The concept of autointoxication maintains the colon is regarded as the human sewer, which stores partially-digested waste and toxic products, which could lead to myriads of diseases. [4-7] This has prompted the development of the enema system by physicians in earlier times, which is hypothesized to reduce exposure times between the colon and toxic by-products through the introduction of water and other types of fluids into the colon via the anus. [8, 9] Among the various methods of enema applications, one of the most practiced forms of enema that has been passed through generations until the modern-day is none other than the coffee enema. [10]

In the 1930s, Dr. Max Gerson was the first to repurpose the coffee enema in cancer treatment. [7]  Based on the concept of the Gerson Regimen, it is believed that caffeine in coffee enema can eliminate circulating toxic by-products located adjacent to the walls of the colon, as well as can cause bile duct dilation, resulting in the facilitation of toxic by-products expulsion hepatically. [7, 11]  The coffee enema has also been utilized in patients with allergies, asthma, urticaria (hives), dyslipidemia (high level of bad cholesterol in the blood), migraines, obesity, as well as chronic constipation.[7]

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Nutrition

Aside from caffeine, other substantial nutrients and anti-oxidative substances, such as melanoidins, polyphenolic compounds, and diterpenoid alcohols, were also noted to be highly enriched in coffee. [12-14]  Moreover, positive reactions to anti-oxidative reactions also were exhibited by chemical compounds detected in coffee, based on other scientific studies. [15]  Studies have shown that compounds like kahweol and cafestol, which are glutathione S-transferase (GST)-augmenting anti-oxidative enzymes, are also found in coffee. [12]  Roasting coffee could also subsequently lead to the formation of melanoidins, which also act as a lipid peroxidation inhibitor,[16] as well as an antioxidant.[13]  Additionally, antioxidative properties are also displayed by caffeic acid, chlorogenic acid and other similar phenolic compounds,[14]  while powerful DNA-protective properties are exhibited by caffeine and other related xanthines. [17]

The procedure of the coffee enema typically involves the introduction of diluted, warm coffee fluid of approximately 500 ml through the anal canal into the rectum and colon, where the patient will usually be required to hold the coffee enema solution for approximately 10 to 15 minutes prior to defecation. [7] However, the amount of caffeine expected to be absorbed is limited. [7] Gerson further addressed that boiled coffee that has not been passed through fine paper filters, or simply unfiltered boiled coffee, is most preferred due to its highly concentrated anti-oxidative bioactive molecules.[2]

Teekachunhatean and colleagues mentioned in their studies that with the aforementioned volume and duration, single or even multiple applications of coffee enema would not result in detrimental hemodynamic effects on the enema users because the half-life of caffeine is only around 24 hours [18]  Their previous studies also unveiled that multiple administrations of up to three times per week did not alter the male subjects’ hemodynamics or produce any electrolyte disturbances. [15]  Despite the fact that coffee enema is claimed to be safe even with multiple doses, caffeine is mainly metabolized via cytochrome P-450 1A2 (CYP1A2), [19] a liver enzyme which is genetically expressed at different levels in each individual. [7]  Thus, individuals who have a more extensive expression of CYP1A2 will theoretically have less circulating caffeine, while those with lower expression of this particular enzyme will have more circulating caffeine, possibly leading to more conspicuous hemodynamic effects. [7]

When the administration of coffee enema is not properly carried out, it could also lead to rectal damage induced by the boiling coffee enema, [20, 21] inflammation of the colon and rectum (proctocolitis), [22, 23] gastrointestinal-related systemic infection (septicemia) [24], and even death. [25] Therefore, only trained individuals using sterilized tools should be permitted to carry out this procedure. [7] Also, the coffee enema is contraindicated (not advised) in patients with gastrointestinal conditions such as colorectal cancer, diverticulitis, recent bowel surgery, colostomy, hemorrhoids, intestinal obstruction, and Crohn’s disease. [7]

Coffee is highly-enriched with various kinds of nutrients and its application in medicine has been implanted in our society since ancient times. [1]  Today, the coffee enema is becoming more and more prevalently practiced, especially in integrative cancer settings. The major medical benefits of the coffee enema are hypothesized to be associated with anti-oxidative properties as well as its ability to detoxify circulating toxins from the liver. [11, 13, 14] The previously mentioned coffee enema method of application was based on Gerson’s regimen, but in real life practice, the type of coffee, volume, duration of coffee fluid retainment can vary depending on each individual’s preference, [7]  however, severe side effects can result. [20-25] To avoid this, a coffee enema is best administered by skilled personnel. [7]

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As cancers are becoming more and more resistant to standard chemotherapy and other forms of treatments, different kinds of drugs have to be developed to more specifically tackle these issues. One treatment that is becoming more prevalent is targeted cancer therapy.

Targeted cancer therapy blocks a specific molecular target, either by inhibiting a specific protein or gene that is important for cancer cell growth, progression, or metastases (spread of cancer). [1] In contrast to the traditional chemotherapy that targets all rapidly-proliferating cells, be it normal or cancer cells, targeted therapy explicitly thwarts cancer cells, and does not cause damage to rapidly-dividing normal cells. [1]

Like standard chemotherapy, targeted therapies also consist of many different subtypes, including hormonal therapies, signal transduction inhibitors, gene expression modulators, apoptosis (cell-death) inducers, angiogenesis (new blood vessel formation) inhibitors, immunotherapies, and toxin delivery molecules. [1]

Immunotherapies

One of the more common and readily available types of targeted therapy is the immunotherapies, which are monoclonal antibodies that exhibit inhibitive effects on over-amplified genes, such as human epidermal growth factor receptor 2 or simply referred to as HER-2. [2] This gene is known to be up-regulated on the surface of epithelial cells and is responsible for cellular growth, differentiation, as well as tumorigenicity, especially in gastric and breast cancer cells. [2–6]

Over-expression or gene amplification of HER2 is implicated in approximately 20-25% of all invasive breast cancer and typically associated with poorer prognosis.2 HER2-positive breast cancer is regarded as the second-poorest prognosis as compared to the other subtypes and is also generally corresponded with poorer disease-free and overall survival rates. [3]

Since up-regulation of HER2 is observed in many types of cancer — especially breast cancer, which is also associated with poorer prognosis — treatment that specifically targets this gene may be of particular interest and will confer great therapeutic benefits for these groups of patients. Trastuzumab, or Herceptin, a recombinant humanized monoclonal antibody that directly targets the extracellular domain IV of HER2 was the first targeted cancer therapy ever to be approved by the Food and Drug Administration (FDA), with clinical evidence showing high success rates for treating breast cancer. [3, 5]

Herceptin has been approved by more than 125 countries as standard therapy for HER2-positive patients with locally advanced or metastatic breast, gastric or gastroesophageal junction (GEJ) cancer. [7]

Herceptin can be administered either intravenously (into a vein) or subcutaneously (under the skin); many clinical studies have revealed that serum concentration of the subcutaneous Herceptin is on par to that of the intravenous counterpart, both of which could achieve a complete pathological response. [8] Based on recent statistical reports, more than two million breast cancer patients were treated with Herceptin, 80,000 of which received it subcutaneously. [9]

Furthermore, the subcutaneous forms of Herceptin can also either be delivered via a hand-held syringe from a subcutaneous vial or a single-use injection device (SID), which is less time-consuming and associated with less pain, discomfort and other related side-effects according to patients’ feedbacks. [9]

As an adjuvant therapy

Herceptin is typically administered as adjuvant therapy in patients who either display over-amplified HER2 with positive nodal status alone or negative nodal and hormone-receptor status (ER/PR negative) together with one high-risk feature. High-risk features include tumor size more than 2cm, tumor grade 2 or 3 and age less than 35 years. Adjuvant Herceptin is generally given as a regimen consisting of Doxorubicin, Cyclophosphamide, and either Paclitaxel or Docetaxel. It can also be administered in conjunction with Docetaxel and Carboplatin or solely after receiving multi-modal Anthracycline-based treatments. [10]

In patients with over-amplified HER2 metastatic breast cancer, Herceptin is to be administered in conjunction with Paclitaxel as the first-line therapy, while it is to be delivered as a single agent for HER2-positive patients who had undergone at least one chemotherapeutic regimen. [11] Moreover, those with HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma without prior treatment are recommended to have Herceptin along with Cisplatin and Capecitabine or 5-Fluorouracil.

According to research studies, Herceptin should be administered for one year with a one-week or three-week interval, depending on the regimen. [10]

Three mechanisms of Herceptin on cancer cells have been proposed: [3,10]

• It can lead to degradation of HER2 on cancer cells;
• It can lure immune cells to HER2-over-expressed tumor sites, referred to as antibody-dependent cellular cytotoxicity (ADCC);
• The most established action of this drug is its ability to inhibit MAPK and PI3K/Akt pathway, which eventually leads to cell cycle arrest and termination of cell growth and proliferation.

Are there side effects?

Side effects commonly found in breast cancer patients receiving Herceptin include fatigue, fever, increased cough, difficulty breathing, nausea, vomiting, infusion reactions, diarrhea, headache, rash, neutropenia (low number of neutrophils), anemia and muscle pain. [12] In the worst-case scenario, it can result in cardiotoxicity but is typically reversible. [13]

The most common side effects related to Herceptin for metastatic gastric cancer include diarrhea, fatigue, neutropenia (low number of neutrophils), anemia, stomatitis (inflammation of mouth and lips), weight loss, upper respiratory tract infections, fever, thrombocytopenia (low number of platelets) and mucosal-related inflammation. [12]

Targeted cancer therapy, such as Herceptin, serves as a promising therapeutic option since it can specifically impede certain over-expressed proteins or genes in malignancy, especially in breast and gastric cancers. This drug is typically delivered post-chemotherapy or an adjunct to chemotherapy, which leads to cancer cell death via several cellular mechanistic actions.

Adverse side effects are typically mild, and mostly are gastrointestinal-related symptoms; however, in the worst-case scenario, it can lead to cardiac problems. Thus, prevention of such adverse events can be avoided by close monitoring of the patient throughout and after the course of the therapy. [14]

Despite the possible occurrences of adverse side effects, clinical evidence has shown that Herceptin is well-tolerated. [7] It also has been approved as the standard treatment in treating HER2-positive cancers along with other chemotherapeutic agents due to the increased disease-free, progression-free, as well as overall survival rates of this drug. [2,5]

The post Herceptin as a targeted therapy for breast cancer appeared first on Cancer Tutor.