Is Pakistani Herbal Tea a New Cancer-Fighter?

Folks in rural Pakistan might be on to something.  They have long used extracts from a common herbal tea ingredient, the plant Fagonia cretica, known as virgin's mantle, to treat breast cancer. Now researchers at Aston University, Birmingham, England, and Russells Hall Hospital, Dudley, England, have evidence that this is more than folklore—an extract of the plant might actually work to repair cell damage in cancer cells without affecting healthy cells.  So far, their studies have been confined to laboratory analysis, but they hope to now determine what elements in the plant are the active cancer-fighters, with the hope of eventually beginning clinical trials.

In previous laboratory research, virgin's mantle repaired damage caused by p53 expression, which is associated with triple-negative breast cancer.  

In a news release, Professor Helen Griffith of Aston said,  "More research is needed to establish the role of the extract in cancer management and It now needs to be demonstrated that this extract is as effective in killing cancer cells inside the body as it is within laboratory."

Virgin's mantle is found in arid regions of Pakistan, India, Africa and parts of Europe.

Sharing Good News One Case at a Time

Here's one face of TNBC as I have seen it this week:

A reader wrote that his 36-year-old wife, who had been diagnosed in February with stage 3b TNBC, just got a glowing report from the doctor after a mastectomy and 8 rounds of ACT: Her chances of long-term survival are excellent.  They are meeting with the radiation oncologist soon.

So thanks to Walt for keeping me current and lifting my spirits.    When I first heard from him in late March, they were reeling from the diagnosis, and she was sleeping off the anti-nausea drugs. (I stopped taking them because they did little for nausea and made me feel worse.)

Walt says they modified their diet after her diagnosis.  Here's what he says about their new approach: 

I started juicing for us nightly.  I usually throw in: Kale, carrots, celery, blue berries, ginger, cucumber, and apple.... Also, we've dropped milk from our diet, and switched to decaf coffee and decaf tea.  Otherwise, we were pretty healthy before so not much has changed—oh, less red meat (but that wasn't a lot to start with).

That is similar to my approach, but I do have some milk—always low-fat organic. And I have my blueberries whole in the morning, not as party of my nightly juice.

I love hearing from readers and will start sharing bits of it with all of you who are on the same journey.

More Genetic Research Helping Define TNBC: Oncogene FAM83B

NEWS RELEASE

Newswise — A team of researchers at Case Western Reserve University School of Medicine, led by Dr. Mark W. Jackson, have developed a novel method to identify genes that, when overexpressed, make normal cells behave like cancer cells. Using this method, the Jackson laboratory has identified a new oncogene, which is a gene that contributes to the development of cancer, named FAM83B.

“We made our discovery in a model of breast cancer,” said Mark W. Jackson, Ph.D., Assistant Professor, Department of Pathology, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center. "Using an unbiased screening approach, we let the biology of cancer formation tell us what genes are important and FAM83B was one of the genes that came out of our screen. When FAM83B was overproduced in normal breast cells, it transformed the normal cells, causing them to behave like breast cancer," stated Jackson.

There are relatively few oncogenes that are critical to breast cancer growth, and only one other breast cancer oncogene has been identified in the last 6 years. Breast cancers are classified clinically into subgroups based on the presence of specific proteins, including estrogen receptor (ER), progesterone receptor (PR), and HER2.

"Analysis of breast cancer revealed that elevated FAM83B expression is associated with the more aggressive, triple negative subgroup which lacks ER, PR and HER2,” said Jackson. “In short, patients with triple-negative breast cancer would benefit most from the development of new therapeutics.”

Novel oncogenes provide opportunities for drug development that may expand the number of therapies available for eradicating cancer and extending the life of patients. "Our discovery provides the foundation for developing new therapies that can inhibit FAM83B in these aggressive cancers, which have traditionally been difficult to treat." We are currently trying to identify drugs that that can inhibit the function of FAM83B." stated Jackson.

This study will appear in The Journal of Clinical Investigationand will be co-published with a discovery from the laboratory of Dr. Mina Bissell at Lawrence Berkley National Laboratories. Dr. Bissell’s laboratory discovered an oncogene called FAM83A. Both FAM83A and FAM83B belong to an eight member family of genes that both laboratories propose may drive tumor formation and therapeutic resistance.

Dr. Jackson is the principal investigator leading a multidisciplinary team with investigators that include: Rocky Cipriano, James Graham, Kristy Miskimen, Benjamin Bryson, Ronald Bruntz, Sarah Scott, H. Alex Brown and George Stark. Additional support for the research came from the Case Comprehensive Cancer Center, the United States National Institutes of Health (R01CA138421 to M.W.J; T32CA059366 to R.C), the Department of Defense Breast Cancer Research Program (M.W.J), the American Cancer Society (RSG-10-072-01-TBG to M.W.J) and the McDonnell Foundation (to H.A.B).

The pharmaceutical company EntreMed has announced a Phase 2 study of ENMD-2076 in triple-negative breast cancer.  

Jennifer R. Diamond, MD, of the University of Colorado, says, 

"We are encouraged by the data from the Phase 1 study of ENMD-2076 in patients with advanced solid tumors, including triple-negative breast cancer. ENMD-2076 has also demonstrated significant anti-tumor activity against preclinical models of breast cancer with more robust activity against triple-negative breast cancer alone or in combination with standard chemotherapies. This single-agent Phase 2 study is designed to determine the activity of ENMD-2076 by the clinical benefit rate in patients with previously treated locally advanced or metastatic triple-negative breast cancer."

For more information, check out the news release.

What We Can Learn From Hospice Patients

NOTE:  The article below is essentially a press release about a new book, and I don't normally share these things until I can read the book.  However, I like what Gourgey has to say about the qualities of dying patients--essentially they demonstrate how we all should live, especially the part about love not being self-interested.  

Does our society hold too narrow a view of what defines strength? 

The things many would point to as indicators – youth, wealth, a fully capable body – fall short, says Charles Gourgey, a veteran hospice music therapist and author of Judeochristianity: The Meaning and Discovery of Faith (www.judeochristianity.org), a book that explores the unifying faith elements of Judaism and Christianity. 

“Youth is ephemeral, abundant wealth is for just a few, and we all experience some kind of disability, usually at several points in our lives,” he says. “A car accident, the loss of a job or a home, grief over a loved one’s dying: such things can happen to anyone and easily destroy our happiness.” 

Gourgey says some of the greatest strength he’s ever seen was demonstrated by certain of his patients facing imminent death. 

“Some people have complete love and grace when facing death – it’s how they’ve lived their lives, and at the end of their lives, it’s what supports them,” he says. “Those who, at the end, are peaceful, grateful and confident share some common characteristics.” 

They are: 

• Their love is non-self-interested. When we have awareness of and deepest respect and reverence for the individuality of others, we overcome the high walls of ego and experience a tremendous sense of freedom, says Gourgey. He says he continues to be inspired by patients who cared more for the well-being of others, including their fellow hospice patients, than themselves while facing their own mortality. Non-self-interested love – loving others for themselves without expecting or needing anything in return – is the greatest form of love, he says. 

• They had an unwavering faith that transcended religious dogma. Faith is the knowledge that there is more to life than the apparent randomness of the material world; a sense that we are known to a greater reality and will return to that reality. No matter what their religion, the patients who were most at peace with their life’s journey were those who had faith in something higher than themselves. The problem with many concepts of faith, Gourgey continues, is that people attach specific doctrines to it, which means some people will always be excluded. A unifying faith – that all people are connected and love is the force that binds us – allows for trust, compassion and caring. 

• They were motivated by an innate sense of what is good. They didn’t get mad at themselves; they didn’t beat themselves up for mistakes they might have made in the past. That’s because they were always guided by their sense of what is good, and they made their choices with that in mind. That did not prevent them from making some bad choices or mistakes over the course of their lives, Gourgey says. But when they erred, they addressed the problem with the same loving compassion they extended to others. “Their compassion overcame even any self-hate they may have experienced.”

Many patients left lasting impressions on Gourgey, and taught him valuable life lessons. He remembers one in particular. 

“She was in hospice, a retired nurse who had developed a rare, incurable disease,” he recalls. “She would go around every day, checking to see what she could do for the other patients. She fetched blankets for a 104-year-old lady who always complained of cold feet. She sat with and listened to patients who needed company and someone to talk to. She had an attentive awareness about her, like she was fully in touch with her soul.” 

Gourgey was with the woman when she died. 

“She was radiant, she just glowed. She kept repeating how grateful she was for her life,” he says. “It was as if the life of love she’d lived was there to transport and support her at the end.” 

About Charles “Carlos” GourgeyCharles “Carlos” Gourgey, PhD, LCAT, MT-BC, is a board-certified and New York state-licensed music therapist. He has more than 20 years of experience working in hospices and nursing homes, and for 10 years was music therapist for Cabrini Hospice in New York City. He has published articles on psychology and religion in various journals.

Botanical Formula Shows Promise in Fighting Metastatic TNBC

A botanical formula that includes medicinal mushroom, flavonoids, botanicals, and extracts of cruciferous vegetables may be effective against triple-negative metastases, according to a study published in the  journal Oncology Reports.

The study was conducted at the Cancer Research Laboratory, Methodist Research Institute, Indiana University Health. It was presented at the annual meeting of the American Academy for Cancer Research.  Its publication in Oncology Reports marks the third peer-reviewed study demonstrating the anticancer effects of the formula.

Researchers implanted triple-negative human breast cancer cells in the breast tissue of mice.  The tested group was given the formula orally for four weeks; the control group received no treatment.  

According to a news release from Indiana University Health:

The cancer metastasized to the lungs in only 20 percent of the treated group as compared to 70% of the untreated, control group. Furthermore, in the treatment group that did metastasize, the number and size of the lesions was dramatically reduced in comparison to the control group. 

Gene analysis showed that the formula down regulated (suppressed and reduced) two genes implicated in cancer metastasis -- PLAU (urokinase plasminogen activator, uPA) and CXCR4 (C-X-C chemokine receptor-4). These results further substantiate previous cancer cell studies published on this formula, which similarly demonstrated a down regulation of these cancer promoting genes. 

The  formula includes ingredients that have been shown in previous research to have anti-cancer properties:

• Medicinal mushrooms Trametes versicolor, Ganoderma lucidum, Phellinus linteus reduce cancer growth and invasiveness.• Extracts from the botanicals Scutellaria barbata, Astragalus membranaceus and Curcuma longa induce programmed cell death (apoptosis) and reduce cancer metastasis.•The flavonoid, quercetin, reduces cancer cell proliferation and helps suppress tumor growth.• DIM (3, 3'-Diindolylmethane), an active component of cruciferous vegetables, reduces cancer growth, migration and invasiveness.

      Source: Jiang J, Thyagarajan-Sahu A, Loganathan J, Eliaz I, Terry C, Sandusky GE, Sliva D. BreastDefend prevents breast-to-lung cancer metastases in an orthotopic animal model of triple-negative human breast cancer. Oncol Rep. 2012 Jul 26. doi: 10.3892/or.2012.1936.

Protein Kinase Thwarts TNBC Cell Migration and Invasion

NEWS RELEASE

ScienceDaily (Aug. 1, 2012) — By identifying a key protein that tells certain breast cancer cells when and how to move, researchers at Michigan State University hope to better understand the process by which breast cancer spreads, or metastasizes.
When breast cancer metastasizes, cancer cells break away from a primary tumor and move to other organs in the body, including the lungs, liver and brain. In work published recently in the journal Cancer Research, MSU researchers Kathy Gallo and Jian Chen show a protein called MLK3 (mixed lineage kinase 3) is a critical driver of breast cancer cell migration and invasion.More importantly, Chen and Gallo showed that in triple-negative breast tumor cells, which are more aggressive and for which targeted therapies are needed, it is possible to thwart that cell migration and invasion."While the classical approach to cancer drugs has been to find drugs that kill tumor cells, there recently also is an interest in finding drugs that interrupt metastasis," said Gallo, a professor in MSU's Department of Physiology. "The hope is that such drugs in combination with conventional therapies may lead to better outcomes in patients."As part of their study, Gallo and Chen, a biochemistry graduate student, also found that eliminating MLK3 prevented tumors in animals from metastasizing to the lungs, providing the foundation for future research on targeting MLK3 pathways as an approach to preventing the spread of cancer.The researchers identified how key cellular proteins were instructed by the MLK3 protein -- through the addition of molecular tags called phosphates -- to interact with one another, leading cancer cells to move. Specifically, MLK3 promotes the addition of phosphates to another protein called paxillin, which is known to control how cells move.Gallo and Chen then stopped cell movement in breast cancer models by eliminating MLK3 altogether or using a drug called CEP-1347 to block MLK3's ability to add phosphates to other proteins. The experimental results indicate that when certain cancer cells lose MLK3, the ability to add phosphates is impaired, eventually crippling the cell migration machinery and diminishing cell movement."Our research suggests that the intracellular pathways involving MLK3 that control cell movement could provide new targets for the treatment of patients with metastatic cancer," Chen said. "Drugs developed for combating the MLK3 activity may be useful in reducing the spread of breast cancer."Gallo added that MLK3 is a protein kinase, and these types of proteins have proven to be good drug targets in cancers and other diseases."While drugs such as chemotherapy kill all cells, research has shown drugs that inhibit kinases often can be effective with fewer side effects," she said.The next step for the researchers is to test whether an MLK3 inhibitor can prevent cancer from metastasizing in animal models."Cancer is a very complex collection of diseases, but we believe that certain types of cancers may be sensitive to MLK inhibitors," Gallo said, "and targeting MLK3 may provide a very useful weapon in the fight against cancer."The team's research was supported by grants from the Department of Defense's Breast Cancer Research Program and the Elsa U. Pardee Foundation. The MLK inhibitor, CEP-1347, was provided by Cephalon Inc., a wholly owned, indirect subsidiary of Teva Pharmaceuticals Industries Ltd.

Drug Combo May Stop TNBC Growth

From Medical Daily

Two drugs approved by the Food and Drug Administration for blood cancer treatment may also be used to treat triple negative breast and kidney cancer. researchers say.

The drugs are romidepsin and decitabine. Together they can activate a gene sFRP1 (secreted frizzled related protein one) that can stop the growth of cancer cells. 

"We now have the basis for a clinical trial aimed at providing effective therapy for two drug-resistant cancers and perhaps many more tumor types in the future," said Dr. John Copland, biologist from Mayo Clinic. The trials were conducted on cell lines of cancers where the combination of drugs was effective in halting the cell growth. 

"Individually, each drug did not induce any form of cell death but, together, they killed all of the different cell lines of kidney and triple negative breast cancer that we tested in the laboratory," said Simon Cooper, a Mayo Clinic molecular biologist who specializes in renal cancer and lead author of the study. 

Nearly, 80,000 people are affected each year by these two types of cancers in the United States.

It was observed that certain types of cancer suppress the gene sFRP1. Activation of this gene by the drugs can stop the growth of cancer cells. Even cancers that affect colon, ovary and lungs grow by suppressing this gene.
Researchers say that this gene could act as a biomarker to test the effectiveness of the combination drug therapy on certain kinds of cancers. 

"But now, not only do we have a very promising lead on future therapy, but if this combination treatment works as we hope it does, we will have a biomarker to be able to test which patients might benefit the most. In other words, a biopsy test could identify patients whose tumors had lost sFRP1 function," said Edith Perez, MD, deputy director of Mayo Clinic Cancer Center and co-author of the study. The combination therapy can help fight cancers that have become resistant to other drugs and as these drugs are clinically approved the human trial phase would be faster.

 "This type of interdisciplinary preclinical research effort is important, not only because of the value of the science, but also because the drugs are already in the clinic and that will facilitate translational efforts and hopefully confirm the preclinical findings in patients with advanced malignancies," said Michael Menefee, MD, an oncologist and co-author of the study.  

The study was published in Molecular Cancer Therapeutics.