Jul
14
2018

Less Chemotherapy For Breast Cancer Patients

A new clinical trial suggests that less chemotherapy for breast cancer patients is necessary than what is the custom today.

70% of the common form of breast cancer, which is estrogen positive, but HER2 negative (more info below) has received treatment with surgery and subsequent chemotherapy. However, there was no scientific basis for this and this is what this large clinical trial was all about. The trial is discussed under this link. It has its origin in a medical research paper in the New England Journal of Medicine.

Estrogen positive, HER-2 negative breast cancer

The majority of breast cancers belong into this category. They have no signs of metastases and the Oncotype DX Breast Recurrence Score test has a score between 0 and 10. A woman with breast cancer like this does not need to undergo chemotherapy, because her long-term survival will not be any better on chemotherapy, and she can save all of the complications of chemotherapy.

The Oncotype DX Breast Recurrence Score

With this relatively new test 21 genes are tested in breast tissue from biopsies and surgical specimens. Dr. Otis Brawley, chief medical and scientific officer for the American Cancer Society, who was not part of the study explained: “What that test does is look at 21 different genes to see if each is turned on or off and then if it is over-expressed or not. So we have two yes-no answers for each gene. It looks at all 21 of those answers and gives that cancer a recurrent score between 0 and 100.” This number based on genetic cancer markers determines how likely the breast cancer is to reoccur in the next 10 years.

Relevance of genetic score test

A low score of between 0 and 10 on this test is indicative of good long-term survival. These patients will not need any chemotherapy. A medium score of 11 to 25 also has good survival as in this trial. However, scores of over 25 have an association with poor outcomes, when the patient receives only hormone therapy. In these cases the researchers say chemotherapy is also necessary in addition to hormone therapy.

Clinical trial regarding whether or not chemotherapy is necessary in the intermediate risk breast cancer patient

10,273 women were part of this trial between April 7, 2006, and October 6, 2010. 6,711 had test scores between 11 and 25, which placed them in the intermediate risk. Half of them received hormone therapy and chemotherapy. The other half received hormone therapy only. After an average of 9 years 83.3% of those on hormone therapy alone did not develop a recurrence of breast cancer. They also did not develop a second cancer. For the other group on both hormone and chemotherapy the rate was 84.3%. The difference between the two was not statistically significant. This established that the intermediate risk breast cancer patient does NOT require chemotherapy.

Results of clinical trial a surprise

This was a big surprise. Oncologists always included chemotherapy in the routine treatment schedule for these patients. But the trial clearly showed that hormone therapy alone was good enough! This allows thousands of breast cancer patients to avoid the devastating side effects of chemotherapy. Why would a woman undergo unnecessary chemotherapy, loose her hair, vomit and get stomach upsets? She may also suffer osteoporosis and undergo bone marrow suppression, which makes her more prone to serious infections.

Premenopausal women and those younger than 50 

There is a group of women where breast cancer is more aggressive. Research followed this subgroup of women (premenopausal women and women below the age of 50) separately in the trial. More deaths occurred in the group that received hormone therapy alone. But death rates were much lower with a combination of hormone therapy and chemotherapy. If the score in these women was 16 or higher these women should receive the regular treatment consisting of surgery and hormonal measure). But they should also receive chemotherapy at the same time to reduce complications from their breast cancers. It has been known for many years that breast cancer in this particular patient group has a more aggressive growing habit. This trial showed that survival was a lot better in the group that did receive chemotherapy as well.

Surface markers of breast cancer

1. BRCA1 and BRCA 2

BRCA1 and BRCA 2 are rare mutations in some women who get early breast cancer, often on both breasts and often ovarian cancer as well. These are women who benefit from bilateral mastectomies, even when there is no cancer present yet.

2. HER2

HER2 is a protein that is expressed on the cell surface of some breast cancers. It leads to faster cell proliferation. Only about 30% of all breast cancers are HER2 positive. They respond to Herceptin and other medications listed in this link. In the past the prognosis for HER2 breast cancer was poor, now with better medication against this condition it has one of the more favorable outcomes.

3. ER and PR surface receptors

Estrogen receptor (ER) positive cancer cells will lead to faster tumor growth, when the patient receives estrogen. It also grows faster under the influence of estrogen or progesterone. About 65% of all breast cancers are hormone receptor positive (ER or PR). They will respond to drugs like Tamoxifen and others.(See this link)

Less Chemotherapy For Breast Cancer Patients

Less Chemotherapy For Breast Cancer Patients

Conclusion

Breast cancer diagnosis and treatment is rapidly changing. A clinical trial from the New England Journal of Medicine with over 10,000 women with breast cancer showed the following:

It is safe to treat women with an intermediate risk of breast cancer with surgery of the primary cancer and follow this up with hormone therapy. In the past these women were undergoing chemotherapy in addition, which has not shown better survival rates. On the other hand, premenopausal women or women below the age of 50 should receive treatment with chemotherapy to improve their long-term survival. Other factors to consider are the hormone receptors (ER and PR) and the HER2 marker. The Oncotype DX Breast Recurrence Score test has added a completely new dimension to breast cancer treatment as the New England Journal of Medicine article has shown. Overall breast cancer treatment has improved, which is good news for women.

Jan
13
2018

Immune Support For Cancer Patients

Immune support for cancer patients is necessary when their platelets are decreasing from chemotherapy. Dr. John L. Hall gave a talk at the 25th Annual World Congress on Anti-Aging Medicine in Las Vegas, Dec. 14-16, 2017. He pointed out that when cancer patients receive chemotherapy their platelet counts in the blood decline. Dr. Hall participated in a 2010 study that investigated the use of RNA fragments to protect stem cells in the bone marrow from chemotherapy. The study showed how  fragments coming from E.coli protected patients’ bone marrow cells. This immune support for cancer patients allowed physicians to carry on with regular dosing of chemotherapy treatments for the patients’ cancer. There was no dosage reduction necessary and no interruption of the treatment schedule. The optimal dose was 80mg sublingually of RNA derived from E. coli, and patients self-administered the dosage every other day.

Low platelets mean bleeding

Normally patients would bleed or bruise easily when they received chemotherapy without protection by RNA fragments. There would be frequent nosebleeds, bleeding in the gums or in the mouth. Patients would also have blood in urine and get petechia on their skin.

Consequences of low platelet count on cancer patients

There are several consequences for cancer patients, when their platelets are low with chemotherapy.

  • Patients with low platelets have fatigue
  • They experience limitations with regard to physical function
  • When platelets are low, patients need platelet perfusions
  • There is compromise of their cancer treatment because chemotherapy needs adjustment of  or the dosage, or the therapist needs to postpone further treatment.
  • Their survival rates are lower due to cancellation of chemotherapy treatments
  • More medical resources are necessary because of platelet transfusions

How do RNA fragments work?

RNA fragments act as primers triggering DNA synthesis in bone marrow stem cells. Fragmented RNA is also protective of bone marrow cells when the patient receives chemotherapy. In animal experiments, where toxic chemotherapy was given, fragmented RNA allowed these animals to survive. This prompted oncologists to introduce this treatment modality into end stage cancer patients who are receiving chemotherapy. Results were stunning. The patients from age 18 to 80 tolerated the RNA fragments well. They were able under the influence of the RNA fragments to continue with their regular chemotherapy to completion of the therapeutic course. When laboratory tests measured platelets, the results were normal. The investigators concluded that the RNA fragments protected the bone marrow stem cells of platelets.

The tumors in this trial involved pancreatic cancer, head and neck cancer and cancer of the breast. In addition physicians also treated colon cancer, esophageal cancer and lung cancer .

More details about RNA fragment therapy in cancer patients requiring chemotherapy

Cancer patients who had no protection by RNA fragments had platelet levels that became lower and lower with every chemotherapy treatment cycle. Some patients never returned to normal platelet levels even once the chemotherapy stopped. Other cancer patients’ platelets took month before they returned to normal. Patients in this group either needed to either reduce  their chemotherapy dosage or put treatments on hold. Alternatively their treatment stopped prematurely.

In contrast patients whose bone marrow received protection by RNA fragment therapy had stable platelet levels. Their platelet levels recovered quickly to normal after each cycle of chemotherapy. No unplanned chemotherapy reduction was necessary and no platelet transfusions were required. All the patients were able to complete the treatment plan.

The physicians also observed that with RNA fragment therapy the peak platelet counts were still in the normal range despite chemotherapy. When patients recovered from the chemotherapy effect the platelets stayed in the normal range.

Insulin potentiation therapy

Research has shown that cancer cells have more insulin receptors than normal cells. Physicians used this fact  with a form of chemotherapy where the patient receives small doses of insulin first. Following that the patient can receive lower doses of chemotherapy. Dr. Donato Perez Garcia MD is the inventor of the insulin potentiation therapy (IPT). With this treatment the patient can receive lower than normal chemotherapeutic agents , which reduces the toxic side effects of chemotherapy. Unfortunately the side effect of the lower dose of chemotherapy still hits the bone marrow. As a result the platelets are dangerously low. Dr. Hall mentioned that RNA fragments are also effective with insulin potentiation therapy. This keeps the platelets in the normal range and patients can complete the course of insulin potentiation therapy.

More background about the insulin potentiation therapy

Dr. Robert Baratz has reviewed the merits of IPT thoroughly. He came to the conclusion that the so-called research about the effectiveness regarding IPT has not been done properly. In his opinion it is not proven that less chemotherapy is required when pretreatment with insulin has been done. There are also dangers that connect with insulin therapy. If the insulin dosage is too high blood sugar will go into dangerously low levels. The FDA has never accepted that the IPT procedure would be superior to standard chemotherapy. However, regardless of the chemotherapy dosage these chemicals are bone marrow toxic. Particularly the toxic effect on stem cells of platelets will cause diminished platelet counts in the blood with both procedures. In both cases RNA fragment therapy will overcome the toxic effect on the bone marrow stem cells.

Immune Support For Cancer Patients

Immune Support For Cancer Patients

Conclusion

Bone marrow suppression by chemotherapy has been a limiting factor for many years prior to the detection of RNA fragment therapy (RFT). RNA for RFT is derived from E. coli cultures. RNA fragments act as primers triggering DNA synthesis in bone marrow stem cells. This leads to the production of platelets that protect the patients from the toxic effects of chemotherapy on bone marrow. RFT allows the patient to receive treatment with chemotherapy without having to worry about bone marrow toxicity. No chemotherapy dose reduction is necessary and no platelet transfusions are needed. RFT should be a regular accompaniment to chemotherapy treatments for any cancer patient.

Incoming search terms:

Jun
11
2014

Multiple Myeloma Cured With Measles Vaccine

Mayo Clinic physicians were desperate when two patients with end stage multiple myeloma, a vicious bone tumor, did not respond to chemotherapy; so they tried something unconventional: high doses of the measles vaccine in an attempt to stimulate the immune system.

Canadian researchers had reported in 2011 that oncolytic viruses created by genetically modifying smallpox vaccine viruses would enter tumor cells of patients, but not damage normal cells. A high percentage of the end stage patients responded with tumor regression. Now the Mayo Clinic clinicians used high doses of a modified measles vaccine to attack the multiple myeloma cells of two end stage patients and it worked on at least one patient who is cancer free after a recheck of the bone marrow 6 months later. The other patient experienced a significant remission, something not heard of in an incurable end-stage condition. Here is the story as reported recently in the press. This research is a new beginning for cancer researchers as in the past the general thinking was that something as bad as cancer must be fought with something strong and toxic to get rid of the cancer cells. The emphasis was on “fighting the cancer cell”.

Now the emphasis is to stimulate the immune system, which will fight the cancer much better. As a past cancer researcher I would say that it is about time to take this new approach as the old approach of attacking the cancer cell like an enemy with radiation and chemotherapy did not work well. The new thinking is: why not stimulate the immune system to such an extend that it becomes newly activated, but to such a degree that there is no chance for the cancer cells to fight back. I searched the recent literature on PubMed regarding this topic and came across several other interesting human clinical trials. They are all smaller, but very encouraging. Here is a brief summary of what I found:

Multiple Myeloma Cured With Measles Vaccine

Multiple Myeloma Cured With Measles Vaccine

1. Prostate cancer vaccines: In this article a review of the use of various vaccines with dendritic cells, viruses, or DNA are described directed against the prostate-specific antigen on the surface of prostate cancer cells. 

2. Pancreatic cancer: This cancer is very difficult to detect in the early stages and as a result the outlook for chemotherapy or radiotherapy is extremely poor. Several approaches have been tried to use as an alternative. Immunotherapy is an option and the Mayo clinic researchers have already announced that the measles vaccine approach will likely be applicable to pancreatic cancer treatment as well in the near future. However, other clinical trials are on the way to use other vaccination procedures.

3. Cervical cancer: The HPV (human papilloma virus) vaccine is targeting patients exposed to the high-risk HPV16 strain most often causing cervical cancer. However, researchers have noticed that in some cases a phenomenon called the “HPV immune escape” has allowed in some vaccinated women to still develop cervical cancer. So, a group of researchers are investigating how the vaccine could be improved by finding out how the immune system is being tricked in these cases by the HPV virus to bypass the antibodies of the vaccine.

4. Brain tumors (glioblastoma multiforme): This deadly brain tumor has a survival rate of only 15 months with conventional combination therapy. However, new anti-tumor vaccines are being tested in clinical trials, which already have shown much less toxicity than conventional therapies and they have longer survival times.

5. Melanoma treated with special vaccine: In the early 1970’s the anti tuberculosis vaccine BCG was used to find that about 25% of patients had long-term survival advantages with this adjuvant treatment. Recently several smaller clinical trials involving end stage melanoma patients utilizing various vaccines showed encouraging results with tumor regressions. Melanoma is a particularly vicious pigmented skin tumor. And yet, when messenger RNA (mRNA) was combined with dendritic cells and made into a vaccine, the antigen presenting T-cells that previously did not react against the melanoma tumor suddenly became very active destroying the tumors. This line of immune treatment is very promising and clinical trials continue to go on.

6. Another multiple myeloma treatment approach: Apart from the measles vaccine approach mentioned at the beginning of this blog, there is another approach that is being pursued at the Ohio State University Comprehensive Cancer Center where immune cells of patients with multiple myeloma are being modified in tissue culture to be more aggressive against a CS1 marker that is expressed on the surface of 95% of multiple myeloma cells in patients with this deadly cancer.  The modified T cells are grown in culture and are re-injected into the patients. In mice this research team found that 100% of animals treated with these CS1 activated T lymphocytes were alive at 44 days after treatment was started versus only 29% and 17% of two control groups. A phase I clinical trial on patients is being started soon.

Conclusion:

The encouraging news is that several of the clinical trials on humans seem to be showing breakthroughs with better survivals than in the past. In addition it is also encouraging to see that these new treatment modalities are non-toxic treatments, which compare very favorably with traditional chemotherapy and radiotherapy methods. Also, there is some recognition among cancer researchers that although mice or other animal species may be a good first screening method, the ultimate goal is to treat human patients. This means that cancer researchers need to concentrate on human cell lines and work with cancer patients. It will be interesting to see the outcome all of these trials and new approaches; hopefully we will see better survival rates for these patients in the near future.

More information on multiple myeloma: http://nethealthbook.com/cancer-overview/bone-cancer/multiple-myeloma/

Last edited Nov. 8, 2014

Oct
12
2013

Music More Powerful Than Anti-Anxiety Drugs

When was the last time you saw your physicians for anxiety and you were given a prescription that said: “for anxiety listen to your favorite music!” instead of receiving a prescription for an anti-anxiety drug (anxiolytic). This is exactly what a recent study suggests that showed prior to surgery you can control your anxiety either with anti-anxiety drugs or by listening to your favorite music. Listening to your favorite music will do you no harm, while many drugs do have harmful side effects.

How singing can change the brain chemistry

Other studies have investigated how singing can change your brain functioning in terms of brain chemistry. The researchers found that singing will release dopamine in your brain, which is responsible for feeling pleasure; it will stimulate your immune system by elevating immunoglobulin A and decreasing cortisol (the stress hormone). This in turn will preserve your immune cells (lymphocytes). Oxytocin levels of your brain are increased, which promotes social affiliation. It also calms down the autonomic nervous system resulting in a better airway opening, calming of your heart rate and soothing the wave-like muscle contractions in your gut, medically called peristalsis. You would refer to that as “butterflies in your stomach”. Music therapy reduces pain and anxiety by 50% and is important for children and adults alike.

Pain and anxiety reduced

A study in Germany showed that pain and anxiety were significantly reduced with music therapy. A Taiwanese study of women in labor found that music therapy significantly reduced pain and anxiety of women during labor. Ref. 1 explains that music therapy is useful as an adjunct to treating cancer pain, and reducing anxiety associated with colposcopy procedures. It also can help when treating patients who had heart attacks in the setting of a cardiac care unit.

Music More Powerful Than Anti-Anxiety Drugs

Music More Powerful Than Anti-Anxiety Drugs

Hypnosis and guided imagery

Music has been successfully combined with clinical hypnosis and guided imagery where words are carefully chosen to help the patient experience pleasant feelings, which counteract the experience of pain, anxiety or fear of dying. A simple relaxation CD or tape with soothing background music will facilitate this type of therapy. This is useful for patients in a palliative care unit where they prepare themselves to accepting the inevitable death from an incurable disease. But chemotherapy patients undergoing these procedures for cancer treatments also have benefitted from a significant reduction in nausea, vomiting (side effects of chemotherapy) and pain.

Autism and music therapy

A Cochrane study showed that autistic children did better in terms of communication skills when music therapy was incorporated into the treatment protocol. One of the core deficits in autistic children is in the area of communication and social skills. This is where music therapy was most effective. Behavioral problems (stereotypic behavior) in autistic children did not respond to music therapy. A comprehensive treatment program for autistic children should therefore incorporate music therapy. Here is a blog that describes what difference music therapy can make in the lives of autistic children written by a member of the American Music Therapy Association.

Substance abuse and music therapy

An area where you may not expect music therapy to have a role is in the area of drug and substance abuse rehabilitation , which is discussed in more detail in this site. The beauty about music therapy is that it is not a drug, yet the natural endorphins that are released by the brain help the affected person getting through withdrawal easier. Music therapy helps building up self-esteem, participating in group activities, promoting self awareness and expressing feelings.

Mood disorders in adolescents

One important area where music therapy has been employed is with anxiety and depression in adolescents. Adolescents spend an average of 4 hours per day listening to music. So they are already programmed to listen to music. With the help of a music therapist they can be directed to listening to the type of music that will help them get motivated, relax more, make them feel accepted and be part of their peer groups. In this study the authors suggested to combine music therapy with dance and art therapy. In this way the whole person gets involved in the treatment and this can be integrated with conventional antidepressant treatments at reduced doses (with less side-effects) or with cognitive therapy.

General objectives of music therapy

Music therapy is best incorporated into a treatment protocol as an adjunct. It can help reduce the use of drugs for psychiatric patients, for people with anxiety and for patients with pain conditions. The Cleveland clinic has a useful summary about music therapy, which describes the uses of it for reducing anxiety, for helping with coping skills, mood improvement and distraction from pain. There are registered music therapists you can ask for help. The website of the American Music Therapy Association may have other useful links for you.

Conclusion

Music therapy is a treatment modality with no side effects, but providing effective treatment for quite an impressive range of clinical conditions as discussed. Music therapists are widely available in the US and many other countries. This treatment can be integrated with conventional or complementary treatments. It helps people to heal the body as a whole unit (mind and body).

More information on anxiety disorders: http://nethealthbook.com/mental-illness-mental-disorders/anxiety-disorders-panic-disorders-phobias-ocd-ptsd-anxiety-others/

References

1. Rakel: Integrative Medicine, 3rd ed.© 2012 Saunders. Chapter on Integrative Therapy; subchapter of Mind-Body Therapy.

Last edited Nov. 7, 2014

Nov
22
2012

New Breast Cancer Treatment

For decades the dogma in medicine has been that any kind of cancer, including breast cancer would be treated with surgery, radiotherapy and/or chemotherapy. However, the 5-year survival rates were disappointing as this table shows. In the 1980’s the idea of adjuvant treatments for cancer came up and one of the popular methods was hyperthermia treatment. Cancer cells of a variety of cancers were found to be very heat sensitive, but the limiting factor in treating with hyperthermia systemically was the fact that   bone marrow cells were found to be very heat sensitive, which limited this application. With respect to breast cancer a review of data pooled from 5 trials showed that there was an 18% survival advantage due to the added step of hyperthermia in addition to radiotherapy. With radiotherapy alone a group of advanced breast cancer patients had a 5-year survival of 41%, but a comparable group treated with a combination of radiotherapy and hyperthermia had a survival of 59%.

Let’s back track for a moment and ask what breast cancer is. In the past we thought it developed out of one mutated cell, a breast cancer cell that would multiply into a clone of cells, which would first grow locally and then spread as metastases throughout the body at a later time. Unfortunately further research has shown that breast cancer can simultaneously occur in several spots in one breast or even in both breasts. The spreading of the cell clones to distant areas can occur very early on, but cells can lay dormant for years and start growing again at a time when the immune system is weak. With these facts in mind it can readily be seen that surgery cutting out a “local breast lump” will not be successful in the long term as a treatment of breast cancer, even when radiotherapy treatment is added to sanitize the local lymph glands of local cancer metastases.  Adding chemotherapy to eradicate distant metastases may  sound like a good idea, but chemotherapy is very toxic to bone marrow cells and to the immune cells that are supposed to kill the last breast cancer cells. As a result, chemotherapy has its own problems. Medical researchers had to start thinking outside of the box to discover a breakthrough in breast cancer treatment.

Fast forward to 2012. We still need a breast cancer treatment method that is non-toxic, that kills the breast cancer cells and that ensures that there will be no recurrences in the future.

New Breast Cancer Treatment

New Breast Cancer Treatment

This new treatment method is called “laser-assisted immunotherapy“, and it is being studied in a pilot study right now. 62.5% of end stage breast cancer patients had a response rate, something that has never been achieved before. The systemic side-effects of hyperthermia are overcome by heating only locally and directing the laser beam to the diseased tissue. The quality of the Laser beam is close to the infrared frequency of light . This is amplified by injecting the FDA approved compound indocyanine green, which absorbs more heat from the laser beam right in the cancer cells where it is needed for local hyperthermia treatment. The immune cells and the bone marrow cells are not harmed. The killed cancer cells release the cancer antigens that the immune system could not recognized before, as the immune cells were suppressed by suppressor T lymphocytes. With this added immune booster which is called “glycated chitosan” the cancer patients’ immune cells(called “killer T lymphocytes”)  are now being stimulated and are in a position to eradicate the last trace of cancer cells anywhere in the body. This is similar to a vaccination procedure that takes place within the body of the cancer patient. The T lymphocytes remember the surface antigen of the cancer cells that were killed. As a result the same type of tumor will never reoccur in that person’s life. It also takes care of the dilemma of the past that sometimes more than one cell type clone was found among the biopsy material of a cancer patient.

At this point the trial has not reached the 5 year mark of survival. Only 15 patients of the total of 45 patients have so far been enrolled. But 80% of the 15 patients have survived 2.5 years, which is unheard of with stage IV (late stage) breast cancer. In an experimental breast cancer model in rats where laser assisted immunotherapy was first shown to be effective, there was 100% survival of the treated group. However, it was noted that it was essential that all three components of the new treatment modality were followed. The protocol for the human pilot study therefore is as follows:

1. After placement of an anesthetic in the tumor area the indocyanine green is injected into the tumor (placement of the photosensitizer).

2. The laser beam near infrared frequency of light is applied in the tumor area (or over the palpable metastases). This application takes about 10 to 12 minutes and two courses are given over two weeks. An option of a third course within one year may be considered, but did not have to be done so far.

3. The adjuvant immune booster (glycated chitosan) is injected into and underneath the tumor right after the laser treatment is finished.

This triple therapy is the secret to the success of the new breast cancer treatment as each step is augmenting the other steps resulting in a complete destruction of the breast cancer and an active immunization against any of the residual cancer cells.

At this point the offshore Caribbean breast cancer treatment pilot study has been chosen to bypass frustrating FDA slow-downs in the US. But I suspect that proper protocols in a much bigger randomized US based study will follow the obvious successes in these late stage breast cancer cases. New cancer therapies are urgently needed. They are typically introduced by treating “incurable” (late stage) patients first. We are about 2 1/2 years away from the completion of this pilot study so that 5-year cures rates can be compared to older studies with the conventional cancer treatment approach. I am convinced that this new approach will not only help breast cancer patients,  but will also help prostate cancer patients and pancreas cancer patients (these three come to mind as they all are glandular cancers). Surgery for the removal of lymph gland metastases in prostate cancer patients and breast cancer patients using laser assisted surgery with indocyanine green stained lymphatic tissue has already been pioneered. It also opens up possibilities of modifying the method to suit other types of cancers.

More information about breast cancer: http://nethealthbook.com/cancer-overview/breast-cancer/

Last updated Nov. 6, 2014