Cancerous tumors sometimes form at the site of chronic wounds or injury, but the reason why is not entirely clear. Now researchers at Washington University School of Medicine in St. Louis have engineered mice with a persistent wound-like skin condition, and the mice are helping them understand the tumor-promoting effects of long-standing wounds and injuries.

“The chronic skin condition in the mice led to the growth of skin tumors,” says Raphael Kopan, Ph.D., professor of developmental biology and of dermatology. “And what we learned from this process fit very well with the emerging realization that a tumor’s surroundings play a critical role in its development.”

Past clinical evidence has linked chronic skin wounds such as leg ulcers to an increased risk of skin cancer, and some scientists have suggested that chronic injury can predispose various organs to cancer.

In this study, published in the July 7 issue of Cancer Cell, the researchers found that the chronic skin condition led to secretion of molecules that activated dermal cells, increased the number of blood vessels and increased local inflammation, reinforcing the idea that wound repair mechanisms and inflammation are important agents in promoting cancer. The skin condition was engineered in the mice by inactivating a gene called Notch1 in patches of skin cells, leaving the rest of the skin intact. Notch1 is a master controller for normal skin development and was thought to suppress tumor growth in skin cells in which it resides.

Without Notch1, patches of the mice’s skin developed abnormally and became thickened and inflamed. As the mice aged, benign tumors called papillomas formed. About 10 percent of these tumors spontaneously progressed to basal cell carcinoma, the most common type of skin cancer in people.

Importantly, further analysis showed that skin tumors had originated from both mutant and normal skin cells. Because normal cells contain active Notch1, they were not expected to form tumors, and that was an important clue that factors other than the missing Notch1 were responsible for tumor formation in skin.

“Loss of Notch1 signaling in the mutant skin cells generated a wound-like environment in which both the mutant and normal skin cells became prone to cancer,” Kopan says.

The research team showed that the mutant skin patches encouraged the growth of tiny blood vessels and production of growth factors that when expressed transiently help repair skin damage. The persistent expression of these factors provided cells with nutrients and proliferation signals that promoted tumor formation, Kopan says. Numerous immune cells secreting additional factors infiltrated the abnormal skin patches and adjacent cells, contributing to inflammation.

Recently, drugs that lower Notch1 activity have been used to manage Alzheimer’s disease and to treat some forms of cancer - because paradoxically Notch1 can be a tumor promoter in tissues other than skin. Kopan says that his study shows that skin is very sensitive to reduction of Notch1 activity. The long-term use of such medications and others that compromise skin integrity could contribute to an increased likelihood of skin cancer, he says.

“The study suggests that as researchers develop drugs, they should be mindful of their potential effect on the skin, particularly those that cause chronic damage to skin integrity,” Kopan says. “Studies like ours help define the range of possible complications in drug design and help tailor therapies to avoid them.”

The researchers also plan to use Notch-deficient mice to provide a system in which to identify molecules and cellular interactions responsible for the oncogenic effect of chronic wounds. Based on such analyses, new drug targets might be identified to develop therapies for cancers of the skin and perhaps other organs.

“It’s very reasonable to assume that chronic wounds in a variety of tissues have similar characteristics,” Kopan says. “The skin of these mice is easy to monitor and will give us the ability to further analyze tumor promotion and find answers that might apply to any chronic wound.”

Demehri S, Turkoz A, Kopan R. Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment. Cancer Cell. July 7, 2009.

Funding from the National Institute of General Medical Sciences supported this research.

Source:
Gwen Ericson

Washington University School of Medicine

How does Hollywood impact radiation perception? Can we treat cancer with microscopic particles acting like a Trojan horse? How does the radiation exposure our astronauts receive during space travel compare to their routine diagnostic radiology exams?

These and other questions will be addressed at the 54th Annual Meeting of the Health Physics Society (HPS), which will take place July 13-16, 2009 in Minneapolis, MN, at the Hilton/Minneapolis Convention Center. Approximately 900 attendees are expected, with nearly 280 presentations throughout the four days. The opening plenary session will highlight invited speakers from Lovelace Respiratory Research Institute, Washington State University and others discussing radiation doses from internally deposited radionuclides.

SPECIAL SESSIONS

Monday afternoon

1. Stakeholder engagement

2. Nanotechnology
   
   Current and future medical applications
   
   Risk-benefit and ethics

Tuesday morning

1. Indoor radon
   
   Measurement techniques
   
   Epidemiology

Tuesday morning and afternoon

1. Accelerators
   
   Mitigating radiation risks
   
   The Stanford synchrotron radiation lightsource

2. Power Reactors
   
   International and U.S. perspective on the nuclear energy resurgence
   
   Advanced technologies
   
   Public exposure considerations

3. Homeland Security
   
   Advanced detection to combat terrorism
   
   Global threat reduction initiative

4. Academy of Health Physics
   
   Radiation exposure of the U.S. population
   
   Health effects of ionizing radiation
   
   Indoor radon risk

Wednesday morning

1. Medical health physics
   
   CT dose assessments in clinical practice
   
   Medical events

2. Federal government nuclear detonation preparedness
   
   Effects and impacts in the urban environment
   
   Sheltering and evacuation recommendations

Wednesday morning and afternoon

1. Case studies in health physics
   
   Human factors at Three Mile Island
   
   Health effects of ionizing radiation
   
   Indoor radon risk

MORE HIGHLIGHTS

• Predicting cancer risks from naturally occurring radionuclides in drinking water (MPM)

• Upgrading the transuranium and uranium registries’ pathology database (MPM)
• Risks to armored combat vehicles occupants from depleted uranium (MPM)
• How does Hollywood impact radiation perception? Can we treat cancer with microscopic particles acting like a Trojan horse? How does the radiation exposure our astronauts receive during space travel compare to their routine diagnostic radiology exams?

  These and other questions will be addressed at the 54th Annual Meeting of the Health Physics Society (HPS), which will take place July 13-16, 2009 in Minneapolis, MN, at the Hilton/Minneapolis Convention Center. Approximately 900 attendees are expected, with nearly 280 presentations throughout the four days. The opening plenary session will highlight invited speakers from Lovelace Respiratory Research Institute, Washington State University and others discussing radiation doses from internally deposited radionuclides.

  SPECIAL SESSIONS

  
  Monday afternoon

  1. Stakeholder engagement

  2. Nanotechnology
     
     Current and future medical applications
     
     Risk-benefit and ethics

  
  Tuesday morning

  1. Indoor radon
     
     Measurement techniques
     
     Epidemiology

  
  Tuesday morning and afternoon

  1. Accelerators
     
     Mitigating radiation risks
     
     The Stanford synchrotron radiation lightsource

  2. Power Reactors
     
     International and U.S. perspective on the nuclear energy resurgence
     
     Advanced technologies
     
     Public exposure considerations

  3. Homeland Security
     
     Advanced detection to combat terrorism
     
     Global threat reduction initiative

  4. Academy of Health Physics
     
     Radiation exposure of the U.S. population
     
     Health effects of ionizing radiation
     
     Indoor radon risk

  
  Wednesday morning

  1. Medical health physics
     
     CT dose assessments in clinical practice
     
     Medical events

  2. Federal government nuclear detonation preparedness
     
     Effects and impacts in the urban environment
     
     Sheltering and evacuation recommendations

  
  Wednesday morning and afternoon

  1. Case studies in health physics
     
     Human factors at Three Mile Island
     
     Health effects of ionizing radiation
     
     Indoor radon risk

  MORE HIGHLIGHTS

  • Predicting cancer risks from naturally occurring radionuclides in drinking water (MPM)

  • Upgrading the transuranium and uranium registries’ pathology database (MPM)
  • Risks to armored combat vehicles occupants from depleted uranium (MPM)
  • Hollywood’s impact on radiation perceptions (MPM)
  • Exposure of the U.S. population from medical sources (TAM)
  • New study results related to low dose and low-dose rate radiation exposures (TAM)
  • Radiofrequency field strength fluctuations due to digital conversion of television signals (WAM)
  • Screening systems for personnel and cargo vehicles (WPM)
  • Radiation from granite countertops (THAM)

  The entire preliminary program can be found at http://hps.org/documents/54_annual_meeting_preliminary_program.pdf.

  Source:
  Kelly Classic
  
  Health Physics Society

  Tags: Medical Health Physics, Microscopic Particles, Stanford Synchrotron Radiation

  Comments (0)

  Non-Communicable Diseases - The Next Health Tsunami

  Posted by: admin in Prescription Cancer Drugs on July 16th, 2009

  The International Diabetes Federation (IDF), the International Union Against Cancer (UICC) and the World Heart Federation (WHF) havecalled on the UN’s Economic and Social Council (ECOSOC) to take immediate action to avert the fastest growing threat by non-communicable diseases (NCDs) to global health.

  NCDs which include cardiovascular disease, diabetes, cancer and chronic respiratory disease, cause 60% of all deaths globally and 80% of these are in low- and middle-income countries. WHO projects that globally NCD deaths will increase by 17% over the next 10 years. The greatest increase will be seen in the African region (27%) and the Eastern Mediterranean region (25%). The highest absolute number of deaths will occur in the W. Pacific and S.E. Asia regions.

  The global call, issued by the three organizations at the meeting of the UN ECOSOC in Geneva, demands five essential actions:

  1. Call for an ‘MDG Plus’ containing NCD progress indicators in the 2010 Millennium Development Goals (MDGs) review

  2. Support the availability of essential medicines for people living with NCDs
  3. Support a UN General Assembly Special Session on NCDs
  4. Support the immediate and substantial increase of funding for NCDs
  5. . Integrate NCD prevention into national health systems and the global development agenda

  The UN MDGs state that health is critical to the economic, political and social development of all countries, yet they contain no goals or targets for NCDs, which are the largest threat to health systems.

  Public health experts are expecting ECOSOC leaders to show the way in confronting this health crisis faced by millions. The emerging epidemic of NCDs is threatening to overwhelm healthcare systems worldwide unless action is taken.

  “This tsunami didn’t arise yesterday; it evolved over time and is getting worse. We need a revolution to change the trajectory if we are serious,” stated Dr Leslie Ramsammy, Minister of Health, Guyana at this morning’s WHO Ministerial breakfast meeting. The World Economic Forum’s 2009 Global Risks report supports this with evidence that the incidence of chronic disease is rising across both the developed and developing world. Medical advances and awareness can reduce the risk severity but chronic non-communicable diseases are still the main cause of death worldwide.

  Evidence shows that up to 80% of NCDs can be prevented by addressing risk factors like unhealthy diet, physical inactivity and tobacco use and those that are non-preventable can be treated inexpensively with essential medicines. While medicines such as aspirin, penicillin, insulin and morphine have been on the Essential Medicines List for years, they still remain beyond the reach of many.

  The three NGOs request that the final declaration of the ECOSOC High Level Segment include a call for NCD indicators to be included in the 2010 review of the MDGs to form an ‘MDG Plus’, as this fast emerging global threat has not, to date, been addressed.

  The three organizations together represent 730 member organizations in over 170 countries and vast networks of health care professionals, patient, and civil society organizations. They have joined forces to create a powerful voice for change and urge ECOSOC to take action in the face of the NCD epidemic.

  Source:
  Kerrita McClaughlyn
  
  International Diabetes Federation

  Tags: Millennium Development Goals, Un Ecosoc, World Heart Federation

  Comments (0)