CV

cv

http://www.box.net/files#0:f:9953556

Meeting Minutes 11/13/2007

Present: Michael, Ernest, Ahra, Gautham
Time: 10AM
Location: 621 Stanley - Meeting was moved due to room availability.

Topics:
Discussed everyone's progress so far.
Began making the update of our progress for Friday's ~5 minute presentation.

Action Items:
-Read and provide feedback for everyone's drafts. Focus on content and clarity for now, but if you catch obvious spelling/typos, bring those up too.
-Make sure you know enough about our project for the talk on Friday. Everyone should be familiar enough our project to give the talk, even if they are not talking.
-Decide if you want to volunteer to be the first speaker. Ernest has agreed to do the second part.
-Ernest will post the power point we have so far. Review and help edit the presentation and make backup slides if you have any additional information.

Next Meetings: Friday 16 November - Discussion section presentation at 11 AM (458 Evans?)
Future group meeting time TBD.

Gliadel wafers

Here's an article about Gliadel wafers which are an attempt at localized chemotherapy in the brain.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17938702

Meeting Minutes 10/30/2007

Present: Michael, Ernest, Ahra, Gautham
Time: 10AM
Location: 421 Stanley

Topics:
Decided to write the paper first and base the talk off of the paper. This will make it easier to pick the key points for our talk.
Divided up the work for the paper based on the outline sections. Coordinate with anyone who overlaps your section to make sure everything is covered appropriately. We will do the last 2 sections after we choose a material.

Action Items:
-Write a first draft of your section(s) before the meeting next week Thursday (Nov 8). Make it as long or short as you deem appropriate to include the relevant information. When you are done writing, post it in the google group so that others can access it. Be prepared to briefly present what you wrote to the group at the next meeting.
-Continue to do research if there is further information you need to adequately do your section. We especially need more quantitative materials information about possible materials and brain ECM.
-Think of ways to apply the theories we learned in class to the problem at hand. For example, consider protein adsorption to various possible materials using DLVO theory.

Next Meeting: Thursday Nov. 8, 10AM, 221 Stanley

New outline

Please review Project Outline 3.3 in the Google Groups. Note the thing in yellow has to have a citation. I don't know what it would be so if you do, please add it in. Also if you have other citations please add them. At 11 PM I will be printing it out, so please look it over by then and let me know.

Don't forget to do that library sheet by tomorrow. Good luck with the homework if you haven't done it all yet.

Outline modified

possible materials/methods section is modified.
File can be accessed on google group website.
-Ernest

Project Outline Review

Please review the Project Outline3.doc file (found in the google group) and post your comments either in the comments section of this post or by posting a revised file in the google group. Please try to do this by 8PM Sunday if possible so I can incorporate everyone's input and send out a second copy for review.

Note that the citations have not been added to the outline yet. If something sounds like it was originally written by you, please make sure it has a citation if necessary.

Outline

Problem

Current treatments for glioblastoma multiforme are limited to palliative measures. The diffusive nature of glioblastoma cells promotes a recurrent tumor which, in more than 90% of cases, develops immediately adjacent to the resection margin or within several centimeters of the resection cavity [Journal of Clinical Oncology]. Patients are subject to several resection procedures, suggesting a reason for the lack in the practice of filling voids with biomaterials.


Current Methods

Several experimental treatments have been conducted. In one instance, hyaluronic acid-poly-D-lysine-based three dimensional hydrogel has been implanted in the void. The hydrogel composition is determined to mimic the conditions of the ECM, which contains high concentrations of hyaluronic acid. In addition to providing a biocompatible matrix, the acid used in conjunction with poly-D-lysine, creates a matrix with a porous microstructure from the cross-linking of HA and PDL. The matrix is implanted to serve as a scaffold to elicit cell regeneration and to bridge the gap in neural tissue [HA PLD 3D Hydrogel]. The positive charge on PLD has been suggested to promote cell adhesion, assisting in cell regeneration.

Research is currently being conducted to halt the migration of malignant gliomas. Research is directed in elucidating the signal pathway of glioma migration and interfering with the pathway by protein modification. Studies have shown that monoclonal antibodies directed against the α3β1 integrin reduces the level of tumor astrocyte migration on laminin [Journal of Clinical Oncology]. Studies have identified the combination of adhesion, invasion, and motility in causing glioma migration, all of which serve as sources from which the suppression of glioma migration and proliferation can be targeted.

Possible Materials/Solutions

Potential design strategies
- From the investigation in HA-PDL hydrogel matrix, it has been noted that the use of positively charged biomaterials promotes cell adhesion.
- Freeze drying a hydrogel with water as the poring agent promotes the formation of a porous structure
- Incorporation of tumor suppression with scaffold for regeneration
o E.g. coating the scaffold with molecules targeted to interfere with tumor migration pathway.
o Implantation of the scaffold itself serves only as a palliative treatment to limit pain and improve quality of life.


Define Improvement

Performance Testing

- Degradability: exposing of matrix to cytosolic conditions – relatively high pH
- SEM analysis – to observe the performance of the matrix as a scaffold – the migration and adhesion of cells can be observed
- Rheological Analysis – to compare the mechanical properties of the matrix with those of the ECM – similar mechanical properties limits undue stress at the matrix-brain interface

Economics

Meeting Minutes 10/12/2007

Present: Michael, Ernest, Ahra, Gautham
Time: 11AM
Location: 321 Stanley

Topics:
Reviewed the outline sections which were completed last night. Improvements will be made over the next two days. The outline should be completed by the end of Saturday for review by the team members.
Created a Google Group for file posting. All team members should become members of the group.
Discussed the progress with Professor Healy at the end of the meeting.


Action Items:
-Sign up for the Google Group.
-Post your files to the Google Group and link them in the blog with a short description.
-Fill out the source evaluation form (the one from the library) by Tuesday Oct. 16.
-Cite the appropriate sources in the section you wrote for the outline by the end of Friday.
-Create a list of your sources for the bibliography - even if we haven't cited them - by the end of Sunday. Earlier for the sources cited in the outline.
-Review the draft of the outline some time after it is posted. Reply to the appropriate blog posting in the 'comments' section with your feedback. Gautham will post the file with an accompanying blog entry.

Next Meeting: TBD

brain tumor treatments

These are the current methods to remove a brain tumor.

1. Surgery: Most common method. Using computerized devices called surgical navigation systems, the surgeon can accurately determine the size, location, and position of the tumor. Surgeons make large opening in the skull, and use the surgical navigation system to remove the tumor.
2. Radiation: Radiation is applied to brain tumors to selectively kill the tumor while leaving normal tissue unharmed.
3. Chemotherapy: It is the treatment of disease with chemicals or drugs. It works by causing cell damage that is better repaired by normal tissue than by tumor tissue.
4. Immunotherapy: The body's immune system should recognize tumor cells as abnormal, and then attack and destroy them.
5. Antiangiogenesis: using substances (antiangiogenesis factors) that inhibit blood vessels, thereby starving the tumor cells.
6. Gene therapy: It is to correct the underlying defects in the genes that lead to tumor control.

I will post the pdfs that I found on these later, when I find out how to do it.

Meeting Minutes 10/11/2007

Note: Please note the typo in the next meeting. It was listed as 221 Stanley. The correct room is of 321 Stanley.

Present: All
Time: 10AM
Location: 221 Stanley

Topics:
Discussed the research people did during the last week.
Looked over the beginnings of the outline. Everyone will be adding portions based on what they researched. We will discuss the work everyone does at the next meeting.

Action Items:
-Make sure you can post to the blog. If you need help with posting files, ask Gautham
-Write a draft of information your sections for the outline. Also consider the information for the later sections. Post your section to the blog by the end of tonight.
-Fill out the source evaluation form (the one from the library) by Tuesday Oct. 16.
-Create a list of your sources for the bibliography - even if we haven't cited them - by the end of Sunday.

Next Meeting: Friday Oct. 12, 10AM in 321 Stanley

Meeting Minutes 10/05/2007

Present: All
Time: 12 noon
Location: 2nd floor Stanley workroom

Topics:
Introduction to project based on what was presented in class.
Discussed possible issues we may have to consider for a biomaterial:
-Density
-Osmolarity/Biological performance
-Other bulk material properties
-How does the brain remodel around the hole vs. around a material?
-Synthesis of artificial material or mimicking/growing artificial tissue.

Discussed the outline due on Tue. Oct 16:
1)Problem - what, why, problems, compsition of brain ECM
2)Current methods - pros and cons
3)Possible materials
4)Define improvement
5)Performance testing
6)Economics - production costs/methods

Action Items:
-Investigate the topic you were assigned (current methods or possible materials)
-Become aware of background information
-Come to next meeting prepared with research to start building the outline

Next Meeting: Thursday October 11, 10AM Stanley Atrium

Research and Ideas for Current Methods and Possible Solutions in Outline

Hey guys, here are some of the things I came up with from my research of the literature.

Current Methods
Currently, patients who suffer from Glioblastoma multiforme are treated surgically. But even after the brain tumor is physically removed, the mean survival time of the patient is very short (about one year) due to the cancer cells’ ability to rapidly invade the surrounding brain tissue following excision. In the past, various forms of “combination therapy” have been used in an attempt to extend the life expectancy of these patients. This includes combining surgical treatment with chemotherapy following the removal of the tumor. But even then, the mean survival of the patients is on average only increased from a year to about 19 months. In other cases, some patients who qualify actually undergo repeat surgeries to remove the cancer cells that have grown in the surrounding brain tissue. However, the mean survival time of patients who undergo this treatment is increased to only about 15 months following the initial operation.

New forms of treatment following surgery are needed to address the aggressive nature of Glioblastoma multiforme.


Possible Solutions
It may be possible to discourage cancer cells from migrating into the surrounding brain tissue after surgery with the placement of an implant into the empty cavity following excision of the tumor. Past studies have shown that the process of invasion of gliomas involves their secretion of various proteolytic enzymes that digest the ECM of the brain. These proteases also play a role in maintaining the microenvironment necessary for survival of the cancer cells in the brain. Furthermore, various compounds that have been found in the surrounding matrix of glioma cells include glycosaminoglycans, fibronectin, and vitronectin. Since the ECM of the brain has been found to consist largely of type-IV and type-V collagens, it may be possible to synthesize a collagen gel seeded with the compounds necessary for cancer cell migration and survival to induce the tumor to grow inward into the empty cavity rather than into the surrounding brain tissue following surgery (Of course, this might have the opposite affect of simply increasing the overall rate of tumor growth in all directions, in which case this isn’t a very good idea at all. I’ll have to do more research to find out what induces these cancer cells to migrate and in which direction. Another approach might involve finding ways to inhibit protease secretion). The density of the gel can be tailored to match that of the brains ECM.

Define Improvement
Improvement can be measured in terms of the mean survival time following surgery.

background information about brain tumor

this is a very good website that explains brain tumor.
http://neurosurgery.mgh.harvard.edu/abta/primer.htm

SECTION 1 What is a brain tumor?
SECTION 2 What are the parts of the brain and what does each part do?
SECTION 3 Who gets brain tumors?
SECTION 4 What are the symptoms of brain tumors ?
SECTION 5 How are brain tumors diagnosed?
SECTION 6 What are the different types of brain tumors ?
SECTION 7 How are brain tumors treated?
SECTION 8 Figures.
This is the contents of the website. enjoy!

Background Papers

edit: Please see the Google Group for these papers.

File Index
3d peptide channels: Guiding neurite outgrowth in a HA hydrogel matrix.
ECM heterogeneity: Good information about the composition of brain ECM. Please especially read section 2.
Glioblastoma Review: Review papers are always good to catch you up to speed on things.
HA-Poly-D-Lys Hydrogel: Development of a hydrogel matrix for traumatic brain injury.
MolecularTargetsGliomaInv: Has some pictures of the abscesses so you can see what we're dealing with.

GBM background information

Glioblastoma Multiforme
Some highlights:

The most common and aggressive type of primary brain tumor, accounting for 52% of all primary brain tumor cases and 20% of all intracranial tumors.

The five year survival rate of the disease has remained unchanged over the past 30 years and stands at less than three percent.

Tumor recurrence after surgery or radiation is almost inevitable, usually within 2 cm of the original site, and 10% may develop new lesions at distant sites. Reoperation or brachytherapy has been attempted, with uncertain results. The most aggressive therapy, a second surgery and chemotherapy, is generally used in those under 40 years of age whose original operation was many months earlier. If the PCV regimen has not been used, it may be tried; else, the newer agent temozolomide may be used. However, these regimens usually only increase the symptom-free interval, rather than prolong survival.

bioe/mse118

you can post your papers!
-Ernest