Development of an effective treatment against advanced tumors remains a major challenge for cancer immunotherapy. Approximately 50% of human melanoma is driven by B-Raf proto-oncogene mutation (BRAF-mutant). Tumors with such mutation are desmoplastic, highly immunosuppressive, and often resistant to immune checkpoint therapies. We have shown that immunotherapy mediated by low dose doxorubicin-induced immunogenic cell death was only partially effective for this type of tumor, and not effective in long-term inhibition of tumor progression. Wnt family member 5A (Wnt5a), a signaling protein highly-produced by BRAF-mutant melanoma cells, has been implicated in inducing dendritic cell tolerance and tumor fibrosis, thus hindering effective antigen presentation and T cell infiltration. We hypothesized that Wnt5a is a key molecule controlling the immunosuppressive tumor microenvironment in metastatic melanoma. Accordingly, we have designed and generated a trimeric trap protein, containing the extracellular domain of Fizzled 7 receptor that binds Wnt5a with a Kd ~278 nM. Plasmid DNA encoding for the Wnt5a trap was delivered to the tumor by using cationic lipid-protamine-DNA (LPD) nanoparticles. Expression of Wnt5a trap in the tumor, although transient, was greater than in that of any other major organs including liver, resulting in a significant reduction of the Wnt5a level in the tumor microenvironment without systematic toxicity. Significantly, combination of Wnt5a trapping and low dose doxorubicin showed great tumor growth inhibition and host survival prolongation. Our findings indicated that efficient local Wnt5a trapping significantly remodeled the immunosuppressive tumor microenvironment to facilitate immunogenic cell death-mediated.
Below is one of the added sugar-less recipes for those, who are ready to sacrifice their sweet tooth.
This banana bread is excellent to pack for your work lunch.
To my "workday menu", I would add a few slices of cheddar cheese, apples and carrots.
In addition to being free of added sugar, the bread is rich in fiber! And by the way, it would taste sweet along with a cup of black coffee.
Banana bread
Ingredients
1 ¾ cups whole wheat flour
1 ½ teaspoon baking soda
3 eggs
½ cup unsweetened apple sauce
¼ cup yogurt
1 teaspoon vanilla extract
4 ripe bananas, mashed
1 cup of chopped walnuts
½ cup raisins
Directions
Combine the flour and baking soda. Beat together the eggs, apple sauce, yogurt and vanilla. Incorporate by mixing the mashed bananas, flour mix, walnuts and raisins. Transfer to a pan sprayed with PAM, and bake at 325°F for 50 minutes (or until a knife inserted in the bread comes out clean).
Tofu with sunflower seeds spread
Ingredients
14 oz extra-firm tofu
½ cup raw sunflower seeds
2 - 3 Tbsp apple cider vinegar
2 Tbsp olive oil
crushed garlic (to taste)
salt (to taste)
dried basil (to taste)
Directions
Break down the tofu into handfuls and squeeze out as much liquid as possible. Combine all ingredients in a food processor and pulse until smooth. The salt, garlic and basil are optional and to taste. You can try any herb that is in season. I am planning on using dill next time.
Spinach-feta cheese spread
Ingredients
14-oz can leaf spinach
2 Tbsp plain yogurt
1 cup crumbled feta cheese
1 - 2 Tbsp apple cider vinegar
2 Tbsp olive oil
crushed garlic (to taste)
salt (to taste)
Directions
Combine all ingredients except for the feta cheese in a food processor and pulse until creamy and smooth. Remove from the processor and combine with the feta cheese. At this time, you may re-adjust again the salt and vinegar.
Do you have the urge to scratch your anus? It is not a symptom easy to admit, but if the sensation drives you insane, you may start looking for information and help on Internet. You may even see a doctor or two. This is what happened with me. When the itch was there, I could not sleep, I could not think during the day.
My condition was recurrent. It started more than 6-7 years ago and ever since, it was on and off. The doctors did not help. They tested me for various infections but did not find any.
Since my condition was improving from time to time on its own, I never tried to find out remedies that could alleviate the symptoms. However, since my last onset expanded into more than half a year, and the itchy sensation sometimes escalated to pain, I desperately started to search for solutions and explanations of the condition.
Below is the summary of what I found and what worked for me (at least for now).
The condition has a name: pruritus ani.
Pruritus ani is described as “the sensation that induces scratching of the skin around the anal orifice” or “an intense urge to scratch the perianal skin”.
Supposedly, up to five per cent of the population is affected by the condition. The condition is usually “idiopathic”, which means that the cause cannot be not identified.
Since the cause is usually unknown, the treatment/management of the condition is difficult.
According to Song S-G and Kim S-H (Pruritus Ani. J. Korean Soc Coloproctol 2011, 27: 54), a wide range of factors may trigger the condition. The causes could be related to colorectal and anal problems (e.g., anal creases, hemorrhoids, fissures, etc), systemic diseases (e.g., diabetic mellitus, leukemia, iron deficiency, etc), psychogenic conditions, dermatologic diseases, poor hygiene, irritants (various chemicals, dyed and scented toilet paper, sanitary pads, etc.), diarrheal state, drugs, infections, diet (e.g., coffee, tea, alcohol, spicy foods, etc.). For a full list of the causes, please refer to the report.
When I studied the list of possible causes, I focused on the iron deficiency because I have been anemic all my life. I have also had a few severe episodes of anemia from time to time (e.g., fainting, vertigo). Therefore, my first step was to take an iron supplement. Whenever I have an episode of severe anemia, I take my iron supplement for only three to four weeks. Excess of iron in the organism has deleterious consequences. Therefore, I try to get my iron from iron-rich foods rather than from a supplement.
While taking the iron pills, I serendipitously found out that I had a container of shea butter in my medicine cabinet. I had bought it more than a year ago with the intention of trying a few cosmetic recipes. When I re-discovered the container, I remembered the anti-inflammatory and soothing properties that shea butter was supposed to have. In my desperation, I decided to try it.
Keep in mind that before the shea butter trial, I had applied almost everything that is recommended to calm itchy skin. I had tried pure aloe vera gel, jojoba oil, coconut oil, petroleum jelly, diluted apple cider vinegar, combinations of these, and every single over-the-counter anti-itch cream. All the drugstore creams relieved the condition only for hours. None of the other remedies helped. Sitz baths with or without Epsom salt irritated even more my skin.
Until the shea butter. Finally, there was some relief!
How do I use the shea butter? After showering (usually twice a day, in the morning and evening), I apply a small amount of shea butter on the affected area. Since shea butter melts at body temperature, it is easy to spread and is rapidly absorbed by the skin. I use a cotton pad to cover the area and prevent staining my underwear. By the way, I stopped using any scented/dyed hygienic products, towels, toilet paper. I use only cotton underwear. I have noticed that anything scented and dyed irritates my skin.
The relief in my case was not instantaneous; however, the itchy and painful sensation subsided somewhat after the very first applications. Approximately two to three weeks of use allowed most of the symptoms to disappear. Meanwhile, I stopped taking the iron supplement, but I am still using the shea butter.
Because of the beneficial effect of shea butter, I researched its properties to find out whether there were any dangers and contraindications. Based upon what I found, it seems that this natural product is safe for topical use. However, I am NOT a trained clinician. If you decide to try this natural remedy (or any other), do a skin patch test. Apply a small amount to your forearm and wait for 24 hours to check for an allergic reaction.
So, what is shea butter? Shea butter is extracted from the nuts of an African tree, Vitellaria paradoxa. My container of shear butter contained a solid substance of yellow color. I bought the product in a local store offering natural and organic products; however, I found the same container to be available on Internet.
Shea butter is used mostly in preparing cosmetics; however, it is also edible. Once I get a new container of shear butter, I may try a few hair conditioner recipes (like this one and this).
Why does shea butter sooth and inhibit inflammation?
According to a 2010 report by Toshihiro Akihisa et al., shea butter contains triterpene acetates and triterpene cinnamates. All of these compounds are characterized as anti-inflammatory since they inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. Some of these compounds also exhibit a moderate anti-tumor development effect. Here is also a 2012 report on the molecular mechanisms of the anti-inflammatory effects of shea butter.
I hope this post helps at least one person. Please, let me know if shea butter or something else has worked for you. Also, keep in mind that if you do have a persistent itchy skin, there could be many other (serious) causes, and it is always better to first see a doctor. If the doctor cannot pinpoint a cause, and the condition seems to be “idiopathic”, then probably it is time for you to try some shea butter. Do not forget to do the skin patch test first (see above).
