Differences in Breast Cancer Cell Metabolism

            Breast cancer is a disease that affects 1 in 8 American women. In 2017, around 250,000 women will be diagnosed with breast cancer, and almost 41,000 of those women will die from the cancer (American Cancer Society, 2017). For those patients who die from breast cancer, the primary reason is because the cancer metastasized. Thus, trying to find therapies that prevent cancer from metastasizing is crucial. Health Minute (2017) reports on a new study that was published in Nature Communications discussing how breast cancer that metastasizes utilizes a different nutrient metabolism than non-metastasizing cancer cells. This is exciting because identifying the pathways by which the cancer cells metastasize can lead to therapies that prevent metastasis from occurring.  

            More specifically, the researchers identified proline as an important component of energy production. Elia et al. (2017) utilized 2D and 3D conditions, meaning that some breast cancer cells were grown in spheroids while others were grown as a monolayer. Cells in the 3D condition utilized protein catabolism more often than 2D cells using the enzyme proline dehydrogenase (Prodh). When Prodh was inhibited, there was less breast cancer metastasis in vitro. Prodh is important because it has been show to contribute electrons into the electron transport chain, helping to generate ATP. So it would make sense that cells that want to travel to different parts of the body would utilize an enzyme that helps produce more energy. However, the researchers note that the role of Prodh is more pronounced in early metastasis rather than in secondary tumors. Although this research found that proline catabolism is what drives metastasis, the researchers note that proline biosynthesis also seems to affect how the cancer cells progress. Thus, it is evident that more research needs to be done on proline metabolism and its role in cancer cells. Nonetheless, the authors believe that there research show lead to new therapies targeting Prodh.  

           Although this is promising research, it is clear that we do not have a full understanding of how proline metabolism works. If a compound were identified that could inhibit Prodh, it leads to the question of whether or not it is ethical to begin recommending clinical trials even though there is not a clear understanding of proline metabolism in cancer cells? Although these researchers have good intentions with wanting to find more therapies, would it do more harm than good for the patient? 

References:

American Cancer Society. (2017). How Common Is Breast Cancer? Retrieved December 03, 2017, from https://www.cancer.org/cancer/breast-cancer/about/how-common-is-breast-cancer.html

Elia, I., Broekaert, D., Christen, S., Boon, R., Radaelli, E., Orth, M. F., . . . Fendt, S. (2017). Proline metabolism supports metastasis formation and could be inhibited to selectively target metastasizing cancer cells. Nature Communications,8, 15267. doi:10.1038/ncomms15267

Health Minute. (2017). Nutrient metabolism that drives breast tumor metastasis. Health Minute . Retrieved from https://healthminute.org/2017/11/nutrient-metabolism-that-drives-breast-tumor-metastasis/

   

Is informed consent always required in research?

In the US, colon cancer is the third most common cancer and the second leading cause of cancer death. It usually affects men and women of all racial and ethnic groups alike, and is most common in people 50 years or older. Colon cancer is highly treatable when discovered early. It first develops as polyps (abnormal growths in the colon or rectum), but can become cancerous if not removed (medical news today, 2017).

The New England Journal of Medicine published a study regarding ethical issues and the overgeneralizations of research conventions, such as informed consent. A health system (name of health system not provided) has proposed to send birthday cards to patients when they turn 50 to promote colorectal screenings. The health system has three different reminder interventions and randomizes each patient to one intervention; however, since the word “randomization” is in play, should the IRB be involved in this study?

The three interventions implemented by this healthy system consists of 1) a whimsical card (“it’s your birthday, treat yourself to a colonoscopy”), 2) a birthday card with a prescheduled colonoscopy appointment, or 3) a usual message (control intervention). The health system is obviously conducting research by randomizing patients to different interventions with the hope of seeing a change in screening rates which can implemented in other healthy system; thus promoting justice. However, the IRB from this health system indicates that by not asking for permission, the patient’s rights not to participate is violated. Patients who turn 50 will be receiving a reminder from this health system anyways; therefore, the IRB insists on receiving consent from the patients.

The IRB is essential in protecting patient rights, but when the word “randomization” is used, it alarms the IRB to request consent. Asch et al., (2017), argues that the IRB is misdirected since the plan implemented by the health system does not involve more than minimal risk, the rights and welfare of subjects are not affected, and if patients were to consent, it would throw off the purpose of the research. Furthermore, the approaches are well-meaning, plausible, safe, and are consistent with clinical guidelines; thus, they are promoting the ethical value of beneficence. 

These regulations when conducting low-risk science studies, can make it difficult to do better science such as randomized studies which yield better results. Thus, it would leave scientist to rely on uncontrolled projects with pre-and post-evaluations which may not give accurate results of the general population. What is your opinion on the ethical issue? Should informed consent be required for low-risk science studies, such as the colorectal screening reminders?

References

Asch, D. A., Ziolek, T. A., & Mehta, S. J. (2017). Misdirections in Informed Consent - Impediments to Health Care Innovation. The New England Journal Of Medicine, 377(15), 1412-1414. doi:10.1056/NEJMp1707991

https://www.medicalnewstoday.com/articles/155598.php

https://www.ccalliance.org/get-information/what-is-colon-cancer/

Cruelty Free Beauty Products

Animal testing has roused much controversy between animal lovers and those who find it acceptable to test on animals for the safety of humans. Many beauty companies thus, have made a stance on such a controversial and ethical topic by making sure that their products are not tested on animals. This means that the cruelty-free labeled product has been certified to have not been tested on animals. Many consumers then, have also realized their “pocket power” and those who value the integrity of animals have decided to invest cruelty-free items, specifically when it comes to beauty products.

But what other kinds of testing are being done on these products? And how do these ensure the safety of beauty products for humans?

Cruelty Free International states here, that “Alternatives to animal tests are often cheaper, quicker and more effective”.They list types of alternatives including cell cultures, use of human tissues, and computer models. Yet, this still doesn’t necessarily simulate the comprehensiveness and cohesiveness of a living body in all cases. Cruelty free international also supports volunteer studies and human medical breakthroughs citing “An Australian doctor used himself in an experiment to discover the main cause of stomach ulcers. He drank a culture of bacteria and became sick before curing his symptoms with antibiotics.”

PETA lists here, human patient simulators as an alternative, but otherwise backs similar alternatives to Cruelty Free International.

In contrast, many of these techniques are still being developed and take time to develop, and beauty products are being sold and bought every day. Moreover, we still use animals as model organisms for scientific studies that have nothing to do with beauty.

What should be done?

"The Off Switch to Menstrual Pain"

Every month (or so), adolescent and reproductive aged females around the world have their period, and shed their endometrial uterine lining. An unfortunate side effect of this is often pain or cramps called Dysmenorrhea which is often also accompanied by other symptoms including vomiting, diarrhea and shaking or tremors.

Dysmenorrhea is thought to be caused by the excessive release of prostaglandins in the menstrual fluid, which causes uterine contractions and thus pain (this is also happens during childbirth). Elevated anti-diuretic hormone (ADH) levels have also been reported in many women with primary dysmenorrhea, which makes sense because increasing uterine contraction and pain can be a result of vasoconstriction.  

This condition is affecting the lives of between 20 and 90% of menstruating individuals and is the leading cause of recurrent short-term school absence in adolescent girls. Most women either suffer through the pain or take pain medication to relieve themselves, but one company has come up with a way to fix this problem so that neither of these are necessary. Livia is an FDA approved wearable menstrual pain relieving device that is said to stop the connection between the brain and endometrium via pulses that eliminate or reduce pain signals and registration by your body. Out of a clinical trial of 163 people, “80% of the women said that Livia allowed them to significantly or completely eliminate the use of pain medications” -Livia.

In description and function, this unit works exactly like a Transcutaneous Electrical Nerve Stimulation unit (TENS unit), which is usually used for pain derived from nerve related conditions. TENS machines work by sending stimulating pulses across the surface of the skin and along the nerve strands.

What do you think? 

References: 

Hong Ju, Mark Jones, Gita Mishra; The Prevalence and Risk Factors of Dysmenorrhea, Epidemiologic Reviews, Volume 36, Issue 1, 1 January 2014, Pages 104–113, https://doi.org/10.1093/epirev/mxt009

Link to Dysmenorrhea PDF: http://www.aafp.org/afp/2005/0115/p285.pdf 

3 Blind Mice

In the Gospel of John, disciples of Jesus see a blind man and turn to Jesus, asking if the man or his father had sinned to put him is such a decrepit state. According to the story, Jesus said that it was neither, and healed him of his blindness, which he declared a work of God. Whether you buy the story or not, it gives us insight into how marginalized those experiencing blindness have been in history. Unfortunately, physicians do not have the miraculous capabilities that Jesus was said to have, and so 2.3% of Americans still experience blindness.  However, many incredible steps are being made in science to try to understand the mechanisms behind blindness and use resources available in other species to cure human blindness.

           The National Institute of Health funded a study that took a protein from green algae and inserted it in the retina of blind mice. This specific protein (channelrhodopsin-2 or ChR2) is light sensitive and fires an action potential when exposed to light, helping the process of photosynthesis in green algae. However, when it is inserted into mice that are bread to be blind, it has incredible effects. Blind mice who undergo the ChR2 protein injection were suddenly able to complete visual behavioral tasks, such as following blinking light for a reward of food. Researchers determined that the majority of ChR2 treated mice received input into their visual cortex, when such input was absent prior to treatment.

            The implications of such research are huge, in that it makes a cure for blindness in humans seem much more attainable in the near future. Clinical trials have not yet been taken on, but The National Eye Institute (NEI), has voiced its desire to take research a step further and explore how more complex visual stimulus can be processed through similar mechanisms as the ChR2 treatment that mice experienced. Through their work, we might soon be able to tackle such huge and debilitating conditions such as blindness in humans.

https://www.nih.gov/news-events/news-releases/blind-mice-recover-visual-responses-using-protein-green-algae 

The Struggle to Maintain Maternal Health in the U.S.

Maternal health and medicine has advanced significantly over the years and global trends have shown that maternal deaths, defined as deaths due to complications from pregnancy or childbirth, continue to decrease. However, the U.S. is defying all odds: it is still one of the leading countries with a high maternal mortality rate, and the rate continues to increase. Multiple studies and analyses have shown that maternal mortality rates have increased overall, but especially for non-Hispanic black women. The U.S., one of many leading innovators in medicine, science, and technology, is still struggling to help women with their health and the question is, why? Furthermore, how can we move forward to help alleviate this social problem?

Experts have explored several reasons that might attribute to the high mortality rate in the U.S. First, researchers have hypothesized that the obesity epidemic may heavily contribute to maternal deaths. Obesity is linked with cardiovascular disease and diabetes that exponentially complicate pregnancy and childbirth. The lack of access to nutritional food and healthcare coupled with chronic stress could explain the increased risk of maternal death, especially those seen in communities of color. Second, researchers contributed the maternal mortality rate to the increase in age (45 years or older) that women became pregnant. However, they found that there was an increase in death rates among all age groups. Finally, people think the U.S. has a high rate of maternal deaths due to the fact that that there are more minorities and more economically disadvantaged people. Nevertheless, studies have shown that if the analysis was limited to white women, the U.S. still ranks behind other developed nations.  Despite the multifaceted complexities that are involved, the United States should invest resources into researching an issue that directly affects half of the population and to provide services that help women navigate their health and quality of life.

Women’s bodies, and thus their reproductive rights, is heavily regulated politically, legally, and morally. Everyone has a right to their opinions and beliefs; however, as we all have learned at Regis, we need to have a care for the whole person and to think about what we ought to do. This is an important topic for me to explore because I hope to have the opportunity to work with women in underrepresented communities, most notably women of color and women in rural communities, who historically have not had access to quality healthcare.  The challenges women face trying to obtain quality healthcare, especially regarding their reproductive health, is an ugly reality. It is our duty as future health care professionals and scientists to advocate for our patients and to explore new ways to improve their quality of life.

References:

Howard, Jacqueline. “Childbirth is Killing Black Women, and Here’s Why.” CNN, Cable News Network, 15 Nov. 2017, http://www.cnn.com/2017/11/15/health/black-women-maternal-mortality/index.html.

Tavernise, Sabrina. “Maternal Mortality Rate in U.S. Rises, Defying Global Trend, Study Finds.” The New York Times, 21 Sept. 2016, https://www.nytimes.com/2016/09/22/health/maternal-mortality.html.

Vaccinating Against Cancer: The Ethics of the HPV Vaccine

Cervical cancer is the 2nd most frequent cause of cancer-associated death in females worldwide, and the 14th most common cancer in the United States (Chattopadhyay, 2011). Approximately 0.6% of American women are diagnosed with cervical cancer within their lifetime (NIH.gov). Cervical infection with an oncogenic type of the human papillomavirus (HPV) is a necessary precursor in the etiology of cervical cancer in almost 100% of documented cases (Chen, Jiang, Shen, & Hu, 2011). One in four Americans, approximately 80 million, are infected with HPV. It is the most common sexually transmitted infection. Approximately 30,000 cases of HPV-associated cancers occur in the United States every year. In addition to cervical cancer, HPV is the cause of many vulvar, vaginal, throat, tongue, tonsilar, anal and penile cancers (White, 2014). HPV vaccination, in conjunction with an increase in worldwide cervical screening, can significantly decrease the future incidence and morbidity rates of cervical cancer. However, ethical concerns over the morality, safety, and efficacy of the HPV vaccine have stifled the uptake of the vaccine in comparison with other vaccines (Nicol et al., 2016).

The ideal time to begin the HPV vaccine series in both sexes is before the age of commencing sexual contact. Within three years of experiencing their first vaginal intercourse, 50% of sexually active females are infected with HPV. Half of those infected contract the virus within the first three months of initiation of intercourse (Chen et al., 2011). There are two FDA approved vaccines against HPV, Gardasil and Cervarix. These vaccines target persistent infections of oncogenic HPV-16 and HPV-18. Both approved HPV vaccines help prevent HPV infection in uninfected females, and Gardasil is approved to prevent HPV infection in uninfected males. The vaccines are only effective if administered prior to initial HPV infection. Even so, some parents are hesitant to vaccinate their children and some physicians are hesitant to strongly advocate that they do. As of 2017, only 63% of girls and 50% of boys in the target age are vaccinated (White, 2014). One argument against the vaccination of younger children is that vaccinating against a sexually transmitted disease may encourage sexual contact or promote high risk sexual practices. Given the vaccine is a proven method of preventing against infection of the strains targeted in the vaccine, the argument that the vaccine can prevent cervical cancer is far more persuasive than the counterargument to discourage pre-marital sex or high risk sexual practices (Nicol et al., 2016).

Other arguments against HPV vaccination include concerns over the overall safety and long-term efficacy of the vaccine. The research shows that the most common side effects are headache and soreness at the injection site. These common side effects pose very little risk to health. Reports of more severe side effects following vaccination are rare. The majority of studies show a positive risk-benefit from vaccination with minimal adverse effects on par with the administration of most childhood vaccines (Nicol et al., 2016). Even so, the long-term efficacy of the vaccine is still uncertain. Only time will tell if vaccinating adolescent males and females against HPV will reduce the occurrence of HPV associated cancers. The vaccines undoubtedly reduce the incidence of infection and without infection, the mutagenic events that cause HPV associated cancers will likely never occur. The almost complete effectiveness of the vaccine to prevent pre-cancerous lesions caused by the HPV oncogenic viral subtypes make the minor side effects reported in the majority of cases and the lack of time to prove long-term efficacy, worth the risk of vaccination (White, 2014).

Parents and physicians need to remain actively involved in the education process and continue to advocate for children. Parents ultimately retain the right to decide whether or not to vaccinate their children. However, parents look to the clinician for the recommendation, or not, to vaccinate. Therefore, it is imperative that independent research into the safety and long-term efficacy of the HPV vaccine continues and that physicians carefully educate parents on the benefits and risks of this vaccine that may protect their children from HPV associated cancers, even into adulthood.  

References

Chattopadhyay, Koushik. “A Comprehensive Review on Host Genetic Susceptibility to Human Papillomavirus Infection and Progression to Cervical Cancer.” Indian Journal of Human Genetics (2011): 132-144.

Chen, Xiaojun, Jie Jiang, Hongbing Shen, and Zhibin Hu. “Genetic Susceptibility of Cervical Cancer.”  Journal of Biomedical Research (2011): 155-164. NCBI. Web. 16 June 2016.

“NIH Fact Sheets: Cervical Cancer.” NIH.gov. National Institutes of Health. (2013).

Nicol, A. F., Andrade, C. V., Russomano, F. B., Rodrigues, L. L. S., Oliveira, N. S., & Provance, D. W. (2016). HPV vaccines: a controversial issue? Brazilian Journal of Medical and Biological Research, 49(5), e5060. http://doi.org/10.1590/1414-431X20155060

White, M. D. (2014). Pros, cons, and ethics of HPV vaccine in teens—Why such controversy? Translational Andrology and Urology, 3(4), 429–434. http://doi.org/10.3978/j.issn.2223-4683.2014.11.02