MEDICINE: ‘DIABETES’ – RISKS & DIAGNOSIS (BMJ PODCAST)

In this episode of the JIM Podcast, Editor-in-Chief Richard McCallum speaks with David Cistola of Texas Tech University Health Sciences Center El Paso about American Diabetes Month.

MEDICINE: NEW ‘SMART CELL’ THERAPIES TO TREAT CANCER

Finding medicines that can kill cancer cells while leaving normal tissue unscathed is a Holy Grail of oncology research. In two new papers, scientists at UC San Francisco and Princeton University present complementary strategies to crack this problem with “smart” cell therapies—living medicines that remain inert unless triggered by combinations of proteins that only ever appear together in cancer cells.

Biological aspects of this general approach have been explored for several years in the laboratory of Wendell Lim, PhD, and colleagues in the UCSF Cell Design Initiative and National Cancer Institute– sponsored Center for Synthetic Immunology. But the new work adds a powerful new dimension to this work by combining cutting-edge therapeutic cell engineering with advanced computational methods.

For one paper, published September 23, 2020 in Cell Systems, members of Lim’s lab joined forces with the research group of computer scientist Olga G. Troyanskaya, PhD, of Princeton’s Lewis-Sigler Institute for Integrative Genomics and the Simons Foundation’s Flatiron Institute. Using a machine learning approach, the team analyzed massive databases of thousands of proteins found in both cancer and normal cells. They then combed through millions of possible protein combinations to assemble a catalog of combinations that could be used to precisely target only cancer cells while leaving normal ones alone.

In another paper, published in Science on November 27, 2020, Lim and colleagues then showed how this computationally derived protein data could be put to use to drive the design of effective and highly selective cell therapies for cancer. “Currently, most cancer treatments, including CAR T cells, are told ‘block this,’ or ‘kill this,’” said Lim, also professor and chair of cellular and molecular pharmacology and a member of the UCSF Helen Diller Family Comprehensive Cancer Center.

“We want to increase the nuance and sophistication of the decisions that a therapeutic cell makes.” Over the past decade, chimeric antigen receptor (CAR) T cells have been in the spotlight as a powerful way to treat cancer.

In CAR T cell therapy, immune system cells are taken from a patient’s blood, and manipulated in the laboratory to express a specific receptor that will recognize a very particular marker, or antigen, on cancer cells. While scientists have shown that CAR T cells can be quite effective, and sometimes curative, in blood cancers such as leukemia and lymphoma, so far the method hasn’t worked well in solid tumors, such as cancers of the breast, lung, or liver.

Cells in these solid cancers often share antigens with normal cells found in other tissues, which poses the risk that CAR T cells could have off-target effects by targeting healthy organs. Also, solid tumors also often create suppressive microenvironments that limit the efficacy of CAR T cells. For Lim, cells are akin to molecular computers that can sense their environment and then integrate that information to make decisions. Since solid tumors are more complex than blood cancers, “you have to make a more complex product” to fight them, he said.

POST COVID: “THE FUTURE OF ELDERLY CARE’ (VIDEO)

Across the rich world around half of covid-19 deaths have been in care homes. Countries need to radically rethink how they care for their elderly—and some innovative solutions are on offer.

COMMENTARY:

This video has a lot of information that would be of help to anyone who has a spouse or parent who is aging, especially if their frailty includes dementia. There were several good, general points.

As hard as it is to get old, it is even harder to be a caretaker of someone whose aging includes memory loss. Hired caretakers burn out at a high rate. The video highlighted Indonesia as a location that is compassionate, and gives quality care at about half the cost in developed countries.

The percentage of the elderly population needing care may well be 50% in 2050. I would not have guessed it, but the video asserts that 50% of individuals over 65 years of age need some help.

It is much better to stay at home, and medical sensor technology is making this increasingly possible. AI would be able to detect changes in a person’s routine that could be flagged.

Of course, it is much better to stay healthy longer. My posting “growing old” addresses this.

–Dr. C.

DR. C’S MEDICINE CABINET: THE BENEFITS OF “IRON”

Iron is the most common element, by weight, on earth, so it should come as no surprise that it has evolved to be an essential component in the mechanism that is life.

The ENERGY of the eukaryotic cell is dependent on the Iron in mitochondria, which are elaborate electron-transfer mechanisms. To quote Nobel Laureate Albert Szent Gyorgyi, “Life is nothing but an electron looking for a place of rest”.

Iron is essential, so it is possible to have too little of it. There is no physiologic pathway to get rid of it and so you can have too much iron in your body, which comprises a disease called Hemochromatosis. Excessive Iron can be TOXIC to the body, and produce damaging free radicals.

Deficiency of iron will produce ANEMIA. Regulation of incoming Iron is the body’s way of keeping excessive Iron out. It is absorbed only in the upper part of the small intestine, and a special protein called Hepcidin can block it from release into the circulation. It is carried through the blood by Transferrin and also Ferritin, which stores the iron that is not in the hemoglobin of RED BLOOD CELLS, the main storehouse of iron.

Blood loss is a common problem which leads to increased Iron requirement, This is reflected in the increase in RDA of Iron in Women during their menstruating years. Colonic Cancer, among other conditions, can also bleed and lead to the anemia of Iron deficiency. This is the reason for Doctors ordering a test for “occult”, or hidden, blood in the stools. My reason for taking Iron is a continuing loss of blood from the small intestine.

I have had multiple colonoscopies and Gastroenteroscopies to rule out cancer and other blood-losing conditions in the lower and upper intestinal tract. The small intestine is the “silent” area to gastroenterologists, and I cannot have the Capsule/camera examination because of my small bowel surgery.

I must take extra iron, and hope that this will be sufficient to keep me from developing anemia again. Green vegetables and red meat are more satisfactory sources, but insufficient for me. I worry a little about the recent finding that Heart Failure has been associated with Ferritin levels below 100 ng./ml.

I struggle to keep mine at 50 ng. by taking 2 tablets of feosol daily and dealIng with the subsequent constipation. An ANNUAL PHYSICAL and laboratory examination is important for the maintenance of health. Enough Iron and blood are important factors for vigorous Well-being. —

–Dr. C.

INFOGRAPHIC:

THE DOCTORS 101 CHRONIC SYMPTOMS AND CONDITIONS #26: HYPERTENSION

Hypertension places an extra load on the blood vessels and heart, and eventually causes them to become diseased. High Blood Pressure is therefore bad for the entire body, which depends on the blood vessels for delivering the nutrients and oxygen necessary for life.

Most hypertension happens from subtle changes in the body’s signalling systems, and often runs in families; This is called “essential hypertension”. Additionally, there are a number of diseases and conditions of which hypertension is a symptom. It is important to know if you have hypertension, and fortunately it is easy to discover.

A visit to the doctor, or even to the pharmacy will make a reading available, and if you are concerned, an automatic cuff is available for $20. A healthy lifestyle and weight Will help prevent and treat hypertension, as in so many other chronic conditions.

A variety of medications are available to treat hypertension, but ANY MEDICATION CAN PRODUCE SIDE EFFECTS. It is rare for an effective medication to produce only a single, desired effect on the body. I have never known a person who at some time did not experience some side effect from antihypertensive medications.

Be sure to maintain contact with your Doctor. The dose may be too high, causing episodes of LOW blood pressure with fainting. When I was in practice, any number of patients came to me with a chronic cough, which I “cured” by having their doctor replace their ACE Inhibitor with another medication.

Please read the accompanying Mayo Clinic article for a complete discussion of this important condition.

–Dr. C.

Mayo Clinic article