News development for Breast Cancer and Cancer, aggregated from Google Alerts, for the week ending 8 August 2014.
This week leads with an article on wasp venom. Using venom is nothing new – I’ve heard of blue scorpion venom being used as a cancer treatment. Apparently the main source of the blue scorpion venom is Cuba. It’s not a cheap product (we’re talking hundreds of pounds for a month’s supply). But the reason for the expense is it’s not easy to harvest the venom [and if I were a scorpion, I would make it very very hard if someone came after my venom!]. The harvesting of the venom is not pretty – it involves using an electric probe to get it to sting and release its venom. It’s reached mainstream use too – Prof Nesslehut of dendritic cell vaccine fame uses blue scorpion venom.
This post could also be called the radiotherapy edition with some controversy surrounding the use of brachytherapy [i.e. radiotherapy that is administered intra-operatively, rather than post-surgery].
The material on flaxseed lignans and breast cancer is not new, and I apologise for including it. The internet is full of information on flaxseed and cancer, in fact most cancer nutritionists recommend taking flaxseed. As pointed out by one reader, JustOnePix, the lead author (Thomson LU) of the research article had written as early as 1995 on flaxseed: www.ncbi.nlm.nih.gov/pubmed?term=Thompson%20LU[Author]&cauthor=true&cauthor_uid=24869971 and also a trial in 2005: www.ncbi.nlm.nih.gov/pubmed/15897583. Thank you for bringing this to my attention – it is much appreciated as I want my readers to have accurate information.
1. Wasp Venom Targets Breast Cancer in New Therapy
- Wasp venom may deliver a painful sting, but scientists from the Institute for Biomedical Research (IRB Barcelona) have carried out successful in vitro tests using the venom to kill breast cancer tumor cells, a new study describes.
- The next step will be to test its effectiveness in mouse models.
- Most anti-tumor compounds are accompanied by a series of side effects and may even become resistant, but the IRB Barcelona team designed a new therapy based on a peptide – the binding of several amino acids – from wasp venom for its potential use against breast cancer.
- This peptide has the ability to form pores in the cell plasma membrane, penetrate into the cell and finally, cause its death, either by necrosis or by triggering apoptosis, programmed cell death.
- However, this “natural weapon” could not be directly used in the therapy due to its high toxicity and lack of cell specificity – meaning, it would not only attack tumor cells but healthy cells as well. So, the researchers came up with a way to deliver the venom to the tumor without causing harm to the body’s healthy cells.
- The system consists of a decorated carrier polymer with two components: a peptide that is bound to a tumor cell receptor and the cytotoxic peptide of the wasp venom.
- In vitro experiments show that the substance successfully reaches and kills the tumor cells while leaving healthy cells, like red blood cells, alone.
- Though the experiment is in its early stages and still has to undergo testing in mice, researchers are optimistic that these findings will be put toward anti-cancer therapy in the future.
For more information: http://www.irbbarcelona.org/en/news/irb-researchers-design-a-new-wasp-venom-therapy-against-breast-cancer
1B. How to milk a venom [an extract]
“This is where the milking happens,” says Manuel Valdés, a veterinarian clad in medical scrubs, latex gloves, and a surgical cap and mask. He’s standing inside a small bare room in the Labiofam outpost. In the adjoining acclimatized rooms (71.6 degrees Fahrenheit), every scorpion has an ID number, coded for its region of capture and date of entry. The animals spend 40 days in quarantine — long enough for any pregnant scorpions to give birth and for any potential illness to be detected. Then they enter the venom rotation.
The scorpion twists itself backward as one of Valdés’ colleagues uses two long metal tongs to try to steady the five-inch arachnid. “It takes a certain technique,” Valdés says. The man aims the tail over a small glass jar sitting in a bucket of ice, and the scientist steps on a pedal attached to an electro-stimulus machine. As a jolt transmitted through the tongs reaches the scorpion, it releases six to 12 “micro-drops” of milky-white venom. “Each scorpion is milked once a month for two years,” explains Valdés, who says the average lifespan of R. junceus is ten years. “Then it’s released back into the wild to repopulate the species.” The venom moves on to Havana, where for years it has been diluted with distilled water depending upon a patient’s condition.
2. Flaxseed and its lignans fight breast cancer
- Scientists at University of Toronto in Toronto, Canada published a review to suggest that supplementation with flaxseed and its phytoestrogen lignans can prevent and even help treat breast cancer.
- According to the review, the majority of animal studies indicate that 2.5 to 10% flaxseed supplemented diet or the equivalent amount of lignans or oil (alpha-linolenic acid) reduces breast cancer growth.
- In the dose of 10%, flaxseed and equivalent lignans increase the efficacy of tamoxifen (80 mg per day) while in the dose of 4%, flaxseed oil increases the efficacy of trastuzumab/Herceptin (2.5 mg/kg) against breast cancer.
- In addition to animal studies, observational studies show that flaxseed and lignan intake, urinary excretion, or serum levels are correlated with reduced risk of breast cancer, particularly in postmenopausal women.
- To be exact, lignans may reduce the risk of breast cancer, and all-cause mortality by 33 to 70% and 40 to 53%, respectively, without reducing the effectiveness of tamoxifen.
- Clinical trials too reveal that using flaxseed in a dose of 25 grams with 50 mg linans per day for 32 days reduces tumor growth in breast cancer patients and using lignans in a dose of 50 mg per day for one year reduce risk in prememopausal women.
- The authors say flaxseed and its lignans fight breast cancer by decreasing cell proliferation and angiogenesis and increasing apoptosis via the modulation of estrogen metabolism and estrogen receptor and growth factor receptor signaling.
- The review concludes “More clinical trials are needed but current overall evidence indicates that FS and its components are effective in the risk reduction and treatment of breast cancer and safe for consumption by breast cancer patients.”
For more information: Applied Physiology, Nutrition, and Metabolism, 2014 Jun;39(6):663-78. doi: 10.1139/apnm-2013-0420. Epub 2013 Dec 23, Flaxseed and its lignan and oil components: can they play a role in reducing the risk of and improving the treatment of breast cancer?
3. Weight loss may reverse basal-like breast cancer
- A new study suggests that weight loss induced by a low fat diet may reverse the progression of basal-like breast cancer (BBC), an aggressive form of breast cancer, in obese individuals who follow a high fat obesity promoting diet.
- Obese mice displayed significantly elevated progression of mammary gland tumors which are the same as breast cancers in humans.
- When obese mice started to use a control low fat diet prior just to tumor onset to induce weight loss, the tumor progression was significantly reversed.
For more information: Front. Oncol., 08 July 2014 | doi: 10.3389/fonc.2014.00175, Weight loss reversed obesity-induced HGF/c-Met pathway and basal-like breast cancer progression
4. Artificial anti-cancer molecules created in a jiffy
- In what could lead to new anti-cancer drugs, researchers have developed a new method to produce molecules that have a similar structure to peptides which are naturally produced in the body to fight cancer and infection.
- The peptide mimics have been found to be successful in laboratory tests on colon cancer cells, the study said.
- The new peptide mimics, called triplexes, have a similar 3D helix form to natural peptides.
- Artificial peptides had previously been difficult and prohibitively expensive to manufacture in large quantities, but the new process takes only minutes and does not require costly equipment.
- “The beauty is that these big molecules assemble themselves. Nature uses this kind of self-assembly to make complex asymmetric molecules like proteins all the time, but doing it artificially is a major challenge,” said professor Peter Scott at the University of Warwick in Britain.
For more information: Nature Chemistry 6,797–803(2014)doi:10.1038/nchem.2024, Asymmetric triplex metallohelices with high and selective activity against cancer cells
5. New Breast Cancer Risk Pinpointed for Women With PALB2 gene mutation
- Scientists have filled in another piece of the breast cancer puzzle with a finding that a mutated gene responsible for DNA repair raises the risk for women who carry it, suggesting it should be included in early testing.
- Those with the PALB2 mutation have a 33-to-58 percent chance of developing breast cancer by age 70, depending on their family history, according to the research published in the New England Journal of Medicine.
For more information: New England Journal of Medicine, 2014; 371:497-506 August 7, 2014 DOI: 10.1056/NEJMoa1400382, Breast-Cancer Risk in Families with Mutations in PALB2.
6. Early Breast Cancer To Be Treated Using Single Dose Radiotherapy in the UK
- The National Institute for Health and Care Excellence (NICE) has approved intraoperative radiation therapy (IORT), a single dose of radiotherapy given at the same time as surgery to remove a tumor, as standard practice for patients with early stage breast cancer.
- The therapy should be offered to patients whose breast cancer is restricted to the breast and has not metastasized to the lymph nodes.
- Moreover, patients should be correctly informed of the pros and cons of this therapeutic approach, and doctors will be required to enter breast cancer patients treated with the IORT onto a national register, provide details of the histology at diagnosis, type, size and grade of tumor, and annotate further developments, including local recurrence and disease spread.
- Furthermore, they will be required to audit, review, and document clinical outcomes locally and analyze the relationship between outcomes and patients’ characteristics.
- IORT delivers a concentrated dose of radiation therapy for 20 minutes directly to the tumor bed during surgery, helping to destroy the microscopic tumor cells that can persist after tumor removal, delivering a high dose of radiation in a single treatment session, this way preserving more healthy tissue and reducing side effects.
- Usually, established radiotherapy treatments require a daily dose over a 3-week period, sometimes longer, and can be administered weeks or months after surgery or chemotherapy. However, IORT offers the potential to become a more efficient form of radiotherapy.
- This technique can greatly reduce the disruption, stress and inconvenience of what for some people can be over 15 additional trips to and from hospital, as well as saving the NHS money and time.
For more information: http://radiationtherapynews.com/2014/07/29/iort-approved-nice-set-offered-british-nhs/
7. Protein ZEB1 promotes breast tumor resistance to radiation therapy
- A protein, ZEB1 (zinc finger E-box binding homeobox 1), is now thought to keep breast cancer cells from being successfully treated with radiation therapy, according to a study at The University of Texas MD Anderson Cancer Center in Houston.
- ZEB1 may actually be helping breast tumor cells repair DNA damage caused by radiation treatment by ramping up a first-line of defense known as DNA damage response pathway.
- Radiation therapy causes cell death by inducing DNA ‘ breaks’. The rationale for treating tumors with radiation without damaging normal tissues is that, compared with normal cells, tumor cells are actively dividing and often have defects in DNA damage repair machinery.
- Tumor cells are thus less able to repair DNA damage. But not always. Sometimes the body produces tumor cells resistant to radiation. They are somehow able to “turn on” the DNA damage response apparatus. Until now, the question has always been how?
- Studies have shown that ZEB1 can induce a process known as epithelial-mesenchymal transition (EMT) which allows certain tumor to acquire cancer stem cell properties including radioresistance.
- EMT is one way the body responds to wound healing and it is believed that cancer has found a method for using EMT to promote tumor progression.
- ZEB1 achieves this unfortunate result through a complex chain of events that permit a gene known as ATM to stabilize the protein Chk1 that plays an important role in DNA damage response.
- ZEB1 promotes Chk1’s ability to allow tumor radioresistance through deployment of an enzyme called USP7.
For more information: Nature Cell Biology 16,864–875(2014) doi:10.1038/ncb3013, ATM-mediated stabilization of ZEB1 promotes DNA damage response and radioresistance through CHK1
8. Standard Radiation Yields Higher Rate of Breast Preservation For Older Women With Breast Cancer Compared To Brachytherapy, According To Study
- Researchers at The University of Texas MD Anderson Cancer Center have found that when given brachytherapy treatment, older women suffering from invasive breast cancer had a higher risk of needing a mastectomy later in treatment compared with female patients who had been treated using traditional radiation therapy.
- Brachytherapy administers radiation therapy internally to a targeted region inside the breast through the temporary insertion of a small catheter, decreasing treatment periods and presenting fewer side effects than external beam radiation.
- The use of brachytherapy after lumpectomy is gaining popularity as a treatment for breast cancer, however, data relative to its effectiveness are conflicting and the criteria for patient selection to receive brachytherapy have never been effectively validated.
- Researchers analyzed the American Society for Radiation Oncology’s (ASTRO) criteria for selecting treatment, concluding that within each ASTRO group, EBRT accounted for the lowest subsequent mastectomy risk versus lumpectomy alone, while brachytherapy presented some benefits versus lumpectomy alone, albeit not as much as EBRT.
- However, patients who were deemed ideal for receiving brachytherapy through the use of the ASTRO consensus statement on partial breast radiation had similar breast preservation rates as patients treated with EBRT, with a 1.6% and 0.8% mastectomy incidence, respectively.
- Furthermore, brachytherapy was associated with a higher postoperative infection risk and with the development of seromas, fluid-filled cavities in the breast caused by rupture of blood vessels and infiltration of pro-inflammatory cells.
For more information: International Journal of Radiation Oncology, Volume 88, Issue 2, Pages 274–284, February 1, 2014, Benefit of Adjuvant Brachytherapy Versus External Beam Radiation for Early Breast Cancer: Impact of Patient Stratification on Breast Preservation
9. Scientist tests new method to work out cancer patients’ ideal dose of chemotherapy
- Currently, chemotherapy doses are calculated based upon a patient’s weight and height, but this calculation may not be accurate in patients who are very obese or underweight.
- The effectiveness of chemotherapy, and what side effects are experienced, may depend on the fat and muscle content of a person’s body, so it is important that this is calculated correctly.
- Existing methods to measure body composition, are complex and time-consuming, therefore Dr Ellen Copson, a Senior Lecturer at the University of Southampton and an oncology consultant at the University Hospital Southampton, has been awarded a grant worth around £20,000 by research charity Breast Cancer Campaign, to test a new, simpler method of measuring body composition, called ‘segmental bioelectrical impedance spectroscopy’ (sBIS).
- sBIS uses a machine resembling a weighing scale which estimates body fat using tiny electrical currents that pass through the person’s body.
- Dr Copson is recruiting over 35 people with breast cancer who are about to receive chemotherapy for their treatment, to collect information on ease of use, as well as how accurate this method is compared to existing methods of measuring body composition.
For more information: http://www.southampton.ac.uk/mediacentre/news/2014/aug/14_144.shtml