The document discusses comprehensive genomic profiling (CGP) of solid tumors. It provides examples of genomic alterations that can be detected by CGP in various cancer types, including NSCLC, gliomas, and others. It describes how CGP interrogates many genes through next-generation sequencing to detect mutations, fusions, and other alterations that may be targeted with specific therapies or provide prognostic information.
Lo que un reumatólogo debe saber sobre immunoterapia del cáncerMauricio Lema
FORO ARTE 2019, 22/03/2019
-- Flagship: toda la información que consideré pertinente (217 diapositivas).
-- La presentación de la conferencia en sí se basa en este repositorio
The OncoScan(TM) platform for analysis of copy number and somatic mutations i...Lawrence Greenfield
The OncoScan microarray offers high-quality copy number, genotype, and somatic mutation data with whole-genome coverage and high resolution in cancer genes for use with challenging FFPE samples.
Lo que un reumatólogo debe saber sobre immunoterapia del cáncerMauricio Lema
FORO ARTE 2019, 22/03/2019
-- Flagship: toda la información que consideré pertinente (217 diapositivas).
-- La presentación de la conferencia en sí se basa en este repositorio
The OncoScan(TM) platform for analysis of copy number and somatic mutations i...Lawrence Greenfield
The OncoScan microarray offers high-quality copy number, genotype, and somatic mutation data with whole-genome coverage and high resolution in cancer genes for use with challenging FFPE samples.
Clinical Genomics for Personalized Cancer Medicine: Recent Advances, Challeng...Yoon Sup Choi
I reviewed recent advances, challenges, and opportunities to implement clinical cancer genomics. Case studies of advanced systems, such as Foundation Medicine, MI-ONCOSEQ are introduced for benchmark. A few fundamental limitations to establish personalized oncology are also discussed.
Identification of cancer drivers across tumor typesNuria Lopez-Bigas
Thousands of tumor genomes/exomes are being sequenced as part of the International Cancer Genome Consortium (ICGC), The Cancer Genome Atlas (TCGA) and other initiatives. This opens the possibility to have, for the first time, a comprehensive picture of mutations, genes and pathways involved in the cancer phenotype across tumor types. We have developed computational methods able to identify signals of positive selection in the pattern of tumor somatic mutations, which point to genes and pathways directly involved in the development of the tumors. We have applied these approaches to 3025 tumors from 12 different cancer types of the TCGA Pan-Cancer project, identifying 291 high-confidence cancer driver genes acting on those tumors (Tamborero et al 2013). We have also developed IntOGen-mutations (http://www.intogen.org/mutations), a novel web platform for cancer genomes interpretations, which analyses not only TCGA pan-cancer data but all mutation data from ICGC and other initiatives. The resource allows users to identify driver mutations, genes and pathways acting on more than 6000 tumors originated in 17 different cancer sites and to analyze newly sequence tumor genomes. Among the novel cancer drivers identified there are chromatin regulatory factors and splicing factors, which are emerging as important genes in cancer development and are regarded as interesting candidates for novel targets for cancer treatment. In my talk I will summarize all these recent findings.
More info: http://bg.upf.edu/blog/2013/10/my-slides-on-identification-of-cancer-drivers-across-tumor-types/
In Silico Prescription of Anticancer Drugs Reveals Targeting OpportunitiesNuria Lopez-Bigas
Large efforts dedicated to sequence thousands of tumor genome/exomes are expected to lead to significant improvements of precision cancer medicine. However, high inter-tumor heterogeneity is a major obstacle in the road to develop an arsenal of targeted cancer drugs to treat most cancer patients. Therefore, it is critical to understand the current scope of anti-cancer targeted drugs for different tumor types in order to use them with the highest efficacy, and to define priorities for the development of new ones. We have developed a novel methodology to interpret the genomes of a cohort of tumor samples and to assess their therapeutic opportunities. Starting with somatic mutations detected across the cohort, the methodology identifies the driver genes, highlights those that dominate the clonal landscape of the tumors and determines their mode of action. It then does an in-silico prescription of approved and candidate targeted drugs to each patient in the cohort. The application of this approach to a cohort of 6795 cancer samples of 28 different tumor types showed that the fraction of patients that could benefit from prescribed FDA-approved drugs is strikingly small. Nevertheless, it improves significantly if repurposing opportunities are taken into consideration, with large differences between tumor types. In addition, we identify 80 therapeutically unexploited cancer genes, tightly bound by pre-clinical small molecules or potentially suitable for molecule binding. The resource created with this analysis is also intended to provide interpretation of newly sequenced cancer genomes and to design pan-cancer and tumor type specific sequencing panels for efficient early cancer detection and clinical insight.
More details at http://www.intogen.org
The Presence and Persistence of Resistant and Stem Cell-Like Tumor Cells as a...QIAGEN
Epithelial ovarian cancer is the fifth leading cause of cancer-related deaths of women in the United States and Europe and ranks as the second most common type of gynecological malignancy. Most cases are diagnosed in advanced stages and although the response rates to platinum-based chemotherapy are high, the majority of patients nevertheless have poor survival rates. Although the reasons for these poor outcomes are likely to be multifactorial, one particular area of interest has recently focused on hematogenous tumor cell dissemination that has been shown to originate from disseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in the blood. Here, we demonstrate that the negative prognostic impact of CTCs and DTCs arise from specific cellular phenotypes and are associated with platinum-resistance and stem cell-associated proteins.
Advances in Diagnosis & Imaging Impacting Cancer Treatment Dr.Harsha Doddihal
"Personalized Medicine" is making its way into health care. Oncology is a prime example. This is helped by advancements in imaging and molecular pathology. PET-CT, cancer pathways define how a cancer patient will be treated. Drugs approved by FDA last year gives a glimpse into the progress happening.
Talimogene laherparepvec (T-VEC, OncoVEX GM-CSF) phase 3 data in melanoma pre...Virotherapist
Phase 3 data from the OPTiM study in melanoma with talimogene laherparepvec presented as part of a talk on oncolytic immunotherapy at The Eighth International Conference on Oncolytic Virus Therapeutics, Oxford, UK,9-13 April 2014.
NSA Diagnostic Laboratory has been operating since 1958, founded by Prof. Nasseh Amin. NSA is considered as one of the most advanced labs in Egypt. Maintaining personalized services for its stakeholders, as well as the main role of the lab "Diagnosis"
NSA Diagnostic Laboratory operates through two different segments.
Firstly, a group of stand-alone labs located at prime locations all over Egypt, with the latest and up to date equipments.
Secondly, being the backbone of well reputed hospitals and some polyclinics where NSA is the lab that is responsible for all medical testing there, serving all our patients with class A quality.
Our main focus is delivering quality care and with Cost-value return. NSA plays a key role in improving the health of many Egyptians, by providing access to quality service for more than 200,000 patients annually.
Clinical Genomics for Personalized Cancer Medicine: Recent Advances, Challeng...Yoon Sup Choi
I reviewed recent advances, challenges, and opportunities to implement clinical cancer genomics. Case studies of advanced systems, such as Foundation Medicine, MI-ONCOSEQ are introduced for benchmark. A few fundamental limitations to establish personalized oncology are also discussed.
Identification of cancer drivers across tumor typesNuria Lopez-Bigas
Thousands of tumor genomes/exomes are being sequenced as part of the International Cancer Genome Consortium (ICGC), The Cancer Genome Atlas (TCGA) and other initiatives. This opens the possibility to have, for the first time, a comprehensive picture of mutations, genes and pathways involved in the cancer phenotype across tumor types. We have developed computational methods able to identify signals of positive selection in the pattern of tumor somatic mutations, which point to genes and pathways directly involved in the development of the tumors. We have applied these approaches to 3025 tumors from 12 different cancer types of the TCGA Pan-Cancer project, identifying 291 high-confidence cancer driver genes acting on those tumors (Tamborero et al 2013). We have also developed IntOGen-mutations (http://www.intogen.org/mutations), a novel web platform for cancer genomes interpretations, which analyses not only TCGA pan-cancer data but all mutation data from ICGC and other initiatives. The resource allows users to identify driver mutations, genes and pathways acting on more than 6000 tumors originated in 17 different cancer sites and to analyze newly sequence tumor genomes. Among the novel cancer drivers identified there are chromatin regulatory factors and splicing factors, which are emerging as important genes in cancer development and are regarded as interesting candidates for novel targets for cancer treatment. In my talk I will summarize all these recent findings.
More info: http://bg.upf.edu/blog/2013/10/my-slides-on-identification-of-cancer-drivers-across-tumor-types/
In Silico Prescription of Anticancer Drugs Reveals Targeting OpportunitiesNuria Lopez-Bigas
Large efforts dedicated to sequence thousands of tumor genome/exomes are expected to lead to significant improvements of precision cancer medicine. However, high inter-tumor heterogeneity is a major obstacle in the road to develop an arsenal of targeted cancer drugs to treat most cancer patients. Therefore, it is critical to understand the current scope of anti-cancer targeted drugs for different tumor types in order to use them with the highest efficacy, and to define priorities for the development of new ones. We have developed a novel methodology to interpret the genomes of a cohort of tumor samples and to assess their therapeutic opportunities. Starting with somatic mutations detected across the cohort, the methodology identifies the driver genes, highlights those that dominate the clonal landscape of the tumors and determines their mode of action. It then does an in-silico prescription of approved and candidate targeted drugs to each patient in the cohort. The application of this approach to a cohort of 6795 cancer samples of 28 different tumor types showed that the fraction of patients that could benefit from prescribed FDA-approved drugs is strikingly small. Nevertheless, it improves significantly if repurposing opportunities are taken into consideration, with large differences between tumor types. In addition, we identify 80 therapeutically unexploited cancer genes, tightly bound by pre-clinical small molecules or potentially suitable for molecule binding. The resource created with this analysis is also intended to provide interpretation of newly sequenced cancer genomes and to design pan-cancer and tumor type specific sequencing panels for efficient early cancer detection and clinical insight.
More details at http://www.intogen.org
The Presence and Persistence of Resistant and Stem Cell-Like Tumor Cells as a...QIAGEN
Epithelial ovarian cancer is the fifth leading cause of cancer-related deaths of women in the United States and Europe and ranks as the second most common type of gynecological malignancy. Most cases are diagnosed in advanced stages and although the response rates to platinum-based chemotherapy are high, the majority of patients nevertheless have poor survival rates. Although the reasons for these poor outcomes are likely to be multifactorial, one particular area of interest has recently focused on hematogenous tumor cell dissemination that has been shown to originate from disseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in the blood. Here, we demonstrate that the negative prognostic impact of CTCs and DTCs arise from specific cellular phenotypes and are associated with platinum-resistance and stem cell-associated proteins.
Advances in Diagnosis & Imaging Impacting Cancer Treatment Dr.Harsha Doddihal
"Personalized Medicine" is making its way into health care. Oncology is a prime example. This is helped by advancements in imaging and molecular pathology. PET-CT, cancer pathways define how a cancer patient will be treated. Drugs approved by FDA last year gives a glimpse into the progress happening.
Talimogene laherparepvec (T-VEC, OncoVEX GM-CSF) phase 3 data in melanoma pre...Virotherapist
Phase 3 data from the OPTiM study in melanoma with talimogene laherparepvec presented as part of a talk on oncolytic immunotherapy at The Eighth International Conference on Oncolytic Virus Therapeutics, Oxford, UK,9-13 April 2014.
NSA Diagnostic Laboratory has been operating since 1958, founded by Prof. Nasseh Amin. NSA is considered as one of the most advanced labs in Egypt. Maintaining personalized services for its stakeholders, as well as the main role of the lab "Diagnosis"
NSA Diagnostic Laboratory operates through two different segments.
Firstly, a group of stand-alone labs located at prime locations all over Egypt, with the latest and up to date equipments.
Secondly, being the backbone of well reputed hospitals and some polyclinics where NSA is the lab that is responsible for all medical testing there, serving all our patients with class A quality.
Our main focus is delivering quality care and with Cost-value return. NSA plays a key role in improving the health of many Egyptians, by providing access to quality service for more than 200,000 patients annually.
Analytical performance of a novel next generation sequencing assay for Myeloi...Thermo Fisher Scientific
To support clinical and translational research into precision oncology strategies for myeloid cancers, a next-generation sequencing (NGS) assay was developed to detect common and relevant somatic alterations. To define gene targets that were recurrently altered in myeloid cancers and relevant for clinical and translational research, an extensive survey of investigators at hematology oncology research labs was performed.
Lessons learned from high throughput CRISPR targeting in human cell linesChris Thorne
In just a short period of time CRISPR-Cas9 technology has revolutionized the field of genome editing, and taken the scientific community by storm. Already our understanding of how best to apply this technology has advanced significantly and almost every week new publications appear showcasing its application in basic and translational research.
While CRISPR-Cas9 is applicable across many different cell types, we have found it particularly suited for genome editing in near-haploid human cell lines. This has allowed us to establish a robust pipeline for the inactivation of non-essential genes at unprecedented scale and efficiency.
We have now knocked out over 1500 human genes and have generated a resource that is, to the best of our knowledge, the largest collection of human knockout cell lines available, covering comprehensive subsets of genes clustered by biological pathway (e.g. the autophagy pathway, the JAK/STAT pathway) or by phylogenetic relationship (e.g. kinases, bromodomain-containing proteins).
In this talk we will discuss how, through more than 1500 genome editing experiments, we have started to unravel some of the general principles governing the use of CRISPR-Cas9 in mammalian cells. For example, we have analyzed the impact of variation in the guide RNA sequence on Cas9 cleavage efficiency and characterized the mutational signature arising from CRISPR-Cas9 cleavage.
We will also highlight (with examples) how these learnings are now being applied to introduce other genomic modifications in a high throughput manner, including chromosomal deletions, translocations, point mutations and endogenous gene tags.
Webinar analyzing complex genomic variants in somatic cancer Lisa Owen
Next generation sequencing (NGS) technologies facilitate the accurate detection of genetic and genomic variants. Yet the process of analyzing and classifying more complex alterations remains challenging.
In this slide deck, which is a companion to the webinar presented on February 21, 2019 and located here (https://www.pieriandx.com/analyzingcomplexgenomicvariants) you’ll learn how to analyze complex genomic alterations, such as gene fusions, splice-site mutations, and co-occurring variants within the context of somatic cancer.
Dr. José Baselga - Simposio Internacional 'Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
Clinical molecular diagnostics for drug guidanceNikesh Shah
1. Be familiar with next generation molecular diagnostic techniques that can provide guidance in clinical decision making
2. Identify the utility of these diagnostic approaches with some examples
3. Be aware of the challenges that exist in implementing these tools as part of the routine clinical decision making process, especially in resource limited settings
Making genome edits in mammalian cellsChris Thorne
Looking at the kind of modifications that can be made in mammalian cells, and how at Horizon moving to a haploid model system has significantly improved efficiency of both editing and validation
Similar to Paneles genómicos en tumores sólidos (20)
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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
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.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
11. FoundationOne CDx
FoundationOne CDx™ (F1CDx™) is a next
generation sequencing based in vitro diagnostic
device for detection of substitutions, insertion
and deletion alterations (indels), and copy
number alterations (CNAs) in 324 genes and
select gene rearrangements, as well as genomic
signatures including microsatellite instability
(MSI) and tumor mutational burden (TMB) using
DNA isolated from formalin-fixed paraffin
embedded (FFPE) tumor tissue specimens.
https://assets.ctfassets.net/vhribv12lmne/6Rt6csmCPuaguuqmgi2iY8/e3a9b0456ed71a55d2e4480374695d95/FoundationOne_CDx.pdf
12. FoundationOne CDx
FoundationOne CDx™ (F1CDx™) is a next
generation sequencing based in vitro diagnostic
device for detection of substitutions, insertion
and deletion alterations (indels), and copy
number alterations (CNAs) in 324 genes and
select gene rearrangements, as well as genomic
signatures including microsatellite instability
(MSI) and tumor mutational burden (TMB) using
DNA isolated from formalin-fixed paraffin
embedded (FFPE) tumor tissue specimens.
https://assets.ctfassets.net/vhribv12lmne/6Rt6csmCPuaguuqmgi2iY8/e3a9b0456ed71a55d2e4480374695d95/FoundationOne_CDx.pdf
13. Sample
Adequate sample Clinical CGP can be
successfully performed for solid tumour samples
(generally formalin fixed, paraffin embedded
material), bone marrow, and blood, although
many other tissue samples such as FNAs can
be analysed. In general, a sample
approximately 15 mm2 with a minimal depth of
40 mm is adequate for CGP.
Ross JS. Pathology, 2016
14. Sample
Adequate sample Clinical CGP can be
successfully performed for solid tumour samples
(generally formalin fixed, paraffin embedded
material), bone marrow, and blood, although
many other tissue samples such as FNAs can
be analysed. In general, a sample
approximately 15 mm2 with a minimal
depth of 40 mm is adequate for CGP.
Ross JS. Pathology, 2016
15. Sample
For assays that measure gene copy number,
tumour nuclei should account for at least 20% of
the total nuclei present. When tumour nuclei are
less than 20%, the risk of missing a copy
number gain or homozygous loss increases
dramatically
Ross JS. Pathology, 2016
16. Sample
Contamination with non-cancerous tissue or
high levels of necrosis can affect detection
sensitivity, although macro-dissection can often
be used to enrich the sequenced sample for
tumour nuclei.
Ross JS. Pathology, 2016
17. Detecting alteration
Point mutations that selectively alter enzyme
activity or induce early protein termination,
genomic rearrangements that disrupt genes or
create novel oncogenic molecules, copy number
gains or losses that dramatically change
transcript levels, and small insertions and
deletions (indels) with various effects depending
on the gene and alteration location
Ross JS. Pathology, 2016
18. Bio-informatics
Although managing a clinical CGP assay
requires technical expertise across many
domains, the computational bioinformatics
expertise required for high-quality analysis and
interpretation is key
Ross JS. Pathology, 2016
19. Actionable genomic alterations
The term ‘actionable’ describes a sequencing
result that can direct a specific action by a
treating oncologist
Ross JS. Pathology, 2016
37. Oncomine
Based on robust Ion AmpliSeq™
technology, the assay requires only
10 ng of DNA or RNA per pool,
enabling analysis of even small and
challenging FFPE samples
53. Oligodendrogliomas
1p/19q co-deletion IDH1/2 mutation Median survival
+ + 8.2 years
- + 6.3 years
+ - 1.5 years
L, Knoff DS, Schultz N, et al. Clinical multiplexed exome sequencing distinguishes adult oligodendroglial neoplasms from astrocytic and mixed lineage
IDH1/2 mutations are CRITICAL to prognosis in Oligodendrogliomas.
Comprehensive Genomic Profiling is superior to IHC by 20%.
Ramiksoon LA. Curr Treat Options Oncol, 2018
54. Glioblastoma
Chromosome 7
amplifiaction
CDKN2A/B homozygous
deletion
EGFR amplification
PTEN-loss
TP53 mutation PDGFRA amplification Hemizygous NF1 loss
Common, but not actionable, mutations in GBM
BRAF mutation
Uncommon, but actionable, mutations in GBM
Dabrafenib +
Trametinib
Ramiksoon LA. Curr Treat Options Oncol, 2018
68. Ali SM. The Oncologist, 2017
NSCLC
Comprehensive genomic profiling detected
canonical ALK rearrangements and ALK
rearrangements with noncanonical fusion
partners in a subset of patients with NSCLC with
previously negative ALK FISH results. In this
series, such patients had durable responses to
ALK inhibitors, comparable to historical
response rates for ALK FISH-positive cases.
The Oncologist 2016;21:762–770
77. CRC
Rankin A. The Oncologist, 2017
Missed detection of KRAS non-G12/13
mutations by prior focused molecular testing
78. CRC
Rankin A. The Oncologist, 2017
1644 RAS/RAF wild type
by CGP
31% Genomic alteration associated with
resistance of anti EGFR therapy
PI3KCA PTEN EGFR Her2
79. CRC
Rankin A. The Oncologist, 2017
Quantitation of CRC cases with potential driver alterations and co-occurrence of KRAS
mutations. Breakdown of specific subtypes of RTK, MEK1, PIK3CA, and PTEN alteration
classes and overlap with RAS/RAF alterations.
83. Melanoma
Boussemart L. The Oncologist, 2019
385 BRAF mutations in melanoma detected
with CGP
Records of prior BRAF testing in 79 (21%)
11/57 (19%) V600+ were BRAF
negative with prior testing
16/20 (80%) non-V600 mutated
BRAF were negative with prior
testing
And 2/2 activating BRAF fusions
84. Ali SM. The Oncologist, 2017
Melanoma
CGP identifies diverse activating BRAF
alterations in a significant fraction of cases with
prior negative testing. Given the proven clinical
benefit of BRAF/ MEK inhibitors in BRAF-
mutated melanoma, CGP should be considered
for patients with metastatic melanoma,
particularly if other testing is negative.
The Oncologist 2019;24:1–7
92. Breast
Ross JS. Pathology, 2016
Prognostic assessment ie TP53 mutation
Predicting hormonal
therapy resistance
AKT1, AKT2, BCAR1, BCAR3, EGFR,
ERBB2, GRB7, SRC, TLE3 and TRERF1
Predicting resistance to
targeted therapy
ESR1 and ERBB2 mutations.
93. Breast
Ross JS. Pathology, 2016
Base substitution in ESR1 Tamoxifen resistance
ESR1 fusions and
rearrangements
AI resistance
Acquired ERBB2 mutation in
CDH1 mutated lobular ABC
100% ORR with Neratinib + Fulvestrant
in ERBB2/CDH1 co-mutated lobular BC
31% after prolonged anti HR therapy
94. Breast
Ross JS. Pathology, 2016
ERBB2 amplification Correlates with FISH
ERBB2 activating
mutations
Potential targets to anti-Her2 therapy
Acquired ERBB2 mutation in
Her2 amplified BC
Potential acquired resistance
mechanism for patients with HER2+ by
IHC
2.4%
Acquired PIK3CA/MET/PTEN
mutations in Her2 amplified
BC
Potential acquired resistance
mechanism for patients with HER2+ by
IHC
95. Breast
Ross JS. Pathology, 2016
BRCA1/2 mutations
Sensitivity to Olaparib or
Rucaparib
Mutations in other HR-
associated genes
May be targeted by PARP-inhibition
15%
TMB (>20 per megabase) May benefit from Anti-PD(L)1 therapy
5%
Rare, potentially actionable
mutations
EGFR1 amplification, SRC, ALK/EML4,
Ret-fusions
96. Breast
Ross JS. Pathology, 2016
Basal genomics Acquired mutations Implications
Lobular
CDH1/Pi3k pathway
mutations
Acquired ERRB2
(30-40%)
May benefit from the
addition anti Her2
therapy
Inflammatory breast
cancer
ERBB, MTOR, FGFR and
DNA repair pathways
Mucinous
FGFR1 and ERBB2
alterations
Secretory breast
cancer
ETV6-NTRK3 fusion
Entrectinib/Larotrecti
nib
Adenoid Cystic
Breast Cancer
MYB-NFIB
Similar to salivary
gland carcinomas
Triple-negative and
metaplastic BC
ERBB2 mutations, RTK pathway
mutations, and DNA repair
BRCAness pathways.
Different targets
103. Tumor agnostic
BRCA1/2 mutations
Sensitivity to Olaparib or
Rucaparib
Mutations in other HR-
associated genes
May be targeted by PARP-inhibition
MSI / POLE May benefit from Anti-PD(L)1 therapy
NTRK Larotrectinib/Entrectinib
105. SHIVA
AR over expression Abiraterone
MAPK (PTEN/AKT/RICTOR,
etc)
Everolimus
Her2 amplification Trastuzumab + Lapatinib
PDGFR Sorafenib
ER over expression Tamoxifen
Le Tourneau, Ann Oncol, 2016
106. SHIVA
Le Tourneau, Ann Oncol, 2016
MTA: Molecular
targeted agent
TPC: Treatment at
physicians choice
110. Le Tourneau, Ann Oncol, 2016
The cross-over analysis of the
SHIVA trial identified 37% of patients
who crossed over from TPC to MTA
with a PFSMTA/PFSTPC ratio
exceeding 1.3.
SHIVA
119. Payer issues
Insurance wants you out for two reasons:
1. You requested the test (US 4000-5000)
2. They fail to see the point in using an expensive drug, in an unproven setting…
121. When should you use it?
Consider using CGP in PS0/1 patients, in which ALL
established treatment options have been tried
With a “reasonable” expectation of getting a reliable
CGP test (not home-made)
Good (ie, not only PBS), insurance
International medical coverage
With a “reasonable” expectation of getting MTA
treatment, should it be advised
Today
Also, in PS0/1 patients, with non-curable RARE
tumors with no clear standard of care
122.
123. In the NEAR
future, we will
use CGPs for the
INITIAL
treatment in the
vast majority of
tumors.