20.430J | Fall 2015 | Graduate
Fields, Forces, and Flows in Biological Systems


Project Description

The project for this course is a term paper, based on this journal article:

Provenzano, Paolo P., Carlos Cuevas, et al. “Enzymatic Targeting of the Stroma Ablates Physical Barriers to Treatment of Pancreatic Ductal Adenocarcinoma.” Cancer Cell 21, no. 3 (2012): 418–29.

These articles will provide you with further background information:

Provenzano, P. P., and S. R. Hingorani. “Hyaluronan, Fluid Pressure, and Stromal Resistance in Pancreas Cancer.” British Journal of Cancer 108, no. 1 (2013): 1–8.

Chauhan, Vikash P., Yves Boucher, et al. “Compression of Pancreatic Tumor Blood Vessels by Hyaluronan is Caused by Solid Stress and Not Interstitial Fluid Pressure.” Cancer Cell 26, no. 1 (2014): 14–15.

The main controversy concerns the physicochemical mechanisms that are hypothesized to affect transport of chemotherapeutics to the tumor cells: “Do fluid pressures collapse vessels or do collapsed vessels lead to increased fluid pressures?”


The global objectives of your assignment are:

  1. to provide a detailed critique of the main journal article
  2. to state and explain your opinion on the controversy surrounding the physicochemical mechanisms that are responsible for the successful outcome of carcinoma treatment in mice (and potentially humans) described in this paper.

Your paper is to be no more than 20 pages in length, double spaced, including any figures, graphs, etc. that you may wish to generate, as well as a bibliography listing any additional references that you may wish to quote or consult.


Each paper will represent the combined efforts of a team of three people. On your cover page, please list the three co-authors. Each team can assign each of its members to perform specific tasks, for example:

  1. to understand and critique the “bio”-content of the article,
  2. to check and critique the mathematical formulation,
  3. to initiate and / or provide mathematical / numerical simulations of the experimental results if you think that will help to explain the Data provided in the paper,
  4. to check whether the authors did an adequate literature search, etc.

Each team member would then contribute that expertise to the write-up. Of course, everyone on the team should read and critique each other’s work to produce the best final result. Each team member will be given the same grade for this project.

Suggested Approach

You should first read the paper as if you were asked by a journal editor to provide a review of the manuscript. In such a case, you would first list the strengths and weaknesses of the paper.

For instructions on how to write an effective review, consult the following resources:

Drubin, David G. “Any Jackass can Trash a Manuscript, But It Takes Good Scholarship to Create One (How MBoC Promotes Civil and Constructive Peer Review).” Molecular Biology of the Cell 22, no. 5 (2011): 525–27.

Neill, Ushma S. “How to Write an Effective Referee Report.” The Journal of Clinical Investigation 119, no. 5 (2009): 1058–60.

Your paper should include the following:

  1. A background section (one to two pages) that summarizes the biological problem being addressed, its relevance and / or importance to basic biology or physiology or human health.
  2. A summary of the experimental data: First, describe the approach and the general methods used; then give your opinion of the strengths and weaknesses of the approach and experimental methods; are there any fatal flaws? If so, what?
  3. Outline the controversy surrounding the authors’ proposed mechanisms by which hyaluronidase treatment “works”: Is there a model that has been proposed to explain the experimental data? If not, can you propose a model and additional experiments to test your hypotheses and explain the results?
  4. Improvements: Do you think the paper can / should be modified or improved? How so? Are there additional analyses that you can propose and / or carry out that would lead to a more substantial conclusion?
  5. Your summary recommendation: If you received this document from the editor of the journal as a manuscript for a review, what would be your recommendation?