This document summarizes molecular biology and targeted therapies in lung cancer. It discusses that lung cancer is a leading cause of cancer death worldwide. Historically, lung cancers were classified by histology alone, but it is now known they are driven by specific mutations. Key driver mutations were discovered in the EGFR, ALK, KRAS genes. These mutations activate intracellular signaling pathways like RAS/RAF/MEK/ERK and regulate cell growth. Targeted therapies like EGFR TKIs erlotinib and gefitinib or the ALK inhibitor crizotinib have significantly improved outcomes for patients with specific driver mutations. However, resistance often develops through secondary mutations like T790M, requiring new
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
Lung cancer is a major cause of cancer deaths with approximately 80% of cases accounting to nonsmall cell lung cancer (NSCLC) . In NSCLC target therapy, epidermal growth factor receptor (EGFR) is a promising candidate.
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
Geoffrey Oxnard, MD, discusses the latest research in targeted therapies and molecular testing to treat lung cancer.
This presentation was originally given as part of "Living with Lung Cancer: A Forum for Patients and Caregivers" on Nov. 14, 2015 at Dana-Farber Cancer Institute in Boston, Mass.
Lung cancer: a 2014 update with information about immunotherapiesZeena Nackerdien
In 2006, Dana Reeve – actress, activist, and non-smoker – died of lung cancer. In 2009, Valerie Harper – actress and “Dancing with the Stars” contestant – was diagnosed with lung cancer that has since metastasized to the brain. They are the famous faces of a disease that is the leading cause of cancer deaths. Five-year survival rates for lung cancer, the leading cause of cancer deaths, are very low. Please take a look at some of the ASCO 2014 lung cancer updates on my blog: http://norwalk.patch.com/groups/zeena-nackerdiens-blog/p/american-society-of-clinical-oncology-annual-meeting-2014-key-lung-cancer-abstracts.
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
Geoffrey Oxnard, MD, discusses the latest research in targeted therapies and molecular testing to treat lung cancer.
This presentation was originally given as part of "Living with Lung Cancer: A Forum for Patients and Caregivers" on Nov. 14, 2015 at Dana-Farber Cancer Institute in Boston, Mass.
Lung cancer: a 2014 update with information about immunotherapiesZeena Nackerdien
In 2006, Dana Reeve – actress, activist, and non-smoker – died of lung cancer. In 2009, Valerie Harper – actress and “Dancing with the Stars” contestant – was diagnosed with lung cancer that has since metastasized to the brain. They are the famous faces of a disease that is the leading cause of cancer deaths. Five-year survival rates for lung cancer, the leading cause of cancer deaths, are very low. Please take a look at some of the ASCO 2014 lung cancer updates on my blog: http://norwalk.patch.com/groups/zeena-nackerdiens-blog/p/american-society-of-clinical-oncology-annual-meeting-2014-key-lung-cancer-abstracts.
Role of human papillomavirus and tumor suppressor genesishita1994
Oral cancer is synonymous to Squamous Cell Carcinoma (SCC) of oral mucosal origin that accounts for more than 90% of all malignant presentations at the aforementioned anatomical sites.
More than 300,000 new cases worldwide are being diagnosed with oral SCC (OSCC) annually.
Approximately, 30,000 (US) & 40,000(EUROPE).
Oral cancer is estimated by the WHO to be the 8th most common cancer worldwide.
In India & other Asian countries, oral & oropharyngeal carcinomas (OCs) comprise up to half of all malignancies, with this particularly high prevalence being attributed to the influence of carcinogens & region-specific epidemiological factors, especially tobacco & betel quid chewing.
EGFR TKIs Combinding the inhibition of RAS-ERK signaling in NSCLC Treatmentasclepiuspdfs
Epidermal growth factor receptor (EGFR) mutations and EGFR overexpression have become the key factor to the occurrence of non-small cell lung cancer (NSCLC). EGFR tyrosine-protein kinase inhibitors (EGRR-Tyrosine Kinase Inhibitors, EGFR-TKIs) were used in clinic to treat NSCLC by blocking the EGFR signaling pathway. Due to the existence of rare EGFR mutations and secondary mutations under drug load, the first generation, second generation, and third generation of EGFR TKIs have been used in clinical practice. In addition, EGFR secondary mutation and abnormal activation of EGFR downstream signaling molecules or bypass signaling pathways are the reasons for NSCLC resistance to EGFR TKIs. The combination of EGFR TKIs and EGFR downstream signal molecule inhibitors can improve the efficiency of targeted therapy for NSCLC. Based on clarifying the mechanism of resistance of NSCLC to EGFR TKIs, this paper introduces new inhibitors targeting RAS-ERK signaling downstream of EGFR. This paper also reviews progresses in a combination of EGFR TKIs and downstream signal molecule inhibitors in the treatment of NSCLC.
Cellular Signaling Pathways have direct implications on our understanding of tumor cell behavior. A general overview is presented here followed by a brief discussion of some of the major pathways currently implicated in cancer progression : Ras/RAF/MAP kinase pathway and PI3K/AKT/mTOR pathway s
It contains introduction on basic molecular biology followed by detailed description on discovery , mechanism of oncogene activation, their effect on tumerogenesis , name of important oncogenes , their detection and targeted therapies against oncogenes in treating cancer
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
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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
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.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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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
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.
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!
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
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.
2. Introduction & History
• Lung cancer is the most common cause of cancer-related death in
men and women worldwide, responsible for over 1 million deaths
annually.
• Although 1-year survival has improved over the past few decades,
overall 5-year survival has remained relatively unchanged at 12% to
16% over the past 30 years.
• A key discovery in the past decade has been that some lung cancers
harbor specific mutations that are essential for malignant growth,
which lead to gain of function of oncogenes or loss of function of
tumor suppressor genes .
3. • Historically, nonsmall cell lung cancer (NSCLC) has been classified
histologically as squamous cell carcinoma, adenocarcinoma, and large cell
carcinoma, and various chemotherapeutic regimens have been used to
treat different histological subtypes.
• It is now realized that NSCLC is a collection of diseases that are identifiable
by specific molecular abnormalities, personalized therapy became a goal
for patients with NSCLC.
• Between 1980 and 2000, NSCLC driver lesions that were investigated
included mutations in the Kirsten rat sarcoma viral oncogene homolog
(KRAS) and protein 53 (p53) genes, loss of specific chromosomal loci, loss
of heterozygosity, and DNA methylation of TSGs.
• In 2004, driver mutations in the epidermal growth factor receptor (EGFR)
gene, a membrane-bound receptor tyrosine kinase (RTK) that regulates cell
growth, were discovered in NSCLC, especially in adenocarcinomas
• In 2007, the existence of the echinoderm microtubule-associated protein-
like 4 (EML4) translocation to the anaplastic lymphoma kinase (ALK) gene
resulting in an EML4-ALK fusion gene was discovered in NSCLC.
4. REGULATION OF CELL GROWTH AND SURVIVAL
• MEMBRANE-BOUND RECEPTOR TYROSINE KINASES
• INTRACELLULAR KINASES AND TARGETS: RAS/RAF/MEK/ERK PATHWAY
• CELL CYCLE REGULATION
5. MEMBRANE-BOUND RECEPTOR TYROSINE
KINASES
• Membrane-bound RTKs share a common general structure composed of an
extracellular region that contains a ligand-binding domain, an extracellular
juxtamembrane region, a hydrophobic transmembrane domain, a
cytoplasmic TK domain, and a cytoplasmic tail with tyrosine residues that
serve as sites for receptor phosphorylation.
• Driver lesions in the membrane-bound RTKs result in deregulated signaling
or in a effector that cannot be shut off.
• RTK activation in cancer may occur via overexpression of wild-type
receptor due to gene amplification (resulting in excess signaling), excess
ligand production, ligand overstimulation, activating mutations,
translocations resulting in activated fusion proteins, or reduced receptor
downregulation.
6.
7. • The prototypical RTKs involved in lung cancer are members of the
ErbB family.
• The ErbB family of RTKs includes ErbB1 (EGFR; HER1), ErbB2
(HER2/Neu), ErbB3 (HER3), and ErbB4 (HER4).
• In the lung, these RTKs are expressed by the pulmonary epithelium
(e.g., alveolar type II cells and bronchial cells) and fibroblasts.
• Members of the epidermal growth factor (EGF) family of peptide
hormones serve as ligands for ErbB RTKs, and include EGF,
transforming growth factor-α, betacellulin, and epiregulin for ErbB1;
and the neuregulins for ErbB3 and ErbB4.
8. INTRACELLULAR KINASES AND TARGETS:
RAS/RAF/MEK/ERK PATHWAY
• Downstream of membrane-
bound RTKs is the
RAS/RAF/MEK/ERK pathway,
which is a pivotal intracellular
signaling pathway that transmits
RTK signals to the nucleus via a
cascade of specific protein
phosphorylation.
9. RAS
• The RAS family of oncogenes includes
neuroblastoma RAS viral oncogene
homolog (NRAS), KRAS, and Harvey
rat sarcoma viral oncogene homolog
(HRAS).
• KRAS is the gene that is most
commonly involved in lung cancer
• Approximately 20% to 30% of NSCLC
harbor activating point mutations in
RAS genes.
• Mutations occur most frequently in
the KRAS gene (90%), specifically in
codons 12, 13, and 61
10. • RAF
• RAF is a family of serine–threonine kinases that includes A-RAF, B-
RAF, and C-RAF.
• Although RAF is activated by RAS, activation can also occur
independently of RAS through other activators such as Src, c-Jun NH2-
terminal kinase, interferon-β, protein kinase C-α (PKC-α), or through
dimerization between RAF isoforms.
• Activating mutations of the B-RAF gene have been reported in up to
3% of NSCLC tumors, most of which are adenocarcinoma
11. CELL CYCLE REGULATION
• In nontransformed pulmonary
epithelial cells, cell division is a
tightly regulated process with
multiple checkpoints that assess
extracellular growth signals, cell
size, and DNA integrity.
• Cyclins and their associated cyclin-
dependent kinases (CDKs) are the
central machinery that control cell
cycle progression.
• Alterations in these proteins may
lead to a bypass of the checkpoints
that assess a cell’s readiness to
divide.
12.
13. • Rb
• The product of the retinoblastoma susceptibility gene, Rb, plays a central
role in the G1-S transition, and Rb is considered a tumor suppressor gene.
• Therefore, loss of normal function of this gene removes its suppressor
effect leading to cellular transformation.
• p53
• p53 is a transcription factor that can activate the transcription of numerous
genes, including the CDK inhibitor p21.
• Mutation of the p53 gene results in a protein that fails to bind DNA
effectively. Therefore, expression of the CDK inhibitor p21 gene is
decreased, and p21 protein production is decreased.
• p21 protein is not available to stop the entry of the cell into S phase, again
resulting in unregulated cell cycle progression.
• Mutations of the p53 gene occur in nearly 50% of NSCLC and abnormalities
of p53 protein may play an important role in the tumorigenesis of lung
epithelial cells.
14.
15. Targeted Therapy
• EGFR
• EGFR gene mutations are much more commonly found in female
never smokers of East Asian origin with adenocarcinoma histology.
• Whereas the incidence of EGFR mutations in Asians is 25% to 35%,
the incidence in North American and Western European patients is
approximately 15%.
• However, the strongest predictor of EGFR mutation status appears to
be absent or low smoking history.
17. • Erlotinib, Geftinib, Crizotinib are TK inhibitors.
• A large number of retrospective series have demonstrated that the
response rate of EGFR mutation-positive patients to EGFR TKIs
exceeds 60%.
• Another strategy to block EGFR kinase function in patients with NSCLC
focuses on the use of monoclonal antibodies directed against EGFR.
• Cetuximab, matuzumab, necitumumab and panitumumab are
monoclonal Ab against EGFR.
18. Erlotinib
• Dose 150mg per day, orally
• It is metabolized by Liver.
• FDA approved erlotinib in 2013 in pt with locally advanced and metastatic
NSCLC who has failed atleast one prior chemotherapy regimen.
• Side effects :
• Rash - The Journal of Clinical Oncology reported in 2004 that "cutaneous
[skin] rash seems to be a surrogate marker of clinical benefit, but this
finding should be confirmed in ongoing and future studies.
• Interstitial pneumonitis, diarrhea, ingrown hairs are common
• GI perforation, SJ syndrome, BOOP, pulmonary fibrosis are rare side effects
19. Gefitinib
• On July 13, 2015, the FDA approved gefitinib as a first-line treatment
for metastatic NSCLC , which are positive for EGFR gene mutation.
• Dose 250mg per day orally , till progression of disease of
unacceptable side effects
• Side effects
• Rash, acne, diarrhea, stomatitis, paronychia, asymptomatic elevation
of liver enzymes
• Rare side effects – interstitial lung disease, corneal erosions
20. TKI Resistance
• Virtually all patients who initially respond to EGFR TKI therapy will develop
resistance and suffer a clinical relapse.
• Approximately 50% of the cases of acquired TKI resistance are attributed to
a secondary EGFR gene mutation, the threonine to methionine point
mutation at amino acid 790 (T790M) in exon 20.
• Afatinib is the Drug Of Choice.
• The LUX-Lung 3 trial investigated the efficacy and safety of afatinib
compared with pemetrexed/cisplatin in patients with EGFR mutation-
positive stage IIIB/IV lung adenocarcinoma.
• Treatment with afatinib led to a significantly prolonged PFS versus
pemetrexed/cisplatin (median 11.1 vs. 6.9 months).
• Sequential blockade is another approach to treat TKI Resisitance.
22. • EML4-ALK
• In 2007, Soda et al. reported a new molecular abnormality involving
the fusion of ALK with EML4 in lung adenocarcinoma.
• The fusion protein results from an inversion in the short arm of
chromosome 2 that fuses the N-terminal domain of EML4 to the
intracellular kinase domain of ALK, leading to constitutive activation
of the ALK kinase.
• In the original report by Soda and colleagues, 6.7% of unselected
NSCLC patients had the EML4-ALK fusion protein.
• Characteristic of pt.
• Mutually excludes RAS, EGFR
• Patients with EML4-ALK-positive stage III or IV NSCLC treated with
crizotinib, competitive inhibitor targeted to the ATP-binding pocket of
the ALK TK , demonstrated an overall response rate of 60.8%.
23. • KRAS
• 20 – 40 % of pt with NSCLC has RAS mutation.
• 90% are KRAS
• More common in smokers, Adenocarcinoma
• Associated with worse prognosis.
• Current therapeutic approaches targeting RAS fall into three major
categories:
• inhibition of RAS protein synthesis,
• alteration of RAS membrane localization - Salirasib
• inhibition of effector molecules downstream of mutant RAS –
Sorafenib,AZD6244
24. TKI in Squamous Cell Carcinoma
Comprehensive genomic characterization of squamous cell lung cancers
The Cancer Genome Atlas Research Network*