Yam Code
Sign up
Login
New paste
Home
Trending
Archive
English
English
Tiếng Việt
भारत
Sign up
Login
New Paste
Browse
Liquid biopsies encompass a number of new technologies designed to derive tumor data through the minimally invasive sampling of an accessible body fluid. These technologies remain early in their clinical development, and applications for patients with osteosarcoma are actively under investigation. In this chapter, we outline the current state of liquid biopsy technologies as they apply to cancer generally and osteosarcoma specifically, focusing on assays that detect and profile circulating tumor DNA (ctDNA), microRNAs (miRNA), and circulating tumor cells (CTCs). At present, ctDNA assays are the most mature, with multiple assays demonstrating the feasibility of detecting and quantifying ctDNA from blood samples of patients with osteosarcoma. Initial studies show that ctDNA can be detected in the majority of patients with osteosarcoma and that the detection and level of ctDNA correlates with a worse prognosis. Profiling of ctDNA can also identify specific somatic events that may have prognostic relevance, such as 8q gain in osteosarcoma. miRNAs are stable RNAs that regulate gene expression and are known to be dysregulated in cancer, and patterns of miRNA expression have been evaluated in multiple studies of patients with osteosarcoma. While studies have identified differential expression of many miRNAs in osteosarcomas compared to healthy controls, a consensus set of prognostic miRNAs has yet to be definitively validated. Recent studies have also demonstrated the feasibility of capturing CTCs in patients with osteosarcoma. The development of assays that quantify and profile CTCs for use as prognostic biomarkers or tools for biologic discovery is still in development. https://www.selleckchem.com/products/ipi-549.html However, CTC technology holds incredible promise given the potential to perform multi-omic approaches in single cancer cells to understand osteosarcoma heterogeneity and tumor evolution. The next step required to move liquid biopsy technologies closer to helping patients will be wide-scale collection of patient samples from large prospective studies.Osteosarcoma relapses not only herald a very poor prognosis but also opportunities to treat this genetically diverse complex cancer in new ways. This review will attempt to show that the field is a rapidly evolving one in which not only cytotoxic agents but also local control strategies and the immune system can be harnessed to improve the prognosis of relapsed patients. The molecular heterogeneity and the difficulty of effectively treating most common patterns of relapse with surgery and/or radiation (lung and/or bone metastases) have been responsible for a wide variety of approaches to learning whether agents are active against osteosarcoma. This chapter will highlight past, current, and potential future approaches to provide more effective systemic therapy for the problem of recurrent metastases of osteosarcoma. These include single-agent trials with a wide variety of agents, radiopharmaceuticals, and immune therapies. Finally, how such efforts are integrated into more effective local control strategies is also discussed.The prognosis for metastatic osteosarcoma (OS) is poor and has not changed in several decades. Therapeutic paradigms that target and exploit novel molecular pathways are desperately needed. Recent preclinical data suggests that modulation of the Fas/FasL pathway may offer benefit in the treatment of refractory osteosarcoma. Fas and FasL are complimentary receptor-ligand proteins. Fas is expressed in multiple tissues, whereas FasL is restricted to privilege organs, such as the lung. Fas expression has been shown to inversely correlate with the metastatic potential of OS cells; tumor cells which express high levels of Fas have decreased metastatic potential and the ones that reach the lung undergo cell death upon interaction with constitutive FasL in the lung. Agents such as gemcitabine and the HDAC inhibitor, entinostat/Syndax 275, have been shown to upregulate Fas expression on OS cells, potentially leading to decreased OS pulmonary metastasis and improved outcome. Clinical trials are in development to evaluate this combination as a potential treatment option for patients with refractory OS.Inhalation therapy remains a suitable approach to treat lung diseases including cancer. This approach has been used to deliver various therapies including chemotherapy. The rationale for using the inhalation route vs. the systemic route has been the fewer side effects encountered when drugs are administered via inhalation. Furthermore, this approach overcomes one of the major limitations of systemic chemotherapy that results from inability of the drug to reach high concentrations in the lungs. Local delivery overcomes this limitation and spares exposure of vital organs to the drug, resulting in a more effective delivery system.Pulmonary metastasis of osteosarcoma (OS) remains a major cause of death and is very difficult to treat. Using various OS mouse models, we demonstrated that aerosol chemotherapy causes regression of pulmonary metastases and improves survival of mice with OS. In these studies, we used gemcitabine, a nucleoside analog that is effective against various solid tumors. An initial phase I study done in Europe in patients with primary lung cancer demonstrated aerosol gemcitabine therapy to be feasible and safe. In this chapter, we describe different chemotherapeutic agents delivered by inhalation to treat lung diseases with an emphasis on an ongoing study of aerosolized gemcitabine for patients with solid tumors and lung metastases developed at the MD Anderson Cancer Center that uses a convenient approach to track patient lung health with the ultimate goal of implementing this therapy at home.In this chapter, we will review studies of HER2 in osteosarcoma and discuss the controversies that have existed in this field. Our present understanding of HER2 in the context of osteosarcoma is that it is expressed on a subset of patient samples, but that expression is not prognostic. We will review the two trials that have been conducted in osteosarcoma which have targeted HER2. Use of an antibody, trastuzumab, did not suggest activity, but a smaller study using HER2-targeted CAR T cells suggested activity may be present. A trial of an antibody-drug conjugate targeting HER2 for recurrent osteosarcoma is under consideration. Trials targeting other surface proteins for the treatment of osteosarcoma have occurred or are in development. Indeed, this leads us to discuss in a broader fashion therapeutic approaches to targeting surface proteins. It is hoped that some of these approaches will lead to new effective therapies for patients with osteosarcoma.
Paste Settings
Paste Title :
[Optional]
Paste Folder :
[Optional]
Select
Syntax Highlighting :
[Optional]
Select
Markup
CSS
JavaScript
Bash
C
C#
C++
Java
JSON
Lua
Plaintext
C-like
ABAP
ActionScript
Ada
Apache Configuration
APL
AppleScript
Arduino
ARFF
AsciiDoc
6502 Assembly
ASP.NET (C#)
AutoHotKey
AutoIt
Basic
Batch
Bison
Brainfuck
Bro
CoffeeScript
Clojure
Crystal
Content-Security-Policy
CSS Extras
D
Dart
Diff
Django/Jinja2
Docker
Eiffel
Elixir
Elm
ERB
Erlang
F#
Flow
Fortran
GEDCOM
Gherkin
Git
GLSL
GameMaker Language
Go
GraphQL
Groovy
Haml
Handlebars
Haskell
Haxe
HTTP
HTTP Public-Key-Pins
HTTP Strict-Transport-Security
IchigoJam
Icon
Inform 7
INI
IO
J
Jolie
Julia
Keyman
Kotlin
LaTeX
Less
Liquid
Lisp
LiveScript
LOLCODE
Makefile
Markdown
Markup templating
MATLAB
MEL
Mizar
Monkey
N4JS
NASM
nginx
Nim
Nix
NSIS
Objective-C
OCaml
OpenCL
Oz
PARI/GP
Parser
Pascal
Perl
PHP
PHP Extras
PL/SQL
PowerShell
Processing
Prolog
.properties
Protocol Buffers
Pug
Puppet
Pure
Python
Q (kdb+ database)
Qore
R
React JSX
React TSX
Ren'py
Reason
reST (reStructuredText)
Rip
Roboconf
Ruby
Rust
SAS
Sass (Sass)
Sass (Scss)
Scala
Scheme
Smalltalk
Smarty
SQL
Soy (Closure Template)
Stylus
Swift
TAP
Tcl
Textile
Template Toolkit 2
Twig
TypeScript
VB.Net
Velocity
Verilog
VHDL
vim
Visual Basic
WebAssembly
Wiki markup
Xeora
Xojo (REALbasic)
XQuery
YAML
HTML
Paste Expiration :
[Optional]
Never
Self Destroy
10 Minutes
1 Hour
1 Day
1 Week
2 Weeks
1 Month
6 Months
1 Year
Paste Status :
[Optional]
Public
Unlisted
Private (members only)
Password :
[Optional]
Description:
[Optional]
Tags:
[Optional]
Encrypt Paste
(
?
)
Create New Paste
You are currently not logged in, this means you can not edit or delete anything you paste.
Sign Up
or
Login
Site Languages
×
English
Tiếng Việt
भारत