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Property "Has original text" (as page type) with input value "Ellagic Acid
This is a family of phenolic compounds present in fruits and nuts, including raspberries, blueberries, strawberries, pomegranate juice, and walnuts. In laboratory experiments it has been shown to potently inhibit the growth of various chemical-induced cancers, with the basis of the effect being an arrest of cell division in the G stage, thus
inducing the programmed cell death known as apoptosis. While there have been no trials to assess its clinical effects with brain cancer, a recent clinical trial, performed at UCLA with prostate cancer demonstrate its potential (288). Patients with prostate cancer, whose PSA levels were rising after initial treatment with either surgery or radiation, drank pomegranate juice (8 oz/ daily), which contains high levels of eligitannnins (precursors to ellagic acid). The dependent measure was the rate of increase in the PSA level, which typically rises at a steady rate for this category of patients. Pomegranate juice produced �an increase in PSA doubling time, from 15 months at baseline to 54 months after consuming the juice. Of the 46 patients in the trial, 85% exhibited a notable increase in the doubling time, and 16% had decreases in their PSA.
Fish oil (source of omega-3 fatty acids)
The major omega-3 fatty acids found in cold-water fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have also been demonstrated to have potent cytotoxic effects on cancer cells in various laboratory experiments. Part of their mechanism of action is similar to that of GLA, in that the metabolism of these fatty acids creates high levels of free radicals. In addition, a recent laboratory study has shown that EPA-treated tumors showed a significant arrest of cell division due to inhibition of cyclins at the G1 phase of cell division, which resulted in an increased rate of programmed cell death known as apoptosis (241).
A clinical trial comparing fish-oil supplements versus a placebo has also been reported, involving patients with several different types of advanced cancer (242). Thirty malnourished patients suffering from cachexia were randomly assigned to receive 18 g of fish oil per day or a placebo sugar pill. An additional thirty subjects, adequately nourished, received a similar random assignment. For both groups the fish oil significantly increased survival. For the malnourished patients the median survival times, as estimated from their survivor functions, were 110 days for the patients receiving placebo and 210 days for patients in the fish oil group. For the adequately nourished patients, the corresponding numbers were 350 versus 500 days.
In laboratory studies (243) fish oil has also been shown to increase the effectiveness of chemotherapy and radiation. A phase II trial involving 25 heavily pretreated metastatic breast cancer patients, used 1.8 g/day of DHA, one of the two major fatty acids in fish oil, in combination with standard anthracycline-based chemotherapy (244). Patients previously had failed both chemotherapy and hormone treatments and many had multiple metastases, including many liver metastases. Because this was a phase II trial, there was no control group that received chemotherapy alone, but patients were subdivided according to their level of plasma DHA. The two groups were approximately equal with respect to all major prognostic variables. Median survival for the high DHA patients was 34 months, vs. 18 months for the low-DHA patients.
A second clinical trial presented 2200 mg of EPA plus 240 mg of DHA to patients with advanced non small cell lung cancer (245). Patients either received only the standard of care of chemotherapy, or the same treatment in combination with daily fish oil. Response rate (tumor regressions) was 60% in the fish oil group and 26% in those receiving only the standard of care. One-year survival was 60% in the fish oil group versus 39% in those receiving only chemotherapy. Chemotherapy toxicity was also decreased in those using fish oil." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
Property "Has original text" (as page type) with input value "Celebrex (and other NSAIDs)
Carcinogenesis of several types involves an inflammatory process. When anti- inflammatory drugs such as aspirin or ibuprofen are taken on a regular basis the incidence of colon cancer is reduced as much as 50%. This substantial effectiveness has motivated investigation of the mechanisms of these benefits. One component of the inflammatory process is angiogenesis, which is now believed to be a critical component of cancer growth. COX-2 enzymes play an important role in inflammation, so that COX-2 inhibitors should reduce angiogenesis and inhibit tumor growth. Many nonsteroidal anti- inflammatory drugs (NSAIDs) are known to be COX-2 inhibitors, but most (e.g., ibuprofen) also inhibit COX-1 enzymes, which are necessary for healthy maintenance of the stomach lining, which is why many users of NSAIDs eventually develop intolerance to them. Thus, much recent attention has been given to the new COX-2 inhibitors such as Celebrex that were developed to avoid COX-1 inhibition for the purposes of arthritis treatment. Because inhibition of angiogenesis is one of the major new approaches to the treatment of cancer, some oncologists have begun adding Celebrex to their regular treatment protocols, based on laboratory findings that COX-2 inhibitors inhibit tumor growth. In recent meetings of American Society for Clinical Oncology (ASCO), there
have been various clinical trials reported that combined one or another COX-2 inhibitor with conventional radiation, chemotherapy, and new targeted treatments. The great majority of these were phase 2 clinical trials which had only historical controls with the conventional treatment alone to assess the value of the added COX-2 inhibitors, but most concluded there appeared to be a significant benefit, Some larger randomized clinical trials (115, 116) have shown substantial outcome improvements when celebrex has been added to standard chemotherapy protocols, but others have failed to find a benefit.
Two clinical trials have been reported that have used celebrex in the treatment of gliomas In a clinical trial conducted jointly by several hospitals in New York, Temodar was combined with celebrex (117). For the 46 patients in the study (37 with GBM), the PFS-6 was 35%. However, an unusual schedule of Temodar was also used, so whether the results were due to the new schedule or the celebrex is uncertain. Celebrex has also been combined with CPT-11 (118), a chemotherapy agent used widely for colon cancer, with �patients with recurrent tumors, and produced a PFS-6 value of 25%.
Because of the mild toxicity of NSAIDS, considerable recent research has investigated the mechanisms of their clinical benefit. Whereas initial research focused on the anti- angiogenic properties of this class of drugs, several other mechanisms have been identified, including the enhancement of various aspects of the immune system, and inhibition of the genes that prevent damaged cells from undergoing apoptosis (119). It is critical to note that many of the mechanisms by which NSAIDS work are strongly involved in the growth of high-grade gliomas, and that the expression of the cyclooxygenase enzyme that is the target of COX-2 inhibitors correlates strongly with the proliferation rate of glioblastoma tumors and correlates inversely with survival time (120, 121)." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.
