Cool Videos: Regenerating Nerve Fibers

If you enjoy action movies, you can probably think of a superhero—maybe Wolverine?—who can lose a limb in battle, yet grow it right back and keep on going. But could regenerating a lost limb ever happen in real life? Some scientists are working hard to understand how other organisms do this.

As shown in this video of a regenerating fish fin, biology can sometimes be stranger than fiction. The zebrafish (Danio rerio), which is a species of tropical freshwater fish that’s an increasingly popular model organism for biological research, is among the few vertebrates that can regrow body parts after they’ve been badly damaged or even lost. Using time-lapse photography over a period of about 12 hours, NIH grantee Sandra Rieger, now at MDI Biological Laboratory, Bar Harbor, ME, used a fluorescent marker (green) to track a nerve fiber spreading through the skin of a zebrafish tail fin (gray). The nerve regeneration was occurring in tissue being spontaneously formed to replace a section of a young zebrafish’s tail fin that had been lopped off 3 days earlier.

Along with other tools, Rieger is using such imaging to explore how the processes of nerve regeneration and wound healing are coordinated. The researcher started out by using a laser to sever nerves in a zebrafish’s original tail fin, assuming that the nerves would regenerate—but they did not! So, she went back to the drawing board and discovered that if she also used the laser to damage some skin cells in the tail fin, the nerves regenerated. Rieger suspects the answer to the differing outcomes lies in the fact that the fish’s damaged skin cells release hydrogen peroxide, which may serve as a critical prompt for the regenerative process [1]. Rieger and colleagues went on discover that the opposite is also true: when they used a cancer chemotherapy drug to damage skin cells in a zebrafish tail fin, it contributed to the degeneration of the fin’s nerve fibers [2].

Based on these findings, Rieger wants to see whether similar processes may be going on in the hands and feet of cancer patients who struggle with painful nerve damage, called peripheral neuropathy, caused by certain chemotherapy drugs, including taxanes and platinum compounds. For some people, the pain and tingling can be so severe that doctors must postpone or even halt cancer treatment. Rieger is currently working with a collaborator to see if two protective molecules found in the zebrafish might be used to reduce or prevent chemotherapy-induced peripheral neuropathy in humans.

In recent years, a great deal of regenerative medicine has focused on learning to use stem cell technologies to make different kinds of replacement tissue. Still, as Rieger’s work demonstrates, there remains much to be gained from studying model organisms, such as the zebrafish and axolotl salamander, that possess the natural ability to regenerate limbs, tissues, and even internal organs. Now, that’s a super power we’d all like to have.

Reference:

[1] Hydrogen peroxide promotes injury-induced peripheral sensory axon regeneration in the zebrafish skin. Rieger S, Sagasti A. PLoS Biol. 2011 May;9(5):e1000621

[2] Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish. Lisse TS, Middleton LJ, Pellegrini AD, Martin PB, Spaulding EL, Lopes O, Brochu EA, Carter EV, Waldron A, Rieger S. Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):E2189-E2198.

Links:

Chemotherapy-Induced Peripheral Neuropathy (National Cancer Institute/NIH)

Learning About Human Biology From a Fish (National Institute of General Medical Sciences/NIH)

Sandra Rieger (MDI Biological Laboratory, Bar Harbor, ME)

NIH Support: National Institute of Dental and Craniofacial Research; National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke

Snapshots of Life: Finding a Cube for Cancer

 

Targeted drug delivery systems for cancer treatment

Jenolyn F. Alexander and Biana Godin, Houston Methodist Research Institute; Veronika Kozlovskaya and Eugenia Kharlampieva, University of Alabama at Birmingham.

Creative photographers have long experimented with superimposing images, one over the other, to produce striking visual effects. Now a group of NIH-supported scientists at Houston Methodist Research Institute and their colleagues have done the same thing to highlight their work in the emerging field of cancer nanomedicine, using microscopic materials to deliver cancer treatments with potentially greater precision. In the process, the researchers generated a photographic work of art that was a winner in the Federation of American Societies for Experimental Biology 2015 Bioart competition.

The gold cubes are man-made polymer microcarriers, just 2 micrometers wide (by comparison, human cells generally range in diameter from 7 to 20 micrometers), designed to transport chemotherapy drugs directly to tumor cells. These experimental cubes, enlarged in the upper left part of the photo with a scanning electron microscope for better viewing, have been superimposed onto a second photograph snapped with a confocal fluorescence microscope. It shows similar cube-shaped microcarriers (yellow) inside cultured breast cancer cells (nucleus is purple, cytoplasm is turquoise).

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Different Cancers Can Share Genetic Signatures

Cancer types floating over a cell with unraveling DNA

NIH-funded researchers analyzed the DNA of these cancers.

Cancer is a disease of the genome. It arises when genes involved in promoting or suppressing cell growth sustain mutations that disturb the normal stop and go signals.  There are more than 100 different types of cancer, most of which derive their names and current treatment based on their tissue of origin—breast, colon, or brain, for example. But because of advances in DNA sequencing and analysis, that soon may be about to change.

Using data generated through The Cancer Genome Atlas, NIH-funded researchers recently compared the genomic fingerprints of tumor samples from nearly 3,300 patients with 12 types of cancer: acute myeloid leukemia, bladder, brain (glioblastoma multiforme), breast, colon, endometrial, head and neck, kidney, lung (adenocarcinoma and squamous cell carcinoma), ovarian, and rectal. Confirming but greatly extending what smaller studies have shown, the researchers discovered that even when cancers originate from vastly different tissues, they can show similar features at the DNA level

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Human Folate Receptor Model May Aid Antifolate Drug Design

Model of the human folate receptor and three antifolate drugs used in chemotherapy

Caption: A model of the human folate receptor (top) and three antifolate drugs used in chemotherapy: aminopterin (left), pemetrexed, and methotrexate (right).
Credit: Charles Dann III / Courtesy of Indiana University

Vitamin B9 or folic acid, which is found in dark green leafy vegetables, is essential for cells to grow and divide rapidly—as they do in a growing embryo. This is why women are advised to take folic acid supplements before conception and during pregnancy: inadequate folate raises the risk of brain and spinal cord defects. But while folic acid is key to normal cell growth, rapidly dividing cancer cells also have a tremendous appetite for this vitamin.

Drugs called antifolates have been used for decades in chemotherapy to starve cancer cells of folate, which can help kill the tumor. These drugs have also been used to treat inflammatory diseases like rheumatoid arthritis and Crohn’s disease. But many of these drugs have nasty side effects because they also enter normal healthy cells, depriving them of this essential compound. Continue reading

New Understanding of a Common Kidney Cancer

Purple stained kidney tissue

Caption: Histologic image of clear cell kidney cancer
Slide courtesy of W. Marston Linehan, National Cancer Institute, NIH

Understanding how cancer cells shift into high gear—what makes them become more aggressive and unresponsive to treatment—is a key concern of cancer researchers. A new study reveals how this escalation occurs in the most common form of kidney cancer: clear cell renal cell carcinoma (ccRCC). The study shows that ccRCC tumors acquire specific mutations that encourage uncontrollable growth and shifts in energy use and production [1].

Conducted by researchers in the NIH-led The Cancer Genome Atlas (TCGA) Research Network, the study compared more than 400 ccRCC tumors from individual patients with healthy tissue samples from the same patients. Researchers were looking for differences in the gene activity and proteins in healthy vs. tumor tissue. Continue reading