Uncaria tomentosa (Ut)—Adjuvant Treatment for Breast Cancer: Clinical Trial

9th Monday, 2012  |   Breast Cancer, Herb or Compound  |  no comments

do Carmo Santos Araújo M, Farias IL, Gutierres J, et al. Evidence-Based Complementary and Alternative Medicine Volume 2012 (2012), doi:10.1155/2012/676984

Ut or cat’s claw is a safe and effective adjuvant treatment in reducing adverse chemotherapy effects.
Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.

Uncaria tomentosa enables the stimulation of the immune system, increasing resistance to diseases when the body is immunosuppressed due to stress, malnutrition, or due to the effect of some medication.Many herbal medicines are used for various purposes, in various combinations (along with allopathic and homeopathic, medicines, etc.) based on historical or personal evidences generally not being associated with any adverse effects [1]. Therefore, this study, through a randomized clinical trial, evaluated the efficacy of Ut as a complementary therapy to chemotherapy.The cytotoxic effect of chemotherapeutic agents is not selective for neoplastic cells, being also harmful to other body cells. Hematopoietic suppression is the major complication limiting dosage of such cytostatic agents; neutropenia and thrombocytopenia are the most frequent ones [2]. Treatment should be discontinued when neutrophil count is below 500 cells/mm3 [3]. Thus, the success of the treatment process depends on the neutrophils content. Prevention of chemotherapy-induced neutropenia should be considered a clinical priority [4]. Once it is known that neutropenia predisposes to serious infections, often resulting in delays in treatment cycles and dose reductions.

Treatment using a daily dose of 300 mg dry Ut extract was effective in reducing the main chemotherapy effect, which is neutropenia. The effects of chemotherapy on blood cells tend to become more pronounced during treatment. However, our results show that in cycle six, which corresponds to the end of chemotherapy, the differences in the leukocytes and neutrophils counts were even more significant, as the group that was supplemented with Ut presented values twice as high of neutrophils when compared to the cancer group (without supplementation). In the group without supplementation, 67.89% of patients had neutropenia. Similarly, there was an increase in activated monocytes, as the activated precursors were common to both strains.Our findings are corroborated by other studies that had already shown that the Ut extract has a stimulating effect on growth and differentiates the CFU-GM from mice bone marrow and spleen, using the model for listeriosis [5]. Increased leukocytes numbers were also detected using Ut aqueous extract for six consecutive weeks in volunteers [6]. The recovery of leukocytes was also observed in mice using a model for chemotherapy-induced leukopenia (Doxorubicin) using Granulocyte Colony-Stimulating Factor (Neupogen) as a positive control [7].

Our group confirmed these results using a model for ifosfamide-induced neutropenia in mice, which caused a severe neutropenia. Bioassays showed that treatment with Ut significantly increased neutrophils counts, and a power of 85.2% was calculated in relation to Filgrastim (rhG-CSF) at the corresponding doses tested (5 and 15 mg/day of Ut, and 3 and 9 mcg/day Filgrastim, resp.) [6]. Through in vitro assays in human hematopoietic stem precursor cells (hHSPCs) obtained from umbilical cord blood (UCB), we reach the conclusion that this effect happened due to proliferation of Forming Units-Granulocyte-Macrophage (CFU-GM) [6].In this study, no differences were observed in lymphocyte counts between groups, either supplemented or not with Ut, over the chemotherapy cycles; however, its counts presented decrease due to chemotherapy when compared to the control group. These differences were not observed in the CD4+ and CD8+ subpopulations.This paper reports the effects of different Uncaria tomentosa extracts. The aqueous extract that has the highest concentration of quinic acid and low concentrations of oxindole alkaloids, being related to immunomodulatory properties is mediated by cytokines such as TNF-

Five Cancer Practices That Must Stop

9th Monday, 2012  |   Others  |  no comments

From Medscape Medical News > Oncology http://www.ccsettings.com/blog-posts/five-cancer-practices-that-must-stop/?goback=.gde_3660202_member_130001990 by Zosia Chustecka April 5, 2012 — Five common cancer procedures and tests have been identified that are not supported by evidence and should no longer be used, according to the American Society of Clinical Oncology (ASCO). Oncologists should stop the unnecessary use of chemotherapy in patients with advanced cancers who are unlikely to benefit, and should limit their use of colony-stimulating factor (CSF) drugs in patients undergoing chemotherapy. They should also curb their use of advanced costly imaging technologies for staging of early breast and prostate cancers, and for detecting breast cancer recurrences. These recommendations, compiled after an extensive review of the literature and with input from more than 200 ASCO members, were published online April 3 in the Journal of Clinical Oncology. The move is part of the Choose Wisely campaign, organized by the American Board of Internal Medicine, in which many different medical specialties identified tests and procedures that could be skipped. In total, 45 procedures and tests were deemed unsupportable by evidence. This campaign started when Howard Brody, MD, PhD, professor of family medicine at the University of Texas in Galveston, challenged each medical specialty to take a critical look at its field and identify 5 practices that are commonly performed despite a lack of evidence (N Engl J Med. 2010;362:283-285). “At ASCO, we took that challenge to heart,” lead author Lowell Schnipper, MD, from the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, and chair of the ASCO Cost of Care Task Force, said in a statement “By tackling the overuse of treatments and tests for some of the most common cancers, we hope to achieve substantial improvements in the quality of cancer care in the United States,” he added. Avoiding treatments that have little or no benefit means that “we also do our part to address the unsustainable cost increases that threaten our nation’s healthcare,” said Michael Link, MD, president of ASCO. Stop Chemotherapy Perhaps the most controversial of the new proposals is the recommendation to stop using or to withhold chemotherapy in patients with advanced solid tumors who are unlikely to benefit, and to focus instead on symptom relief and palliative care. This whole area has stirred fierce debate in recent years, and attempts in the United States to introduce legislation for end-of-life discussions were stalled after accusations that this was a form of “soft euthanasia” and that these were “death panels” to persuade people not to use medical resources. In their paper, Dr. Schnipper and colleagues emphasize that stopping chemotherapy is recommended only for a specific subgroup of patients with advanced solid tumors — those with low performance states (3 or 4) who are not eligible for a clinical trial, and in whom there was no benefit from previous evidence-based interventions and no strong evidence supporting the clinical value of further anticancer treatment. “If a patient’s cancer has grown during 3 different regimens, the likelihood of treatment success is so poor and toxicity so high that further anticancer treatment is not recommended,” the authors write. They cite results from the largest series of patients with nonsmall-cell lung cancer (NSCLC) from the M.D. Anderson Cancer Center in Houston, Texas, which showed that only 2% had a documented response to third-line chemotherapy, and 0% had a response to fourth-line chemotherapy (Lung Cancer. 2003;39:55-61). However, despite the evidence for lack of effect, administering nth-line chemotherapy is common, the authors note. They cite several studies showing that many NSCLC patients receive 4 lines of chemotherapy, and that many patients with solid tumors are still being given chemotherapy within days of death. “This practice is not being driven by profit, but by a desire to help patients,” the authors note, and “by the inability of patients, families, and their oncologists to make end-of-life transitions.” Oncologists admit that they find this difficult, as previously reported by Medscape Medical News. Stopping chemotherapy can feel like failure and “giving up,” and sometimes patients or their relatives can demand more — in one instance, because the “chemotherapy cheers her up.” “Stopping anticancer treatment should always be accompanied by appropriate palliative and supportive care and referral to a hospice,” the authors state. “Best practice would be continuation of palliative care started concurrently at the time of diagnosis for ‘any patient with metastatic cancer and/or high symptom burden,” they add. This reiterates the recent provisional clinical opinion issued by ASCO. Limit Use of G-CSF Products Another recommendation related to chemotherapy is to cut down on the use of granulocyte CSF (G-CSF) products for the primary prevention of the chemo-induced adverse effect of febrile neutropenia. Two G-CSFs are available in the United States: filgrastim (Neupogen) and sargramostim (Leukine). ASCO guidelines state that G-CSFs are recommended in patients who have “a high risk” (more than 20%) of developing febrile neutropenia as a complication of chemotherapy. In practice, however, there is a “clear overuse of these agents.” Use is inconsistent; the products are used both appropriately and inappropriately, the authors write. They note that these products are “costly” and should be used only in patients who are at high risk of developing febrile neutropenia, as specified in the guidelines. Stay Away From High-Tech Imaging The remainder of the new recommendations steer oncologists away from using advanced imaging technology in specific groups of cancer patients. One instance is patients with early-stage prostate cancer and early-stage breast cancer, who have a low risk for metastasis. In these cases, advanced imaging technologies, such as positron emission technology (PET), computed tomography (CT), and radionuclide bones scans, should not be used to determine whether the cancer has spread, the authors note. “These tests are often used in staging evaluation of low-risk cancers, despite a lack of evidence suggesting that they detect metastatic disease or survival,” the authors state. “Unnecessary imaging can lead to harm through unnecessary invasive procedures, overtreatment, and misdiagnosis.” In addition to the potential harm from unnecessary exposure to ionizing radiation, best results with cialis as well as anxiety, there is also a huge monetary cost from such scans, the authors note. The list price of a fluorodeoxyglucose PET with concurrent CT scan is around $2500 to $5000, depending on the scan and location. In many instances, patients are directly responsible for a portion of these costs. The other instance where advanced imaging is discouraged is in patients who have been treated for breast cancer with curative intent who are now asymptomatic. “The majority of patients with breast cancer diagnosed today present with early-stage, node-negative disease that is found on screening mammography,” the authors write. “As a result of earlier diagnosis and the efficacy of adjuvant therapies…most of these women have a normal life expectancy and a low risk of recurrence.” Several studies have now shown that in such patients, there is no benefit from routine imaging with PET, CT, or radionuclide bone scans, or from serial measurement of serum tumor markers, including CEA, CA 15-3, and CA 27-29, the authors state. In addition to no benefit, there might be harm from false-positive results, leading to unnecessary invasive procedures, over-treatment, and misdiagnosis, they add. Instead, such patients should be followed with mammography, with careful attention paid to patient history and physical examination, they suggest. Breast magnetic resonance imaging is not recommended for routine surveillance, because it has a high-false positive rate. Lower Cost to Patients and Society Reconsidering the use of these top 5 cancer treatments, tests, and procedures is likely to improve the value of cancer care, the authors note. This means achieving the desired clinical outcome at the lowest cost to the patient and society. At the same time, each patient with a life-threatening disease is a challenge. In each case, the oncologist must take the unique features of each individual into consideration when making decisions on the management of their cancer, they add. Source: Schnipper LE, et al. J Clin Oncol. doi: 10.1200/JCO.2012.42.8375 Published online April 3, 2012.

This is the exception, not the rule

6th Friday, 2012  |   Uncategorized  |  no comments

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Toxicity in Chemotherapy — When Less Is More

3rd Tuesday, 2012  |   Others  |  no comments

Alessandro Laviano and Filippo Rossi Fanelli. N Engl J Med 2012; 366:2319-2320 June 14, 2012

Food is a potent inducer of metabolic responses. Specific nutrients enhance muscle accretion, while others modulate the inflammatory response or boost appetite. On the other hand, caloric restriction under normal conditions (i.e., the prolonged intake of approximately 20 to 40% fewer calories than are required) has been shown to protect against the development of chronic diseases.1 Exploiting the differential effects of food and its absence on metabolic pathways during disease may be one strategy to enhance the efficacy of drug therapies.
Significant improvements in the field of oncology have enhanced prevention, screening, early diagnosis, and treatment. Nevertheless, the prevalence of cancer remains high, the costs of treatment are great, and cures for most cancers have yet to be found. The possibility that a patient’s response to anticancer therapy might be improved through changes in diet is attractive, since this approach is likely to be affordable and readily accessible.
Normal cells and cancer cells differ in their ability to respond to fasting. In the absence of nutrients, normal cells switch their metabolism toward maintenance pathways, whereas tumor cells are unable to activate this protective response. The differences in metabolism between normal cells and cancer cells could be used to enhance anticancer therapy by selectively increasing the resistance of normal cells to chemotherapy — that is, by augmenting differential stress resistance rather than by developing more aggressive and toxic drugs

Figure 1. Modulating the Effects of Chemotherapy by Means of Fasting.
Chemotherapy-induced oxidative stress reduces the rates of both the proliferation and the survival of cancer cells. It yields an objective response that can be quantified on the basis of shrinkage of the tumor volume (Panel A). However, chemotherapy also affects normal cells, leading to toxic side effects. Lee et al.2 recently reported that short-term fasting before or after chemotherapy, or at both times, induces differential stress resistance in normal and cancer cells. In normal cells, fasting activates protective metabolic pathways that confer resistance to oxidative stress (Panel B). In contrast, yeast transformed with an activated oncogene is unable to turn on the protective response and thus remains sensitive to oxidative stress. Additional experiments using mouse models of human cancer showed that fasting specifically augments levels of oxidative stress and sensitivity to oxidative damage (e.g., that inflicted by chemotherapeutic agents) in cancer cells and that these effects are accompanied by DNA damage and apoptosis

Lee et al.2 recently described data that support this approach. They found that short-term starvation increased the sensitivity of yeast cells that expressed an activated form of oncogene to oxidative stress, and thus to chemotherapy, as compared with its effect on wild-type yeast cells. Also, they found that restricting glucose and growth factors in the culture medium for 24 hours before and 24 hours after treatment with doxorubicin and cyclophosphamide rendered 15 of 17 cell lines more sensitive to these drugs.

To confirm these effects in vivo, Lee et al. studied mice with subcutaneous allografts of murine cancers or xenografts of human cancer cells. They observed that 48 to 60 hours of food deprivation retards tumor growth, in some cases as effectively as chemotherapy does, and they noted a synergy between starvation and drug therapy. Then, to investigate the effects of short-term starvation on metastatic advanced cancer, they studied mice bearing melanoma, neuroblastoma, or breast-cancer cells and observed that fasting potentiated the effects of chemotherapy and extended survival in these animals. They investigated the molecular mechanisms underlying these biologic effects, although only in breast-cancer allografts. After fasting, proliferation-associated genes were down-regulated in normal tissues but were up-regulated or unaffected in cancer cells. In addition, levels of phosphorylated Akt and S6K were elevated in the cancer cells of animals that had fasted, suggesting that levels of oxidative stress and sensitization to oxidative damage (a primary effect of chemotherapy in these cancer cells) were increased.

It is tempting to integrate these exciting results into the current comprehensive approach to patients with cancer.3 But this action would be premature. During the period of refeeding after fasting, several of the experimental cancers observed by Lee et al. returned to a size similar to those in control animals. The use of caloric restriction, as opposed to short-term starvation, is not advised in patients with cancer who are already prone to malnutrition owing to the tumor or to the side effects of anticancer therapies. Studies in animals suggest that it could take months of caloric restriction to bring about an antitumor response in humans, if at all. Malnutrition would inevitably develop, leading to increased morbidity and mortality.

Clinical trials could be considered as a way of testing the effects of fasting or of restricting specific nutrients for 2 or 3 days during and after chemotherapy. With respect to palliative care, preliminary results suggest that the integration of differential stress resistance may enhance patients’ responsiveness to and compliance with anticancer therapies. In a case series of 10 patients with cancer who voluntarily underwent short-term fasting prior to or after chemotherapy (or at both times), fatigue, weakness, and gastrointestinal side effects were reduced.4 Clinical trials are currently under way to test the effect of short-term fasting on chemotherapy-associated toxicity (ClinicalTrials.gov numbers, NCT01304251, NCT00936364, and NCT01175837). Although strong evidence has yet to be obtained to support the use of differential stress resistance as achieved through fasting for improving the response to chemotherapy, it may not be long in coming.5

1. Fontana L, Partridge L, Longo VD. Extending healthy life span — from yeast to humans. Science 2010;328:321-326
2. Lee C, Raffaghello L, Brandhorst S, et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med 2012;4:124ra27-124ra27
3. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010;363:733-742
4. Safdie FM, Dorff T, Quinn D, et al. Fasting and cancer treatment in humans: a case series report. Aging (Albany NY) 2009;1:988-1007
5. Laviano A, Seelaender M, Sanchez-Lara K, Gioulbasanis I, Molfino A, Rossi Fanelli F. Beyond anorexia-cachexia: nutrition and modulation of cancer patients’ metabolism: supplementary, complementary or alternative anti-neoplastic therapy? Eur J Pharmacol 2011;668:Suppl:S87-S90

At the school in North Delta, 11584 Lyon Rd

3rd Tuesday, 2012  |   Uncategorized  |  no comments

Padua is a 2004 graduate of Glendale High School. Marine Corps Pfc. Edwin A. No Host Bar from 6 pm, Buffet Dinner at 7 pm. Also silent auction, Reverse Draw for $1,000, 50/50 draws. At the school in North Delta, 11584 Lyon Rd. According to official counts, more than 17,800 people have been infected with Ebola virus in this epidemic and more than 6,300 have died since this outbreak’s first known case in rural Guinea in December 2013. Many on the front lines believe the actual numbers are much higher and in any event, they continue to rise steeply. The virus has traveled to Europe and North America, where the resulting fear exceeded any actual threat to public health.

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