Two proteins interact in a previously unknown molecular mechanism that may have broad implications in future studies looking for the causes of defective organs in fetuses, metastatic cancers and other diseases, according to researchers at Cincinnati Children’s Hospital Medical Center.

Reporting their work in Genes & Development, the researchers said the mechanism coordinates cell identity and behavior in the forming organs of embryos.

“Our study helps address the current challenge of finding out where cell specificity comes from, how cells do what they do in the context of disease and development, and how these activities are regulated,” said Aaron Zorn, Ph.D., a researcher in the division of Developmental Biology at Cincinnati Children’s and the study’s corresponding author. “This helps inform research into how we tell early stem cells what to become. If someone has diabetes, for example, how do we tell a cell to become a pancreas cell so it will produce insulin?”

The study involved embryos of Xenopus frogs, a species indigenous to Africa often used in early biomedical studies. The scientists discovered a signaling protein very common in developmental biology, Wnt11 (Wingless), has to be inhibited by the modulating protein Sfrp5 (Secreted Frizzled Related Protein), a known antagonist of Wnt. Without this restriction, Wnt signaling runs amok and the frog’s foregut, liver and pancreas form improperly from a cascade of disorganized cell growth.

“We point out that Wnt has two key roles here - one controlling the cell expression pathway to tell cells what they are supposed to be, and the other controlling the pathway for cell movement, behavior and adhesion,” said Dr. Zorn, also associate professor of pediatrics at the University of Cincinnati (UC) College of Medicine. “Without Sfrp5 controlling what Wnt does in both pathways, things go horribly wrong in the developing foregut and its organs.”

The Wnt signaling pathway is a complex network of proteins best known for their role in stimlating cell behavior during embryo development and in cancer. They also are involved in normal physiological processes in adult animals. Parts of the Wnt pathway have been conserved between species during the long course of evolution, all the way from simple roundworms to humans.

Previous research in Xenopus has established that a low level of activity from a molecule called B-catenin - which promotes cell-to-cell adhesion and is part of the Wnt pathway - is necessary to maintain accurate foregut formation and initiate liver and pancreas development. Unknown before the study by Dr. Zorn’s team was which Wnt genes are involved and how Wnt and B-catenin activity are regulated along the frog’s developing anterior-posterior body axis.

During the very early phases of embryo development - when the organism is still essentially flattened layers of cells called an endoderm - Dr. Zorn’s team found Wnt’s stimulation of B-catenin must be restricted in the anterior region so the tissue of forming foregut organs maintain its integrity. Their experiments showed that Sfrp5 steps in at the right time and place to repress Wnt signaling, allowing the cells to form an epithelial sheet, or lining - an essential step in organ development.

Read the rest of this entry »

Primary HCC is a major cancer related to HBV viral infection in Asian countries, including Japan. Recently, the primary liver cancers are successfully treated by surgical resection including liver transplantation and non-surgical locoregional therapy. Although infrequently, extrahepatic spread to the lungs occurs. So-called lung metastasis from liver cancer is a dilemma, because it is often believed that diseases are very advanced and too late for adequate treatment. It is partly true that most of the patients with lung metastasis from liver cancer do not survive for more than 1 year. However, surgical resection has gained the benefit of better survival in a selected group. It is not well understood regarding when and how to undergo surgery for lung metastasis. Although small in numbers, successful results after collaborative treatments for lung metastasis from liver cancers were achieved.

Read the rest of this entry »

Brain tumour advocates throughout the world have achieved their target of walking the equivalent of three times the distance around the Earth at the Equator.

The target was 120,000 kms and 28,618 walkers in over 100 separate walks in 15 different countries in North and South America, Europe and Asia, have so far reached a combined total of 123,024 kms with more results still to arrive.

Read the rest of this entry »

A study published in the journal Clinical Cancer Research, a journal of the American Association for Cancer Research, validates a non-invasive screening method with future potential for detection of human papillomavirus (HPV)-positive head and neck cancers.

Read the rest of this entry »

NEW YORK (Reuters Health) Nov 03 - Etravirine, a new nonnucleoside reverse-transcriptase inhibitor (NNRTI), appears safe in combination with other antiretroviral drugs for treating HIV-1 infection, according to a report in the October 1st issue of Clinical Infectious Diseases.

“For the most part, etravirine appears to be safe and well tolerated in the short term and the same can be stated for the long term,” Dr. Julio Montaner from University of British Columbia, Vancouver, Canada told Reuters Health.

Read the rest of this entry »

NEW YORK (Reuters Health) Nov 03 - A vaccine based on a recombinant replication-limited Mycobacterium bovis BCG mutant, designed for immunosuppressed patients, is safer and more efficacious than BCG in a guinea pig model of pulmonary tuberculosis, according to a report in the November issue of Infection and Immunity.

Read the rest of this entry »

November 4, 2008 — Because unvaccinated healthcare personnel (HCP) can be a primary cause of influenza outbreaks in healthcare settings, the US Food and Drug Administration (FDA) is urging healthcare organizations to ensure that HCP have access to influenza vaccination programs.

“Annual workplace immunization programs decrease the likelihood of contracting influenza and the chance of infecting others,” the FDA states in a Center for Biologics Evaluation and Research bulletin. “Therefore, the mission to ensure patient safety in each health care setting should include influenza vaccination of personnel.”

Although the protective effects of immunization are well documented, only 40% of US HCP are vaccinated each year, according to estimates by the US Centers for Disease Control and Prevention. Evidence to date suggests that low rates of HCP vaccination increase the risk for influenza outbreaks in hospitals and other healthcare settings.

Read the rest of this entry »

NEW YORK (Reuters Health) Oct 27 - IMVAMUNE, a third-generation smallpox vaccine, can be safely given to HIV-infected patients; its immunogenicity in these patients is comparable to that seen in HIV-negative controls, the results of a phase 2 clinical trial suggest.

The vaccine could become important in the event of a biological attack with smallpox.

Dryvax and other classic, replication-competent smallpox vaccines can cause serious complications, particularly in immunocompromised individuals. IMVAMUNE, by contrast, is a non-replicative vaccine derived from the 1974 Modified Vaccinia Ankara strain.

Read the rest of this entry »

October 28, 2008 (Washington, DC) — A humanized monoclonal antibody, PRO 140, which targets CCR5-tropic virus, might be a viable approach to treating human immunodeficiency virus (HIV). Tantalizing data were presented here at the 48th Annual ICAAC/IDSA 46th Annual Meeting, a joint meeting of the American Society for Microbiology and the Infectious Diseases Society of America.

The results are from an interim analysis of the first 15 patients in a dose-escalation study. The patients had to have not started therapy or to have been off it for 12 weeks prior to enrollment. Their baseline averages were 35,480 HIV RNA copies/mL and a CD4 cell count of 403 cells/µL. A single dose of placebo or the monoclonal antibody was administered, and the patients were followed for 58 days.

Read the rest of this entry »

October 28, 2008 (Washington, DC) — Initiating vs deferring highly active antiretroviral therapy (HAART) at a CD4 count between 351 and 500 cells/mm³ is associated with a 70% reduction in mortality rates. The study was a late-breaker presentation here at the 48th Annual ICAAC/IDSA 46th Annual Meeting: A Joint Meeting of the American Society for Microbiology and the Infectious Diseases Society of America.

It entailed an unusual collaboration between all 22 HIV research cohorts in North America and a standardization of data to allow their integration and analysis. Patients were those with a CD4 count between 351 and 500 cells/mm³ who were in active follow-up between 1996 and 2006. Individuals with previous antiretroviral treatment and those who already had experienced an AIDS-defining illness (1993 Centers for Disease Control and Prevention criteria) were excluded.

Some 2473 patients initiated HAART (8358 person-years), whereas 5901 (16,636 person-years) deferred treatment during the period of the study. Those who began therapy were more likely to be male sex, older, have a lower Centers for Disease Control and Prevention count, and have a higher viral load at baseline, but the median differences between the 2 groups were not large.

Those who deferred starting HAART had a mortality relative hazard 1.7 times that of patients who began therapy within that CD4 range (P < .001).

Lead author Mari Kitahata, MD, a researcher at the University of Washington Center for AIDS Research, said the observational methodology they used should approximate the findings of a randomized clinical trial. The size and characteristics of the study also means that the results likely are applicable to most settings where HAART is widely available.

“These data strongly support the use of antiretroviral treatment for patients at a CD4 count of 500 and below, regardless of the presence of symptoms,” she later said at a news conference.

Read the rest of this entry »