Direct and indirect approaches to fight cancer (first appeared in The Norwalk Patch)

Cancer– a group of at least 200 disease forms and many more subtypes – wreaks havoc in the human body through uncontrolled growth of cells. While debatesabout a suitable 21st-century-definition continue (to avoid over-management of these conditions), it is clear that genetic surveys inform the diagnosis and treatment of many cancers. Catalogs such as The Cancer Genome Atlas, funded by the National Cancer Institute and National Human Genome Research Institute, have informed the understanding of diverse tumor characteristics.

However, the atlas may only have revealed 1/10th of the needed genetic information e.g., researchers estimated that they would need 100,000 samples to find most genes involved in the 50 most common types of cancer. Structural features of each tumor may also hamper the search for effective cancer-fighting therapies. According to Dr. Rakesh K. Jain, director of the Steele Laboratory for Tumor Biology at Massachusetts General Hospital and author of a Scientific American article [1], blood vessels constricted by a tumor constituent or matrix could retard the dispersion of potentially lifesaving medications throughout the neoplasm. Preclinical studies from his laboratory showed that depleting the matrix with a blood pressure medication could improve the perfusion of anticancer drugs in a neoplasm and improve survival rates [1]. Researchers are currently investigating angiotensin inhibitors as matrix-depleting agents combined with chemotherapy in patients with pancreatic ductal adenocarninoma (the fourth leading cause of cancer deaths in the United States) [1, 2]. Should the results bear fruit in the future, Dr. Jain envisions that treatment may consist of targeted cancer cell-killers, vessel-normalizing drugs, and matrix-depleting agents. Patients unable to take anti-hypertensives may potentially also benefit from alternative agents attacking other abundant tumor constituents. Ultimately, laboratory tests could be employed to measure the response of the matrix to different test agents [1].

Cancer researchers are in the midst of exploiting genetic and physical information to understand the etiology of diseases that are increasingly affecting poor- and middle-income countries. Hopefully the global toll of 8.2. million deaths in 2012 could be slowed with these approaches.

References

1.  Jain, R.K., An indirect way to tame cancer. Scientific American, 2014. p. 48-53.

2.  Hezel, A.F., et al., Genetics and biology of pancreatic ductal adenocarcinoma.Genes & Development, 2006. 20(10): p. 1218-1249.

 

Cancer immunotherapy (first appeared in The Norwalk Patch)

Effective immunotherapy i.e. enlisting the patient’s own immune system to fight disease may mark a milestone in the fight against certain cancers. Three lymphocytes – T cells, B cells and NK-cells – involved in specific immune responses against cancers and other diseases. T cells recognize specific antigens via a T-cell antigen-receptor. The two main types of T cells, CD4- and CD8 T-cells, are categorized according to their respective CD4 and CD8 surface markers. The latter group includes cytotoxic T cells, also known as killer T lymphocytes. These cells kill invading pathogens or other disease-causing agents. Scientists discovered that a type of protein receptor, cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), prevented T cells from launching immune attacks [1]. In the early 1990s, another “brake” was discovered in dying T cells namely programmed death 1 or PD-1. The rationale underlying cancer immunotherapy is that exposing CTLA-4, PD-1 or using other appropriate immune-system-based therapies may enable the release of the immune system to destroy cancer.

Genetically engineering a patient’s T cells to target tumor cells marked one of the promising turning points in cancer immunotherapy. A research group from Memorial Sloan Kettering Cancer Center reported last year that T cell therapy ( chimeric antigen therapy [CAR]) in their studies put 45 of 75 adults and children with leukemia into complete remission, although some relapses were occurred at a later date [1]. Researchers from other institutions have reported promising resultssuch as tumor regression with advanced melanoma. The hope, according to Dr. S. Rosenberg, is that CAR T cell therapy may eventually “become the standard of care for B-cell malignancies” like acute lymphoblastic leukemia and chronic lymphocytic leukemia.

For some patients with metastatic disease, cancer immunotherapy may offer a chance, although researchers have yet to figure out why the treatment works in some patients and not in others. In addition, there are side-effects such as the release of signaling proteins regulating interactions between immune cells, also known as cytokines. Cytokine-release syndrome can be mild and therefore treatable or the rapid and massive release of these molecules could lead to declines in blood pressure and debilitating fevers.

Nevertheless, buoyed by promising results, scientists are turning their attention to developing engineered T cells for other cancers, including pancreatic and brain tumors.

Source

1.   Couzin-Frankel, J., Breakthrough of the year 2013. Cancer immunotherapy.Science, 2013. 342(6165): p. 1432-3.

Thomas Young and Vladimir Nabokov

Occasionally I intend to post stories that are unrelated to the main topics in my book, but reflect one of my other passions i.e. history. This is a post that first appeared in The Norwalk Patch:

To many scientists the words “interdisciplinary research” refer to cross-fertilization of ideas and experiments within subcategories of their chosen field, or collaborating with clinicians, engineers, and physicists. Usually, when scientists strayed into areas of music, film, and literature, or when artists strayed into science, it was within the framework of communicating the latest discoveries to laymen or using creative images to transmit the impact of the latest breakthroughs. Another possibility is simply demonstrating the beauty of nature for its own sake. By and large, the motto seems to be “to each his own.”

History has provided us with figures that break the traditional mold, either in the breadth of their scientific expertise or by their achievements in the seemingly separate worlds of science and literature. Thomas Young, an English polymath (1773-1829), is an example of the former, and Vladimir Nabokov, a Russian-American author (1899-1977), is an example of the latter.

Nabokov is, of course, widely known for his novel, Lolita, composed while on butterfly collecting trips in the western United States. He combined teaching “all things Russian” with his interest in lepidoptery at both Wellesley College and Harvard University. Harvard students may be familiar with Nabokov’s collection of male butterfly genitalia stored at the university’s Museum of Natural History and his expertise in microscopic comparisons of these specimens. Several butterfly and moth species, as well as the genus Nabokovia were named in his honor.

Thomas Young broke boundaries in many areas of science. He established the wave theory of light, overcoming a century-old view that light was a particle—an assessment made by Sir Isaac Newton. The roll call of his achievements includes founding the field of physiological optics, establishing the theory of capillary phenomena based on the principle of surface tension as well as related equations, making contributions to haemodynamics, medical writings on consumptive diseases, and developing a rule for children’s drug dosages. Young’s interest in Egyptian hieroglyphics was evidence that this genius did not only confine his mind to scientific matters. His publication,Account of the Recent Discoveries in Hieroglyphic Literature and Egyptian Antiquities, may have influenced the Frenchman, Jean-François Champollion, who deciphered the Rosetta Stone.

Although Young and Nabokov were completely different in terms of temperament, interests, and accomplishments, one might argue that both flourished as creative individuals because interests and success in one field stimulated success and further accomplishments in other areas. Stephen Jay Gould, noted paleontologist and essayist, held an alternative view that may apply to both Nabokov and Young, namely, success in science and other fields may be rooted in a love of detail, contemplation, and symmetry.

References:

http://en.wikipedia.org/wiki/Thomas_Young_%28scientist%29

http://en.wikipedia.org/wiki/Vladimir_Nabokov

Diabetes and pernicious anaemia (Appeared 2013 in The Norwalk Patch)

The Pernicious Anaemia Society members will already be familiar with Martyn Hooper’s book,”Pernicious Anaemia: the Forgotten Disease – the causes and consequences of vitamin B12 deficiency”(1). Briefly,  a complicated immune orchestra destroys cells in the stomach lining, increasing gastric pH, allowing bacteria (normally suppressed by low pH) to thrive, to possibly interfere with absorption of indispensable micronutrients, including vitamin B12 (2). The net result of progressive inflammation is the severe form of vitamin B12 deficiency, pernicious anemia (PA).

What happens when this misguided attack on the stomach lining is accompanied by a a second autoimmune/comorbid disease attacking a different organ in the body? This prospect is increasingly likely, given the rise in chronic diseases in aging populations. Stomach problems that may occur concurrently with the insidious progression from autoimmune gastritis to PA, can sometimes be a clinical signal of damage to another organ tucked behind the stomach, i.e. the pancreas. The pancreas secretes insulin, a critical hormone, that assists the body in absorbing glucose and other nutrients from food. Insulin and its precursors are also targets for autoimmune attack, leading to Type 1 or “juvenile” diabetes, a condition affecting 5-10% (3) of all diabetics. Adult-onset or type 2 diabetes (more information can be found in the Diabetes Portfolio [4]), which accounts for 90% (5) of all diabetic cases, occurs as a consequence of insufficient insulin production or resistance of the body’s tissues to normal or higher amounts of this hormone.

While PA is thought of as an under- or misdiagnosed disease (present in up to 2% of the general population) (6), for a variety of reasons,2 the number of known diabetics total more than 371 million across the globe (7). Autoimmune gastritis and PA are increased up to 5-fold in Type 1 diabetics (6). Moreover, metformin, a popular, oral antidiabetic medication, may contribute to vitamin B12 deficiency (8). These points underscore the need for a holistic approach in the management of PA and co-occurring illnesses.

References

1.   Hooper M. Pernicious Anaemia: the Forgotten Disease – the causes and consequences of vitamin B12 deficiency London: Hammersmith Health Books; 2012.

2.    Neumann WL, Coss E, Rugge M, Genta RM. Autoimmune atrophic gastritis-pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol. 2013.

3.     Apple J, Aviad Mea. ASweetLife-Diabetes. 2013; http://asweetlife.org/diabetes/. Accessed July, 2013.

4.      Nackerdien Z. Diabetes Portfolio. 2013;http://znacke1.wix.com/diabetesportfolio. Accessed July, 2013.

5.       International Diabetes Federation. Types of Diabetes. 2013;http://www.idf.org/types-diabetes. Accessed July, 2013.

6.       De Block CE, De Leeuw IH, Van Gaal LF. Autoimmune gastritis in type 1 diabetes: a clinically oriented review. J Clin Endocrinol Metab. 2008;93(2):363-371.

7.        International Diabetes Federation. IDF  Diabetes Atlas. 2012;http://www.idf.org/diabetesatlas/5e/Update2012. Accessed July, 2013.

8.        Warner J. Peripheral Neuropathy Patients Who Take Diabetes Drug May Have Vitamin B12 Deficiency. 2009; http://diabetes.webmd.com/news/20090608/metformin-linked-to-b12-deficiency. Accessed July, 2013.

Diabetes and Alzheimer’s disease

Information in this 2013 post (first published in The Norwalk Patch) continues to be relevant today.

Diabetes

Look around you and it seems as if the “healthy body, healthy mind” campaign is in full swing. Adherence to the latest health and fitness mantrasmay seem impossible to people coping with a sluggish economy, a confusing healthcare reform process and their own aches and pains. However, the latest epidemiology data from the International Diabetes Federation about this chronic disease [1] – which is linked to a host of other illnesses, including Alzheimer’s disease (AD) – may serve as an impetus to discard the fog of confusion in favor of pro-active health maintenance. An estimated total of 382 million people had diabetes in 2013 and this number is anticipated to rise to 592 million by 2035 [1]. Additionally, North America and the Caribbean lead other global regions in terms of money spent on the disease [1].

Having a healthy body and mind may empower diabetics awaiting solutions to the American healthcare paradox. The public-health specialists, Elizabeth Bradley and Lauren Taylor, have described the paradox as follows: “American per-capita spending on health far exceeds that of any other country on earth, the results achieved fall well short of other nations that spend much less. This includes such basic measures as life expectancy, maternal and infant mortality, and infant birth weight, for example.” For diabetics focused on also maintaining a healthy mind, these words may sound ominous as they grapple with a national fear of getting AD.

Alzheimer’s disease

A 4-minute captioned video depicting the brain changes characteristic of AD can be viewed at the National Institute on Aging’s  website. While the animation illustrates the advances that has been made in the understanding of AD progression, it does not address the complexities involved in accurately diagnosing the disease, especially within the context of comorbid illnesses such as diabetes. Scientific evidence is accumulating that suggests a link between Type 2 diabetes and AD, the most common form of dementia and the seventh leading cause of death in this country. The data pointing to an association between AD and low brain insulin levels has led some researchers to refer to this dementia sub-type as Type 3 diabetes.

A middle-aged or older diabetic  (≥40 years old) exhibiting one or more AD warning signs is likely to visit a primary care physician. In the absence of a lifelong relationship with a trusted clinician, any patient and family caregiver(s) will have to provide comprehensive medical histories to numerous doctors in order to facilitate optimal AD management in the context of diabetes. This task – usually assigned to caregivers – may be daunting, since recall bias or the presence of significant memory loss may hinder the collection of information. Nevertheless, ascertainment of complete medical histories will aid in the differential diagnosis of AD. Patients and members of their care team also need to remain vigilant about the potential for misdiagnosis and its accompanying excess costs [2].

References

1.       International Diabetes Federation. IDF Diabetes Atlas, 6th edition. Brussels, Belgium: International Diabetes Federation, 2013. http://www.idf.org/diabetesatlas

2.       Jeffrey, S. The High Cost of Alzheimer’s disease Misdiagnosis, 2013.  Medscape Medical News from the Alzheimer’s Association International Conference (AAIC),  2013

Jack and Jill

Hi Everyone!

This is another one of my old Norwalk Patch stories that I thought readers might enjoy:

Robert Frost ended his poem,” Mending Wall,” with the famous line: “Good fences make good neighbors.” In today’s world, it could mean the difference between minding one’s own business or becoming absorbed in the reality TV-antics of one’s neighbors. We all have stories to tell to illustrate the point. One urban legend that I am perpetuating relates to Jack and Jill (the story usually becomes more colorful as time passes). Given my urban surroundings and the anonymity of today’s world, I should really have been unaware of Jack and Jill’s business. Unfortunately, the paper-thin, apartment walls and their late-night arguments that frequently woke me up, meant that I had a front-row seat to the inner workings of their dysfunctional relationship. The fights about money and cheating were fodder for a Jerry Springer show.  On nights when the volume of epithets reached epic proportions, I visualized the Springer audience shouting in unison:”kick him to the kerb.” That would be the course of action of any rational person, but love or co-dependency (call it what you will), rarely goes together with rational thought. Besides, in real life villains are rarely one-dimensional and situations are complicated. Jack was well-loved because he helped little old ladies and did handiwork without insisting on being paid. He also treated Jill to an occasional dinner on the patio or whisked her away for a weekend at the local casino. They were also sickeningly sweet with their public displays of affection. So Jill stayed with Jack for years. During the day I would nod my head and scurry by, fearful of getting dragged into the morass of their problems.

 

One day I woke up in the early hours of the morning. I could hear Jack on the phone. Was he drunk-dialing someone? No. Jill had gone out of town and he was confiding his inner thoughts to a long-lost relative. He sounded simultaneously happy and sad. Apart from catching up, he was also trying to figure out what had happened to his other siblings that were placed in different foster homes. His dream had been to become a rap impresario a la Jay Z, but that sputtered when the talent he had scouted opted for the joys of selling weed instead of entertaining hipsters in a night club. Now he spent his days cleaning the house, cooking or drinking between part-time jobs. I drifted off to sleep. It seemed the preferred option compared with listening to this drama.

 

Jill eventually dumped Jack. Or maybe it was vice versa? After all, there had been many prior occasions where Jill had actually begged Jack not to leave her. In any event, a slammed door and “I’m outta here” followed by the sound of a car engine, heralded the demise of that relationship. Romantics rejoice. Jill is now in a stable relationship. She finally found a quiet guy. They moved out and, in a modern-day twist to the fairy tale ending, they put a deposit down on one of those foreclosed homes that you can get at bargain basement prices these days. Mary J. Blige would approve. Jack has probably found another Jill and will be cooking up a storm for her to prove his love. Thankfully, the new neighbors are discreet and I am finally enjoying a good night’s rest.

My journey (related to diabetes)

Hi everyone!

One of my brothers died two years ago due to complications from Type 2 diabetes. That tragic event caused me to channel my inner nerd and write a series of public-health-related articles about the disease that can be found here: http://znacke1.wix.com/diabetesportfolio. After much soul-searching I also started drafting my first book, “The Heroine Next Door.” It is very gratifying to receive positive feedback and I am happy to report to interested readers that a second manuscript is in the pipeline.

Enjoy your day.

The human spirit (first appeared in The Norwalk Patch – a tribute to adventurer, Barbara Hillary)

The Hollies may have serenaded “The Air that I Breathe”, but polluted air can be detrimental to the lungs.  According to Kurt Straif, head of The International Agency for Research on Cancer’s section that ranks carcinogens, the risk of cancer (depending on location and level of exposure) was found to be similar to that of breathing in second-hand tobacco smoke. Add air pollution to other known risk factors predisposing individuals to lung cancer, and one begins to understand some of the possible reasons why non-smokers such as Dana Reeve, activist and wife of Christopher Reeve, perished from this disease. Treatment strategies have been outlined by the American Lung Association and recent discoveries on ways to break through cancer’s shield have led to the development of promising immunotherapies for lung and other cancers.

However, these facts may provide little comfort to a patient diagnosed with an illness that accounts for about 27% of all cancer deaths (American Cancer Society). An initial shocked reaction may eventually be replaced by proactive participation in disease management, scouring the Internet for newsworthy clinical trial results, and cooperating with the FDA to create better treatments for lung cancer. Survivors may also seek social support online via sites such as cancer.im. On the other hand, they could channel their inner adventurers and ski to the North and South Poles.

Lung cancer survivor, Barbary Hillary, decided to defy the odds and undertook these arduous Arctic journeys in 2007 and 2011. Barbara’s preparations and trip to the North Pole were vividly recounted in a 2007 USA Today article. Successfully crossing the same regions as the polar adventurers, Roald Amundsen and Ernest Shackleton, placed the retired African-American woman in a league of her own. Her tenacity in the face of medical challenges and age can serve as an inspiration to everyone.

The importance of literacy for peace and empowerment (and the impact of women)

An infographic from UNESCO (Institute for Statistics) spells out the importance of literacy for peace, development, poverty eradication, empowerment, health, and gender equality.  Approximately 776 million people in the world are still nor able to read or write. The situation is especially dire in the Muslim world, according to one report: 40% of Muslim world’s population unable to read or write: Study Thirty countries participating in the study reported that gender parity for adult literacy is estimated to be achieved in 2015. However, much more remains to be done. Dr. Bruce Wydick’s (University of San Francisco) infographic shows the ripple effect of educating girls in poverty.

female-literacy-infographic-large

Frederick Douglass and “Hide Thou Me”

I am re-posting this 2012 article (based partly on information obtained from the archives at The Norwalk Museum) in remembrance of Black History Month in the USA:

We have just celebrated Black History Month and it is therefore fitting to pay homage to Frederick Douglass (February 1818 – February 20, 1895) , an African-American social reformer and statesman who was the antithesis of the notion that slaves “did not have the intellectual capacity to function as independent American citizens.”

Wikipedia provides one with an overview of  his life, from his birth in Talbot County, Maryland to his successful escape across the Susquehanna River and final arrival in the house of the abolitionist, David Ruggles, in New York. His abolitionist activities, involvement in women’s rights, travels, fight for emancipation and suffrage during the Civil War years, role as a statesman during the Reconstruction era and writings (including his celebrated autobiography [Narrative of the Life of Frederick Douglass, an American Slave, published in 1845]) are cataloged online and in print at the Schomburg Center in Harlem, New York as well as at other locations. Schools, prizes, stamps and a bridge bear his name.

In today’s fast-paced, attention-deficit-prone world one could be forgiven for thinking of him as a bronze statue in a park or a remote historical figure of interest to only specific segments of society. However, even a cursory interest reveals glimpses of a charismatic man who defied the status quo in every possible way. After burying Anna  (his wife of more than four decades with whom he had five children) in 1882,  Douglass married a white woman, Helen Pitts (a graduate from Mount Holyoke College) in 1884. His response to the outrage at the time was that his first marriage had been to someone the color of his mother and the second had been to someone the color of his father.

It is in the yellowing pages of  the Norwalk Gazette dated 27 February 1895 that one comes across another facet of the man. Douglass apparently loved the hymn, “Hide Thou Me,” and sang it the day before he died. Part of the lyrics reads as follows:

Sometimes I feel discouraged

And I think my works in vain

I’m tempted oft(en) to murmur

To grumble and complain

But then I think of Jesus

And all he’s borne for me

Then I cry

Oh rock of ages

Hide thou me

Ohh rock of ages

Hide thou me

This was a powerful reminder how a hymn helped to sustain a former slave in his daily life and fight for disfranchised countrymen, just as it continues to strengthen peoples’ faith and resolve today.

Flipping back through the archived newspapers, it was interesting to note how Douglass was viewed through the prism of his own generation. Upon his death, the Norwalk Gazette of 23rd February 1895 felt the need to temper their effusive praise for Douglass by mentioning that he “lacked the scholarship” of a noted editor, Wendell Phillips, or the “masterful rhetoric” of the prominent American abolitionist, Lloyd Garrison.

However, in the vein of “a famous person passed through our town,” the article ended with a mention of Douglass visiting Norwalk a couple of times, where he was once the guest of Senator and Mrs. O.S. Ferry. The Norwalk Gazette redeemed itself with a moving description of the Douglass funeral on 27 February 1895. One could imagine being there as the train bearing his coffin entered Central Station in Rochester, New York. Throngs of people watched the funeral procession wound its way first to City Hall, where the body rested in state for several hours, and then to the Central Church, where the invocation was delivered by Dr. H. H. Stebbins. A male quartet sang his favorite hymn, “Hide Thou Me,” before the service concluded and Douglass was finally laid to rest.