Tuesday, April 16, 2024

OVARIAN CANCER: A DIAGNOSTICIAN'S DIRECTIVE (R. Bard, MD)

OVARIAN CANCER AT A GLANCE: (NIH)

* Estimated New Cases in 2023: 19,710
* % of All New Cancer Cases:  1.0%
* Estimated Deaths in 2023: 13,270
* % of All Cancer Deaths:  2.2%
* (2013–2019) 5-Year Relative Survival:  50.8%

Rate of New Cases and Deaths per 100,000: The rate of new cases of ovarian cancer was 10.3 per 100,000 women per year. The death rate was 6.3 per 100,000 women per year. These rates are age-adjusted and based on 2016–2020 cases and deaths.   Lifetime Risk of Developing Cancer: Approximately 1.1 percent of women will be diagnosed with ovarian cancer at some point during their lifetime, based on 2017–2019 data. Prevalence of This Cancer: In 2020, there were an estimated 236,511 women living with ovarian cancer in the United States.


OVARIAN CANCER: A DIAGNOSTICIAN'S  DIRECTIVE
By: Dr. Robert L. Bard
[PDF DOWNLOAD] 

Ovarian Cancer continues to be identified as the "SILENT DISEASE" primarily due to its ability to remain undetected until it has metastasized. Often, metastasis goes to the liver and bones, starting off with a very small cystic area in the ovary. Ideally, we need specialized equipment that can show 3 and 4cm tiny cystic areas in an organ that normally has 2-3cm cysts where the mass often goes undetected. The way we accomplish this is to do high resolution ultrasound scans with 3D reconstruction and with Doppler blood vessel ultrasound imaging. Because a normal ovarian follicle cyst is clear and has no tumor vessels in it, we distinguish a benign normal ovulation cyst from a cyst that is suspicious and could grow or metastasize. We observe the lining of the cyst where a benign cystic area is smooth outside and inside, while a cancerous cyst has inner wall irregularity, thickening and possibly a serrated outside as well. More importantly, since tumor growth relies on feeding blood vessels we image the  vascular network with the same ultrasound probe that finds the suspicious cystic area. 


TREATMENT WITH IMAGE GUIDANCE
In 1980, my partner and I co-authored the first textbook on ultrasound of the pelvis, including gynecologic tumors. At that point, we could distinguish between a solid area and a benign fluid filled cyst. We were able to detect ovarian cysts (which are normal in the reproductive area). Technology continued to evolve with higher resolution scanning and 3D imaging 20 years ago that is used for scanning the faces of baby in the womb. One could visibly see the fingers and the nose as well. As this technology became more refined quantification of  tumor vessels in the ovary became available about 10 years ago whereby the volumetric imaging of a tumor is able to see the entire 3D outline of a tumor and its malignant blood supply.  This made it possible to find out where the cancer was (and where it wasn't) as well as if and where it was spreading. By simply moving the probe to nearby areas tracking the ovarian pathology metastasis to the liver or lymph nodes allowed staging so some MRI or nuclear scans were avoided. In some cases  bones involvement or lung  fluid from metastatic disease is demonstrable.

Normal blood flow from tumor vessels is distinguished by specific velocity changes. Malignant flow graph is smoother while inflammatory blood vessels have a "spiky" graphic display. More importantly, in addition to seeing the abnormal circulation we measure the aggression by the number of tumor vessels in the area. An elevated number of tumor vessels in the area helps determine the level of treatment. Under continued monitoring, treatment success is measured by the reduction in vessel density.  Diagnostic imaging greatly assists in navigating the selected treatment modality as well as its dosage/intensity. 

THE LATEST: ADVANCEMENT IN EARLY DETECTION OF OVARIAN CANCER
According to the Society for Women's Health Research, "Over 20,000 women will be diagnosed with ovarian cancer this year in the United States and women have a 92% chance of surviving for five years post-diagnosis. However, more than three-fourths of women are not diagnosed until later stages." [1] Abnormal ovaries are often benign simple cysts, however the complex cysts are classifiable with the new ultrasound scoring system as to how suspicious they may be. The same way we detect prostate tumors by routine yearly ultrasound screening in high risk patients, we could save many lives because sometimes the first sign of ovarian cancer is a gland in the neck that pops up, a mass under the arm or jaundice because the liver is filled with metastatic tumor. (visit full feature)


CONTRIBUTORS: 

ROBERT L. BARD, MD, PC, DABR, FASLMS - Advanced Imaging & Diagnostic Specialist
Having paved the way for the study of various cancers both clinically and academically, Dr. Robert Bard co-founded the 9/11 CancerScan program to bring additional diagnostic support to all first responders from Ground Zero. His main practice in midtown, NYC (Bard Diagnostic Imaging- www.CancerScan.com) uses the latest in digital Imaging technology has been also used to help guide biopsies and in many cases, even replicate much of the same reports of a clinical invasive biopsy. Imaging solutions such as high-powered Sonograms, Spectral Doppler, sonofluoroscopy, 3D/4D Image Reconstruction and the Spectral Doppler are safe, noninvasive, and does not use ionizing radiation. It is used as a complement to find anomalies and help diagnose the causes of pain, swelling and infection in the body’s internal organs while allowing the diagnostician the ability to zoom and ‘travel’ deep into the body for maximum exploration. 
https://drrobertbard.com/

ROBERTA KLINE, MD (Educational Dir. /Women's Diagnostic Group) is a board-certified ObGyn physician, Integrative Personalized Medicine expert, consultant, author, and educator whose mission is to change how we approach health and deliver healthcare. She helped to create the Integrative & Functional Medicine program for a family practice residency, has consulted with Sodexo to implement the first personalized nutrition menu for healthcare facilities, and serves as Education Director for several organizations including the Women’s Diagnostic Health Network, Mommies on a Mission. Learn more at https://robertaklinemd.com/

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SPOTLIGHT: OVATIONS FOR THE CURE OF OVARIAN CANCER

In our continued search for leadership in outreach, advocacy and support for research, the Women's Health Collaborative applauds the committed work of SUSAN PATTERSON of Boston, Mass.  Our editors found her organization, OVATIONS FOR THE CURE OF OVARIAN CANCER at nancyslist.org and proceeded to learn about the origins and the mission behind her crusade. 

Ovarian Cancer continues to be one of the most insidious and challenging cancers to battle. Known as the 'silent disease', organizations like "Ovations for the Cure" understand the importance of continued research in finding answers to someday gather enough clinical data and produce innovative solutions to eliminate ovarian cancer from attacking our global community.


INTERVIEW WITH SUSAN PATTERSON 

We started back in 2007, which at that time, there wasn't much for ovarian cancer.  It wasn't talked about- and you didn't tell anybody you had it. It was a secret. My friend had it... her mother had it before her, but she did not know that because they didn't talk about it. So when she was diagnosed, she had a vision of leaving something behind.  After years of treatment, she finally ran out of options. 

Patty was a talker and she would go into the hospital and she'd talk to everybody- reminding women that they were not alone. They don't have a sisterhood. They don't have a group. They're lone survivors out there and that's sad. So we have made our focus support for the women while they're in treatment- and what that involved was to help them and their whole family. We work with a local company similar to HelloFresh. We make sure they have the proper diet and nutrition. The whole family has meals, transportation, any type of thing that comes up along the way that they need help with. 

The other thing we did was we created what my founder called the sisterhood for every woman nationwide.  We would work with social workers at different hospitals and connect with women that are diagnosed to get a free gift from us.  Right now, it's a teal butterfly bracelet in the hopes that they will see another woman wearing this bracelet during their treatment and can open a conversation. What this also does is when they apply for the treatment, they join our email list and we connect them with other women in their area as well. 

We're in Boston- and our local annual awareness event (in November) is a Learning for Living symposium. We call it a day of hope and healing.  We do it at the Four Seasons Boston for women and their care partners. The morning they hear about  updated medical information from the local doctors at the area hospitals.  Dr. Ursula Matulonis, who is one of the top research doctors at Dana Farber and is on our board of directors.  She chooses the speakers and best topics.  This is followed by a lunch where all the women can connect and share what they heard about today. The other half of it is the non-medical world. In a separate room of the hotel they have some one-on-one time with Reiki and support groups and other nonprofits, which I started last year.  I was searching for other local nonprofits to let the women know there's other people here to help them. So it's all about these women for one day at no cost to anybody. This is all paid for by our sponsors, and the Four Seasons has been wonderful. 

We also work with women and families to create a lot of smaller and local events. We help them create an event to remember her- and we do that year round. We try to have small community events so that the family members can remember and spread the awareness about this disease.  We do videos and we also do a big team fundraising at the Jimmy Fund walk every year to go directly to Ursula Matulonis Ovarian Cancer Research Fund. To date, we've donated over 1.7 million and for a small one person organization, we are pretty darn proud of that. So the focus is always on awareness, education, and research.


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Saturday, February 24, 2024

MUSICIANS FOR CANCER CAUSES (part 1)

MAKING OF THE MUSICFEST: 
An interview with Joe Cappello (Co-founder of the Are You Dense? Foundation)

The concept of the Musicfest is an event that we started producing 15 years ago as a fundraiser to support the Are You Dense? mission. For many years, we have done legislative work while bringing awareness and education to the public about the cancer concerns linked to Dense Breast Tissue. The musicfest was our largest finance producer and we need it every year. It's very exciting to have bands from all over the country come in to perform-- both well-known and not-so well-known groups. 

Many organizations fundraise through golf club outings and things like that. We thought to do better- by bringing families together under one roof for a memorable night of "joyful noise".  As a musician myself, I found beauty in bringing people together with music.

This year marks our 15th year doing the Musicfest. On April 6th, we're having a fabulous band called EagleMania, known as the best EAGLES tribute band. They have serious national presence and as tribute bands goo, these guys really hit the mark. We're having excellent sales with tickets and there's a lot of buzz about them- the best we've had about a band in 15 years. 


MUSIC AND CAUSES
There is a tremendous connection between music and the community of charitable people who believe in the magic of music. God gave us the love for music... and it does bring people and families  together. It can make you cry or laugh or clap your hands and stomp your feet. It transcends and moves you! Music is magic, and that's what we produce here once a year at the Are You Dense? MusicFest. 

My wife (Nancy) and I started Are You Dense? to spread the word about dense breast tissue. We made enough noise to make a difference in the state of Connecticut and eventually, around the world. The mission truly enlightened all our followers and it's brought us to a point where we've actually seen a tremendous need for research and change in the clinical community for the better. Even though my wife has passed five years ago, we continue to carry on this mission. That's why it's so important to me personally. I don't know what other thing we could do to make such an impact on people's lives. 



 

Saturday, November 11, 2023

Intl. Cancer Research Summit 2023@ Multi-Expert Presentation Panel


The following is a presentation from the SELECTSCIENCE Cancer Research Summit 2023 (on Nov. 14. 2023): exploring the latest developments in cancer research with fellow scientists, manufacturers, and regulatory experts

Introduction:
SelectScience® Cancer Research Summit is celebrating its third year, bringing together the scientific community and pioneering manufacturers to foster collaboration and facilitate the dissemination of crucial updates in cancer research. Each year, scientific presentations by expert speakers deliver the latest findings in their respective topics, offering practical skills through engaging technology showcases, interactive resources by industry leaders- helping the community to harness the power of networking to drive impactful collaborations.

For the second year in a row, ICRS top clinical advocate Dr. Noelle Cutter was elected to be one of the headliners of this global (virtual) medical event. With her, she brought fellow cancer researchers and two powerhouse publishers in women's health- Dr. Robert L. Bard (Sr. Cancer Imaging Radiologist) and Dr. Roberta Kline (OBGYN/ Genomics Expert). Together, Dr. Cutter's presentation promises to empower the medical community with the most comprehensive report on "Molecular Changes in Dense Breast Tissue" and its metabolic correlation with Breast Cancer.

This video presentation is comprised of 3 presentations which can be accessed in full assembly or as separate clips: (1) Dr. Noelle Cutter -part 1 (2) Dr. Robert Bard (3) Dr. Roberta Kline (4) Dr. Noelle Cutter -  Part 2.  Scroll below for direct access to all presentations and transcripts.



TRANSCRIPT & VISUAL PRESENTATION
By: Dr. Noelle Cutter (Part 1)

Hi everybody.  I'm coming to you from Molloy University where in my lab, we study molecular changes in breast cancer. Joining me today, I have Dr. Robert Bard and Dr. Roberta Kline. Dr. Bard is an internationally recognized leader in the field of 21st century 3D ultrasonic volumetric doppler imaging. Dr. Bard specializes in advanced 3D sonography to detect cancers in numerous organs including the breast. Also with us is Dr. Roberta Kline, a board certified OB GYN Air Force veteran and a functional genomics and mind-body expert.  She bridges conventional and alternative worlds to harness the best technologies and knowledge to create better health. 

The complexity of cancer can be reduced to a small number of underlying principles, all share common traits or hallmarks that govern transformation of normal cells to malignant cells. The famous Hanahan and we Weinberg paper was redesigned since its first publication back in 2001. The latest publication in 2022 included non mutational, epigenetic reprogramming and global changes in the epigenetic landscape are now recognized as a feature of many cancers.

Breast cancer is the most common cancer worldwide, recently surpassing lung cancer in 2020. Globally, it is the number one cancer in both developed and underdeveloped countries and affects more than 2.3 million people, both men and women worldwide, despite its global abundance. Knowledge about the first steps in tumor initiation is important for early detection. However, the exact mechanisms of tumor initiation are still unknown. The median age of diagnostics is 62 to 63 years old, but more recent data also shows that breast cancer is the most common type of cancer among young women. 

Ages 15-39 accounting for 30% of all cancers in this age group, understanding both the genetic and environmental makeup of the cancer will help drive better treatment for our patients. Mammographic density captured on film screen mammograms refers to the content and architectural structure of adipose, connective and epithelial tissues of the breast. In epidemiological studies, a high percentage of mammographic density confers up to a four to sixfold elevated risk of developing breast cancer. Mammographic density is to a large degree in inherited trait, although it is influenced by environmental factors as well. Levels of density are described using a reporting system called the Breast Imaging Reporting and Data System known as birads. The levels of density are a almost entirely fatty, which indicates that the breasts are almost entirely composed of fat. About one in 10 women have this result.

Fig-B (R) shows scattered areas of fibro-glandular density, which indicates that there are some scattered areas of density, but most of the breast tissue is non dense. About four in 10 women will have this result. Heterogeneously dense indicates that there are some areas of non dense tissue, but that most of the breast tissue is considered dense. About four in 10 women will have this result. Extremely dense indicates that nearly all of the breast tissue is considered dense. About one in 10 women have this result. This slide shows a box plot for mammographic density and breast cancer subtypes. Um, the percentage of mammographic density tumors in each of the subtypes are shown for basal HER2, LumA, LumB, and normal. (to be continued below)


TRANSCRIPT & VISUAL PRESENTATION

The first question people ask when there's a cancer diagnosis is "how do we treat it?" As you can see from the 109th annual meeting in Boston, we can find cancer of the breast and treat it with image guidance using ultrasound and MRI with focal therapies. Dr. Barens is now the current chair of research for the Tuck University in the Netherlands. So (enclosed) we see the cancer, it's dark on the ultrasound and it's vascular. We can mention the tumor vascularity and also with the the scan we see it's already metastasized. So we do everything staging with non-invasive imaging, non-bio, back to biopsy. Where do you biopsy? (Enclosed) is the mass. You put it here and get a good biopsy report or do you put it here and said that you, you got dead cells? Repeat the biopsy. So there are false positives, not only with biopsies and false negatives with biopsies, there are false positives.

PET scans, (enclosed) is a silicone in a lymph node from cosmetic surgery. (Enclosed is) a PET scan which showed three nodes but only one was positive with a 36% vessel density. This is the measure we use. This is the quantitative marker that shows how aggressive it is because when the 36 goes down to 2%, treatment is working. When it goes up to 55%, treatment is failing, start a different treatment. (Enclosed is) an advanced digital PET CT showing what are the nodes. So we have lots of tools in our armamentarium to find and to treat cancers. (Enclosed is) a metastatic rib focus and again, we can see that the tumor is high grade because there's a high vessel density and this is used to follow treatment. False positives. A rib fracture will show up on a PET CT scan as a cancer focus or a rib metastasis. This was thought to be benign keloid in this post-op area and the mass by the sterner is actually pitting and eroding into the sternal bone, which you can see on the sixth centimeter tumor that's just beneath the skin and it's breaking into the sternal bone at two points.

Another lump, just the fatty tumor is the skin. That black line is simply the epidermis. So we have fantastic imaging.  This mass is a granuloma from the suture and this is a fat necrosis with calcification, both benign. (Enclosed is) a axillary suture fibrosis. This was missed by all imaging and the patient kept pointing on, this is where I heard. So we put the prob bon and this is a suture fibrosis. (Enclosed is) a good case. You (will) see the skin is abnormal. We did a thermogram, we showed it's highly positive. So the red is is tumor vascularity, same patient. This is the mass. Notice how the mass is eating into the bottom of the epidermis. So it changes it from a stage one to a stage two because it's spread to the skin.

Now this looks like a dense breast, but it isn't. This looks like a not dense breast, but it is because (enclosed is) the cancer. It's a huge six millimeter cancer on the outside of the breast and what does it look like with ultrasound? So is this a rash, a red breast? No, this is the epidermis again, and this is a five millimeter to six millimeter epidermal lymphatic cancer. Rare it's an inflammatory breast cancer rare, but this is the best way to find it. And sometimes the only way, again is an inflammatory cancer or a allergic reaction. Again, sonogram is 5.2 millimeters depth, which should be 1.2 with the allergen. And since the nipple and skin can be involved, we also use optical systems that see the microanatomy and see if the tumor has invaded the nipple tissue or the skin. How do we find that? Well, with looking at the skin, this is a intradermal white area.

It's a plaque, and the 4D scan shows multiple plaques. So this is uranium toxin, which is in the skin. You can find it and measure it. Let me leave you with the world conference showing that angiogenesis and vascularity are the key to finding cancer progression and seeing if the validated anti-cancer treatment works. (Enclosed is) something common. This is a reactive lymph node from from COVID. This is a metastatic lymph node. Notice the difference tumor vessels on the outside penetrating, and this is benign inflammatory vessels. (Enclosed is) a mass under the arm and a patient receiving biologics. So they thought it was a fatty tumor. No, it's a lymphoma. And notice this is connected with a vascular pedicle to the big subclavian artery. So you put a needle in (enclosed is) and it bleeds. This was courtesy from one of the heads of the ultrasound society in Europe.  Notice the right side. This white line and blue line show that it's it's soft tissue area and on the left side the white line is thicker, thicker and now it's red, which shows that it's inflammatory tissue. So this is a case of benign fasciitis, which was treated with steroids instead of a metastatic tumor. So basically this is what the world is doing and we can be doing it by adopting all the new imaging technologies.



TRANSCRIPT & VISUAL PRESENTATION

I'm Dr. Roberta Kline. I'll be discussing the role of epigenetics. Gene expression is the final result of many systems interacting with each other. Now while alterations in DNA such as genetic SNPs and mutations are the best study, epigenetic changes are emerging as very important regulators, and both of these interact with the exosome or the sum total of all environmental exposures over a person's lifetime. These interactions are multi-directional. The exosome influences epigenetic changes. DNA affects how we respond to the exosome as well as our ability to create these epigenetic changes. And then the resulting genetic expression provides yet another feedback loop to influence all of these systems. Epigenetics literally means above the genome and it's our body's way of adapting to environmental cues without changing the actual DNA code. There are three main ways in which this occurs. There's methylation of DNA modification of histones, and then non-coding RNA.

Depending on the type, these can activate or inhibit gene expression. We'll now focus specifically on DNA methylation. DNA. Methylation occurs at very specific sites in the DNA sequence involving cytosine and guanine nucleotides. While we tend to see global trends in changes to methylation across the genome as we age, it's felt to be abnormal patterns associated with specific sites on specific genes that lead to increased risk of cancer. These patterns are most commonly seen as hypermethylation of sites that result in turning off tumor suppressor genes and hypomethylation of sites that result in turning on oncogenes. Unlike DNA epigenetic changes are dynamic and DNA methylation, therefore is a reversible process. Specific enzymes called DNA methyl transferases are responsible for both attaching and removing the methyl group that comes from snail methionine as the universal methyl donor. Snail methionine is the connection between epigenetics and folate and the broader pathways of trans methylation and transation, along with their genes.

As we learn more about what causes higher breast density at the molecular and genetic levels, the role of epigenetics is emerging. In a recent epigenomic wide association study, hypermethylation of a number of regions called differentially methylated regions or DMR were found to be associated with higher breast density. These same regions overlap significantly with ones that have been associated with breast cancer, highlighting potential common pathways and mechanisms mediated through epigenetics. In addition to specific functional pathways involving oncogenes and tumor suppressor genes, there is evidence that epigenetic alterations in genes linked to the microenvironment itself also play a role in breast density and breast cancer. These epigenetic changes are in genes across multiple biological systems that are involved in the maintenance of the microenvironment and disruptions are associated with increased breast density as well as with the development of progression of breast cancer. Soon we'll be able to go beyond hormone receptor and HER two status to provide even more personalized strategies using epigenetics.

Resistance to chemotherapy is also a huge concern and a hot topic of research that is now pointing to epigenetics as a potential solution. There are multiple clinical trials ongoing in various phases looking at intervention with some of these epigenetic agents. Most of these are focusing on two main enzymes, the methyl transferases, and another key epigenetic mechanism that involves enzymes called histone diacetyl asis. Nutritional epigenetics offers application of nutritional strategies including the use of specific phytonutrients that can modulate these epigenetic mechanism. Here on the left, you can see a list of various phytochemicals and how they interact with different epigenetic mechanisms or cancers including breast cancer. And on the right you can see this pictorially in terms of how they're acting with the epigene. Now these strategies are ones we can use today as part of a comprehensive personalized approach for the prevention and the treatment of elevated breast density and breast cancer. 

Thank you.





TRANSCRIPT & VISUAL PRESENTATION
By: Dr. Noelle Cutter (Part 2)

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Molecular profiling of gene expression of breast cancers has demonstrated that tumors are remarkably heterogeneous. More recently, molecular analysis of the microenvironment has demonstrated similar heterogeneity, but the epidemiological clinical and pathological correlations of this variation are not well studied. Recent advances of breast cancers and the surrounding and microenvironment have revealed important stromal and epithelial interaction and have led to the speculation that the microenvironment may actually be dominant over tumor biology, especially early in the stage of progression when invasive cancer cells are still forming.

Clinical questions we ask in the lab are centered around identification of genetic signatures in that microenvironment of patients with dense breasts. If we can identify molecular changes, we can identify targets that are druggable using publicly available data to identify subsets of genes that are differentially expressed in breast cancer and correlated with high mammographic density. To identify important biological pathways is one of the methods that we've been utilizing in our labs. Um, using a bioinformatic parameter, we wanted to establish an in vitro, invitro 3D cell culture analysis that will accurately represent mammographic density. We are also interested in studying how gene suppression can be mimicked through the epigenetic mechanism of methylation. The methylation should induce suppression of transcription factors and that can be modeled within our in vitro system using a CRISPR Cas nine system. Once introduced into the cells growth characteristics and functional features can be studied. We propose that the analysis of these candidate genes that are identified in our study will help physicians make better clinical decisions when treating their patients.

We used a subset of genes quantified by the cancer genome atlas, which represent copy number variation where the CNV is low and downregulation of gene expression is seen, or we can look at copy number variations and gene upregulation for our functional genomic study. We next correlated this data to methylation changes across the genome using a platform known as MoMA, which is a methylation detection array. The image presented represents a sample representation of the heat met, which included 749 differentially methylated probes showing the segregation of mammographically dense and non mammographically dense patients with breast cancer. Since this analysis is based on the comparison of the two co cohorts of mammographically dense and non mammographically dense, there are regions that are found more frequently methylated in mammographically dense or non mammographically dense, breaking down to approximately 60% methylated in mammographically dense and 40% methylated in non mammographically dense tumors. For these regions that differentiate between the mammographically dense and non mammographically dense, we next determine which methylation event potentially represses transcription.

DNA methylation is an important epigenetic modification that defines the properties of cells. Genome-wide hypomethylation as well as hypermethylation of CPG islands is associated with tumor suppressor genes and developmental regulators and are characteristics of cancer cells changes in DNA methylation patterns associated with carcinogenesis progression gradually with the cell proliferation. CPG island methylation primarily targets promoters characterized by low gene expression. DNA methylation is a chemical modification that defines cell type and line lineage through the control of gene expression and genome stability. Disruption to the patterns of DNA methylation control mechanisms that are contributed to a bunch of diseases, especially cancer. Cancer cells are characterized by a barrant methylation such as genome-wide hypomethylation, and site-specific CPG hypermethylation, mainly targeting those CPG islands in gene expression regulatory elements. In particular, the early findings that a variety of tumor suppressor genes are target of DNA Hypermethylation in cancer has led to the proposal of a model in which a Barr DNA methylation promotes cellular oncogenesis through tumor suppressor gene silencing.
The cancer genome atlas, which I referred to earlier in this talk, is a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large scale genome sequencing. The collaborative effort of the cancer Genome Atlas program advances personalized medicine. 

When we analyze our subset of genes identified by the cancer genome atlas and shared publicly that are differentially expressed in patients with breast cancer and high mammographic density, we then uploaded our methylation gene list to a bioinformatic platform known as David to help identify any enriched themes in um, biological functionality for the subset of our genes. The David platform is the database for annotation visualization and integrated discovery and provides a comprehensive set of functional annotation tools for investigators to understand the biological meaning behind some of the large gene lists, such as the one that we isolated for our mammographically dense and our non mammographically dense patients. The star on the slide indicates pathways that are currently under validation in our lab and the hashtag indicates publications that have already been accepted for our gene analysis. That list.

This slide (R) shows a subset of genes that are both downregulated transcription repressed and methylated from our large subset of genes, which included the 749 probes found in the MoMA data. Also highlighted on this slide are two of the genes which we found upregulated in our dataset that have gone on for further functional analysis in our lab analysis of a selection of genes up upregulated in breast cancer and associated with epithelial to mesenchymal transition or EMT was performed utilizing the cancer genome atlas set and the database for functional annotation visualization and integrated discovery. Using the DAVID platform for pathway analysis, our results indicated an upregulation of two genes, tumor necrosis factor alpha in mammographically dense and non mammographically dense breast cancer cells, and the upregulation of zinc finger ebox binding protein one or ZEB one only. In the mammographically dense cells, TNF alpha is a pro-inflammatory cytokine and ZEB one is a transcription factor which directly affects the chromatin. We know that ZEB one regulates e deering expression and is a major cell to Sian protein and known to be a tumor suppressor protein in some cancers. Downregulation of eide and primes the detachment of cancer cells increases migration and invasion as well as metsis. Because of the crucial role of ZB one in this derrin regulation, ZEB one is considered a key regulated of EMT and tumor metastasis.

Our studies have shown that gene expression upregulation of these two key genes, ZB one and TNF Alpha, also induced functional changes in our cell lines, which include cellular proliferation and invasion. Being that TNF alpha and ZB one promote cell displacement and invasive myth through that EMT pathway, we hear and propose that these genes employ a pathogenic mechanism to render mammographically dense cells to metastasize. EMT is an overly complex but also reversible event. Therefore, further investigation into these genes in the an inhibition of either TNF alpha or Zev one might be an effective strategy for personalized medicine and cancer therapy.

Breast cancer tumors consist not only of tumor cell and cancer stem cells, but contain other cells within the tumor promoting functions such as cancer associated fibroblasts, normal fibroblasts myofibroblasts, mesenchymal stem cells, tumor associated adipocytes, endothelial cells, and various immune cells. These could include macrophages, neutrophils, natural killer cells, and regulatory T cells. We are currently in the process of further functional validation of our subset of genes and utilization of our three D cell culture model to model dense breast tissue in women Translational relevance. 

Mammographic density is the strongest risk factor for nonfamilial breast cancer among women apart from older age, but its mechanistic underpinnings are poorly understood. We hypothesize that mammographic density would be associated with different subtypes of breast cancer based on their defining molecular pathways. Some of those pathways have be, have been delineated in our functional analysis study. Our results show that these well-defined molecular subtypes of normal tissue are strongly associated with both mammographic density and breast tissue composition, establishing novel molecular correlations of mammographic density to our gene expression analysis.

Many of the pathways enriched in patients such as epithelial to mesenchymal transition with higher mammographic density are certainly targetable raising the possibility of developing prevention strategies for mitigating density associated breast cancer risk. Future work in the lab will include clinical analysis with the Bard Cancer Center to validate some of our in vitro findings through both our expression array data, our gene subset, as well as our three dimensional cell culture analysis. We will continue to validate the three D cell culture model as well as confirm some of the genetic changes and epigenetic changes that we have already seen in our subset of gene. We plan to do further functional analysis to test the validated candidates and then provide a platform where we can undergo a personalized medicine approach using targeted therapeutic approaches.


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Thursday, May 11, 2023

MEET PRENUVO: ADVANCED FULL BODY MRI FOR CANCER SCREENING & MONITORING

By: Lennard M. Gettz / NYCRA NEWS Editorial Team  

The NY Cancer Resource Alliance and HealthTech Reporter proudly introduces the latest installation of the Prenuvo clinic in New York City. All Prenuvo facilities offer the most current diagnostic advancement in whole body MRI imaging. Recognized for its volume of diagnostic-quality images acquired under one hour, Prenuvo's capacity to capture whole-body imaging through its unique, cutting edge analytic software offers a comprehensive array of next generation applications for early detection and real-time monitoring of complex diseases and cancers.  

On April 20, NYCRA NEWS conducted a special interview with DR. RAJ ATTARIWALA, Nuclear Medicine Radiologist, PhD Biomedical Engineer and  Founding Radiologist of Prenuvo. Known commonly as "Dr. Raj", he shares his commitment to improving on the current state of modalities in cancer diagnostics by offering  advancements on the performance, range and design of our current MRI technology.  

INTERVIEW PART 1: FROM CONCEPT TO DEVELOPMENT by Dr. Raj Attariwala
I bought my first MRI machine in 2009 and published my concepts about the very first whole body diffusion images at a conference called the International Society for Magnetic Residence and Medicine or ISMRM back in 2011. It was well received and led to an invited review on the topic in the Journal of MRI in 2013. The imaging society recognized this as a powerful and highly beneficial solution at a time when most facilities can only scan individual organs or body parts (ie. prostate, breast, chest, abdomen etc). Scanning the entire body is really challenging from an MRI hardware and software point of view because MRI machines and associated software were simply not designed to do that.  

The need 'to see more' has always been part of the diagnostic equation. In the field of nuclear medicine which looks at function of tissue, we often  scan the whole body when we inject a radioactive tracer, because you don't ever want to bring a patient back and re-inject them again. The beauty of MRI's absence of radiation and the ability to combine traditional anatomic (form) images with the power of functional imaging techniques invited the idea of covering more (actually the entirety) of the body without the need for any injection. I learned about the power of combining form and function years ago here in New York when I was training in the emerging field of PETCT at Memorial Sloan Kettering.

This collaboration cycle to build the whole body paradigm was a continuous process between MRI Physicists/ ENGINEERS and RADIOLOGISTS to expedite the design and prototyping stage. Having a doctorate in both fields made me the translator to both groups who commonly do not 'speak' the same language. Materializing concepts mean communicating  features radiologists need to see with those who could build programs and luckily, the progress became fairly streamlined and this process does not alter the FDA approval of a MRI.  


THE FULL-BODY STRATEGY FOR CANCER SCANNING
In simplistic terms, having a full-body access comports to the fact that everything is connected in one way or another.  Tumor cells start somewhere, but they can spread almost anywhere they want. If we find a cancer in stage one (which usually means confined to the organ of origin) what happens afterwards is to ask if it is IN FACT confined to that organ, or if it has spread somewhere else. This is called staging.

After a cancer is detected, patients often go into a panic asking "What stage is it? ... Is it metastatic?" Working with the conventional MRI or CT of the past, they would have to wait to get a brain MRI, then a chest, abdomen, pelvis study and a bone scan etc. With our technology, we already have all that. We've routinely found people with stage  one cancer as part of early detection. This is a good basis where you want to find it. From here, searching 'full  body' is the best next step to make sure that it's not anywhere else in the body. Using an MRI with diffusion, we can see it  all.  

An MRI is known as the most detailed imaging available for scanning a tumor anywhere in the body. Creating a treatment strategy becomes more effective when you know no areas have been overlooked. Patients and physicians both have a higher and more confident level of understanding about what they're dealing with. A great example is confirming that the pounding headache that a patient suffers from after a diagnosis of cancer is stress related, not due the fear of a metastasis...Whole body MRI coverage can preempt this concern.


REPLACING CONTRAST?
From a tumor perspective, you frequently get an increased number of cells which contributes to increased metabolism which often requires more energy. Injecting contrast – ie MRI gadolinium or CT iodine – ends up going to areas of increased blood flow where there is more energy needed, whereas FDG Positron Emission Tomography delivers increased glucose to the cells that are growing and have more energy demand. Instead of contrast our diffusion system works to track cellular density – whereby increased cellular density usually means a high concentration of cells (which is a tumor) which gives off a lot of signal. So as a result we're actually looking with diffusion at cells at a cellular level to see how dense (or hard) they  are. That's how we're able to characterize what the tissue is composed of with that functional diffusion sequence.  


COMMUNICATION TOOLS FOR EARLY DETECTION
Ideally, we want to find things in stage one, but the only way we can do that is to SCREEN. To create a full-body baseline scan of anyone offers a new layer of peace of mind whether we find something or not. In our decade long history, we have luckily found many early stage cancers in patients who were not expecting anything wrong – and this adds to the success and fortunately efficacy of the treatment phase.  

After a Prenuvo scan, diagnostic-quality images are provided to each patient, which are available for review between patient and physician. For those who receive a Prenuvo scan because of potential concerns, correlating what is on the images with their possible symptoms is a major benefit to confirming a disorder. If a patient has concerns of symptoms expressing  as night sweats, unusual weight loss, bone pain etc, a one hour Prenuvo scan can provide almost unequivocal imaging answers, or at the very least eliminates most major concerns and provide peace of mind, because with MRI we have looked through the entire body where the eyes cannot see.

Once an issue is identified, our radiology team communicates the report. For continuity of care, our team of health practitioners will go through and explain what's going on. If there's no  cancer per se, then the report goes directly to the patient with the findings combined with simplification of terms  so anyone can understand what it means. However if there is a finding, the scans directly go to a group of health practitioners who discuss next steps directly with that patient and ensure they're connected into the medical system. We remain involved with the entire patient journey and want to be part of the whole imaging continuity of  care  spectrum that the patient should have.






"CANCER DETECTIVE" FINDS GROUNDBREAKING SCAN

5/20- Dr. Bard receives the 2023
NY Cancer Resource Award 
On April 20th @ 4:30PM, Dr. Robert Bard scheduled his first FULL-BODY MRI on 312 West 34th Street.  Prior to its opening date on 4/27, PRENUVO welcomed special guests to test drive their cutting-edge imaging solution.  Positioned in NYC as the 8th installment is a significant landmark in Prenuvo's international footprint.  As a prominent figure in cancer diagnostic imaging and non-invasive research, Dr. Bard found great interest in experiencing this full-body innovation firsthand.
For over 3 decades, Dr. Bard has committed his life's work in the use and support of diagnostic imaging to detect cancer tumors. He is aligned with a global network of fellow cancer 'detectives' and clinical specialists.  He is often called to 'test drive' the latest ultrasound upgrades as part of developers' R&D, prior to market deployment. In addition, Dr. Bard is also a clinical researcher using ultrasound imaging to quantify therapeutic effects of non-invasive medical devices.

On April 27, 2023, Prenuvo officially announced the opening of their first New York City clinic. Founded in Vancouver, Canada, the company is recognized for their design of proactive whole-body imaging for the early detection of cancer and other diseases. With this expansion, New Yorkers will now have access to the fastest, safest, non-invasive whole-body screening on the market so that they can take personal control of their health and seek proactive solutions. [Source: Prenuvo press release]

PRENUVO REBOOTS HOLISTIC IMAGING WITH FULL BODY MRI By: Robert Bard, MD | Originally published in HealthTechReporter.com 

Unlike the many MRI's without contrast of almost every part of my body over the years, this was actually an interactive and possibly enjoyable experience. In addition to not having to worry about getting a contrast infusion, the fact that it was getting so much of the body minus the hands and feet offers an excellent overview. Because disease in one part of the body may cascade dysfunction in other parts of the body, the developers of this full body scan offers a diagnostic solution to address this. For example, a gallstone can drop into the pelvis, or an ovarian tumor can spread to the axilla or a melanoma of the calf can metastasize to the brain. The idea of full body imaging to rule out any kind of metastatic disease or primary disease like an aneurysm or an unsuspected kidney cancer is very important.

For such a comprehensive scan that takes a little more than an hour without any preparation is quite impressive to me.  In the case of abdominal imaging (specifically) for prostate studies, the fact that you don't need an enema or pre-op work is a major upgrade. Conducting a procedure becomes much easier due to the multiple areas of monitoring that are simultaneously available. This means you're getting more than one “workup”.

What I find special about the Prenuvo experience is that after the scan, you are contacted by a specialist who will explain the procedure and your imaging report.  For non-medical people, this process is invaluable. Also the video presentations of the pathology are placed before you in a three dimensional hologram- making it easy to navigate through the scans. 

Prenuvo promotes their technology as a PREVENTATIVE tool for anyone interested in a full-body view of their health.  This also works as part of an EARLY DETECTION protocol because the sooner you can catch something, the more time you have to address it- especially with cancers. Also, this is an advantage with inflammatory disease since psoriasis of the nail or the fingers can involve the joints anywhere in the body, especially in the pelvis and the sacroiliac joints. This would tell you if the treatment you are getting is responding slowing or if the progression is not working at all.  This full body scan offers a whole look at where the problem is and where it isn't and lets you confidently focus on the treatment technology in a more suitable direction.

INTELLIGENT SCAN FOR COMPLEX DISORDERS
Currently, the modern thinking of disease has changed. Something like psoriasis (a worldwide skin disease) not only affects the skin and the joints, but gives you an increased risk of stroke and cancer development. So when you get the full body scan, you check if your heart or brain are involved by the vasculitis. This is an inflammatory disease- and because it's a whole body disorder, we want to treat the whole body. As a matter of fact, it makes sense to scan the whole body first- making the Prenuvo ideal for producing a proper base line. 

The same thing goes with metastatic cancer. You need to see where it is, where it's going to and where it hasn't gone to. The conundrum occurs with a tumor vs. the inflammation that usually appears with a tumor. We are seeing this more often- where a large cancer is actually part-cancer, part scarring fibrosis and part-inflammation.  In other words, what you see and feel isn't necessarily disease. Through advanced imaging, you may distinguish suspicious tissue from fibrosis, an inflammatory tissue or cancer which is where the ultrasound compliments the full body imaging.




TECH TALK: PRENUVO'S UNIQUE APPROACH TO WB-MRI

MRI technology has now matured over the past 20-years where we can actually effectively perform diagnostic-quality WB-MRI. Via careful MRI protocol design and optimization, we have developed a specialized WB-MRI focused screening service that has been of significant clinical utility to our patients and referring-clinician colleagues. 

Our approach to whole-body MRI imaging is one that is geared for early detection, fast yet comprehensive, safe and comfortable. Our standard Prenuvo screening protocol is a comprehensive multiparametric Whole-Body MRI study (anatomically covering the head, neck, chest, abdomen, pelvis, whole-spine, and lower-extremities through the ankles)  that takes under 1 hour without compromising diagnostic quality. This technique is effective to detect, localize, characterize, and even stage a very wide-spectrum of pathology (ranging from solid-tumors even at small early/localized stages, to benign cysts, to brain aneurysms, and many other diverse pathologies) with a very high-level of sensitivity and specificity for a screening evaluation.  We do this without undesirable radiation or contrast. 

What makes our approach different from traditional MRI approaches, which typically rely primarily on more anatomically-focused imaging, is that we also combine this with an important specialized functional-focused MRI-technique known as Diffusion-Weighted-Imaging (DWI) covering the whole body. DWI has been clinically-demonstrated to play a very valuable role particularly in oncological-imaging; and, in the screening setting DWI significantly enhances  our ability to discriminate oncologically-concerning lesions from benign lesions. DWI can be thought of as an MRI-analogue to PET-imaging (whereas PET highlights hypermetabolism of cancerous tissue, DWI highlights hypercellular-density or “tissue hardness” characteristic of cancerous tissue). 

Our DWI technique, in conjunction with the multiple other well established multiplanar multiparametric MRI sequences in our protocol, afford us the requisite level of sensitivity and specificity needed to provide clinical value in the context of desired proactive screening. Most standard MRI systems are not capable of performing these specialized WB-MRI sequences at an acceptable speed, image resolution, and similar multiparametric comprehensiveness. 

MRI SCREENING vs HOSPITAL CONVENTION-  Prenuvo scans capture 2000 images in 28 areas in under an hour at diagnostic quality, with 1B+ data points acquired, compared to the 4-5 hours it would take through conventional MRI. Conventional MRIs also use pre-programmed protocols that are not optimized for whole-body speed capture without compromising diagnostic quality. We've taken a different approach and verticalized our hardware and designed software acquisition protocols for whole-body diagnostic yield in under one hour.  





















Friday, June 28, 2019

RETIRED FIREFIGHTERS GET CRASH COURSE ON CANCER SOLUTIONS




First Responders Cancer Awareness Program "Turns Up the Heat" with Top Cancer Expert Dr. Jesse Stoff. 

New Hyde Park, NY - 6/25/19--The NY Cancer Resource Alliance (NYCRA) presented their First Responders Cancer Awareness & Resource program at one of the largest RMA (Retired Member’s Association/FDNY) meetings this year.  Earmarked by their giveaway button, “Get Checked Now!” has been educational mantra to promote the proactive self‐care message for all 9/11 survivors and career rescue personnel.

Founded in 1946, the RMA has been one of the largest national fraternal organizations dedicated to supporting the access of much needed information to all retired members.  Former firefighter and senior awareness ambassador Sal Banchitta defined NYCRA’s curriculum as a “one-two punch” – the first being about current SCREENING & DIAGNOSTICS solutions, and then bringing out the second part of the cancer battle: a REVIEW OF ALL TREATMENT OPTIONS. “We couldn’t think of a better event to bring out this heavy topic than RMA’s largest meeting of the year, nor a better doctor to deliver it”, stated Mr. Banchitta. “This overview about cancer treatments carry the root message that there’s a lot of smarter and safer choices out there to consider than ‘chemo and radiation’… I think this alone is such a life‐saving angle by opening people’s eyes to getting more insight as to what’s REALLY available to us these days.”

SAVING LIVES- A TIME-BASED PRIORITY
Volunteer program developer Lennard Gettz was second on the mic and started with the latest news headline quotes and mortality rates as far as the continuing rise in new cases that plague all responders. He also included other rare new findings like Male Breast Cancer cases that are (now) beginning to grow in numbers in the firefighter community. “I echoed the many advocates of 9/11 cancer victims who emphasize TIME as the most limited asset and that's what ‘NOW‘ means in our “Get Checked Now!” slogan. Experience shows that there is rarely a warning as to who will get hit next, but when it does happen, your response time to addressing it is crucial.  We can stay above the curve by thinking ‘prevention’ and subscribing to early detection exams.”

The NYCRA speakers' featured guest was top cancer expert and integrative clinical immunologist Dr. Jesse Stoff of Westbury, NY. Dr. Stoff delivered a resounding 'opening pitch' for this awareness 2.0 presentation. “Based off of my experience with my patients, there is no one answer to cancer," starts Dr. Stoff. "That's a very important take‐home message. If your doctor tells you that you’ve got cancer and presents THE treatment program, well that's just not true. There are many different strategies for approaching and dealing with cancer. Yes, we have chemo, radiation & surgery and we’ve had them for decades‐ but other proven options like Immunotherapy have been around for decades too‐ performing in many cases with lightning‐fast response, much less toxicity, and much better overall survival.”


As cancer continues to plague the community of potentially at‐risk rescuers, the visiting health advocates from NYCRA were well‐received by the almost 200 attendees. The focus and attention from the generation of retired rescuers reflects on their concerns for looming health issues as the new cancer cases and recent fatalities that continue to hit the news each week. "In all of our meetings, after the pledge of allegiance, they would read off the list of firefighters passing away and the list is getting longer all the time... we appreciate these speakers who are so dedicated to reminding us to get checked, especially the doctor (Stoff)‐‐ they called him the 'Cancer Encyclopedia'... he was so effective as a speaker with so much information for us. I haven't seen any doctors ever come out to speak to our groups like this ‐ not even with an appointment!" ‐ says retired Chief Bob Checco.

The First Responders Cancer Awareness group continues its schedule of presentations in firehouses and personnel meetings all across the New York area. As the medical expert and head writer for NYCRA’s review on cancer treatments, Dr. Stoff continues his advocacy for first responders in the new Cancer Awareness video podcast program “So you think you know CANCER?” where he delivers his expanded review about the many cancer solutions available worldwide. “In my professional opinion, unless you're working with somebody who is aware of these kinds of breakthroughs and knows how to test for their use, then you're going to be looking at old off‐the‐shelf generic therapies that can have much poorer overall survival... and that's not what you want.” His new cancer awareness video series is scheduled to launch in the Fall of 2019.

NYCRA and the First Responders Cancer Resource are volunteer, self-funded advocacy organizations whose members are dedicated to the sharing of free-access information, educational materials about cancer, videos, group presentations and a catalog of all cancer resources. For more information, visit: www.HealthScanNYC.org. Media contact: nycralliance@gmail.com or call 631-920-5757
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OVARIAN CANCER: A DIAGNOSTICIAN'S DIRECTIVE (R. Bard, MD)

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