Fom ls 2021 advances in gist - d raghunadharao
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This document discusses advances in gastrointestinal stromal tumors (GIST), including: 1. Common mutations found in KIT (CD117) receptor tyrosine kinase that are associated with GIST and their sensitivity to tyrosine kinase inhibitors (TKIs). 2. Treatment algorithms for patients with resectable or unresectable/metastatic GIST based on mutational profiling. 3. Studies of various TKIs for imatinib-resistant GIST as well as novel agents targeting mTOR and HSP90 pathways for refractory disease.
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This document discusses co-stimulation blockade using the drug Belatacept as an immunosuppressive treatment for renal allograft rejection. It summarizes results from two key clinical trials comparing Belatacept to cyclosporine. The Phase II trial found similar acute rejection rates at 6 months between Belatacept and cyclosporine, but Belatacept was associated with better renal function and lipid/blood pressure levels. The Phase III trial also found similar patient and graft survival between Belatacept and cyclosporine, but Belatacept was associated with better renal function despite a higher rate of acute rejection episodes. Both trials demonstrated Belatacept's potential to preserve renal function compared to calcineurin inhibitors like
Gene Profiling in Clinical Oncology - Slide 4 - L. Lacroix - New markers to d...
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The document summarizes key information from a conference on gene profiling in clinical oncology, including:
1) New markers such as EGFR, KRAS, ALK, HER2, and PI3K mutations are defining subsets of non-small cell lung cancer and informing targeted therapy approaches.
2) Drugs like erlotinib, gefitinib, and crizotinib, which target EGFR, ALK, and c-MET mutations respectively, have shown efficacy in molecularly selected patient populations.
3) Comprehensive genomic profiling of lung tumors is needed to discover new targets, as around a third of cases still have unknown driver mutations.Gene Profiling in Clinical Oncology - Slide 4 - L. Lacroix - New markers to d...
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The document summarizes a presentation on using gene profiling and biomarkers to better classify and treat non-small cell lung cancer (NSCLC). It discusses current and emerging markers like EGFR mutations, ALK translocations, and FGFR1 amplifications that define NSCLC subtypes and can guide targeted therapies. Integrating multiple genomic analyses may help characterize unknown abnormalities in a third of NSCLC tumors and identify new treatment opportunities.MCO 2011 - Slide 31 - P. Casali - Spotlight session Sarcoma
This document summarizes information about sarcoma medical therapy including:
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- Common sites of sarcoma spread
- Chemotherapy regimens used to treat localized and advanced soft tissue sarcomas
- Targeted therapies used for different sarcoma subtypes based on molecular alterations
- Use of imatinib and other targeted therapies for gastrointestinal stromal tumors (GIST)
- Mechanisms of resistance that emerge with tyrosine kinase inhibitors for GIST
Journal club on Ca Anal Canal
This document summarizes key findings from several clinical trials on the treatment of anal squamous cell carcinoma. The UKCCCR ACT I trial showed improved local control and colostomy-free survival with chemoradiation (CRT) compared to radiation alone. Subsequent trials found improved outcomes with mitomycin-C compared to 5-FU alone. The RTOG 98-11 and ACT II trials found no advantage to cisplatin over mitomycin-C in CRT or with maintenance chemotherapy. The current standard is CRT with 5-FU and mitomycin-C.
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Addressing Imatinib-resistant CML
1. Nilotinib is a potent and selective inhibitor of BCR-ABL that is more effective than imatinib at inhibiting BCR-ABL driven leukemia cell growth.
2. A phase I study found high rates of hematologic and cytogenetic responses in CP-CML and advanced phases of CML resistant or intolerant to imatinib.
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IMATINIB RESISTANT CML
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This document provides an overview of chemotherapy for head and neck cancer. It discusses the cell cycle effects of chemotherapy drugs and classifications including cytotoxic, targeted, and hormonal agents. Specific drugs are explained including mechanisms of action, indications, and side effects. The document also reviews landmark clinical trials establishing concurrent chemoradiotherapy as the standard of care for locally advanced head and neck cancer. Targeted agents like cetuximab are now being used for recurrent/metastatic disease.
Gist
This document provides an outline and overview of gastrointestinal stromal tumors (GISTs). Some key points:
- GISTs are rare cancers that arise from interstitial cells of Cajal in the gastrointestinal tract. Most common in stomach and small intestine.
- Majority have activating mutations in KIT or PDGFRA genes leading to uncontrolled cell growth. 5% are hereditary syndromes.
- Diagnosis involves imaging (CT/MRI), endoscopy with biopsy for immunohistochemistry and genetic testing.
- Prognosis depends on tumor size, location, mitotic rate and genotype. Surgery is the main treatment, while tyrosine kinase inhibitors like imatininb are also
Receptor Tyrosine Kinases
1. Receptor tyrosine kinases (RTKs) drive key cancer pathways and can be exploited as therapeutic targets, as shown by drugs like imatinib that inhibit mutated kinases in cancers.
2. RTK inhibitors have shown efficacy against cancers dependent on single kinases, but resistance often emerges through secondary mutations or bypass pathways.
3. Effective combination therapies are needed to overcome resistance, such as combining RTK inhibitors with other drugs that block downstream or bypass pathways.
Recent advances in paediatric oncology
This document discusses recent advances in paediatric oncology and cancer immunotherapy. It provides details on adaptive cell transfer therapy including TIL therapy, TCR therapy and CAR-T cell therapy. It summarizes key studies demonstrating the regression of cancer using TILs and the use of T cells transduced with TCRs or CARs. It also outlines the structure and components of CARs including antigen targeting domains, costimulatory domains and signalling domains. The document discusses clinical trials demonstrating high response rates in ALL patients treated with CD19-targeted CAR T-cell therapy. It summarizes treatment approaches and outcomes for different subtypes of ALL including Ph-like ALL.
VIH. novedades terapéuticas
Presentación realizada por Piedad Arazo Garcés, en el curso de la Jornada Pacientes y Salud: “Foros en el CIBA”. Novedades terapéuticas e importancia del paciente informado, el 12 de noviembre de 2014.
Protein-protein interaction
The document discusses various strategies for targeting protein-protein interactions (PPIs) for drug development, including small molecule inhibitors, peptides, and allosteric modulation. PPIs are important for many cellular pathways but have been challenging to target with drugs. Examples are given of peptides being developed into peptidomimetics to inhibit PPIs like integrins. Fragment-based approaches and structure-based design have also produced PPI inhibitors for targets like interleukin-2 receptor. Covalent modifiers and stabilizing allosteric sites are additional strategies discussed.
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Introduction: Substance use education is crucial due to its prevalence and societal impact.
Alcohol Use: Immediate and long-term risks include impaired judgment, health issues, and social consequences.
Tobacco Use: Immediate effects include increased heart rate, while long-term risks encompass cancer and heart disease.
Drug Use: Risks vary depending on the drug type, including health and psychological implications.
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Harm Reduction Strategies: Safe use practices, medication-assisted treatment, and naloxone availability aim to reduce harm.
Seeking Help for Addiction: Recognizing signs, available treatments, support systems, and resources are essential for recovery.
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一比一原版(EUR毕业证)鹿特丹伊拉斯姆斯大学毕业证如何办理
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The Power of Superfoods and Exercise.pdf
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Join us for a comprehensive 90-minute lesson designed specifically for Compliance Officers and Practice/Business Managers. This 2024 HIPAA Training session will guide you through the critical steps needed to ensure your practice is fully prepared for upcoming audits. Key updates and significant changes under the Omnibus Rule will be covered, along with the latest applicable updates for 2024.
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Texting and Email Communication: Understand the compliance requirements for electronic communication.
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Expert Instructor: Brian Tuttle, with over 20 years in Health IT and Compliance Consulting, brings invaluable experience and knowledge, including insights from over 1000 risk assessments and direct dealings with Office of Civil Rights HIPAA auditors.
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Ensure your compliance strategy is up-to-date and effective. Enroll now and be prepared for the 2024 HIPAA audits.
Enroll Now to secure your spot in this crucial training session and ensure your HIPAA compliance is robust and audit-ready.
https://conferencepanel.com/conference/hipaa-training-for-the-compliance-officer-2024-updates
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Fom ls 2021 advances in gist - d raghunadharao
- 1. Advances in GIST D Raghunadharao MD DM FAPAS FRCP FACP
- 2. KIT (CD117) receptor tyrosine kinase structure and common mutations found in GIST. Arrows indicate the corresponding mutations in the exons.
- 3. KIT (CD117) gene structure and common mutations in GIST Arrows indicate the positions of common mutations in the KIT gene
- 4. KIT and PDGFRA downstream signalling pathways
- 5. Sensitivity of KIT mutations to approved TKIs green = sensitive; red = resistant; IM = imatinib; SU = sunitinib; RE = regorafenib; ABD = ATP-binding domain; AL = activation loop.
- 6. Schematic distribution of KIT or PDGFRA receptor mutations, frequency of mutations and TKI
- 7. Location & frequency of primary mutations in KIT and PDGFRA
- 8. Molecular classification of GISTs
- 9. Treatment algorithm for patients with resectable GIST and mutational profiling
- 10. High-risk features 1. Tumour rupture 2. Diameter >10 cm 3. Mitotic rate >10 per 50 HPF 4. Mitotic rate >5/50 HPF and diameter >5 cm; 5. Mitotic rate >5/50 HPF and diameter >2 cm and non-gastric GIST 6. Diameter >5 cm and non-gastric GIST
- 11. Treatment algorithm for patients with unresectable or metastatic GIST and mutational profiling
- 12. How to interpret mutation data in GIST Mutation Treatment Implication KIT exon 11 Sensitive to Imatinib & Regorafenib KIT Exon 9 Responsive to higher dose of Imatinib, sunitinib sensitive Secondary KIT Mutations: Exons 13, 14, 17, 18 Sunitinib sensitive PDGFR D842V (exon 18) Imatinib resistant, dasatinib sensitive KIT/PDGFRA WT Imatinib resistant, dasatinib sensitive, regorafenib sensitive, if SDH - deficient SDH: succinyl dehydrogenase
- 14. TKIs for imatinib-resistant GIST Study Drug Population N Response Sunitinib Imatinib resistant 312 TTP 27 weeks Sorafenib Imatinib & Sunitinib resistant 38 ORR 68% Nilotinib Imatinib & Sunitinib resistant 248 No difference in PFS or OS Sorafenib Imatinib & Sunitinib resistant 41 ORR 37.6% Dasatinib Imatinib & Sunitinib resistant 47 PR 32% Abbreviations: TTP time to progression; ORR overall response rate; PR partial response
- 15. Study Drug Population Number Response Regorafenib Imatinib & Sunitinib resistant 33 SD 86% Masitinib First Line 30 PFS 41 months Crenolanib Selective for D842V mutation Blocks Kinase activity of PDGFRA D842V PTK 787/ZK222584 Imatinib resistant 15 ORR 67% AMG 706 Imatinib resistant 138 ORR 33% Abbreviations: SD stable disease; PFS progression free survival; ORR overall response rate New TKIs for GIST
- 16. Novel agents for GIST Drug Class Indication No Response Everolimus mTOR Inhibitor TKI resistant 58 PFS 29% Everolimus mTOR inhibitor Refractory GIST 15 ORR 27% Sirolimus mTOR Inhibitor D842V mutation 3 Some activity Ganetespib HSP90 inhibitor Failure of prior therapy 26 SD 52% Retaspimycin HSP 90 inhibitor Failure of TKIs 47 Too toxic Perifosine AKT pathway inhibitor Imatinib resistant 41 Minimal activity Abbreviations: SD stable disease; PFS progression free survival; ORR overall response rate
- 17. NCCN Guidelines