fordoctors

Like to eat meat? Consider this unappetizing truth: When you gulp down a nice juicy steak or hamburger, you are contributing to tumor-fueling inflammation in your body.In fact, eating a diet rich in red meat has long been linked to a host of ills including an increased risk of several types of cancer. But what is it about meat consumption that could impact cancer growth? Now scientists at the University of California, San Diego School of Medicine, have found a mechanism that explains how eating red meat, as well as milk, could spur the growth of malignancies. The new study, headed by Ajit Varki, M.D., suggests that inflammation resulting from a molecule introduced through eating these foods could make cancer grow. The research is set for upcoming publication in the Proceedings of the National Academy of Sciences (PNAS).Dr.Varki, UC San Diego School of Medicine distinguished professor of medicine and cellular and molecular medicine and co-director of the UCSD Glycobiology Research and Training Center, and his research team studied a non-human glycan, or sugar molecule, known as N-glycolylneuraminic acid (Neu5Gc). Although this molecule is not produced naturally in the human body, it’s incorporated into human tissues if you eat red meat. The body then develops antibodies against Neu5Gc – and this immune response could potentially trigger a low-grade chronic inflammation, spurring the growth of cancer. In a statement prepared for the media, Dr. Varki explained it has been recognized by scientists for some time that chronic inflammation can stimulate cancer progression."We've shown that tumor tissues contain much more Neu5Gc than is usually found in normal human tissues. We therefore surmised that Neu5Gc must somehow benefit tumors,” Dr. Varki said in the press statement. So the scientists came up with this hypothesis: The fact that Neu5Gc accumulates in human tumors despite circulating anti-Neu5Gc antibodies suggests a low-grade, chronic inflammation has developed, and caused the tumor to grow. To test this idea, the researchers worked with specially bred mice. The animals lacked the Neu5Gc molecule , just as humans do before they eat red meat and the molecule is absorbed into their bodies, and they had tumors.Anti-Neu5Gc antibodies were given to half of the mice . In those animals, the antibodies induced inflammation and their cancers started growing faster. In the control group comprised of mice that were not treated with antibodies, their tumor growth was far less aggressive.Building on previous research that has shown that humans who take non-steroidal anti-inflammatory drugs (commonly known as NSAIDs) have a reduced risk of cancer, the researchers tried giving NSAIDs to the mice with cancerous tumors fueled by anti-Neu5Gc antibodies. The result? The anti-inflammatory treatment blocked the effect of the Neu5Gc antibodies and the tumors became smaller."Taken together, our data indicate that chronic inflammation results from interaction of Neu5Gc accumulated in our bodies from eating red meat with the antibodies that circulate as an immune response to this non-human molecule – and this may contribute to cancer risk," Varki said in the media statement.For anyone interested in reducing inflammation through natural, non-drug methods, here are seven top strategies to incorporate into your lifestyle:1. Stop eating meat and dairy products.2. Concentrate on a Mediterranean flavored style of eating with lots of fruits, vegetables, whole grains , olive oils and nuts. Research has shown these foods lower inflammation levels.3. Don’t smoke and avoid those who do – second hand smoke can contribute to inflammation.4. Know your oils. Avoid all inflammation-causing trans-fats, hydrogenated and partially hydrogenated oils as well as saturated animal fats. Instead, add inflammation-fighting omega-3 oils like flaxseed, canola and walnut oil to your diet.5. Lose weight if you need to. Research has shown that a waist that measures over 40 inches in a man or over 35 inches in a woman is a sign of probable high inflammation.6. Don’t skimp on sleep. Previous studies have concluded less than six hours of sleep can result in inflammation .7. De-stress. Try yoga, meditation, walking and other forms of exercise. Staying continually stressed out means your body is releasing excess, inflammation-promoting stress hormones . Schedule a minimum of 20 minutes a day to let your worries go.

Multiple Myeloma: Drug combination proves effective against myeloma in Phase I trial

Drug combination proves effective against myeloma in Phase I trialTwo "new generation" drugs for the bone marrow cancer multiple myeloma may work even better together than they do individually, according to the results of a multicenter Phase I clinical trial to be presented by Dana-Farber Cancer Institute scientists at the annual meeting of the American Society of Hematology in Orlando, Fla.The trial the first and largest reported to date to test the drugs bortezomib (Velcade®) and lenalidomide (Revlimid®) in combination involved 38 myeloma patients whose disease had recurred after previous treatment and was progressing despite other therapies. Participants were divided into groups that received successively higher doses of the drugs. Some also received dexamethasone, a standard myeloma medication which adds to the effects of both bortezomib and lenalidomide, if the combination alone no longer controlled their disease.The researchers, led by Paul Richardson, MD, and Ken Anderson, MD, of Dana-Farber, found that 58 percent of 36 evaluable patients responded to lenalidomide and bortezomib, including six percent who had complete remission, despite being heavily pre-treated and, in most cases, having received both classes of drug before. The median length of remission was six months, with some patients having disease control for up to two and a half years. The combined therapy also produced only mild fatigue or peripheral neuropathy (nerve damage signaled by tingling or numbness), researchers found. Patients who received dexamethasone because their disease continued to progress on the drug combination found the additional drug tolerable, and it produced a response or disease stabilization in about three quarters of them."It is remarkable to see the combination prove both tolerable and engender such durable responses in resistant disease," Richardson says. "We are hopeful that this combination will prove to be a key therapeutic backbone in improving outcomes for our patients, both early and later in their course."Both Velcade and Revlimid are relatively recent additions to doctors' arsenal against multiple myeloma. Velcade thwarts myeloma cells by interfering with their ability to break down and dispose of certain proteins. Revlimid also attacks the tumor cells directly and disrupts their interactions with surrounding tissue in the bone marrow.The trial was based on preclinical work that found Revlimid increases myeloma cells' vulnerability to Velcade and dexamethasone, which suggested that patients might benefit from a combination of them. The encouraging results of the Phase I study have prompted investigators to begin Phase II trials of the combined therapy in patients with newly diagnosed myeloma and in hard-to-treat, relapsed cases. Phase III trials are also planned.

Velcade: A New Strategy Treating Multiple Myeloma

Abstract: Velcade is a new drug that acts in a different way from typical chemotherapy drugs. It is rapidly becoming a standard treatment for patients with multiple myeloma who have relapsed after other treatments, and is now being explored in clinical trials in newly diagnosed patients. This article describes how this new drug works, its side effects, and its effectiveness. It also discusses new areas of research with Velcade in patients with multiple myeloma.Article: Velcade (bortezomib is the generic name) was approved by the Food and Drug Administration (FDA) in May 2003 for patients with multiple myeloma who had recurrence of disease after other treatments. It is the first proteasome inhibitor to be tested in humans and in early clinical trials Velcade showed impressive anticancer activity in patients with multiple myeloma. The proteasome is a multi-enzyme complex present in all cells that normally degrades proteins that regulate cell growth and proliferation. Such degradation is important for normal cellular function since it allows the cell to remove defective proteins that are no longer useful; proteasomes, therefore, ‘clean-up’ the cell. The ability of Velcade to inhibit the proteasome in myeloma cells results in the accumulation of excessive levels of these defective proteins. This forces the cell to undergo a specific type of cell death called apoptosis. Inhibition of the proteasome has also been shown to interfere with growth signals from other cells in the bone marrow which can stimulate myeloma cells. Thus, Velcade is a unique drug that does not work like typical chemotherapy agents that directly damage the DNA of rapidly dividing cells.Velcade’s dosing and administration schedule have been well established. It is administered intravenously (through a vein) over three to five seconds twice per week for 2 weeks followed by a 10 day rest period (or in terms of a 21-day cycle: days 1,4, 8 and 11). It is usually given for a maximum of 8 cycles, but if a patient has a good anti-cancer response and minimal side effects, then additional maintenance dosing may be given for a longer period of time. It is also common practice, for oral dexamethasone, a drug commonly used for multiple myeloma, to be given along with Velcade to improve the chance for response if little benefit is noted after the initial two cycles of Velcade alone. Velcade’s anti-cancer activity has also been well established in Phase I, II and III clinical trials. Phase I studies are done to determine the safety of a drug by treating patients with progressively higher doses and observing them closely for side effects (toxicity). A dose that causes an acceptable level of side effects is then chosen for future studies. In a Phase II trial the chosen drug dose is given to patients with a specific type of cancer to determine if the drug has anti-cancer activity, meaning can the drug shrink the tumor or improve the patient’s symptoms. In a Phase III trial, patients with a specific cancer are randomly assigned to receive either the new drug (or treatment) or standard treatment. The response rate and survival of each group of patients can be compared to determine if the new treatment is better than the pre-existing standard therapy. Many times a Phase III trial is required for a drug to receive approval from the FDA. In a large, multi-center, Phase II trial (called the SUMMIT trial), 193 patients with relapsed multiple myeloma were treated with Velcade. Thirty-five percent of patients showed a significant fall in their myeloma protein (1). Such a fall in the myeloma protein is called either a partial response (declines by >50 %) or a complete response or near complete response (complete or almost complete normalization of the myeloma protein). The overall response rate is defined as the percentage of patients who achieve either a partial, complete or near complete response. In the SUMMIT trial, 10% of patients experienced a complete or near complete response and 18% had a partial response. Importantly, over 90% of the patients in this trial had previously received three or more types of treatment for their disease and had not responded to their most recent treatment. The median duration of response to Velcade was 12 months, and patients with a response had improvement in quality of life, kidney function, and blood counts. In a recent large, randomized, multi-center trial (the APEX trial), the effectiveness of Velcade was compared to dexamethasone in 669 patients with relapsed multiple myeloma (2). The overall response rate was 38% in patients treated with Velcade and 18% in patients treated with dexamethasone. Thirteen percent of patients who received Velcade achieved either a complete or near complete response and 32% had a partial response. In contrast, only 2% who received dexamethasone achieved a complete or near complete reduction in the myeloma protein. Importantly, one-year survival was 80% in patients treated with Velcade versus 66% in those treated with dexamethasone. Response to Velcade is rapid, usually occurring within one or two cycles of the therapy. Based on the effictiveness demonstrated in these trials, Velcade has become a standard treatment for patients with myeloma who have relapsed following initial treatment.. Additionally, Velcade, unlike other anti-myeloma drugs such as melphalan, does not damage the blood stem cells and can therefore be given prior to a bone marrow transplant. Also, Velcade remains effective in patients whose myeloma cells exhibit a genetic deletion of DNA on chromosome 13q, an abnormality that confers resistance to several other anti-myeloma drugs (3).Velcade does have side effects such as nausea, vomiting, diarrhea, constipation, thrombocytopenia (low platelet count), fatigue, numbness or pain in the hands and feet, anemia (low red blood cell count), fever, and low blood pressure. Although a significant decrease in the platelet count (platelets circulate in the blood and prevent bleeding) occurs in about 30% of patients, the platelet count usually rebounds quickly before the next cycle of treatment (4). Numbness or pain in the hands and feet develops in 30-40% of patients. The condition is more frequent in those who have preexisting nerve injury (as can occur in patients with diabetes) or who have previously received certain types of chemotherapy (such as vincristine) that can cause nerve damage. In the initial phase II studies, 18% of patients discontinued Velcade therapy due to drug-related side effects (1). In the large APEX trial, 37% of patients discontinued Velcade early due to side effects (2). Reductions in the dose of Velcade can be made to improve or lessen certain side effects. Given the impressive response rates seen in patients with relapsed myeloma, Velcade is now undergoing testing in patients with symptomatic, newly diagnosed multiple myeloma. In two small trials, the combination of Velcade and dexamethasone as initial therapy resulted in an overall response rate greater than 65%, with over 20% of patients achieving a complete or near complete response (5,6). This high level of complete response is usually seen only after high-dose chemotherapy and stem cell transplantation. Most patients on these trials were able to complete Velcade therapy, and all were subsequently able to undergo successful stem cell harvest for stem cell transplantation. Studies in the laboratory or in animals have shown a potential benefit of combining Velcade with traditional chemotherapeutic agents. Research in myeloma cell lines demonstrated that Velcade made the cells more susceptible to traditional chemotherapeutic drugs, such as doxorubicin and melphalan (7). However, this was not the case for dexamethasone. Importantly, myeloma cell lines that were resistant to doxorubicin, became sensitive to doxorubicin in the presence of Velcade. For example, treatment of myeloma cells from a patient with refractory multiple myeloma with doxorubacin or Velcade alone did not result in cell death. However, the combination of the two drugs resulted in significant cell death. Early clinical testing of Velcade and doxil (a different formulation of doxorubicin) in patients with relapsed malignancies, showed that 16 of 22 patients with multiple myeloma had a significant response (8). Another study of Velcade and melphalan showed a response rate of 50%, with minimal toxicity (9). The combination of Velcade and thalidomide appears equally promising with an overall response rate of 60% and a near complete response rate of 20% in patients with relapsed myeloma (10). Many of these combinations with Velcade and other drugs are currently being further evaluated in large phase III randomized trials (11). Because of the high level of anti-myeloma activity seen with Velcade alone, and the high response rates noted when Velcade is used with doxil or dexamethasone we are testing the combination of all three agents in patients with both relapsed and newly diagnosed, symptomatic multiple myeloma. In the setting of relapsed disease, we have treated over 20 patients and noted that over 80% have demonstrated either a complete or partial response. While these results using combinations of Velcade and traditional chemotherapy are encouraging, they are early, and will need to be confirmed by larger trials in more patients. In summary, Velcade is showing impressive results in patients with relapsed multiple myeloma and is being tested in clinical trials in newly diagnosed patients. The role of Velcade combined with traditional chemotherapy and its role in relation to traditional bone marrow transplant remains to be determined from future clinical trials