PTEN hamartomatous tumor syndromes (PHTS): rare syndromes with great relevance to common cancers and targeted drug development

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor gene located on chromosome 10q22-23 that negatively regulates the pro-survival PI3K/Akt/mTOR pathway by functioning as a lipid phosphatase. Signaling through this pathway promotes cellular transformation and survival as well as resistance to chemotherapy and radiation. Loss of PTEN function is commonly observed in human cancers through somatic mutation, hypermethylation, and/or enhanced degradation. PTEN hamartomatous tumor syndromes (PHTS) are a collection of rare clinical syndromes marked by germline PTEN loss. Compared to the general population, PHTS patients have an increased risk of developing certain cancers and can develop benign tumors in virtually any organ. These patients provide a unique opportunity to examine the role of PTEN in human tumorigenesis, as well as study genotype-phenotype relationships. Because these patients are at higher risk of developing malignancies and have no established medical therapies, early screening, surveillance, and preventive care are important issues. Inhibitors of the PI3K/Akt/mTOR pathway that are being developed as cancer therapeutics could provide new therapeutic options for these rare patients, and could be credentialed as pathway inhibitors prior to testing in the general oncology population.     

Tobacco cessation in acute and critical care nursing practice: challenges and approaches

Recently, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) implemented new national core measures, including tobacco-cessation interventions for patients hospitalized because of pneumonia or other pulmonary-related illnesses, acute myocardial infarction, or heart failure. All interventions performed for such patients must be documented in the patient's chart. Because the JCAHO standards for tobacco cessation are implemented hospital-wide, acute and critical care nurses must take an active role in their execution. This article discusses the challenges to integrating tobacco cessation in daily acute and critical care nursing practice and makes recommendations regarding cessation approaches designed to improve health outcomes for tobacco-dependent patients.     

Predisposition to atypical teratoid/rhabdoid tumor due to an inherited INI1 mutation

BACKGROUND: Germline mutations of the INI1 gene predispose children to the development of rhabdoid tumors. Reports of familial cases, however, are extremely rare. PROCEDURE: We have identified a three-generation family in which two half-brothers were diagnosed with central nervous system atypical teratoid/rhabdoid tumors (AT/RT). The two boys, diagnosed at 2 months and 17 months of age, had a germline insertion mutation in exon 4 of the INI1 gene that was inherited from their healthy mother. A maternal uncle died in childhood from a brain tumor and a malignant rhabdoid tumor of the kidney, and presumably carried the same germline mutation. As the mother and uncle had different fathers, the grandmother is also an obligate carrier of the mutation. CONCLUSION: The identification of two unaffected carriers in a family segregating a germline mutation and rhabdoid tumor supports the hypothesis that there may be variable risks of development of rhabdoid tumor in the context of a germline mutation. There may be a developmental window in which most rhabdoid tumors occur. This family highlights the importance of mutation analysis in all patients with a suspected rhabdoid tumor.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.