Tag Archive for: cytokines

How Can Advanced Prostate Cancer Care Barriers Be Overcome?

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How Can Advanced Prostate Cancer Care Barriers Be Overcome? from Patient Empowerment Network on Vimeo.

How can barriers to advanced prostate cancer care be overcome? Expert Dr. Isaac Powell from Karmanos Cancer Institute discusses medical mistrust in the African American community and advice he gives to patients about prostate cancer screening and prevention.

See More from [ACT]IVATED Prostate Cancer

Related Resources:

Advanced Prostate Cancer Outcomes: Addressing Disparities and Exploring Solutions

Advanced Prostate Cancer Outcomes: Addressing Disparities and Exploring Solutions

How Can Advanced Prostate Cancer Disparities Be Reduced?

 Are There Worldwide Links to Aggressive Prostate Cancer?

Are There Worldwide Links to Aggressive Prostate Cancer?

Transcript:

Lisa Hatfield:

Are there any challenges unique to minority communities that hinder access to advanced prostate cancer treatments and therapies? And do you have thoughts on how these barriers can be effectively addressed?

Dr. Isaac Powell:

I do. First of all, the diagnosis has to be made. And so that’s made by screening, by the PSA testing and digital rectal exams. Now, some people are talking about, well, we don’t need to do the digital rectal exam. That absolutely is not true. You can have a very aggressive cancer and have a normal PSA. We know that the PSA is not 100 percent accurate in diagnosing, predicting that you may have prostate cancer sometimes.

And I’ve had several patients who had normal PSAs, abnormal rectal exams, and as a result, I’m biased with them. If you don’t do the rectal exam and you have a normal PSA, you may miss aggressive cancers. So definitely have your usual rectal exam, excuse me. And once after that, if you have a biopsy, and if it is positive, then again I think that aggressive therapy is the way to go, if you’re in good shape.

Now, people are afraid of cancer. I mean, afraid of surgery. I’ve had surgery, so I can talk to them about what I’ve had and what you go through. Men are also concerned about losing their sexual function and those kinds of things related to the treatment of prostate cancer. And I can tell them that the quality of life is okay after that because we have ways of treating sexual dysfunction, the pill that everybody knows about, as well as injection and penis and ultimately the penile prosthesis. So that can be fixed.

And the other issue of losing control of the urine, that can be fixed as well. And so those are the things I tell people about not specifically among African Americans. There’s the genetic and the biology that I have to discuss, but one of the things that drives these genetic cells is obesity.

Obesity can produce these pro-inflammatory cytokines. So I always advise them to, if they are obese, to reduce their weight and their fat, particularly belly fat. That’s challenging because people have difficulty losing weight. The other thing is exercise. Exercise is a key that I think it is the most important factor in treating many health conditions, exercise. And what exercise does, and this has been studied in breast cancer, it decreases the expression of the genes that I described earlier. In terms of prior driving the cancer and breast cancer, they’ve found it decreases the pro-inflammatory cytokines. I described the tumor necrosis factors IL-6 and IL-8. So that’s important, exercise. So those are the things that I tell patients. And now in terms of advanced disease there are clinical trials that are there.

And we do these trials to decide what’s the best treatment for cancer, even though we don’t have “a cure.” Now, the problem among African Americans is that they don’t trust these clinical trials because of the abuse that African Americans have suffered through slavery and all the other kinds of things when they’ve been treated as less than human, like animals being operated on without having any anesthesia and many other abuses that have occurred. And so there’s this major distrust now that’s very difficult to eliminate in the Black community, especially if there are very few African American doctors to take care of them. So what I think that we have to fix that question of distrust, and that’s going to take a while, but I talk to them always about this mistrust issue, because I can’t see everybody, although we do need more African American doctors and nurses to take care of them and to encourage them to participate in clinical trials and to be seen as a person who is going to be taking care of them in clinical trials, that’s very important.

Often we talk about access to care, but particularly African Americans that mostly live in large cities where there is access to care. But, in terms of one particular example that’s brought up on occasion is what has occurred in Baltimore and other big cities where I talk to an African American, you know Johns Hopkins is right in the middle of the African American community. So it’s not about access again, it’s about mistrust. And I said, “Well, why don’t African Americans go to Johns Hopkins?” Well, she says, “If you walk past Johns Hopkins, they may steal your bodies.” I said, what? I didn’t believe that, but I’ve been reading literature, particularly one called the Medical Apartheid where they talked about African slavery, where they dug up the bodies of slaves to practice the anatomy.

And so that’s where this idea occurred. At night, they would dig up the bodies and do this, and not only in Baltimore, but other cities as well. So again, the mistrust issue is very difficult to resolve because of those issues. And people talk about that, well, I just don’t trust the white healthcare system, period. And don’t want to go until they’re having symptoms, and then they have no choice. They have to go. And by this time, the cancers are more advanced and cannot even prolong life expectancy in those particular patients. So I’m not sure I answered your question in terms of what a person or what I would do to activate participation in the healthcare of advanced disease.

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Do Prostate Cancer Genetics Differ in African Americans?

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Do Prostate Cancer Genetics Differ in African Americans? from Patient Empowerment Network on Vimeo.

Do the genetics of prostate cancer vary in African Americans? Expert Dr. Isaac Powell from Karmanos Cancer Institute discusses what research has shown about gene expression and what occurs in the body in African Americans versus European Americans.

[ACT]IVATION TIP

“…patients need to take charge by asking questions about the therapy. Again, ‘is it going to cure me, and is the chemotherapy going to cure, immunotherapy going to cure? If not, how long do we think that I will live?’ That’s a good question, that I’d like to know if I were a patient.”

See More from [ACT]IVATED Prostate Cancer

Related Resources:

How Can Advanced Prostate Cancer Disparities Be Reduced?

 How Can Prostate Cancer Disparity Gaps Be Overcome?

How Can Prostate Cancer Disparity Gaps Be Overcome?

 Advanced Prostate Cancer Outcomes: Addressing Disparities and Exploring Solutions

Advanced Prostate Cancer Outcomes: Addressing Disparities and Exploring Solutions

Transcript:

Lisa Hatfield:

So, Dr. Powell, I just read a bit about your really impressive research, particularly with regard to the biology and genetics of prostate cancer. Can you provide an overview of your research focus on how prostate cancer impacts African Americans in comparison to other ethnic groups?

Dr. Isaac Powell:

Yes, I would certainly love to do that. In 2010, we found that the cancer grows faster among African Americans compared to European Americans. And those are the terms we use now, as opposed to Black and white. In science, we use those terms. And so at that point, I thought that this may be driven by the genetics and biology. So in 2013, we used what now has been considered the artificial intelligence.

We use bioinformatics, which is computational biology, and gene interactive and network analysis to evaluate the cancer tissue. And so at that point, we identified, and we asked the question, are there genetic differences between African Americans and European Americans? And what they found were driver genes, driver genes being the genes that drive the cancer, that make the cancers carry out a function, a mechanistic function, as opposed to passenger genes that are just associated with the cancer, just as in a car, the driver is the one that controls the car, the passenger sits there. These passenger genes, yes, they’re associated with aggressive cancer, but they have minimal or no function. The driver genes are the ones that are controlling the cancer, the function mechanism of the cancer progression. And so we identified in our analysis 21 genes that were different between African Americans compared to European Americans, different in terms of the expression of the disease, not different genes, but different expression of the genes.

What we found is that African Americans have a greater expression of inflammatory genes and transcript genes. And I’ll be more specific about that in a moment. Whereas European Americans had a higher expression of lipid metabolism genes. Those are genes that are associated with fatty acids as well as unsaturated fatty acids, specifically omega-6 as opposed to omega-3. But there is a connection between these two gene interactions at one particular molecule called tumor necrosis factor. And this gene then interacts with both the lipid metabolism genes as well as other inflammatory cytokines. And the genes that we found that were more specific in among the inflammatory genes were the pro-inflammatory cytokines, and those were IL-6 tumor necrosis factor, IL-8, and IL-1B as well as CXCR4.

These are what are called pro-inflammatory cytokines and chemokines. And they carry out functions that cause the cancers to invade. First of all, the cancer initial is cancer cells are stuck together. We call them adherent. They have to come apart before they can spread and go elsewhere. Well, these genes cause that it’s called epithelial mesenchymal transition. And once that happens, they’re capable of being transferred to distant sites such as the bone. And they also cause increased blood flow to the cancer. They also cause the oxidative stress that is driven by a molecule called reactive oxygen species.

And we’ll come back to that particular molecule because that’s important. Once it causes the oxidative stress, this causes DNA damaged repair genes to develop as well as mismatch genes. This mismatch means there are gene molecules that are stuck together, and there is an order. This order is upset by this particular oxidative stress, and those are mutated once they are repaired, and they impact on the mitochondria, which is a molecule in the cell nucleus that controls the chemistry of the cell.

And then this activates cancer stem cells, which is really important. And this is where we are going now with the cancer research. So TNF, the tumor necrosis factor IL-6 and IL-8, and the IL means interleukins. That’s what that stands for. They activate that pathway, the oxidative stress pathway. They also individually activate other pathways that lead to cancer stem cells. And I mentioned cancer stem cells because that’s the reason why chemotherapy and immunotherapy and all the drugs that we’ve used don’t work because the cancer stem cells undergo mutations and these mutations change the character of the cell. 

And that’s why the cancer cells resist that after a certain period of time, now these drugs will work and prolong survival, but they do not cure them because of the cancer stem cells. And so the cancer stem cells, in summary, are driven initially by the pro-inflammatory cytokines. So my research currently is to, well, how do we inhibit these pro-inflammatory cytokines? And that’s where we are now trying to develop a drug. We’re at the stage of mouse at this time, mouse biology and testing the drug in mice, not ready yet for human testing. So that’s where my research is headed, and I believe that that is going to work if the drug works.

Lisa Hatfield:

So just a follow-up question to that is, as a if I were a patient of yours or a family member, I might ask, so with your findings, do you think that this could lead to a cure, for example, for advanced prostate cancer?

Dr. Isaac Powell:

Yeah. I hate to use the word cure. The word I use is that we, our goal is to eliminate death from prostate cancer. That’s the term I prefer, because when we talk about cure, we have to know what causes it in order to really be certain as we are curing it. Because I don’t know whether what we’re doing is going to eliminate death, but that’s our goal. So I don’t like to use the word cure, because that’s the magic word and everybody gets excited. So I don’t want to get people excited too soon. So that’s where I am with my research.

Lisa Hatfield:

Well thank you so much for that. And do you have an activation tip for patients for this question, Dr. Powell?

Dr. Isaac Powell:

Yes. I think that, again, patients need to take charge by asking questions about the therapy. Again, is it going to cure me, and is the chemotherapy going to cure, immunotherapy going to cure? If not, how long do we think that I will live? That’s a good question, that I’d like to know if I were a patient. In fact, I’ve had prostate cancer and bladder cancer, so mine was early, so we didn’t get into those kinds of questions. But I like to know whether is this going to be something soon or later? Nobody can tell you when you may pass away from any cancer. I never give a patient any time. If they ask me, “Well, am I going to live six months or three years?” I don’t know. Because everybody’s different. Everybody responds differently to these particular treatments. So, but ask the questions as specific as possible that you’d like to know about the treatments, because there are several treatments, and there may be many answers.

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Myelofibrosis Therapies in Clinical Trials | BET Inhibitors

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Myelofibrosis Therapies in Clinical Trials | BET Inhibitors from Patient Empowerment Network on Vimeo.

What are BET inhibitors? Dr. Lucia Masarova, an MPN specialist and researcher, explains what BET inhibitors are and discusses the role these therapies may play in the treatment of myelofibrosis.

Dr. Lucia Masarova is an MPN Specialist and Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Masarova.

See More from Evolve Myelofibrosis

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Is Stem Cell Transplant the Only Curative Option for Myelofibrosis?

Is Stem Cell Transplant the Only Curative Option for Myelofibrosis?

 Choosing a Myelofibrosis Treatment Plan | Key Questions to Ask

Choosing a Myelofibrosis Treatment Plan | Key Questions to Ask

 How Molecular Markers Affect MPN Treatment | Advances in Research

How Molecular Markers Affect MPN Treatment | Advances in Research

Transcript:

Katherine Banwell:

We’re starting to hear more about BET inhibitors. Could you explain what they are and how they work to treat myelofibrosis? 

Dr. Lucia Masarova:

BET inhibitors are abbreviations for bromodomain inhibition, which is a very relevant regulator of transcription factors that play a significant role for making the blood cells.  

So, just differentiation of red cells or platelets, as well as very significant role in cytokines regulation. We know that myelofibrosis is a disease that is defined by overactive JAK-STAT Pathway that ultimately leads to increased cytokines.  

However, there are other pathways that play a significant role, and one of the very major ones is NF-kB, where the BET inhibitor come in play because they target it and help us to decrease the cytokine load as well as alter the differentiational block that happens in the red cells or megakaryocytes or platelets in these patients. 

So, the combination of bromodomain inhibition, or even using it as a single agent on or after refractory I think is a very promising tool that excludes the only JAK inhibition that we’ve been developing for diseases and opens the door for combination strategies that we were so many years thinking through and trying to find out. 

This is really the most promising compound or way of altering the disease background that we can see.  

Immunotherapy: Which Myeloma Patients Is It Right For?

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Immunotherapy: Which Myeloma Patients Is It Right For? from Patient Empowerment Network on Vimeo.

Dr. Krina Patel, a myeloma specialist and researcher, explains how newer therapies, such as CAR T-cell therapy, are being used in myeloma and which patients these treatments are most appropriate for.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. Learn more about Dr. Patel, here.

Related Resources:

How Does Immunotherapy Treat Myeloma?

 What Are the Side Effects of Myeloma Immunotherapy?

 Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings

Transcript:

Katherine:   

Now, in reference to immunotherapy and CAR T-cell therapy, who are these types of treatments right for?

Dr. Patel:    

So, I think it’s really exciting that we finally are getting standard of care therapies for all these new immune therapies. So, our first CAR T for myeloma got approved a little over a year ago. Our second CAR T got approved just a couple of months ago, and we’re hoping our first bispecific will be approved in just a couple months.

Our fingers crossed. On the clinical trials, I will say our patients who had a good performance status, meaning they’re able to do everything else normally life-wise, those are the patients that got onto those clinical trials; and the reason is safety-wise.

So, T cells when we use them to kill myeloma, they release cytokines or enzymes, you can say, that are inside the T cells and that’s what they use to communicate with other immune cells to come help them kill.

Those are the same cytokines that make people feel really ill when they have the flu, for instance. So, as our immune system tries to fight infections when people get fevers, they feel chills, they feel just fatigued and tired, it’s those same kind of cytokines that, even when you try to kill the myeloma with T cells, people can get that same type of symptoms.

And really, the main, fevers and things like that, we can take care of. But when patients’ blood pressure drops or if their oxygen levels drop really low, that’s where we can run into some trouble. Now, the good news is, in myeloma, most of these new therapies don’t cause really bad CRS [Cytokine Release Syndrome] or really bad neurotoxicity that we can sometimes see. And so, thankfully most patients are okay, but really it’s making sure that none of our patients have bad toxicity. So, most of our myeloma patients, I will say, are eligible for these therapies. However, if someone has really bad heart disease or really bad lung disease, those are patients that maybe these are not the right therapies for.

Empowerment Tools for Nurturing Your Health During Stress

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The pandemic has distorted our livelihood and forced many of us into teleworking whether we were willing or unwilling. We’re plastered to our computers not just in the home office, but at our kitchen tables, or on the bed. We find ourselves having to make adjustments on a regular basis. Responsibilities may have been added to your already hefty plate. Your new work environment may not be favorable. Maybe you simply can’t concentrate. We just can’t seem to escape the pings and alerts from work colleagues. Working from home is new to many of us. However, the concept of work-life balance is not. Yet, instead of home being a sanctuary, it has become a boundless environment for work and stress. Through this journey, we can relearn what work-life balance is, and how intervening factors like stress meddle with our body and mind. We can learn the value mindfulness has in creating boundaries that benefit our health and productivity, and be empowered with tools to build and sustain our immunity.

In the moments we’re experiencing stress we don’t stop to think about the effects it can have on our mind, body, and soul. Being overworked, getting familiar with remote working conditions, or trying to make child-care arrangements can be awfully difficult during a pandemic (Harnois & Gabriel, 2002). Stressors such as these can drive workers into depression, cause sleep disorders, body aches and headaches, and lead to other short- and long- term effects. Job-related stress can affect our immune system by lowering our resistance to infections. Brace yourself, we’re about to hop on the science train, but only for a few stops so you’ll be fine.

Who turned off the lights?

Stress flips the switch on the central nervous system causing it to go into defensive mode (Han, Kim, & Shim, 2012). The body reacts in efforts to regain homeostasis or regain balance. As previously mentioned, stress has the ability to cause depression, sleep disorders, body aches, and a lower immune system. Did you know that stress, sleep, and immunity are related (Han, Kim, & Shim, 2012)? Small immune signaling proteins called cytokines aid in regulating sleep. When these proteins fail to perform properly due to stress, this interrupts phases of sleep. When experiencing this stress, an irregularity in the secretion of the hormone Cortisol occurs.

Depression is a common and complex disorder with the ability to affect your daily life including work and productivity (National Institutes of Health, 2016). The hippocampus, amygdala, and the prefrontal cortex are three parts of the brain that seem to have major roles in depression (Cirino, 2017). When we experience depression, Cortisol secretion increases causing chemical imbalances which can lead to the reduction of brain cells (neurons). In a Korean study published in Stress and Health, individuals who experience work-related stress are at a higher risk of experiencing major depressive issues (Lee, Joo, & Choi, 2013). Symptoms associated with work-related stress include a reduction in the ability to concentrate, fatigue, insomnia, and feeling counterproductive.

An increase in proinflammatory cytokine levels can cause inflammation within the body (Leonard, 2010). This can lead to major depression followed by type 2 diabetes and other inflammatory diseases. Cytokines are involved with adaptive immunity and have been linked to COVID-19 infections (Costela-Ruiz, Illescas-Montes, Puerta-Puerta, et al, 2020). Weakened immune responses have been linked to patients with comorbidities. While the available information regarding COVID-19 is ever changing, what we do know is severe pre-existing conditions, including pregnancy, are linked to weakened immune responses placing these individuals at a higher risk of contracting the virus.

Road to Redemption.

Now that we have a better understanding of stress, learn to set your boundaries to alleviate it. Establish boundaries in all aspects of your life, especially with work. This ensures that your needs and your health are placed at the forefront. Think of them as safeguards for yourself. As difficult as it may be to establish them, understand that they are without question essential for your efficacy in and out of work. Working without boundaries is when stress raids the mind, body, and soul creating an imbalance. Here are a few practices to reclaim your balance: be mindful, create a workable workspace, listen to your body, reevaluate your time, say no.

Being mindful is having that ability to find calm in times of chaos. Be conscious and aware of the moment, relax, and BREATHE. Only you are in control of you. This is a type of meditation that can be implemented in your daily life at any moment. Let’s take a few moments to practice. Stop what you’re doing, turn off the TV, put your laptop to the side, get comfortable, and gently close your eyes. Take a deep breath in, then slowly exhale. If you hear noises, leave them be, continue to breathe. Do this for about 5 minutes. This practice is to help you find your calm, clear your mind, and become hyperaware. This method of nurturing your mind and body has the ability to mitigate stress, anxiety, improve sleep, and improve attention (Mayo Clinic, 2018). There are many practices for mindfulness which can be found on the Complete Guide to Mindfulness.

We are no longer in our offices or confined to our cubicles so we must create workable workspaces, and implement our boundaries. Yes, your new comforter was just shipped from Amazon, but allow the bed to be a place for rest not work. Create a space to enhance productivity yet allow comfort. Here are tips to transform a section of your home into a conducive workspace:

1. Invest in a quality chair and desk/or small table

  • Maintain good posture. If you feel yourself slouching, readjust or move around We want to avoid body aches, so listen to your body. Be aware of its needs.

2. No desk?

  • Use the kitchen table or counter, a coffee table (make sure you have some sort of back support).
  • If you must use your bed because your room is the only place of silence, ensure your bed is made. Sit on top of your new comforter with your back against the headboard

3. Good lighting is a must.

 

4. Keep your workspace organized using bins and folders

  • Disorganization is distracting, limits movement, affects motivation, reduces your performance, and shows lack of control (Roster & Ferrari, 2019).

5. Do not let work leave your workspace. The rest of your home should be designated a non-working area.

Listening to your body is an aspect of creating boundaries. Do not let work interfere with your health. Know when to get up to stretch, grab water, have a snack, or take lunch. If you must, inform your team of the time you will take lunch daily. Having good nutrition is the first thing that will ensure we’re energized and healthy. Instead of ordering something to go for lunch, try meal prepping. Use Sunday as the day to prepare and organize your meals for the week, including your snacks.

Restock on the elderberry! Since we’re all being hyperconscious of where we venture in the world, incorporate things to boost your immune system such as Emergen-C and elderberry. Elderberry is a substance extracted from the elder tree which many use as a dietary supplement to help boost their immune system. It can be consumed in the form of syrup or even gummies. Disclaimer, before the use of any dietary supplement it is best practice to consult your healthcare provider.

Reevaluate your time. You may find that during this time you have accumulated more than 40 hours a week. It’s fine to work additional hours sometimes, but this takes away time from caring for yourself. It interferes with your work-life balance. Although we’re home, this shouldn’t equate to extra time to tap on computer keys. Reevaluating your time takes a level of mindfulness to understand the importance of taking care of you: your mind, your body, your soul.

Saying no can be difficult, especially to a loved one or your boss. However, you should listen to your mind, be aware of what you are capable of, and respect your time. Knowing when to say no in some respects may be less difficult than others. Saying no is powerful. It is the ultimate boundary we can create for ourselves and it is okay.

Our fight with this global pandemic has yet to near the end. If we are equipped with the tools to tackle our stress and adjust as needed, we may be equipped to continue our lives teleworking. We have learned to understand the deteriorating effects stress has on our health. It can disrupt sleep patterns, make us susceptible to depression, and weaken our immune systems. Each one of these conditions are tightly tied together by stress which we must keep unbound. However, the tools to reclaim our balance will aid us in this situation. Being mindful, creating the awareness we need to breathe and focus for productivity in work and life, will assist us in creating needed boundaries. Whether these boundaries are centered around a conducive workspace, listening to our bodies, reevaluating our time, or simply saying no, it is a necessity to properly control and lessen the amount of work-related stress we experience in these crucial times.

References

Cirino, E. (2017). The effects of depression on the brain. https://www.healthline.com/health/depression/effects-brain#1

Costela-Ruiz, V. J., Illescas-Montes, R., Puerta-Puerta, J. M., Ruiz, C., & Melguizo-Rodríguez, L. (2020). SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine & growth factor reviews, S1359-6101(20)30109-X. Advance online publication. https://doi.org/10.1016/j.cytogfr.2020.06.001

Han, K. S., Kim, L., & Shim, I. (2012). Stress and sleep disorder. Experimental neurobiology, 21(4), 141–150. https://doi.org/10.5607/en.2012.21.4.141

Harnois, G. & Gabriel, P. (2002). Mental health and work: impact, issues, and good practices. https://www.who.int/mental_health/media/en/712.pdf

Lee, J., Joo, E., & Choi, K. (2013). Perceived stress and self-esteem mediate the effects of work-related stress on depression. Stress and Health, 29(1), 75–81. https://doi.org/10.1002/smi.2428

Leonard B. E. (2010). The concept of depression as a dysfunction of the immune system. Current immunology reviews, 6(3), 205–212. https://doi.org/10.2174/157339510791823835

Mayo Clinic (2018). Mindfulness exercises. https://www.mayoclinic.org/healthy-lifestyle/consumer-health/in-depth/mindfulness-exercises/art-20046356

National Institute of Health (2016). Depression basics. https://www.nimh.nih.gov/health/publications/depression/index.shtml

Roster, C., & Ferrari, J. (2019). Does Work Stress Lead to Office Clutter, and How? Mediating Influences of Emotional Exhaustion and Indecision. Environment and Behavior, 1391651882304–. https://doi.org/10.1177/0013916518823041