Archive for the ‘antiinflammatory’ Category

Cancer cells accelerate aging and inflammation in the body to drive tumor growth

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Posted 26 May 2011 — by James Street
Category antiinflammatory, Antioxidants, Inflamation, Nutrition and Cancer, Understanding Cancer

Researchers at the Kimmel Cancer Center at Jefferson show that a simple sugar, lactate, is like ‘candy for cancer cells’

PHILADELPHIA— Researchers at the Kimmel Cancer Center at Jefferson have shed new light on the longstanding conundrum about what makes a tumor grow—and how to make it stop. Interestingly, cancer cells accelerate the aging of nearby connective tissue cells to cause inflammation, which ultimately provides “fuel” for the tumor to grow and even metastasize.

This revealing symbiotic process, which is similar to how muscle and brain cells communicate with the body, could prove useful for developing new drugs to prevent and treat cancers. In this simple model, our bodies provide nourishment for the cancer cells, via chronic inflammation.

“People think that inflammation drives cancer, but they never understood the mechanism,” said Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology & Regenerative Medicine at Jefferson Medical College of Thomas Jefferson University and a member of the Kimmel Cancer Center. “What we found is that cancer cells are accelerating aging and inflammation, which is making high-energy nutrients to feed cancer cells.”

In normal aging, DNA is damaged and the body begins to deteriorate because of oxidative stress. “We are all slowly rusting, like the Tin-man in the Wizard of Oz,” Dr. Lisanti said. “And there is a very similar process going on in the tumor’s local environment.” Interestingly, cancer cells induce “oxidative stress,” the rusting process, in normal connective tissue, in order to extract vital nutrients.

Dr. Lisanti and his team previously discovered that cancer cells induce this type of stress response (autophagy) in nearby cells, to feed themselves and grow. However, the mechanism by which the cancer cells induce this stress and, more importantly, the relationship between the connective tissue and how this “energy” is transferred was unclear.

“Nobody fully understands the link between aging and cancer,” said Dr. Lisanti, who used pre-clinical models, as well as tumors from breast cancer patients, to study these mechanisms. “What we see now is that as you age, your whole body becomes more sensitive to this parasitic cancer mechanism, and the cancer cells selectively accelerate the aging process via inflammation in the connective tissue.”

This helps explain why cancers exist in people of all ages, but susceptibility increases as you age. If aggressive enough, cancer cells can induce accelerated aging in the tumor, regardless of age, to speed up the process.

The researchers’ findings were published online June 1st in the journal Cell Cycle in three separate papers.

One paper analyzes the gene profiles of the laser-captured connective tissue, associated with lethal tumors, in human breast cancer patients. In this paper, lethal cancers show the same gene expression pattern associated with normal aging, as well as Alzheimer’s disease. In fact, these aging and Alzheimer’s disease signatures can identify which breast cancer patients will undergo metastasis. The researchers find that oxidative stress is a common “driver” for both dementia and cancer cell spreading.

In another study, the researchers explain that cancer cells initiate a “lactate shuttle” to move lactate—the “food”—from the connective tissue to the cancer cells. There’s a transporter that is “spilling” lactate from the connective tissue and a transporter that then “gobbles” it up in the cancer cells.”

The implication is that the fibroblasts in the connective tissue are feeding cancer cells directly via pumps, called MCT1 and MCT4, or mono-carboxylate transporters. The researchers see that lactate is like “candy” for cancer cells. And cancer cells are addicted to this supply of “candy.”

“We’ve essentially shown for the first time that there is lactate shuttle in human tumors,” said Dr. Lisanti. “It was first discovered nearly 100 years ago in muscles, 15 years ago in the brain, and now we’ve shown this shuttle also exists in human tumors.”

It’s all the same mechanism, where one cell type literally “feeds” the other. The cancer cells are the “Queen Bees,” and the connective tissue cells are the “Worker Bees.” In this analogy, the “Queen Bees” use aging and inflammation as the signal to tell the “Worker Bees” to make more food.

Researchers also identified MCT4 as a biomarker for oxidative stress in cancer-associated fibroblasts, and inhibiting it could be a powerful new anti-cancer therapy.

“If lethal cancer is a disease of “accelerated aging” in the tumor’s connective tissue, then cancer patients may benefit from therapy with strong antioxidants and anti-inflammatory drugs,” said Dr. Lisanti. “Antioxidant therapy will “cut off the fuel supply” for cancer cells.” Antioxidants also have a natural anti-inflammatory action.

High percentage of omega-3s in the blood may boost risk of aggressive prostate cancer Conversely, high percentage of trans-fatty acids linked with lower risk

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Posted 25 Apr 2011 — by James Street
Category antiinflammatory, Diet and Prostate Cancer, Inflamation, Nutrition and Cancer

Contact: Kristen Woodward
kwoodwar@fhcrc.org
206-667-5095
Fred Hutchinson Cancer Research Center

SEATTLE – The largest study ever to examine the association of dietary fats and prostate cancer risk has found what’s good for the heart may not be good for the prostate.

Analyzing data from a nationwide study involving more than 3,400 men, researchers at Fred Hutchinson Cancer Research Center found that men with the highest blood percentages of docosahexaenoic acid, or DHA, an inflammation-lowering omega-3 fatty acid commonly found in fatty fish, have two-and-a-half-times the risk of developing aggressive, high-grade prostate cancer compared to men with the lowest DHA levels.

Conversely, the study also found that men with the highest blood ratios of trans-fatty acids – which are linked to inflammation and heart disease and abundant in processed foods that contain partially hydrogenated vegetable oils – had a 50 percent reduction in the risk of high-grade prostate cancer. In addition, neither of these fats was associated with the risk of low-grade prostate cancer risk. The researchers also found that omega-6 fatty acids, which are found in most vegetable oils and are linked to inflammation and heart disease, were not associated with prostate cancer risk. They also found that none of the fats were associated with the risk of low-grade prostate cancer.

These findings by Theodore M. Brasky, Ph.D., and colleagues in the Hutchinson Center’s Public Health Sciences Division were published online April 25 in the American Journal of Epidemiology.

“We were stunned to see these results and we spent a lot of time making sure the analyses were correct,” said Brasky, a postdoctoral research fellow in the Hutchinson Center’s Cancer Prevention Program. “Our findings turn what we know – or rather what we think we know – about diet, inflammation and the development of prostate cancer on its head and shine a light on the complexity of studying the association between nutrition and the risk of various chronic diseases.”

The researchers undertook the study because chronic inflammation is known to increase the risk of several cancers, and the omega-3 fatty acids found primarily in fish and fish oil supplements have anti-inflammatory effects. In contrast, other fats, such as the omega-6 fats in vegetable oil and trans-fats found in fast foods, may promote inflammation. “We wanted to test the hypothesis that the concentrations of these fats in blood would be associated with prostate cancer risk,” Brasky said. “Specifically, we thought that omega-3 fatty acids would reduce and omega-6 and trans-fatty acids would increase prostate cancer risk.”

The mechanisms behind the impact of omega-3s on risk of high-grade prostate cancer are unknown. “Besides inflammation, omega-3 fats affect other biologic processes. It may be that these mechanisms play a greater role in the development of certain prostate cancers,” Brasky said. “This is certainly an area that needs more research.”

Currently there is no official recommended daily allowance for omega-3 fats for adults or children, although many nutrition experts and physicians recommend 450 milligrams of omega-3 DHA per day as part of a healthy diet.

The study was based on data from the Prostate Cancer Prevention Trial, a nationwide randomized clinical trial that tested the efficacy of the drug finasteride to prevent prostate cancer. While the trial involved nearly 19,000 men age 55 and older, the data in this analysis came from a subset of more than 3,000 of the study participants, half of whom developed prostate cancer during the course of the study and half of whom did not. The clinical trial was unique in that prostate biopsy was used to confirm the presence or absence of prostate cancer in all study participants.

Among the study participants, very few took fish oil supplements – the most common non-food source of omega-3 fatty acids, which are known to prevent heart disease and other inflammatory conditions. The majority got omega 3s from eating fish.

So based on these findings, should men concerned about heart disease eschew fish oil supplements or grilled salmon in the interest of reducing their risk of aggressive prostate cancer? Brasky and colleagues don’t think so.

“Overall, the beneficial effects of eating fish to prevent heart disease outweigh any harm related to prostate cancer risk,” Brasky said. “What this study shows is the complexity of nutrition and its impact on disease risk, and that we should study such associations rigorously rather than make assumptions,” Brasky said.

###

The National Cancer Institute funded this study, which also involved researchers from the University of Texas Health Science Center at San Antonio and the NCI.

At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. www.fhcrc.org

How Curcumin Protects Against Cancer

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Posted 25 Mar 2011 — by James Street
Category antiinflammatory, Combination Treatments, Complementary Therapy, Inflamation, Natural Therapies, Nutrition and Cancer

Life Extension Magazine March 2011
Report

By J. Everett Borger
How Curcumin Protects Against Cancer

According to the American Cancer Society,1 one out of every three women in the United States risks developing some form of cancer over the course of their lives. For men, that number rises to one in two. Since cancer is an age-related disease, the risk of diagnosis increases the longer one lives, making it the second leading cause of death in this country.2,3

These data underscore a stark reality. When it comes to cancer prevention, the medical establishment and drug company profiteers remain grossly negligent in protecting the public. The result is countless avoidable cancer deaths each year. There is an urgent need to provide aging individuals with validated interventions to target cancer’s multiple causative factors before they take hold.

Among the most compelling and underrecognized of these is curcumin. In contrast to mainstream oncology’s focus on single-agent toxic treatments, curcumin has emerged as a potent multimodal cancer-preventing agent, with 240 published studies appearing in the global scientific literature in the past year alone.

In this article, you will learn of the multiple factors involved in carcinogenesis (cancer development). You will discover up-to-date research demonstrating curcumin’s power to disrupt specific molecular mechanisms that lead to cancer—and to even treat the disease in many cases.
System-Wide, Safe, Multimodal Defense

Curcumin is derived from the Indian spice turmeric and possesses several active components, all of which contribute to its anti-inflammatory and chemopreventive power.4-6 In fact, curcumin targets ten causative factors involved in cancer development.

Disrupting any one of these factors gives you a good chance of preventing cancer; disrupting several provides even greater protection, including the prevention of DNA damage.7

By blocking the inflammatory master molecule nuclear factor-kappaB (or NF-kB), curcumin blunts cancer-causing inflammation, slashing levels of inflammatory cytokines throughout the body.8,9 Curcumin also interferes with production of dangerous advanced glycation end products that trigger inflammation which can lead to cancerous mutation.10

Curcumin alters cellular signaling to enhance healthy control over cellular replication, which tightly regulates the cellular reproductive cycle, helping to stop uncontrolled proliferation of new tissue in tumors.11 It promotes apoptosis in rapidly reproducing cancer cells without affecting healthy tissue11-13 and reins in tumor growth by making tumors more vulnerable to pharmacologic cell-killing treatments.11,14

In addition, curcumin regulates tumor suppressor pathways and triggers mitochondrial-mediated death in tumor tissue, thereby increasing the death of cancer cells.11,15

Finally, curcumin interferes with tumor invasiveness and blocks molecules that would otherwise open pathways to penetration of tissue.2 It also helps to starve tumors of their vital blood supply and it can oppose many of the processes that permit metastases to spread.8,16,17 These multi-targeted actions are central to curcumin’s capacity to block multiple forms of cancer before they manifest.
Combating Deadly Cancers in Women

Breast cancers vary widely in their responsiveness to standard treatment. Cancers that depend on the hormone estrogen for survival are more effectively treated with conventional methods. Those that lack receptors for female hormones are far more resistant to treatment. This is where curcumin’s value truly lies, because it has the ability to induce apoptosis (programmed cell death) in a variety of hormone-negative cancers.18-20 Remarkably, curcumin produces virtually no change in healthy breast cells, with very low toxicity even at doses as high as 8,000 mg daily.21

In human cancer patients, curcumin doses as high as 3,600 mg a day have been shown to induce the following favorable anti-cancer effects:

* Paraptosis. A process similar to apoptosis (programmed cell death), curcumin initiates paraptosis only in breast cancer cells, resulting in their rapid destruction.22
* Targeted destruction of cancer-cell mitochondria (leaving mitochondria in healthy cells unaffected).22
* Disruption of the cancer cell cycle. Curcumin can “suspend” cancerous cells in a non-reproductive state within their life cycle, thereby halting their replication.20,23-25
* Cancer cell downregulation. Curcumin blocks a group of molecules vital to the process of metastasis. In animal models, it has been shown to reduce metastatic spread to the lungs via this pathway.17,26,27
* Arrested stem cell development. Curcumin inhibits growth and renewal of so-called cancer stem cells, aberrant cells now believed to be at the root of many cancers, including breast cancer.3,28

Combating Deadly Cancers in Women

Curcumin has also been shown to effectively combat cervical cancer, a leading cause of cancer death in women in developing nations and a common cancer in this country.29 It is caused largely by infection with the human papilloma virus, or HPV. Curcumin’s anti-inflammatory effects break the link that triggers HPV-induced cancer development.29,30

Curcumin further promotes apoptosis of cancer cells within the lining of the uterus and reduces the growth rate of painful but non-malignant uterine leiomyomas (uterine fibroids). 31-34

Collectively, these effects make curcumin attractive both as a primary chemopreventive agent in women at risk for breast cancer and an adjuvant treatment option in those who have already developed the disease.20,21
Prostate Cancer Defense

Prostate cancer is the second leading cause of cancer death in American men.35,44 Fortunately, its long latency period and slow growth rate make it a prime candidate for prevention.36 Curcumin strikes at multiple targets in prostate malignancies, interfering with the spread of cancer cells and regulating inflammatory responses through the master regulator NF-kB.36-38

Like certain breast cancers, prostate cancer is often dependent on sex hormones for its growth. Curcumin reduces expression of sex hormone receptors in the prostate, which speeds androgenic breakdown and impairs cancer cells’ ability to respond to the effects of testosterone.39-42 It also inhibits cancer initiation and promotion43 by blocking metastases from forming in the prostate and regulating enzymes required for tissue invasiveness.44
Combating Gastrointestinal Cancers

Colorectal cancer is the third most common malignancy in adults and the second leading cause of cancer deaths.45,46 Despite aggressive surgical care and chemotherapy, nearly 50% of people with colorectal cancers develop recurrent tumors.47 This may be due in part to the survival of dangerous colon cancer stem cells that resist conventional chemotherapy and act as “seeds” for subsequent cancers.3,48,49

On the other hand, these cancers are excellent candidates for prevention, since they follow a predictable sequence from non-malignant polyps to full-blown cancerous growths, usually requiring a decade to develop.46

Much as with malignancies of the breast, cervix, and prostate, curcumin slows the progression from colon polyp to cancer by damping down the inflammatory cascade triggered by NF-kB and pro-inflammatory cytokines.6 This halts the growth of cancer cells before they can become detectable tumors via a host of interrelated molecular mechanisms.50,51

Curcumin also creates a gastrointestinal environment more favorable to optimal colon health by reducing levels of so-called secondary bile acids, natural secretions that contribute to colon cancer risk.52 That has a direct effect, inhibiting proliferation of cancer cells and further reducing their production.53

Curcumin also suppresses colon cancer when combined with other polyphenols such as resveratrol.46,54 The combination of curcumin with green tea extracts has prevented experimentally induced colon cancer in rats.55

Curcumin also synergizes with standard chemotherapy drugs, helping to boost their efficacy and potentially reduce the dose of toxic chemotherapy products, minimizing needless harm and suffering for cancer patients.45,47-49 Curcumin increases colon cancer cell response to radiation.56

A novel feature of curcumin is its ability to bind to and activate vitamin D receptors in colon cells.57 Vitamin D is known to exert potent anti-cancer properties.

Curcumin is equally powerful at preventing cancers in the stomach. It inhibits growth and proliferation of human gastric cancer cells in the laboratory and is particularly effective in stopping cancers that have become resistant to multiple drug treatment.58-60 Curcumin can prevent gastric cancer cells from progressing through their growth cycle, blocking further tumor growth.60

Infection with the bacterium Helicobacter pylori (H. pylori) is a known cause of gastritis, peptic ulcer, and gastric cancer.61 Curcumin blocks growth of H. pylori and reduces the rate at which stomach cells react by turning cancerous.61,62 This effect is again related to curcumin’s fundamental ability to block activation of inflammatory NF-kB.62
What You Need to Know: Multimodal Anti-Cancer Power of Curcumin

*
Multimodal Anti-Cancer Power of Curcumin
Curcumin has emerged as a potent cancer-preventing agent, with 240 published studies appearing in the global scientific literature in the past year alone.
* Its multimodal effects act to simultaneously counter ten discrete causative factors in cancer development.
* It intervenes at each stage in the complex sequence of events that enable cancer cells to develop, proliferate, and metastasize.
* Its multitargeted mechanisms of action have yielded compelling results in combating a remarkably broad array of cancers, including those of the breast, uterus, cervix, prostate, and GI tract.
* A blossoming body of research reveals curcumin’s promise in countering cancers of the blood, brain, lung, and bladder as well.

Further Preventive Potential

Curcumin’s anti-inflammatory, antioxidant, and gene-regulating powers have been explored in preventing or treating cancers of the blood-forming system (leukemias, lymphomas, and myelomas) as well as those of the brain, lung, and bladder.12,13,63-81 Even aggressive tumors of the head and neck, often following years of smoking, are proving responsive to curcumin treatment.14,82-85 Curcumin is also emerging as a potentially effective intervention for pancreatic cancer—one of cancer’s most lethal and aggressive forms.86-90
Further Preventive Potential
Summary

Cancer is the second leading cause of death in the US, and the risk of developing the disease increases significantly as we age.

Curcumin has emerged as a potent cancer-preventing agent, with 240 published studies appearing in the global scientific literature in the past year. Curcumin’s multimodal effects act to simultaneously counter ten discrete causative factors in cancer development.

It intervenes at each stage in the complex sequence of events that must occur in order for a cancer to develop, progress, invade, and ultimately metastasize to healthy tissue.

The multi-targeted mechanisms of curcumin have yielded compelling results in combating a remarkably broad array of cancers, including those of the breast, uterus, cervix, prostate, and GI tract. A burgeoning body of research demonstrates curcumin’s potential to counter cancers of the blood, brain, lung, and bladder as well.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at
1-866-864-3027.
Ten Key Causative Factors in Cancer Development
Ten Key Causative Factors in Cancer Development

More than many other age-related diseases, cancer results from the cumulative effect of years of discrete, small-scale assaults on the body. Oxidation, inflammation, stress, infection, and other physiological insults take their toll, inflicting lethal damage over time that sets abnormal cell proliferation in motion.91,92

1. DNA damage. Numerous biomolecular assaults strike at the “blueprint” that cells need in order to replicate themselves accurately. DNA damage is often referred to as the “initiator” in cancer development—the first step in the onset of most cancers.

2. Excessive or chronic inflammation. Inflammatory processes trigger the release of a host of disruptive cytokines (cell-signaling molecules) that affect virtually all cellular functions. Inflammation is commonly referred to as a cancer “promoter” for this reason.

3. Disruption of cell signaling pathways. Normal communication within and between cells assures proper regulation of their healthy function. These pathways are easily disrupted by adverse events such as inflammation.

4. Alterations in the cellular reproductive cycle. Cells undergo a four-stage process as they prepare to replicate themselves. The cell cycle itself is controlled by signaling pathways that can be altered or disrupted at each of these stages.

5. Abnormal regulation of apoptosis. Apoptosis is the process of naturally “pre-programmed” cell death that prevents overgrowth of tissue. When apoptosis fails, cells may undergo uncontrolled reproduction.

6. Altered survival pathways. The flip side of unregulated apoptosis: survival of too many healthy cells, paradoxically, can endanger the host by permitting a cancer to take hold by increasing the odds of mutation and proliferation.

7. Excessive cellular proliferation. Certain hormones and other stimuli can directly trigger cells to reproduce without safe limits, especially when the preceding regulatory mechanisms have failed.

8. Aggressive invasion of healthy tissue. This is accomplished by excessive production of enzymes and adhesion molecules that “dissolve” tissue and allow the tumor to literally take root. The word “cancer” itself is derived from the crab-like appearance of fully-developed malignancies, which extend tendrils in all directions into healthy tissue.93

9. Rapid angiogenesis. Tumors require growth of new blood vessels for nourishment. They are endowed with the capacity to spontaneously generate new blood vessels just like healthy tissue. Angiogenesis in cancer tissue is a primary means by which tumors grow.

10. Metastasis. This is the migration of cancerous cells to regions of the body beyond the locus of the primary tumor. Metastases are the distinguishing features of most malignant cancers, and the typically herald the onset of end-stage disease because they disrupt otherwise healthy tissues.
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66. Cotto M, Cabanillas F, Tirado M, Garcia MV, Pacheco E. Epigenetic therapy of lymphoma using histone deacetylase inhibitors. Clin Transl Oncol. 2010 Jun;12(6):401-9.

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*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.

RNAi-mediated knockdown of cyclooxygenase2 inhibits the growth, invasion and migration of SaOS2 human osteosarcoma cells: a case control study

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Posted 06 Mar 2011 — by James Street
Category antiinflammatory, Human osteosarcoma research, Inflamation, Local Recurrence, Lung Metastases, Metastases, metastases, Molecular Osteosarcoma Studies, Osteosarcoma, Understanding Cancer

Cyclooxygenase2 (COX-2), one isoform of cyclooxygenase proinflammatory enzymes, is responsible for tumor development, invasion and metastasis. Due to its role and frequent overexpression in a variety of human malignancies, including osteosarcoma, COX-2 has received considerable attention.

However, the function of COX-2 in the pathogenesis of cancer is not well understood. We examined the role of COX-2 in osteosarcoma.

Methods: We employed lentivirus mediated-RNA interference technology to knockdown endogenous gene COX-2 expression in human osteosarcoma cells (SaOS2) and analyzed the phenotypical changes.

The effect of COX-2 treatment on the proliferation, cell cycle, invasion and migration of the SaOS2 cells were assessed using the MTT, flow cytometry, invasion and migration assays, respectively. COX-2, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) mRNA and protein expression were detected by RT-PCR and western blotting.

Results: Our results indicate that a decrease of COX-2 expression in human osteosarcoma cells significantly inhibited the growth, decreased the invasion and migration ability of SaOS2 cells.

In addition, it also reduced VEGF, EGF and bFGF mRNA and protein expression.

Conclusions: The COX-2 signaling pathway may provide a novel therapeutic target for the treatment of human osteosarcoma.

Author: Qinghua ZhaoChuan WangJiaxue ZhuLei WangShuanghai DongGaoqiao ZhangJiwei Tian
Credits/Source: Journal of Experimental &Clinical Cancer Research 2011, 30:26

Pervasis Therapeutics to Develop Novel Cell-Based Approach to Target Tumor Environment, Prevent Cancer Recurrence

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Posted 20 Jan 2011 — by James Street
Category Antiagiogenesis, antiangiogenesis, antiinflammatory, Inflamation, Local Recurrence, Lung Metastases, Metastases, metastases, Molecular, Personalized, Prostate Cancer, Targeted Cancer Therapy

Bolstered by Landmark Research and Multiple Preclinical Studies, Groundbreaking Therapy Holds Promise to Deliver Safe, Effective Cell Therapy Treatment for Solid Tumors

CAMBRIDGE, Mass., Jan. 19, 2011 /PRNewswire/ — Pervasis Therapeutics, Inc. today announced that the company is pursuing a matrix-embedded endothelial cell-based therapy (PVS-30200) to target and regulate cell stroma (the tumor environment or “ecosystem” that is comprised of various supporting cell types distinct from cancer cells) in order to prevent key processes that play a role in advancing solid tumor growth and metastasis (the spread of cancer cells to secondary locations). A cornerstone of Pervasis’ oncology program, the company has entered into an exclusive patent license agreement with the Massachusetts Institute of Technology (MIT) for all discovery and development activities associated with cellular implants for cancer diagnosis, prognosis and treatment. In addition, supportive evidence from multiple preclinical studies demonstrates the powerful anti-angiogenic, anti-proliferative and anti-inflammatory properties of this endothelial cell-based approach in the presence of various solid tumor cancers, such as brain, lung, breast and prostate.

Pervasis, a clinical stage company based in Cambridge, Mass., is focused on developing breakthrough cell-based therapies that harness the healing power of the endothelium, the thin layer of cells that lines the interior surface of every blood vessel in the body. The company’s other areas of clinical investigation include improving outcomes following common vascular surgical and interventional procedures, such as hemodialysis access, angioplasties, stents and peripheral and coronary bypass grafts — the failures of which result in serious complications and a significant increase in medical costs.

“We are very excited to expand our focus to include the critical area of oncology,” stated Frederic Chereau, president and chief executive officer of Pervasis. “We already have amassed a significant amount of data demonstrating the safety and efficacy of utilizing our novel cell-based approach to improve outcomes associated with the treatment of other serious conditions. We look forward to leveraging this body of knowledge to develop a novel therapy that could lead to a safer, more effective treatment for solid tumors, preventing cancer recurrence and improving outcomes for cancer patients.”

The Role of Endothelial Cells in Regulating Cancer Cell Behavior

Endothelial cells are critical to tissue repair and health, and have a well-understood role in regulating many of the body’s healing processes, including those associated with vascular repair. Endothelial cells work as the body’s “police force” — helping maintain homeostasis and control cells under a range of pathologic stresses. The research done at MIT upon which the licensed patent portfolio is based was led by Elazer Edelman, M.D., Ph.D., Professor of Health Sciences and Technology at MIT and Professor of Medicine at Harvard Medical School, and Joseph Franses, a graduate student in the MIT Division of Health Sciences and Technology. They demonstrated that endothelial cells are a critical component of the tumor cell stroma and serve a similar role in cancer biology as they do in vascular biology, regulating cancer cell behavior, and suppressing proliferation, invasiveness and inflammation.

There is growing evidence that invasive tumor growth results from communication between cancer cells and the surrounding host cell stroma. To that end, the breakthrough MIT research, which was published today in Science Translational Medicine(1), suggests that, in the tumor setting, quiescent endothelial cells are tumor-suppressive and slow the proliferation and invasiveness of cancer cells (as studied in culture and in animals), while disruption of the endothelial cells eliminates their ability to inhibit these actions that cause metastasis. Introducing exogenous functional, healthy endothelial cells to the stromal area can restore homeostasis.

“We are highly encouraged by our initial findings, as we believe they significantly advance our understanding of the critical role endothelial cells play in inhibiting many of the aggressive aspects of cancer,” stated Dr. Edelman, who is one of the original founders of Pervasis and a current member of the company’s Board of Directors. “We believe this research will open the door to vast horizons for future research and the development of novel therapies, and we look forward to the work Pervasis is undertaking to advance these concepts to the clinical stage.”

PVS-30200 – Advantages over Current Cancer Therapies

Many current approaches to treating cancer are plagued by significant limitations such as high toxicity and serious side effects, and are systemic in nature, unable to locally target tumors. In addition, despite addressing the primary tumor, metastasis remains one of the most challenging aspects of treating cancer, and is a process that is often unpreventable and uncontrollable.

PVS-30200 utilizes Pervasis’ proprietary implantable material comprised of healthy allogeneic endothelial cells embedded in a polymer matrix that is delivered locally at the time of tumor excision to prevent cell-proliferation, inflammation and angiogenesis, key processes that lead to tumor growth and survival. The well-studied patented technology on which PVS-30200 is founded has a proven safety profile, as demonstrated by data from six clinical studies, and can be administered and targeted locally at the site of the tumor. A novel cell therapy approach, PVS-30200′s use of allogeneic cells, as opposed to autologous cells, enables “off the shelf” administration, eliminating the challenging logistical processes that are involved with the use of autologous cells.

“We plan to present our preclinical findings as well as the PVS-30200 technology to the oncology community as soon as possible; we believe this therapy has the potential to dramatically advance the promise of cell therapy as an innovative and viable treatment paradigm for cancer,” said Mr. Chereau.

Pervasis’ Current Clinical Programs

Pervasis is currently conducting a Phase 1/2 clinical study of PVS-10200, an investigational new drug under development to prevent restenosis in patients with peripheral arterial disease who undergo angioplasty and stent placement in the superficial femoral artery. The company’s most advanced program, Vascugel®, has demonstrated proof of concept and safety in two Phase 2 trials in patients undergoing arteriovenous access procedures for hemodialysis. In 2010, Pervasis announced that it had reached an agreement with the U.S. Food and Drug Administration (FDA) for its Phase 3 clinical trial of Vascugel under the FDA’s Special Protocol Assessment (SPA) procedure. Through the SPA procedure, FDA formalized its agreement that the design of the Phase 3 trial was acceptable to support a regulatory submission seeking new drug approval.

About Pervasis

Pervasis Therapeutics, Inc. is a clinical stage company developing a broad portfolio of biologically active therapeutics. Building on its deep understanding of the specialized role that the endothelium plays in regulating natural healing and repair processes associated with disease, Pervasis is advancing groundbreaking new therapies to dramatically improve the outcomes of common vascular interventions, such as arteriovenous access, angioplasties, stents, and peripheral and coronary bypass grafts — the failure of which result in serious complications and a significant increase in medical costs. The company’s most advanced program, Vascugel®, has demonstrated proof of concept and safety in two Phase 2 trials in patients undergoing vascular access for hemodialysis. In addition, Pervasis is pursuing a cell-based oncology program focused on targeting and regulating cell stroma in order to prevent key processes that play a role in advancing solid tumor growth and survival. Pervasis is also applying its platform technology to develop products in other key therapeutic areas including inflammatory disease and orthopedic injury.

Pervasis is a privately held company with funding from Flagship Ventures, Polaris Venture Partners, Highland Capital Partners and the Richter Family Fund. For more information, please visit www.pervasistx.com.

This news release contains certain forward-looking statements that involve risks and uncertainties. Such statements are only predictions and the company’s actual results may differ materially from those anticipated in these forward-looking statements. Factors that may cause such differences include the timing of clinical trials, the risk that products that appeared promising in early research and clinical trials do not demonstrate safety or efficacy in clinical trials and the risk that the company will not obtain approval to market its products.

(1) J. W. Franses, A. B. Baker, V. C. Chitalia, E. R. Edelman, Stromal Endothelial Cells Directly Influence Cancer Progression. Sci. Transl. Med. 3, 66ra5 (2011).

Company Contact:

Margaret O’Toole

Pervasis Therapeutics, Inc.

617-871-1201

motoole@pervasistx.com

Media Contact:

Liz Falcone

Feinstein Kean Healthcare

617-256-6622

liz.falcone@fkhealth.com

Inflammation and Cancer

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Posted 30 Dec 2010 — by James Street
Category Alternative Therapies, antiinflammatory, Complementary Therapy, Diet and Prostate Cancer, Natural Therapies, Vitamins and Supplements

In the great war against cancer, conventional treatments like chemotherapy and radiation are at battle at the front lines with the goal of eliminating cancer. However, in recent years, researchers have begun to explore another way to conquer cancer by slowing a key process in the underlying development of the disease: inflammation.

More and more scientific evidence is pointing to the role of inflammation, a cornerstone of the body’s healing response, in the development of chronic diseases. On the body’s surface, it manifests as redness, heat, swelling and pain that has the purpose of bringing more nourishment and more immune activity to a site of injury or infection. Under normal circumstances, the inflammatory response is acute and necessary to boost defenses against microbial infection and spur tissue repair and regeneration. Unfortunately, many people have ongoing internal inflammation in their bodies and those pre-cancerous cells, when in the presence of chronic inflammation, have a prime opportunity to become cancerous.

The Inflammation-Cancer Connection

The relationship between inflammation and cancer has long been recognized. We know that bacterial infections such as Helicobacter pylori can induce inflammation that increases the risk of gastric cancer, and that the hepatitis C virus can bring on liver cancer. But how does a normal healing process go so haywire that it actually promotes disease?

The process of inflammation is initiated by cell-signaling chemicals known as cytokines which contribute to a variety of degenerative diseases. When these cytokines stay overactive long term, health conditions such as dysplasia (abnormal cellular development), and autoimmune disorders, such as lupus, rheumatoid arthritis and fibromyalgia can develop, inflammation is often one of the factors that causes the conversion of precancerous tissue to malignancy and likely what both initiates the disease and advances metastasis. Researchers think that this happens because many of the processes involved in inflammation such as leukocyte migration and dilatation of local blood vessels with increased permeability and blood flow, are more likely to contribute to tumor growth, progression and metastasis than to cause an anti-tumor response. Despite the strong association between chronic inflammation and cancer, scientists have not yet uncovered all the molecules, pathways, and mechanisms involved and many questions about their connection still remain to be resolved.

Treating Inflammation Naturally

Nevertheless, the strong link between cancer and inflammation makes it clear that we need to reduce the external factors that induce inflammation as a preventative measure. Stress, lack of exercise, genetic predisposition, and exposure to toxins all contribute to chronic inflammation and dietary choices also play a big role too. Eating plenty of fruits and vegetables, reducing saturated and trans fats, consuming a good source of omega-3 fatty acids, such as fish or fish oil supplements are very helpful. Reducing intake of refined carbohydrates such as pasta and white rice and eating plenty of whole grains, such as brown rice and quinoa, plus lean protein sources like chicken are other great ways to keep inflammation at bay.

4 Natural Inflammation Fighters

In terms of treatment, clinical trials for anti-inflammatory drugs (e.g., COX-2 inhibitors) to prevent cancer and as a treatment are already underway, but nature has an abundance of anti-inflammatory supplements and nutrients to offer us which can both lower cytokine levels and control the inflammatory response now. Here are a few of the top anti-inflammatory supplements out there that you can add to your nutritional protocol as effective preventatives:

Curcumin: The active ingredient in turmeric, curcumin, has been shown time and time again to be a star when it comes to modulating chronic inflammation. Curcumin has been demonstrated to be safe in numerous human trials and has demonstrated anti-inflammatory activity, which it may exert by inhibiting of different molecules that play a role in inflammation. The antioxidant properties of curcumin seem to prevent the development of numerous inflammation markers that oxidative stress can mediate.

Green tea: Studies have found that those who regularly drink green tea have less inflammation, lower LDL cholesterol and better endothelial function than those who do not. Green tea reduces C-reactive protein and green tea catechins can successfully banish cancer cells, by slowing metastasis, inhibiting cell proliferation and inducing apoptosis. For the best benefits, choose a green tea supplement of the active catechin, EGCG.

Bromelain: A mixture of enzymes found naturally in the juice and stems of pineapples, bromelain is sometimes used the treatment of inflammation and swelling of the nose and sinuses due to surgery or injury. This proteolytic enzyme is believed to help with the digestion of protein and since bromelain appears to be absorbed by the body intact, it is often marketed as a natural anti-inflammatory for conditions such as arthritis.

Medicinal mushrooms: There is growing evidence that the bioactive compounds in mushrooms act to modulate important immune cells, due to structural diversity and variability. Medicinal mushroom polysaccharides have some of the greatest potential for structural variability and the highest capacity for carrying biological information, which means they can stimulate the immune system to fight off cancer.

References:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994795/

http://www.lef.org/protocols/prtcl-017.shtml

http://www.ncbi.nlm.nih.gov/pubmed/12676044

Chiu J. et al. Nutrition. Sept 2009, 25(9): 964-972.

Senthil Kumaran V, Arulmathi K, Sundarapandiyan R, Kalaiselvi P. Attenuation of the inflammatory changes and lipid anomalies by epigallocatechin-3-gallate in hypercholesterolemic diet fed aged rats. Exp Gerontol. 2009; 44;12:745-51.

Ramesh E, Geraldine P, Thomas PA. Regulatory effect of epigallocatechin gallate on the expression of C-reactive protein and other inflammatory markers in an experimental model of atherosclerosis. Chem Biol Interact. 2010 Jan 5;183(1):125-32.

Zaidman BZ, Yassin M, Mahajna J, Wasser SP. Medicinal mushroom modulators of molecular targets as cancer therapeutics. Appl Microbiol Biotechnol. 2005;67:453-468. http://www.uspharmacist.com/content/d/in-service/c/13021/

Zebrafish ‘window on cancer’ shows birth of tumour – and body’s response

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Posted 14 Dec 2010 — by James Street
Category antiinflammatory, Educational, Immune System

15 Dec 2010
Scientists using translucent zebrafish as a “window on cancer” have been able to see in real time how tumour cells are born – and immediately attract cells from the immune system.

This inflammatory response seems to both attack and aid the cancer cells and the balance between the two provides a new therapeutic target for cancer researchers. It also links cancer to the wound healing process, which may even lead to anti-inflammatory drugs being used to treat cancer patients.

Dr Adam Hurlstone, of the University of Manchester’s Faculty of Life Sciences, explained: “This is a very exciting finding. It was a huge surprise to us to see the tumour cells detected by the immune system so quickly: a cancer cell appears, gives a signal and the body’s immune system is immediately alerted.

“The speed of the response and being able to see it so clearly in the zebrafish was very exciting.

“In addition we have established other novel aspects: that hydrogen peroxide is the signal molecule given by both wounded and transformed pre-cancerous cells to the immune system and that the carefully choreographed response can both attack and aid cancer cells at their very birth.

“This link between wound healing and cancer gives us new therapeutic targets and potential therapies such as anti-inflammatory drugs that have already undergone clinical trial.”

The study, published in PLoS Biology today (Tuesday 14 December 2010) and funded at the Manchester end by Cancer Research UK, was a collaboration between Dr Hurlstone, and the team of Professor Paul Martin, the University of Bristol, and of Dr Marina Mione, FIRC Institute of Molecular Oncology in Milan.

The team studied the onset of different cancer types, including melanoma, an extremely aggressive form of skin cancer, in zebrafish larvae. Zebrafish have been used to study embryonic development for years but it is only recently that they have become a popular species for modelling disease, and notably cancer. Mutations in their genes result in the same diseases as humans, while their transparency is extremely useful for seeing the disease’s progress.

The team found that the immune system’s leucocytes (white blood cells) home-in on sites containing only very few cancer cells. They also found that they had been attracted to the site by hydrogen peroxide produced by cancer cells and their neighbours, a molecule also used to trigger the immune system when the body is wounded. The leucocytes immediately began to work at the sites – some attacking the cancer cells, others providing stimulants to them.

Dr Hurlstone said: “We have returned to a classical concept that cancer is a wound that will not heal. We are asking, what is the significance of that? Inflammation is supposed to be a good thing – it is painful but specialist cells zoom in and eat the debris and secrete factors to heal a wound. So with inflammation in cancer, is it fighting or helping the disease? The answer is both.

“That has been addressed before but this is the first time it has been seen at the birth of cancer.

“We have now shown how quickly the immune system responds to cancer, what its role is in the progression of the disease and also made clear the parallels between cancer and wound healing (for instance, the common signal molecule hydrogen peroxide).

“This throws up some exciting leads in terms of clinical applications. We should look at inflammation again from a therapeutic perspective. Now we know the role of hydrogen peroxide in recruiting leucocytes to the area, producers and receptors of that molecule could become therapeutic targets. We could even see anti-inflammatory drugs being used for cancer. Another route is to target the immune system’s response in order to tip the balance from the leucocytes that heal to those that attack in cases of cancer.”

He added: “This study and its novel, significant findings was only possible because we used live cell imaging in the almost transparent zebrafish embryos.”
Notes for editors

Video and still images of immune system cells engulfing the area are available, along with copies of the paper ‘Live imaging of innate immune cell sensing of transformed cells in zebrafish larvae: parallels between tumor initiation and wound inflammation’.

For these or an interview with Dr Adam Hurlstone, contact Media Relations Officer Mikaela Sitford on 0161 275 2111, 07768 980942 or Mikaela.Sitford@manchester.ac.uk.