Early detection of breast cancer based on gene-expression patterns in peripheral blood cells

Introduction

Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. In this study, we investigated whether early detection of breast cancer is possible by analyzing gene-expression patterns in peripheral blood cells.

Methods

Using macroarrays and nearest-shrunken-centroid method, we analyzed the expression pattern of 1,368 genes in peripheral blood cells of 24 women with breast cancer and 32 women with no signs of this disease. The results were validated using a standard leave-one-out cross-validation approach.

Results

We identified a set of 37 genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of these genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defense-related genes was increased in samples from breast cancer patients.

Conclusion

The results show that a blood-based gene-expression test can be developed to detect breast cancer early in asymptomatic patients. Additional studies with a large sample size, from women both with and without the disease, are warranted to confirm or refute this finding.     

Psychosine-induced apoptosis in a mouse oligodendrocyte progenitor cell line is mediated by caspase activation

Imidacloprid is an insecticide which has the nicotinic acetylcholine receptors (nAChRs) as its primary site of action; acetylcholine is the major excitatory neurotransmitter in the insect central nervous system (CNS). In this study, the action of imidacloprid was tested using the synapses of the respiratory central pattern generator of the beetle Tenebrio molitor. The no observed effect concentration (NOEC) for imidacloprid was estimated to be between 0.001 and 0.010 microM. A concentration of 0.10 microM caused hyperexcitation in firing of the respiratory motoneurons, while the concentration of 1.00 microM caused an abrupt increase in their frequency and then a complete inhibition of the activity of the respiratory motoneurons. The possible implication of the action of such low concentrations of imidacloprid in the contraction of the respiratory muscles is also demonstrated and discussed.     

Lymphangioma of the ovary after radiation due to Wilms' tumor in the childhood

OBJECTIVE: To report a case of lymphangioma of the ovary after radiation due to Wilms' tumor in the childhood. PATIENT: A 19-year-old nulliparous female. INTERVENTIONS: The vaginal ultrasound showed the left ovary enlarged to 4.4 cm x 2.9 cm x 4.5 cm in size including a 3.5 cm x 2.6 cm x 3.2 cm measuring cystic solid tumor without hypervascularity. For exclusion of a malignant tumor, a laparoscopy for excision of the tumor and deep incision of the left ovary with a bipolar needle was performed to exclude deeper tumor of stromal origin. The histological examination of the tissue showed a lymphangioma beside normal ovarian tissue. CONCLUSION: To our knowledge, this is the first report of lymphangioma of the ovary after radiation due to Wilms' tumor in the childhood. The impact of this finding on the patient's fertility remains unclear. As in other organs exposed to radiation, lymphangioma can also occur in the ovary. Careful follow up should be considered to this patients, because malignant transformation can not be excluded.     

New developments in the epidemiology and genetics of gout

The prevalence of gout appears to be rapidly increasing worldwide and is no longer a disorder suffered primarily by over-fed alcohol consumers. Emerging risk factors include longevity, metabolic syndrome, and new classes of pharmacologic agents. In some ethnic populations, no obvious risk factors can explain the high incidence of hyperuricemia and gout, suggesting a genetic liability. Studies to identify genes associated with gout have included families with defects in purine metabolism, as well as families in whom the occurrence of gout is secondary to renal disorders such as juvenile hyperuricemic nephropathy and medullary cystic kidney disease. Case-control studies of isolated aboriginal cohorts suffering from primary gout have revealed several chromosomal loci that may harbor genes that are important to the development and/or progression of gout.     

Cytosolic Phospholipase A2α Protects against Ischemia/Reperfusion Injury in the Heart

Studies with sPLA₂ Group X, and cPLA₂α gene‐targeted mice suggest that absence of sPLA₂ Group X results in protection from ischemia/reperfusion (I/R) injury in the heart, and absence of cPLA₂α Group IV is protective in the brain. Although latter studies might suggest a similar deleterious role for cPLA₂α in I/R injury in the heart, the pathophysiology of stroke is intricately related to excitotoxicity and cannot necessarily be extrapolated to the heart. We report here that unlike findings in the brain, cPLA₂α^(−/−) mice have exaggerated injury following I/R in vivo. In contrast, there is no difference in injury induced by simulated ischemia in cardiomyocytes isolated from cPLA₂α^(−/−) versus cPLA₂α^(+/+) mice. This suggests that cPLA₂α does not have an important cardiomyocyte autonomous effect on ischemic injury. Prostaglandin E₂ (PGE₂) levels are significantly reduced in the hearts of the cPLA₂α^(−/−) mice, and the enhanced injury is ameliorated by treatment with the PGE analog, misoprostol. We demonstrate that cPLA₂α is cardioprotective in vivo, and this is likely via cPLA₂α‐mediated production of cardioprotective eicosanoids. These studies are the first to identify a protective role for cPLA₂ in I/R injury in any organ and raise concerns over long‐term inhibition of cPLA₂. Clin Trans Sci 2011; Volume 4: 236–242     

Role of the progressive ankylosis gene in cartilage mineralization

PURPOSE OF REVIEW: Among the myriad of players in the calcification of cartilage, ANK is a relatively new entrant. It is a multipass transmembrane protein that regulates the transport of inorganic pyrophosphate between the cell and the extracellular space. Mutations in ANK result in two distinct calcification disorders: craniometaphyseal dysplasia and familial calcium pyrophosphate dihydrate deposition disease. The purpose of this review is to highlight recent work on the role of ANK in physiological and pathological calcification of articular and growth plate cartilage. RECENT FINDINGS: New information on the function of ANK suggests that the protein is part of a constellation of critical components that interact to regulate the elaboration of inorganic pyrophosphate. In addition to ANK, these components include alkaline phosphatase, the ectoenzyme PC-1, and osteopontin. ANK expression is also regulated by a variety of growth factors and cytokines that may further affect the transport of inorganic pyrophosphate and may be particularly relevant to the increased levels of expression of ANK in cartilage from chondrocalcinosis and osteoarthritis patients. SUMMARY: Additional studies will be required to understand the contribution of ANK in shaping the fine balance of components necessary for crystal deposition in degenerating articular cartilage. Furthermore, the precise role of inherited mutations in ANK on the elaboration of inorganic pyrophosphate, and the ultimate deposition of either basic calcium phosphate or calcium pyrophosphate dihydrate crystals, remains unclear.     

Alexithymia and breast cancer. Survey of 200 women undergoing mammography

The Schalling Sifneos Personality Scale (SSPS) and the Middlesex Hospital Questionnaire (MHQ) have been used in 381 women just before mammography at the Breast Center of the Radiology Institute, University of Bari (Italy). Of the 200 women who accepted to complete the questionnaires 13 were found positive for cancer. Student's t test comparison of the mean SSPS and MHQ scores of the positive for cancer with the negative showed that women with breast cancer have more pronounced alexithymic but not neurotic traits. Our findings suggest that patients with cancer may have something in common with those suffering from so-called psychosomatic pathologies who have a constrained imagination and fantasy and difficulty in verbalizing their emotions. Thus, this study indicates a relationship between alexithymia and cancer.