An association of HIV infection and noma in Niger

We report a case of noma having occurred in an adult female patient with HIV. The strain was characterized as HIV-1 group M subtype G. In order to explore the interactions between HIV/AIDS and this disease, we purpose systematic HIV screening for any case of noma, especially for adult patients.     

Cell lineage analysis of acute leukemia relapse uncovers the role of replication-rate heterogeneity and microsatellite instability

Human cancers display substantial intratumoral genetic heterogeneity, which facilitates tumor survival under changing microenvironmental conditions. Tumor substructure and its effect on disease progression and relapse are incompletely understood. In the present study, a high-throughput method that uses neutral somatic mutations accumulated in individual cells to reconstruct cell lineage trees was applied to hundreds of cells of human acute leukemia harvested from multiple patients at diagnosis and at relapse. The reconstructed cell lineage trees of patients with acute myeloid leukemia showed that leukemia cells at relapse were shallow (divide rarely) compared with cells at diagnosis and were closely related to their stem cell subpopulation, implying that in these instances relapse might have originated from rarely dividing stem cells. In contrast, among patients with acute lymphoid leukemia, no differences in cell depth were observed between diagnosis and relapse. In one case of chronic myeloid leukemia, at blast crisis, most of the cells at relapse were mismatch-repair deficient. In almost all leukemia cases, > 1 lineage was observed at relapse, indicating that diverse mechanisms can promote relapse in the same patient. In conclusion, diverse relapse mechanisms can be observed by systematic reconstruction of cell lineage trees of patients with leukemia.     

Education, income, occupation, and the 34-year incidence (1965-99) of Type 2 diabetes in the Alameda County Study

BACKGROUND: Lower socioeconomic position (SEP) is related to higher prevalence of Type 2 diabetes, yet little is known about the relationship of SEP with incident diabetes. METHODS: The association between SEP, measured by self-reported education, income, and occupation, and Type 2 diabetes incidence was examined in a community sample of 6147 diabetes-free adults from Alameda County, CA. Cox proportional hazards models estimated the effect of baseline (1965) and time-dependent (value changes over time) measures of SEP on incident diabetes over a 34-year study period (1965-99). Demographic confounders (age, gender, race, and marital status) and potential components of the causal pathway (physical inactivity, smoking, alcohol consumption, body composition, hypertension, depression, and health care access) were included as fixed or time-dependent covariates. RESULTS: Education, income, and occupation were associated with increased diabetes risk in unadjusted models. In baseline models adjusted for demographics, respondents with <12 years of education had 50% excess risk compared with those with more education [hazard ratio (HR) = 1.5, 95% confidence interval (95% CI) 1.11-2.04], but income and occupation were no longer significantly associated with increased risk. Further adjustment minimized the significance of all associations. Time-dependent effects were consistently elevated for low education and male blue-collar occupation, but non-significant after full adjustment (HR = 1.1, 95% CI 0.79-1.47 and HR = 1.3, 95% CI 0.91-1.89, respectively). CONCLUSIONS: Socioeconomic disadvantage, especially with low educational attainment, is a significant predictor of incident Type 2 diabetes, although associations were largely eliminated after covariate adjustment. Obesity and overweight appear to mediate these associations.     

CD24+ cells fuel rapid tumor growth and display high metastatic capacity

Introduction

Breast tumors are comprised of distinct cancer cell populations which differ in their tumorigenic and metastatic capacity. Characterization of cell surface markers enables investigators to distinguish between cancer stem cells and their counterparts. CD24 is a well-known cell surface marker for mammary epithelial cells isolation, recently it was suggested as a potential prognostic marker in a wide variety of malignancies. Here, we demonstrate that CD24⁺ cells create intra-tumor heterogeneity, and display highly metastatic properties.

Methods

The mammary carcinoma Mvt1 cells were sorted into CD24⁻ and CD24⁺ cells. Both subsets were morphologically and phenotypically characterized, and tumorigenic capacity was assessed via orthotopic inoculation of each subset into the mammary fat pad of wild-type and MKR mice. The metastatic capacity of each subset was determined with the tail vein metastasis assay. The role of CD24 in tumorigenesis was further examined with shRNA technology. GFP-labeled cells were monitored in vivo for differentiation. The genetic profile of each subset was analyzed using RNA sequencing.

Results

CD24⁺ cells displayed a more spindle-like cytoplasm. The cells formed mammospheres in high efficiency and CD24⁺ tumors displayed rapid growth in both WT and MKR mice, and were more metastatic than CD24- cells. Interestingly, CD24-KD in CD24+ cells had no effect both in vitro and in vivo on the various parameters studied. Moreover, CD24⁺ cells gave rise in vivo to the CD24⁻ that comprised the bulk of the tumor. RNA-seq analysis revealed enrichment of genes and pathways of the extracellular matrix in the CD24⁺ cells.

Conclusion

CD24⁺ cells account for heterogeneity in mammary tumors. CD24 expression at early stages of the cancer process is an indication of a highly invasive tumor. However, CD24 is not a suitable therapeutic target; instead we suggest here new potential targets accounting for early differentiated cancer cells tumorigenic capacity.

Electronic supplementary material

The online version of this article (doi:10.1186/s13058-015-0589-9) contains supplementary material, which is available to authorized users.