PARP Inhibitors in Ovarian Cancer

gdpawel said:

American Association of Cancer Research (AACR) Meeting 2011
The Sunday, April 3, 2011, experimental and molecular therapeutics poster session at the AACR 102nd annual meeting included Dr. Robert Nagourney's Rational Therapeutics presentation on signal transduction inhibitors. Using MEK/ERK and PI3K-MTOR inhibitors he explored the activities, synergies and possible clinical utilities of these novel compounds.

The findings were instructive. First, it saw a good signal for both compounds utilizing the Ex-vivo Analysis of Programmed Cell Death (EVA-PCD) platform (functional profiling). Second, it saw disease-specific activity for both compounds. For the MEK/ERK inhibitor, melanoma appeared to be a favored clinical target. This is highly consistent with expectations. After all, many melanomas carry mutations in the BRAF gene, and BRAF signals downstream to MEK/ERK. By blocking MEK/ERK, it appeared that his lab blocked a pathway fundamental to melanoma progression. Indeed, MEK/ERK inhibitors are currently under investigation for melanoma.

For PI3K inhibitors, the highest activity was observed in uterine cancers. This has interest, because uterine carcinomas are often associated with a mutation in the PTEN gene. PTEN is a phosphatase tumor suppressor that functions to block activation of the PI3K pathway. Thus, mutations in the tumor suppressor unleash PI3K signaling, driving tumors to grow and metastasize. Blocking PI3K provided a strong signal, indicating that this approach may be very active in tumors associated with these oncogenic events.

The third point of interest in the report was, perhaps, its most important. Specifically, that the lab can explore those diseases where MEK-ERK, PI3K and mTOR signaling are less established targets. Cancers of the lung, ovary, colon or breast all manifested profiles of interest. When they combined both pathway inhibitors in a process called horizontal inhibition, renal cell carcinoma popped up as the best target. These results, though exploratory, suggest a superior approach for drug development, allowing the lab to identify important leads much faster than the clinical trial process.

Source: Rational Therapeutics, Inc.

gdpawel said:

Environmental Influences
LaundryQueen

My motivation is the satisfacton of knowing that I've helped to increase the knowledge of informed consent. My bailiwick has been my wife's experience as a cancer patient and my research on cell function analysis, which has no boundaries across cancer types.

Yes, environmental influences can cause the suppression of some gene functions and the activation of others. Our knowledge of genomic complexity tells us that genes and parts of genes interact with other genes, as do their protein products, and the whole system is constantly being affected by internal and external evironmental factors.

What do I mean by environmental influences? The totality of surrounding conditions - the milieu of the cell. What affects the milieu of the cell? Toxins, viruses, carcinogens, diet, essentially everything that our cells are exposed to. Detoxification, followed by the creation of a healthy milieu with appropriate diet and supplements benefits cancer patients.

Patients should receive less toxic, less mutagenic therapy with agents such as high-dose tamoxifen, targeted drugs such as Iressa, Tarceva and anti-angiogenic therapy with agents such as Avastin. Of course, there are a number of new classes of drugs that target VEGF, like Avastin at the protein level. At the tyrosine kinase level (Nexavar, Sutent) and at the intracellular metabolic pathway mTOR (Afinitor, Torisel).

Assay-directed therapy could provide clinical benefit.

Greg

LaundryQueen said:

Such good information
Greg: I hope your wife is doing well. Thanks for your contributions to "Cancer College."

gdpawel said:

My spiritual consigliere
I wasn't going to bring this issue up, but since another has mentioned if my wife was doing well, I need to say that my dearly beloved spouse is still with me in spirit, helping me go over all this split pea soup of cancer medicine. Many times we may think our thoughts are our own, but more often than not, they emanate from our passed on loved-ones. Through these thoughts, the best parts of our creative character come forth. I could not have done my ten years of cancer research without the guidence of my wife. She has inspired each and every avenue of my search for truth. She is intermingled within my own mind. And she was a mensa on earth.

gdpawel said:

I'm serious!
Split Pea Soup Recipe

Ingredients
a.. 1 lb (2 1/4 cups) green split peas
b.. 1 large onion, peeled and chopped
c.. 2 celery stalks, chopped
d.. 1 large leek, chopped
e.. 1 large carrot, chopped
f.. 1 large clove of garlic, halved
g.. 1 herb bouquet*
h.. 2 well-rinsed ham hocks
i.. Salt and Pepper
j.. Optional garnish - small toasted croutons (avoid for gluten-free version)**, chopped parsley or chives
*Herb Bouquet: Tie 3 cloves garlic, 4 allspice berries, 2 bay leaves, 1 teaspoon thyme, 8 sprigs parsley in rinsed cheesecloth or place in bouquet garni muslin bag.

**To make toasted croutons, take 2 or 3 slices of day-old French or Italian loaf bread, cut into cubes. Let dry out a bit (can put in 200 degree oven for 10 minutes to help dry). Melt a tablespoon or two of butter on medium high heat in a large skillet. When hot, add the bread cubes, spread out in a single layer. Let toast on one side and then turn to other sides. Add more butter if necessary. Alternatively you can toss the cubed bread with olive oil and let toast in a 350°F oven until lightly browned.

Method
1 Pick over the peas and remove any stones. Wash and drain peas. Place in a 4 quart pan with the vegetables, herb bouquet, ham hocks and 2 1/2 quarts of water. Bring to a simmer. Skim the scum off the top of the soup for several minutes, until the scum ceases to rise. Cover loosely and simmer about 1 1/2 hours, or until peas are tender, stirring occasionally in case they stick to the bottom of the pan.

2 Remove the ham hocks and herb bouquet from the soup. Purée the soup with a blender. An immersion blender works great for this; if you are using a regular blender, take care to workin batches and only fill the blender halfway if the soup is still hot, and hold down the lid while blending. If you want an exceptionally smooth soup, pass the purée through a sieve.

3 Return the purée to the pot and heat to serve. Add salt and pepper to taste. Ladle into warm bowls and garnish with croutons and parsley or chives.

If you want, don't discard the ham hocks, but cut away the outer skin and remove the meat from the bones. Dice the meat and serve with the soup.

Makes 2 quarts. Serves 6.

[understand this!?] LOL!!!