment options for patients with advanced NSCLC with acquired resistance to EGFR tyrosine kinase inhibitors after a good initial response.
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
Jessica Donington, MD, Natasha Leighl, MD, MMSc, FRCPC, FASCO, and Brendon Stiles, MD, prepared useful practice aids pertaining to the role of immunotherapy in lung cancer for this CME/MOC/CNE activity titled, "The Expanding Role of Immunotherapy in Locally Advanced and Earlier Stages of Lung Cancer: Rationale, Current Evidence, Key Trials, and Implications for Thoracic Surgeons." For the full presentation, monograph, complete CME/MOC/CNE information, and to apply for credit, please visit us at http://bit.ly/2WibbtU. CME/MOC/CNE credit will be available until June 16, 2020.
David R. Jones, MD, and Roy S. Herbst, MD, PhD, prepared useful practice aids pertaining to lung cancer for this CME activity titled "Turning Tides in Targeted Therapy for Early-Stage EGFR-Mutated NSCLC: Latest Data and Practical Guidance for Thoracic Surgeons and the Multidisciplinary Team on the Emerging Role of EGFR-Targeted Therapy in Resectable Lung Cancer." For the full presentation, complete CME information, and to apply for credit, please visit us at https://bit.ly/2PSVELG. CME credit will be available until November 9, 2021.
Discovery and development of 2,7-Disubstituted-Pyrrolo[2,1-f][1,2,4]triazines. A New Class of Anaplastic Lymphoma Kinase(ALK)*Inhibitors with in-vivo Anti-tumor Efficacy
West egfr mutation acquired resistanceH. Jack West
Review by Dr. H. Jack West of current understanding of mechanisms behind and emerging treatment options for patients with advanced NSCLC with acquired resistance to EGFR tyrosine kinase inhibitors after a good initial response.
Roy H. Decker, MD, PhD; Kristin Higgins, MD; and Jyoti D. Patel, MD, prepared useful practice aids pertaining to immunotherapies in lung cancer for this CME/MOC activity titled “NSCLC Tumor Board: Navigating the Evolving Role of Immunotherapy in Multimodal Management of Locally Advanced and Early-Stage Lung Cancer.” For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at http://bit.ly/2mFfEWE. CME/MOC credit will be available until October 22, 2020.
Jessica Donington, MD, Natasha Leighl, MD, MMSc, FRCPC, FASCO, and Brendon Stiles, MD, prepared useful practice aids pertaining to the role of immunotherapy in lung cancer for this CME/MOC/CNE activity titled, "The Expanding Role of Immunotherapy in Locally Advanced and Earlier Stages of Lung Cancer: Rationale, Current Evidence, Key Trials, and Implications for Thoracic Surgeons." For the full presentation, monograph, complete CME/MOC/CNE information, and to apply for credit, please visit us at http://bit.ly/2WibbtU. CME/MOC/CNE credit will be available until June 16, 2020.
David R. Jones, MD, and Roy S. Herbst, MD, PhD, prepared useful practice aids pertaining to lung cancer for this CME activity titled "Turning Tides in Targeted Therapy for Early-Stage EGFR-Mutated NSCLC: Latest Data and Practical Guidance for Thoracic Surgeons and the Multidisciplinary Team on the Emerging Role of EGFR-Targeted Therapy in Resectable Lung Cancer." For the full presentation, complete CME information, and to apply for credit, please visit us at https://bit.ly/2PSVELG. CME credit will be available until November 9, 2021.
Discovery and development of 2,7-Disubstituted-Pyrrolo[2,1-f][1,2,4]triazines. A New Class of Anaplastic Lymphoma Kinase(ALK)*Inhibitors with in-vivo Anti-tumor Efficacy
use of omega-transaminase enzyme chemistry in the synthesis of JAK2 kinase in...Kashif Haider
use of enzyme chemistry is discussed with example of drugs in there synthesis. drugs in clinical trail of jak-2 enzyme inhibitors , and different scheme for enzyme synthesis is covered.
Is the future of medicine chemo pills? In this webinar, we will delve into oral chemotherapy and explain why some patients are offered the option to receive cancer treatment in a pill form. We’ll discuss the advantages and challenges of this emerging treatment option and highlight the current therapies some patients receive. Join us to learn more about the future of treating colorectal cancer via pills.
01.13.09: Chronic Myeloid Leukemia and other Myeloproliferative Neoplasms (MPNs)Open.Michigan
Slideshow is from the University of Michigan Medical
School's M2 Hematology / Oncology sequence
View additional course materials on Open.Michigan: openmi.ch/med-M2Hematology
Mutations in Chronic myeloid leukaemia and Imatinib resistanceDr Sandeep Kumar
some corrections over previous presentation on CML. Covers topics like - pathophysiology of CML, Mutations discussed in detail, TKI resistance in various mutations and treatment options. Also Imatinib resistance has been discussed in detail.
Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2QIAGEN
Advanced prostate cancer is highly heterogeneous but this inter-patient heterogeneity has until recently not been understood. We have through an international research effort dissected the molecular landscape of advanced castration resistant prostate, elucidating key molecular targets in this group of diseases. We have also shown that PARP inhibitors have antitumor activity against a significant proportion of these cancers, mainly in men whose cancers harbor DNA repair defects.
Never-smoker with Lung cancer in Southern California. Never-smokers with lung cancer have distinct genetic changes. Chao Family Comprehensive Cancer Center at UCI Irvine offers cutting edge clinical trials. Please call 1-714-456-8000
NSCLC: diagnóstico molecular, pronóstico y seguimiento; CTCMauricio Lema
Lo nuevo en diagnóstico molecular, pronóstico y seguimiento en NSCLC, y el impacto pronóstico de las Células Tumorales Circulantes. Para evento de cirugía de tórax, Hotel Intercontinental, Medellín, 22.05.2018 (se complementa con las la presentación de lo nuevo en terapia sistémica en NSCLC).
Alphabet Soup - Biomarker testing for colon and rectal cancer patients - KRAS...Fight Colorectal Cancer
Dr. Cathy Eng's presentation regarding biomarkers. Explaining why colon and rectal cancer patients should undergo testing for KRAS, NRAS and other tumor tests.
• Gastric cancer prognosis and cell ratio factors Oleg Kshivets
OBJECTIVE: We examined cell ratio factors (CRF) significantly affecting gastric cancer (EC) patients GCP) survival. CRF - ratio between cancer cells (CC) and blood cells subpopulations.
METHODS: We analyzed data of 799 consecutive GCP (T1-4N0-2M0) (age=57.1±9.4 years; tumor size=5.4±3.1 cm) radically operated (R0) and monitored in 1975-2022 (m=558, f=241; total gastrectomies=173, distal gastrectomies=461; proximal gastrectomies=165; combined gastrectomies=247 with resection of esophagus, pancreas, liver, duodenum, diaphragm, colon transversum, splenectomy, etc; only surgery-S=624, adjuvant chemoimmunotherapy-AT=175 (5-FU + thymalin/taktivin); T1=238, T2=220, T3=184, T4=157; N0=437, N1=109, N2=253, M0=799; G1=222, G2=164, G3=413. Variables selected for prognosis study were input levels of 45 blood parameters, sex, age, TNMG, cell type, tumor size. Survival curves were estimated by the Kaplan-Meier method. Differences in curves between groups of GCP were evaluated using a log-rank test. Multivariate Cox modeling, discriminant analysis, clustering, SEPATH, Monte Carlo, bootstrap and neural networks computing were used to determine any significant dependence.
RESULTS: Overall life span (LS) was 2128.9±2300.3 days and cumulative 5-year survival (5YS) reached 58.4%, 10 years – 51.9%, 20 years – 39%, 30 years – 27.2%. 318 GCP lived more than 5 years (LS=4304.5±2290.6 days), 169 GCP – more than 10 years (LS=5919.5±2020 days). 290 GCP died because of GC (LS=651±347.2 days). Cox modeling displayed that G CP survival significantly depended on CRF: healthy cells/CC, erythrocytes/CC, monocytes/CC, phase transition (PT) in terms of synergetics early—invasive cancer; PT N0--N12, age, G1-3, hemorrhage time, ESS, sex, AT, prothrombin index, residual nitrogen. Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early—invasive cancer (rank=1); PT N0--N12 (2); healthy cells/CC (3), erythrocytes/CC (4), thrombocytes/CC (5), monocytes/CC (6), segmented neutrophils/CC (7), leucocytes/CC (8), lymphocytes/CC (9), stick neutrophils/CC (10), eosinophils/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: GCP survival after radical procedures significantly depended on CRF.
Robert P. Edwards, MD, Chair of OB/GYN/RS, Co-Director of Women's Cancer Program at University of Pittsburgh, offers information about the current state of immunotherapy for recurrent ovarian cancer patients.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...
Crizotinib a8081001 asco 2010 slides
1. Clinical Activity of the Oral ALK Inhibitor,Clinical Activity of the Oral ALK Inhibitor,
Crizotinib (PF-02341066), in Patients withCrizotinib (PF-02341066), in Patients with
ALKALK-positive Non-small Cell Lung Cancer-positive Non-small Cell Lung Cancer
Bang Y,1
Kwak EL,2
Shaw A,2
Camidge DR,3
Iafrate AJ,2
Maki RG,4
Solomon B,5
Ou SI,6
Salgia R,7
Clark J2
1
Seoul National University, Seoul, Korea; 2
Massachusetts General Hospital, Boston, MA, USA;
3
University of Colorado Cancer Center, Aurora, CO, USA; 4
Memorial Sloan-Kettering Cancer
Center, New York, NY, USA; 5
Peter MacCallum Cancer Centre, East Melbourne, Australia;
6
University of California at Irvine, Irvine, CA, USA; 7
University of Chicago Cancer Center,
Chicago, IL, USA
Abstract 3ASCO Annual Meeting 2010
2. Potential Oncogenic “Drivers” inPotential Oncogenic “Drivers” in
Non-small Cell Lung Cancer (NSCLC)Non-small Cell Lung Cancer (NSCLC)
ALK (~5%)
Other
Adenocarcinoma
Massachusetts General Hospital, data on file.
[AT Shaw, personal communication]
ALK = anaplastic lymphoma kinase; EGFR = epidermal growth
factor receptor; Her2 = human epidermal growth factor receptor 2;
PIK3CA = phosphoinositide-3-kinase, catalytic, alpha polypeptide
3. ALKALK PathwayPathway
1. Inamura K et al. J Thorac Oncol 2008;3:13–17
2. Soda M et al. Proc Natl Acad Sci U S A 2008;105:19893–19897
Figure based on: Chiarle R et al. Nat Rev Cancer 2008;8(1):11–23;
Mossé YP et al. Clin Cancer Res 2009;15(18):5609–5614; and Data on file. Pfizer Inc.
*Subcellular localization of the ALK
fusion gene, while likely to occur in
the cytoplasm, is not confirmed.1,2
Translocation
Or
ALK ALK fusion protein*
Tumor cell
proliferation
Inversion
Cell survival
PI3KPI3K
BADBAD
AKTAKT
STAT3/5STAT3/5
mTORmTOR
S6KS6K
RASRAS
MEKMEK
ErKErK
PLC-PLC-YY
PIPPIP22
IPIP33
9. Part 2:
Molecularly enriched cohorts
(ALK and c-MET)
Enrolling patients with ALK-positive NSCLC
after preliminary observation of impressive
activity in a few patients
• Data from database April 7, 2010
• Data presented for 82 patients, study
ongoing
Part 1:
Dose escalation
Crizotinib: First-in-human/Patient TrialCrizotinib: First-in-human/Patient Trial
1 DLT: grade 3 ALT
elevation
2 DLTs: grade 3 fatigue
Cohort 1 (n=3)
50 mg QD
Cohort 2 (n=4)
100 mg QD
Cohort 3 (n=8)
200 mg QD
Cohort 4 (n=7)
200 mg BID
Cohort 5 (n=6)
300 mg BID
Cohort 6 (n=9)
250 mg BID
MTD/RP2D
ALT = alanine aminotransferase
10. Crizotinib Overview of Pharmacokinetics:*Crizotinib Overview of Pharmacokinetics:*
All Patients Enrolled in Dose EscalationAll Patients Enrolled in Dose Escalation
● t1/2 ~53 hours at
250 mg BID
● No evidence of
non-linearity in PK
● No food effect on PK
● Moderate CYP3A4
inhibitor
Ceff = efficacious concentration; CYP = cytochrome P450; t1/2 = terminal elimination half-life; PK = pharmacokinetics
*Please refer to (abstract 2596): Pharmacokinetics (PK) of PF-02341066, a dual ALK/c-MET inhibitor after multiple oral
doses to advanced cancer patients. (9:00 AM, Monday, June 7)
500
400
300
200
100
0
Medianplasmaconcentration,
cycle1day15(ng/mL)
0 2 4 6 8
Time (hours)
50 mg QD 200 mg BID
100 mg QD 250 mg BID
200 mg QD 300 mg BID
Target Ceff (ALK)
11. Clinical and Demographic Features ofClinical and Demographic Features of
Patients withPatients with ALKALK-positive NSCLC-positive NSCLC
N=82
Mean (range) age, years 51 (25–78)
Gender, male/female 43/39
Performance
status,* n (%)
0 24 (29)
1 44 (54)
2 13 (16)
3 1 (1)
Race, n (%) Caucasian 46 (56)
Asian 29 (35)
Smoking
history, n (%)
Never smoker 62 (76)
Former smoker 19 (23)
Current smoker 1 (1)
Histology, n (%) Adenocarcinoma 79 (96)
Squamous 1 (1)
Other 2 (2)
Prior treatment
regimens, n (%)
0 5 (6)
1 27 (33)
2 15 (18)
≥3 34 (41)
Not reported 1 (1)
*Performance status = Eastern Cooperative Oncology Group
12. 60
40
20
0
–20
–40
–60
–80
–100
Progressive disease
Stable disease
Confirmed partial response
Confirmed complete response
Maximumchangeintumorsize(%)
–30%
Tumor Responses to Crizotinib for PatientsTumor Responses to Crizotinib for Patients
withwith ALKALK-positive NSCLC-positive NSCLC
*Partial response patients with 100% change have non-target disease present
*
13. 77% of Patients with77% of Patients with ALKALK-positive NSCLC-positive NSCLC
Remain on Crizotinib TreatmentRemain on Crizotinib Treatment
0 3 6 9 12 15 18 21
Treatment duration (months)
N=82; red bars represent discontinued patients
Individualpatients
• Duration of treatment
(median: 5.7 months)
0–3 mo 13 pts
>3–6 mo 29 pts
>6–9 mo 24 pts
>9–12 mo 9 pts
>12–18 mo 4 pts
>18 mo 3 pts
• Reasons for discontinuation
– Related AEs 1
– Non-related AEs 1
– Unrelated death 2
– Other 2
– Progression 13
14. Clinical Activity of Crizotinib inClinical Activity of Crizotinib in
Patients withPatients with ALK-ALK-positive NSCLCpositive NSCLC
● Objective response rate (ORR): 57% (95% CI: 46, 68%)
– 63% including 5 as yet unconfirmed PRs
– 57% (8/14) for patients with performance status 2 or 3
No. prior
regimens*
ORR
% (n/N)
0 80 (4/5)
1 52 (14/27)
2 67 (10/15)
≥3 56 (19/34)
* Unknown for 1 patient
● Response duration: 1 to 15 months
● DCR†
(CR/PR/SD at 8 weeks): 87% (95% CI: 77, 93%)
†
Disease control rate
15. Median PFS has Not been ReachedMedian PFS has Not been Reached
70% of Patients in Follow-up for PFS70% of Patients in Follow-up for PFS
1.00
0.75
0.50
0.25
0.00
Progression-freesurvivalprobability
0 2.5 5.0 7.5 10.0 12.5 15.0 17.5
Progression-free survival (months)
PFS probability at 6 months: 72%
(95% CI: 61, 83%)
Median follow-up for PFS: 6.4 months
(25–75% percentile: 3.5–10 months) 95% Hall–Wellner confidence bands
17. Treatment-related Grade 3/4 Adverse EventsTreatment-related Grade 3/4 Adverse Events
inin ALKALK-positive NSCLC-positive NSCLC
Adverse event
Grade 3
n (%)
Grade 4
n (%)
Any adverse event 10 (12) 1 (1)
ALT elevation* 4 (5) 1 (1)
AST elevation 5 (6) 0
Lymphopenia 2 (2) 0
Hypophosphatemia 1 (1) 0
Neutropenia 1 (1) 0
Hypoxia 1 (1) 0
Dyspnea 1 (1) 0
Pulmonary embolism 1 (1) 0
*Based on laboratory data (n=71), ALT increase to grade 1, 52%; to grade 2, 4%
(In preclinical toxicology studies, no histologic changes in the liver were observed)
1 patient discontinued for ALT elevation
18. SummarySummary
● Treatment with crizotinib resulted in impressive clinical activity in
patients with ALK-positive advanced NSCLC
– ORR: 57%
– DCR at 8 weeks: 87%
– PFS probability at 6 months: 72%
● Crizotinib was well tolerated
– The most frequent adverse events were mild and moderate
gastrointestinal events and mild visual disturbances
19. ConclusionsConclusions
● These results are an example of rapid clinical development from
target identification, to clinical validation, and supports a
personalized approach to NSCLC treatment
● For patients with ALK-positive NSCLC, crizotinib may offer a
potential new standard of care
20. Current Crizotinib Clinical TrialsCurrent Crizotinib Clinical Trials
PROFILE 1007: NCT00932893; PROFILE 1005: NCT00932451
Key entry criteria
● Positive for ALK by central
laboratory
● 1 prior chemotherapy
(platinum-based)
N=318
PROFILE 1007
Crizotinib 250 mg BID (N=250)
administered on a continuous
dosing schedule
Key entry criteria
● Positive for ALK by central
laboratory
● Progressive disease in Arm B of
study A8081007
● >1 prior chemotherapy
PROFILE 1005
R
A
N
D
O
M
I
Z
E
N=250
Crizotinib 250 mg BID (n=159)
administered on a continuous
dosing schedule
Pemetrexed 500 mg/m2
or
docetaxel 75 mg/m2
(n=159)
infused on day 1 of a 21-day cycle
21. AcknowledgmentsAcknowledgments
Massachusetts General Hospital
● John Iafrate,* Jeffrey Clark, Eunice Kwak,
Alice Shaw, Eunice Kwak, Thomas Lynch,
Panos Fidias, Jeffrey Engelman, Marguerite
Parkman
Dana-Farber Cancer Institute
● Geoffrey Shapiro, Pasi Janne,* James
Butrynski, Leena Gandhi, Andrew Wolanski
Suzanne Hitchcock-Bryan, Charles Lee
Beth Israel Deaconess Medical Center
● Bruce Dezube, Daniel Costa, Myles Clancy
Memorial Sloan Kettering Cancer Center
● Robert Maki, Suresh C. Jhanwar,* Linda
Ahn, Lindsey Burge
Seoul National University
● Woo-Ho Kim,* Dong-Wan Kim, Se-Hoon Lee,
Do Youn Oh, Sae-Won Han, Tae-Min Kim
Peter MacCallum Cancer Centre
● Benjamin Solomon, Alex Dobrovic,* Stephen
Fox,* Hongdo Do*, Toni-Maree Rogers,*
Allison Lamb
University of Colorado
● Ross Camidge, Marileila Garcia,* S. Gail
Eckhardt, Wells Messersmith
University of California – Irvine
● Sai-Hong Ou, Antonio Sanchez, Katie
Gottbreht
University of Chicago
● Ravi Salgia, Mark Ratain, David Geary,
Leonardo Faoro, Rajani Kanteti
Pfizer
● James Christensen, Victoria Cohan, Gina
Emory, Paulina Selaru, Martin Shreeve, Jamey
Skillings, Sreesha Srinivasa, Patricia
Stephenson, Weiwei Tan, Greg Wei, Keith
Wilner
*Molecular profiling contributor
● We would like to thank all of the participating patients and their families, as well as the
global network of investigators, research nurses, study coordinators, and operations staff
● This study was supported by funding from Pfizer Inc. Editorial Support was provided by Jessica Stevens
at ACUMED®
(Tytherington, UK) with funding from Pfizer Inc.
Finally, I’d like to acknowledge contributing investigators from Karmanos Cancer Center, The Mayo Clinic, The University of Alabama-Birmingham, and The Ireland Cancer Center, Case Western Reserve.
I’d also like to acknowledge the efforts of colleagues advancing the MEK inhibitor program at Pfizer…
Click….
And most importantly, I’d like to acknowledge the patients without whose support this ambitious study would not have been possible.
Thank you for your attention.