Jun 30, 2014

Cannot Keep a Good Dog Down

After discovering that my partner in crime and travels, Bud, was sick with myxoid liposarcoma, cancer of the fatty cells (soft tissue) in his chest and under his arms.  He will be going to the canine oncologist possibly to have it removed, so that I can have more time with Bud.  This cancer (I have heard) can spread to other organs, and he does not want any big masses on his chest.

Here is a collection of my travels across the USA with Bud.  Stay strong.

 We are looking into foods, spices, and herbs to help slow down the growth, turmeric (curcumin), bakers yeast, (beta glucans), apigenin (celery, apples, parsley, teas,artichokes).  I know that we can not stop it, but at least give me more time with my best Bud.


 

Great information before you see the doctor or oncologist from the Cancer: What Should You Ask Vet from Dallas Gold.  

Thank you!


Guide to Canine Cancer: Your Common Questions Answer from Dogchannel.com

Six types of cancer treatment: surgery (removal), chemotherapy, radiation, immunotherapy, stem cell, ttf (electromagnetic field around cancer)
Pathology Report from R. Jay Hoffman, DVM, PhD (H&E Biopsy (Light Microscopy))

Description: 

Five sections of a neoplasm from four separate specimens are examines. The neoplasm is composed of tightly packed sheets of round to oval cells containing moderate amounts of amphophilic cytoplasm.  Most of the cells contain one to several clear rounded cytoplasmic vacuoles.  The nuclei are round to oval, have coarsely clumped chromatin and contain one to several large nucleoli.  There are up to 3 mitotic figures per hpf (high-power (400×) fields).  Neoplastic cells (abnormal cells) extend to the histologic borders (tissue).  Scattered throughout the neoplasm are multiple areas of necrosis (death of body tissue).

Histopathologic Diagnosis: 
Mass (4 specimens): Liposarcoma

Texas A&M Veterinary Medical Diagnostic Laboratory

Comments:
Since neoplastic cells extend to the histologic borders, it was not determined whether removal was complete.  

There is a possibility of metastasis (cancer cells have spread).

 CT Scan (of the 180 images of Bud's chest-- negative impacts from CT scan were difficulty standing on back legs, could not eat carrots because of irritation from breathing tube, no bowel movement for 24 hours after anesthesia, and cost $1200).
Four Options were given surgery (remove 3 ribs and the fatty mass tumor (liposarcoma along with muscle tissue), radiation from TX A&M in College Station (radiation dermatitis-burns and scabs), chemotherapy (which may not stop the cancer from growing but may kill off much of his immune system), or do nothing except for pain management and any open wounds that may result from the cancer.

Brief History:
Sternal mass (liposarcoma) present since 02/13 - suspect high grade. History of vestibular disease and ocular disease.

Radiographic Findings:
A pre-and postcontrast CT examination of the caudal cervical region and thorax is available for dictation. A large well-defined 8 cm x 6 cm x 7 cm vascular and heterogenous contrast enhancing mass is associated with the right caudal ventral cervical region. This mass contains fat and soft tissue opacities. This mass is well encapsulated and located adjacent to the first sternebra. This mass lesion does not invade into the thoracic cavity.  This mass is adjacent to the right first and second rib and no periosteal reaction or aggressive bony lesion is identified.  No pleural effusion is present.  No abnormalities are seen within the thorax. The lung fields are normal. No enlarged thoracic lymph nodes are identified.
Radiographic Conclusions:
  1. Large well encapsulated heterogenously contrast enhancing extrathoracic mass lesion measuring 8 cm x 6 cm x 7 cm and is located adjacent to the right cranial thorax/sternum. Neoplasia would be considered highly likely.
  2. Normal lung fields. No metastatic lung disease or thoracic lymphadenopathy is identified. 

Main two causes of liposarcoma is radiation and genetic tracts. Dogs have 78 chromosomes per cell.  Which chromosome has the gene mutations (translocation) that contribute to liposarcoma?  In humans it is chromosome 12 (q13-15 region) from the genome analyses of liposarcoma, specifically gene MDM2 and DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma.

DDIT3 gene can promote a liposarcoma phenotype in human primitive sarcoma cells.  NY-ESO-1, one of the most immunogenic cancer proteins.

Since we do not know Bud's parents or siblings being a rescue dog, then his genetic tracts cannot be evaluated without a Bud genome done.   

Bud used to lie in the sun all day when let in the backyard.  While all the other dogs would be under a tree and in the shade, Bud would find the only sunny spot in the sun and sometimes lie on his back all day even 100+ degree F heat.  For the past 10 years he is mostly an indoor dog and no longer left outside all day.  His stomach is covered with freckles (which I examine regularly for melanoma) and have made the assumption that the UVA and UVB rays may have caused the mutation in the chest cells to contribute to the liposarcoma.  

Last summer Bud lost the ability to walk up and down the steps of the sailboat.  His muscles in his chest were decreasing no matter how much walks and play time that we did.  He always had a strong upper body.  (Examination into rhabdomyolysis, muscle degeneration and myopathy).  Over the past 3-4 years when it gets cold under 60 degrees F, his joints pop after laying down and appears very stiff.  (Whitley, the female golden, never had the upper body strength to walk up the steps, but she does have the leg strength to spring up the boat steps.)

Bud's current diet, morning time, consists of 400g of grain free, salmon formula by Blue, 1/2 cup of chamomile tea, 2-3 grams of circumin (+ 1 pill of turmeric, in supplement form), 1 grams of ground black pepper.  Some of these additional foods may add maybe eggplant skin lightly steamed, steamed bok choy (like leaf part), ginger, peas, shittake mushrooms (beta glucans), (rome) apple peels (would not eat), and scrambled egg (loves).  

A year later Bud is still walking and eating, but has been throwing up (regurgitate) the dry food.  The cancer may be impeding his esophagus.  We switched to tube food of Vital Pet, no grain, which he loves the bison beef or salmon and no more throwing up.  He gets to twice a day.  A cooked hamburger will give him soft stools so that is rarely given.

Treats still include carrots twice a week even though I am reducing his glucose and glutamine intake.
 Read the 2nd edition of the Hallmark of Cancer


Tunicate (chemical in this animal may reduce his liposarcoma, ET 743)
Further examination into Black Pepper
Evidence of use as an anti-inflammatory, analgesic (painkiller), and antioxidant dates back as early as ancient Indian and Egyptian cultures more than 3,000 years ago.  Extracts from P. nigrum have also shown anti-cancerous / cytotoxic facilitation in recent studies.
Piperene is a potent chemical which in addition to the aforementioned properties, also promotes thermogenesis in humans. Thermogenesis is the heat producing catabolism (breakdown) of fats in the body.
In Purple eggplant skin, nasunin 
Delphinidin-3-(p-coumaroylrutinoside)-5-glucoside, antioxidant anthocyanin isolated as purple colored crystals from eggplant peels.  Nasunin suppressed HUVEC proliferation in a dose-dependent manner (50-200 microM)
Limes ( flavonol glycosides: limonin glucoside and kaempferol)
Epidemiological studies have revealed that a diet rich in plant-derived foods has a protective effect on human health. Identifying bioactive dietary constituents is an active area of scientific investigation that may lead to new drug discovery. Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g. tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries and grapes) and in plants or botanical products commonly used in traditional medicine (e.g. Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis).
Some epidemiological studies have found a positive association between the consumption of foods containing kaempferol and a reduced risk of developing several disorders such as cancer and cardiovascular diseases. Numerous preclinical studies have shown that kaempferol and some glycosides of kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti-osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities.
In this article, the distribution of kaempferol in the plant kingdom and its pharmacological properties are reviewed. The pharmacokinetics (e.g. oral bioavailability, metabolism, plasma levels) and safety of kaempferol are also analyzed. This information may help understand the health benefits of kaempferol-containing plants and may contribute to develop this flavonoid as a possible agent for the prevention and treatment of some diseases.

What is Kaempferol?

Pure kaempferol is a yellow colored powder. Amphoral is one of the most important and most widespread flavonoids (containing the typical C6-C3-C6 structure).

Distribution

Kaempferol is a flavonoid present in various natural sources including apples, onions, leeks, citrus fruits, grapes, red wines, gingko biloba, St. John's wort.

Health Benefits of Kaempferol

Keampferol is a strong antioxidant and helps to prevent oxidative damage of our cells, lipids and DNA. Kaempferol seems to prevent arteriosclerosis (thickening walls of arteries) by inhibiting the oxidation of low density lipoprotein and the formation of platelets in the blood. Studies have also confirmed that kaempferol acts as a chemopreventive agent, which means that it inhibits the formation of cancer cells.

An in vitro study by Jan Kowalski (Pharmacological Reports, 2005) showed that kaempferol inhibits monocyte chemoattractant protein (MCP-1). MCP-1 plays a role in the initial steps of atherosclerotic plaque formation.

The flavonoids kaempferol and quercetin seems to act synergistically in reducing cell proliferation of cancer cells, meaning that the combined treatments with quercetin and kaempferol are more effective than the additive effects of each flavonoid. This was a conclusion from a study by ML Ackland et al (In Vivo, Feb 2005) titled "Synergistic antiproliferative action of the flavonols quercitin and kaempferol in cultured human cancer cell lines"".

A study "Inhibition of P-glycoprotein function and expression by kaempferol and quercetin" by the Chiang Mai University, Thailand, found that kaempferol can help to fight cancer because it reduces the resistance of cancer cells to anti-cancer drugs such as vinbalstine and paclitaxel.
More publications to research


MD Anderson Sarcoma Center, Doctors, and Clinical trials for humans

Government sponsored Clinical Trials for Cancer

Research of ET-743, MD Anderson Sarcoma clinical trials, except L-sarcoma (liposarcoma) for Johnson and Johnson pharmaceutical research arm, Janssen Research out of San Diego, Ca (who produces Yondelis (Trabectedin)).

Zeltia Soars with Agreement with Janssen Research for Yondelis
"In April, Zeltia missed out on a $10 million payment from Johnson & Johnson after the New Brunswick, New Jersey-based drug maker withdrew its U.S. regulatory application for the medicine. The Food and Drug Administration requested additional tests before clearing the treatment for patients with ovarian cancer. The drug is approved for sale in that indication in Europe and Canada."

News Articles:

Scientists develop the first cancer immunotherapy for dogs

Treating Cancer With Bacteria Shows Real Promise
 Because it grows best under oxygen-starved conditions, C. novyi targets just the stubborn cancer cells that are hardest for current anticancer treatments to reach.
Among a group of 16 dogs who had soft-tissue sarcomas, six responded to the bacterial treatment. The pets received anywhere from one to four cycles of 1 billion spores each. In three of the animals, the tumors completely disappeared and the animals remain cancer-free nearly two years later. In three others, the growths shrank by at least 30% after 21 days.
Holistic Treatment

Neutering health effects more severe for golden retrievers than Labradors
Neutering and cancers
The data also revealed important differences between the breeds in relation to the occurrence of cancers. In non-neutered dogs of both breeds, the incidence of one or more cancers ranged from 3 to 5 percent, except in male goldens, where cancer occurred at an 11-percent rate.
Neutering appeared to have little effect on the cancer rate of male goldens. However, in female goldens, neutering at any point beyond 6 months elevated the risk of one or more cancers to three to four times the level of non-neutered females.
Neutering in female Labradors increased the cancer incidence rate only slightly.
“The striking effect of neutering in female golden retrievers, compared to male and female Labradors and male goldens, suggests that in female goldens the sex hormones have a protective effect against cancers throughout most of the dog’s life,” Hart said.
Liposarcoma metabolizes differently from other cancers (that grow from glucose).  Current research shows the cells feed on glutamine to grow.  So remove number 7, glutamine, from the following list for liposarcoma (an nonessential amino acid that is high in meats, dairy, and miso).  

Protective Nutrient information and functional foods for the gastrointestinal tract 1,2,3

Eating Hints before, During, and after Cancer Treatments

Different for Dogs with Liposarcoma, soft tissue cancer:

Nutrition in Pets with other Cancers

(from North Houston Veterinary Specialists, Spring, TX)

Common Theories:
Veterinary literature is lacking to suggest which diet is best for these patients.
Common theories regarding metabolism in cancer patients include the Warburg effect (Aerobic glycolysis) which suggests that cancer cells thrive in high glucose environments and so diets that are high in protein and low in carbohydrates and sugar deprive tumors of nutrients and slow the growth of the tumor.

In addition, the Cori cycle hypothesis (Lactic acid cycle-glycogen) of cancer state the cancer cells regenerate glucose from lactate via metabolism in the liver and this not only results in providing energy to the tumor but increases the patients overall nutritional needs. These theories result in the demand for high protein and low carbohydrates diets for cancer patients, although we do no have the evidence to support that feeding this diet will prolong survival.
Guidelines:
Highest percent protein (at least 30%) and least amount of carbohydrates (less that 20%).
  • Boiled or baked fish (white fish, tuna, salmon), chicken or turkey, beef or tofu
  • Boiled or well cooked vegetables to improve digestion
  • Cottage cheese
  • Boiled eggs
Nutritional Assessment and Management:

General guidelines for caloric needs for a dog:
(Bud is 63 pounds = 28.6kg= 1511 calories)
Greater that 30 Kg  = 66.14pounds) = 70 (BW in kg)^0.75
Less than 30 Kg = 70 + 30 (BW in kg) * 1.2 * 1.4

Dihydromyricetin from oriental raisin tree tea, decrease alcohol affects on the brain and reduces inflammation.

Fighting Cancer with proper Nutrition
  • Energy dense: In general, foods with a higher caloric content are preferred. If the dog will eat only a small amount, it is important that the food should contain as many calories as possible.
  • High in fat: Tumor cells are much less likely to use fat for energy, whereas the dog's normal cells find fats an excellent source. It is recommended that foods should be 25-40% fat on a dry matter basis.
  • Moderately high in protein: Since cancer cachexia is associated with a decrease in muscle mass, and muscle is high in protein, moderately high protein levels should be available to dogs with cancer, provided they have normal kidney and liver function. In general, protein levels should be in the range of 30-45% on a dry matter basis.
  • Low in carbohydrates: Since tumor cells prefer carbohydrates, diets low in carbohydrates will theoretically give the tumor cells less to grow on. Carbohydrates should be less that 25% of the food on a dry matter basis. (Liposarcoma cancer is different than other cancers)
Added nutrients
Some dog foods are fortified with certain nutrients that can be beneficial to dogs with cancer. Added nutrients that may be recommended include:
  • Omega-3 fatty acids: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 fatty acids found in fish oils. They may be very beneficial to dogs with cancer. It not only reduces cachexia, it may also have a direct effect on the tumor cells themselves. Since some dog foods already contain increased amounts of omega-3 fatty acids, it is best to consult with your veterinarian before supplementing. Ultra-high doses can be detrimental.
  • Arginine: Arginine is an important amino acid for dogs. Arginine can benefit the immune system and may influence tumor growth. Although the optimal amount of arginine for dogs with cancer has not been determined, a level of 2% of dry matter or higher is generally recommended. Unfortunately, the arginine levels in most dog foods are not available