Epigenomics And Cancer Heterogeneity

There can be considerable heterogeneity in cancers, and this can contribute to progression and resistance to therapy.  This heterogeneity can arise not only from DNA sequence changes (i.e., mutation) but also from epigenetic changes - changes in the modifications of chromosomes - on a single cell level, making one cell different than another with respect to gene expression, even if the gene sequences remain the same.  A paper of interest, abstract:

Cell-to-cell heterogeneity is a major driver of cancer evolution, progression, and emergence of drug resistance. Epigenomic variation at the single-cell level can rapidly create cancer heterogeneity but is difficult to detect and assess functionally.

RESULTS: We develop a strategy to bridge the gap between measurement and function in single-cell epigenomics. Using single-cell chromatin accessibility and RNA-seq data in K562 leukemic cells, we identify the cell surface marker CD24 as co-varying with chromatin accessibility changes linked to GATA transcription factors in single cells. Fluorescence-activated cell sorting of CD24 high versus low cells prospectively isolated GATA1 and GATA2 high versus low cells. GATA high versus low cells express differential gene regulatory networks, differential sensitivity to the drug imatinib mesylate, and differential self-renewal capacity. Lineage tracing experiments show that GATA/CD24hi cells have the capability to rapidly reconstitute the heterogeneity within the entire starting population, suggesting that GATA expression levels drive a phenotypically relevant source of epigenomic plasticity.
CONCLUSION: Single-cell chromatin accessibility can guide prospective characterization of cancer heterogeneity. Epigenomic subpopulations in cancer impact drug sensitivity and the clonal dynamics of cancer evolution.

Identifying these epigenetic changes can be the first step in developing novel approaches to reverse the changes and/or target those cells containing such changes, for therapeutic benefit.

Corn muffins and brownie muffins

The perfect breakfast would meet your savory and sweet cravings without any guilt. Therefore, the perfect breakfast comes into the shape of a corn muffin and a brownie muffin!

The corn muffins below can be enriched by adding some pumpkin or sunflower seeds and flaxseed. 

The added sugar in the brownie muffins comes only from the chocolate chips. These muffins are also rich in fiber; therefore, the sugar spike would be lower after indulging a muffin.


Corn muffins (12 muffins)
 
Ingredients:
1 cup cornmeal
1 cup whole-wheat flour
1tsp salt
1 tsp baking powder
2 tsp baking soda
2 eggs
1 cup whole milk yogurt (plain)
½ cup water
1 cup corn kernels (canned)
¼ cup olive oil
1Tbsp hot pepper flakes (optional)
seeds (optional)
 
Directions:
Preheat the oven to 375°F. Stir together the dry ingredients (flour, cornmeal, salt, baking soda and baking powder, the pepper flakes). In another bowl, combine the three lightly beaten eggs, yogurt, water, oil, and corn kernels. Add the dry ingredients and stir gently. Distribute the dough into an oiled12-muffin pan. Bake for 25 minutes or until golden-brown.

Brownie muffins (12 muffins)

Ingredients:
3-4 ripe bananas (mashed)
4 oz (113 g) of unsweetened applesauce
1 Tbsp vanilla essence
3 eggs (lightly beaten)
1 cup whole-wheat flour
½ cup cocoa powder
2 tsp baking soda
3/4 cup semi-sweet chocolate chips
1 cup walnuts, chopped
 
Directions:
Preheat the oven to 375°F. Oil a muffin pan. Combine the mashed bananas, apple sauce, vanilla and eggs. Add the pre-mixed flour, cocoa powder, and baking soda. Stir to incorporate all. Add the chocolate chips and walnuts, distribute into the 12 slots of the muffin pan. Bake for 25-30 minutes.

Mushroom and pepper soup

Soups are the best nourishment for cold, winter days. At this time of the year, my dinners frequently consist of a bowl of warm soup, a boiled egg and a piece of fruit.
Below is the recipe for a mushroom soup. This could be served with a bit of lemon juice.
Mushroom and pepper soup

Ingredients: 
5-6 cups mushrooms, diced
1 medium size onion, diced
1 medium size red sweet pepper, diced
½ cup bulgur wheat
2-3 medium size potatoes, cut into big chinks
1 tsp turmeric
¼ tsp black pepper
salt to taste
1-2 Tbsp cooking oil
Directions:
Add oil to the soup pot and saute the onion for five minutes. Add the mushrooms and potatoes, continue cooking with a closed lid. Once the liquid of the mushrooms decreases, add some water to keep the potato chinks under the water surface. Once the potatoes are soft, mash them and add water to the desired final volume (I usually add 12 cups of warmed up water). Bring to boil and add the diced pepper. Once the pepper is cooked, add the bulgur, all spices and stop the heat. Cover the pot again and keep the lid on for one hour before serving.

What works for Pruritus Ani (Anal Itching)

I have previously written about my problem with Pruritus Ani or anal itching.

Within the past six months, my itchy-rear-end suffering resurrected itself. I was unable to sleep at night. Daytime, I was unable to find peace and quiet. I was a desperate wreck.

Previously, I had written that shea butter worked a miracle for me. However, shea butter did not alleviate my new episode.
 
I tried all possible over-the-counter remedies from the U.S. pharmacies, including all chemical-based hemorrhoidal ointments, wipes, hydrocortisone creams, etc. Nothing brought any relief. In fact, my rear end became painful.

I also tried sitz baths with Epsom salt, tea tree oil, or smoke tree leaves. The baths relieved slightly the condition; however, the itching sensation returned almost as soon as the bath was over.

As I stated, I had become a desperate wreck.

And then, by chance, I remembered a powerful medication I had acquired previously for inflamed skin, Betasone. The particular ointment I had was with three active ingredients, but the component that  worked the miracle was the betamethasone, an adrenocorticosteroid.

According to WebMD, Betasone treats: seborrheic dermatitis, atopic dermatitis (a type of allergy that causes red and itchy skin), plaque psoriasis, granuloma annulare, itching of the genital area, psoriasis of scalp, itching of the anus, skin inflammation, cutaneous T-cell lymphoma, contact dermatitis, a type of skin rash that occurs from contact with an offending substance, itching, inflammation of the skin due to an allergy, skin rash that becomes thick and discolored from rubbing it.

The warning for this ointment is that its prolonged use causes skin thinning and with time, this thinning may exacerbate the original problem further. Therefore, I used the ointment for five days by tapering it off. The beneficial effect was felt on the first day, with the very first use.
 
During my desperate search for a remedy, I was recommended to try a herb-based hemorrhoidal cream, FitoroiD. It contains essential oils from tree oil, cypress, Mentha piperita, roots of Ruscus aculeatus, gel from leaves of Aloe vera, Hypericum perforatum (known as St John's-wort), jojoba oil, shea butter, and something called “Helydol” - freeze-dried extracts of Helichrysum flowering tops lipophilic fraction.

So, from the Betasone, I switched to FitoroiD.
I was also told about the healing properties of the Bariederm cica-cream for atopic dermatitis. This cream contains copper and zinc to sooth any irritated skin.

Since I was at my wits’ end, I bought and used both FitoroiD and the cica-cream at the same time. Ideally, I would have used them sequentially, to find out which is truly beneficial for the condition. After another four to five days on these ointments, the itch was almost gone.

The final stage was using Alergozan ointment. Its active ingredient is chloropyramine, an antihistamine compound that is approved in Eastern Europe and Russia for the treatment of allergies, conjunctivitis, allergic rhinitis, bronchial asthma, and other atopic (allergic) conditions. This cream helped with the occasional and slight sensations of itching. At present, I am tapering off its use as well.

In conclusion, I believe that I had developed a contact dermatitis, which is an allergic reaction. Menstrual periods and sanitary pads, as well as uncomfortable (non-cotton) underwear have been irritating my skin further. Occasionally, I also develop hemorrhoids and that further exacerbates the problem.

Until the irritants are around, I may have to rely on the above-described ointments. Hopefully, with age, and change of conditions, the dermatitis would disappear.

Warburg Effect And Some Possible Cancer Treatments

The Warburg effect is important in cancer, since cancer cells rely more heavily than do normal cells on glycolysis for energy production.  This may point at therapies targeting this effect for patient benefit.  A paper is here, abstract:

As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models. This treatment, in combination with conventional chemotherapy, has yielded extremely encouraging results in glioblastoma, brain metastasis and lung cancer. Randomized trials are necessary to confirm these preliminary data. The major limitation is the fact that the combination of α-lipoic acid and hydroxycitrate can only be effective if the mitochondria are still present and/or functional. That may not be the case in the most aggressive tumors. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Concomitant correction of this alkalosis may be a very effective treatment in case of mitochondrial failure.

Note that a ketogenic diet is considered one mechanism whereby the Warburg effect can be leveraged for anti-cancer treatment.

Negative Effects Of Dietary Fiber Deficiency

Another role for dietary fiber shown here, abstract:

Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.

Dietary fiber can have many beneficial effects, including the production of short chain fatty acids that are good for colonic health and of course fiber helps with bowel movements to avoid constipation.  This mouse study shows that when there is a deficiency of dietary fiber, the gut microbiota that would normally digest fiber will instead start using the gut mucus as an energy source, eroding the protective lining on the colon and allowing pathogenic organisms to have access.

Eat your fiber!

Short Chain Fatty Acids And Weight Loss

Can short chain fatty acids contribute to weight loss?  A paper looks at this, abstract:

Elucidating the mechanisms by which short chain fatty acids (SCFA) reduce body weight may assist in the development of an effective weight control strategy. Dietary supplementation of acetate, propionate, butyrate or their admixture was shown to significantly inhibit the body weight gain induced by high-fat diet feeding. Supplementation of SCFAs caused significant changes in the expressions of G-protein coupled receptor 43 (GPR43) and GPR41 characterized by increases in the adipose tissue and reductions in the colon. Additionally, they influenced the bacterial community structure in feces, with a reduction in the proportion of Firmicutes and an increase in the proportion of Bacteroidetes. The effects of dietary SCFAs on the GPR expression and gut microbiota composition may further result in body weight reduction by enhancing triglyceride hydrolysis and FFA oxidation in the adipose tissue, promoting beige adipogenesis and mitochondrial biogenesis, and inhibiting chronic inflammation.

Keep in mind that short chain fatty acids can be produced in the colon by the fermentation of dietary fiber by the gut microbiota, with beneficial effects for colonic health.  However, the effects described in this paper required direct supplementation of these agents into the diet of the test mice.  Nevertheless, the findings suggest a role for short chain fatty acids in weight control.

Smoked cheese and mushrooms pizza

The taste is divine if you like smoked cheese!
The recipe below is for two pizzas, eight slices total. Maybe will feed four people.

Ingredients for the dough
4 cups flour
2 cups warm water
1 pack instant yeast
1 teaspoon salt

Ingredients for the topping
10.5 oz cream of mushroom (condensed soup)
1 Tbsp olive oil 
black pepper
salt to taste
1 lb mushrooms
smoked cheese (approximately 0.3 lb)

Directions
Prepare the dough the day before baking the pizza. Mix the flour and salt in a large bowl. Make a well in the middle of the flour, sprinkle the yeast and pour the warm water. Incorporate the flour by hands to a soft ball of dough. Oil the bowl and leave the dough covered with Saran wrap and a towel in a warm place. The next day, divide into two parts and spread on two oiled cookie sheets (press the dough into a thin layer with your hands until the dough covers most of the sheets). Leave the dough at room temperature to rise again for an hour. 
For the topping, clean and cut the mushrooms. Soften them in oil for 10 minutes. Keep the cover on to preserve most of the liquid. Remove from the stove and mix with the condensed soup. Spread on the pizza dough. Add pieces of smoked cheese on top and bake for 20 minutes or less at 400°F.